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Candida in potentially malignant oral disorders.
Sankari, S Leena; Gayathri, K; Balachander, N; Malathi, L
Oro-pharyngeal cancer is a significant component in the global burden of cancer. A considerable proportion of oral squamous carcinomas develop from preexsiting potentially malignant disorder of the oral cavity. The term potentially malignant oral disorders (PMD) were proposed for the precancerous lesions and conditions by World Health Organization in 2007. PMD are considered an in-between clinical state, which showed increased risk for cancer development. Etiology of PMD is multifactorial. Tobacco and alcohol are the major risk factors. In recent years, role of candidal infection is recognized as a significant factor in the development of PMD. There is an enduring discussion whether Candida infection can be a cause of PMD or a superimposed infection in a preexisting lesion. This article highlights the association between Candida and PMD. PMID:26015698
Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions
Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.
Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812
Advances in optical adjunctive AIDS for visualisation and detection of oral malignant and potentially malignant lesions.
Bhatia, Nirav; Lalla, Yastira; Vu, An N; Farah, Camile S
Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812
[Detection of potentially malignant and malignant lesions of oral cavity using autofluorescence visualization device].
Matsumoto, Kanako
Light-based oral cancer screening aids have been developed in identifying potentially malignant and malignant lesions of oral cavity at their earliest stage. The VELscope system is a simple hand-held device that facilitates the direct visualization of oral-cavity fluorescence for the detection of precancerous and cancerous lesions. Some published reports have shown that this system can assist in the detection of precancerous and cancerous lesions, but there is no evidence that it can distinguish between them. We studied whether objective discrimination criteria can be set for this system when observing oral mucosal lesions. We examined 74 cases with biopsy-confirmed oral mucosal lesions; 37 squamous cell carcinoma lesions, 14 moderate to severe epithelial dysplasia lesions, 13 mild epithelial dysplasia lesions and 10 lichen planus lesions. Lesions were examined macroscopically under the conventional overhead light, and then, examined by this device. Each examination was recorded with a digital camera. We contrasted findings with histopathological manifestation, and calculated the attenuation score. It is found that several conditions and sites, such as keratinization and the degree of inflammatory cell infiltration, were associated with detection sensitivity using this device. Based on the attenuation scores, a significant difference was seen between squamous cell carcinoma and epithelial dysplasia. It is suggested that this device might be a valuable adjunct in the early detection of potentially malignant and malignant lesions of the oral cavity. PMID:21827020
Oral lichen planus: progress in understanding its malignant potential and the implications for clinical management
Joel B Epstein; Laura S Wan; Meir Gorsky; Lewei Zhang
Oral lichen planus (OLP) is an inflammatory lesion that has malignant potential, but few cases of OLP progress to malignancy. A diagnosis of OLP should be confirmed on the basis of historical, clinical, and histologic data. The presence of dysplasia in an OLP-like lesion increases the risk of malignant transformation, mandating management and close follow-up. A molecular assessment of OLP
Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature
Gupta, Shikha; Gupta, Sunita
Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma.
Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature.
Gupta, Shikha; Gupta, Sunita
Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339
Oral potentially malignant disorders: A proposal for terminology and definition with review of literature
Sarode, Sachin C; Sarode, Gargi S; Tupkari, Jagdish V
Several attempts to produce internationally accepted terminologies and definitions of �oral precancer� have appeared in the literature. World Health Organizations (WHO) in 1972 subdivided �precancer� into �lesions� and �conditions� with their definitions. Recent working group of WHO is not in favor of such subdivision and recommended the use of the term �oral potentially malignant disorder (OPMD)�. This is mainly attributed to the recent advancement in molecular and genetic aspects of �oral precancer�. But efforts to define OPMDs are few in the literature. �Oral precancer� is ultimately colligated to oral squamous cell carcinoma (OSCC). With this semantics in mind, different OPMD and related terminologies in the literature used till date with their lexicographic analysis have been reviewed in the present paper. Attempt has also been made to propose desirable terminology and definition which suits to the current concept of OPMD. The proposed terminology and definition is based on the authors� opinions with a hope for further suggestions from readers. PMID:25364185
Malignant transformation of oral lichen planus
R. Rajentheran; N. R. McLean; C. G. Kelly; M. F. Reed; A. Nolan
Aims: To investigate the malignant potential of oral lichen planus (OLP), a common mucocutaneous disease of unknown aetiology. The malignant potential of OLP is still controversial, with studies reporting malignant transformation rates of between 0 and 5.6%. We also aimed to identify factors that might be associated with malignant transformation. Methods: We retrospectively reviewed the records of 832 patients with
Longitudinal evaluation of patients with oral potentially malignant disorders using optical imaging and spectroscopy
NASA Astrophysics Data System (ADS)
Schwarz, Richard A.; Pierce, Mark C.; Mondrik, Sharon; Gao, Wen; Quinn, Mary K.; Bhattar, Vijayashree; Williams, Michelle D.; Vigneswaran, Nadarajah; Gillenwater, Ann M.; Richards-Kortum, Rebecca
Dysplastic and cancerous alterations in oral tissue can be detected noninvasively in vivo using optical techniques including autofluorescence imaging, high-resolution imaging, and spectroscopy. Interim results are presented from a longitudinal study in which optical imaging and spectroscopy were used to evaluate the progression of lesions over time in patients at high risk for development of oral cancer. Over 100 patients with oral potentially malignant disorders have been enrolled in the study to date. Areas of concern in the oral cavity are measured using widefield autofluorescence imaging and depth-sensitive optical spectroscopy during successive clinical visits. Autofluorescence intensity patterns and autofluorescence spectra are tracked over time and correlated with clinical observations. Patients whose lesions progress and who undergo surgery are also measured in the operating room immediately prior to surgery using autofluorescence imaging and spectroscopy, with the addition of intraoperative high-resolution imaging to characterize nuclear size, nuclear crowding, and tissue architecture at selected sites. Optical measurements are compared to histopathology results from biopsies and surgical specimens collected from the measured sites. Autofluorescence imaging and spectroscopy measurements are continued during post-surgery followup visits. We examined correlations between clinical impression and optical classification over time with an average followup period of 4 months. The data collected to date suggest that multimodal optical techniques may aid in noninvasive monitoring of the progression of oral premalignant lesions, biopsy site selection, and accurate delineation of lesion extent during surgery.
Programmable bio-nanochip-based cytologic testing of oral potentially malignant disorders in Fanconi anemia.
Floriano, P N; Abram, T; Taylor, L; Le, C; Talavera, H; Nguyen, M; Raja, R; Gillenwater, A; McDevitt, J; Vigneswaran, N
Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage, is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nanochip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA and non-FA patients to brush biopsy samples of a FA patient with OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA-OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient's OPMD confirmed the presence of dysplasia. Our pilot data suggests that the p-BNC brush biopsy test recognized dysplastic oral epithelial cells in a brush biopsy sample of a FA patient. PMID:25662766
Evaluation of an autofluorescence based imaging system (VELscope�) in the detection of oral potentially malignant disorders and benign keratoses.
Awan, K H; Morgan, P R; Warnakulasuriya, S
Early detection of oral cancer is crucial in improving survival rate. Identification and detection of oral potentially malignant disorders (OPMD) allow delivery of interventions to reduce the evolution of these disorders to malignancy. A variety of new and emerging diagnostic aids and adjunctive techniques are currently available to potentially assist in the detection of OPMD. The objective of the present study was to evaluate the accuracy of autofluorescence against conventional oral examination and surgical biopsy. A total of 126 patients, 70 males and 56 females (mean age 58.5�11.9 years) who presented to the Oral Medicine Clinics at King's and Guy's Hospitals, London with oral white and red patches suspicious of OPMD were enrolled. Following a complete visual and autofluorescence examination, all underwent an incisional biopsy for histopathological assessment. Seventy patients had oral leukoplakia/erythroplakia, 32 had oral lichen planus, 9 chronic hyperplastic candidiasis and rest frictional keratosis (13) or oral submucous fibrosis (2). Of 126 lesions, 105 (83%) showed loss of fluorescence. Following biopsy 44 had oral epithelial dysplasia (29 mild, 8 moderate and 7 severe). The sensitivity (se) and specificity (sp) of autofluorescence for the detection of a dysplastic lesion was 84.1% and 15.3% respectively. While VELscope was useful in confirming the presence of oral leukoplakia and erythroplakia and other oral mucosal disorders, the device was unable to discriminate high-risk from low-risk lesions. PMID:21396880
DNA aneuploidy and dysplasia in oral potentially malignant disorders: association with cigarette smoking and site.
Pentenero, Monica; Giaretti, Walter; Navone, Roberto; Demurtas, Anna; Rostan, Isabella; Bertolusso, Giorgio; Broccoletti, Roberto; Arduino, Paolo Giacomo; Malacarne, Davide; Gandolfo, Sergio
To date there are still no reliable biomarkers for oral potentially malignant disorders (PMDs) to predict the risk of progression to squamous cell carcinoma (SCC). Within a prospective clinical trial of patients with PMDs, DNA content flow cytometry (DNA FCM) was evaluated for 60 PMDs using fresh samples obtained by a dermatological curette. There were 6/42 PMDs without dysplasia, but with DNA aneuploidy, versus 8/18 with both dysplasia and aneuploidy (p=0.02). When the tongue and the buccal mucosa, the two most common sites in the present series of cases were compared, dysplastic PMDs were mainly located on the tongue (p=0.01). Tobacco smokers, who preferentially developed PMDs in the buccal mucosa at a younger age than non-smokers (p=0.002), had fewer dysplastic PMDs than did non-smokers (p=0.01). Dysplasia was significantly linked to DNA aneuploidy (p=0.03) in smokers. The present data suggest that aneuploidy is an early event in oral carcinogenesis and that the influence of tobacco varies according to subsite and patient age. When DNA FCM of PMD samples are obtained by curette scraping, extensive areas can be covered with a minimally invasive, rapid, inexpensive procedure. Moreover DNA FCM of these samples appears easy amenable to routine analysis. Further research on larger numbers of PMDs should be carried out to determine whether DNA FCM plays a role in the prediction of risk of PMD transformation. PMID:19457703
Prevalence of oral cancer and potentially malignant lesions among shammah users in Yemen.
Scheifele, C; Nassar, A; Reichart, P A
The purpose of this study was to assess the prevalence of oral precancerous lesions and squamous cell carcinoma (OSCC) in Yemeni users of shammah, a traditional smokeless tobacco habit known in the Arabian Peninsula. The study group comprised 199 male and one female shammah users who were interviewed via a standardised questionnaire and clinically examined in 48 Yemeni villages and cities. Cases with oral leukoplakia (OL) or mucosal burns (MB) were compared with users without any lesion. MB were detected in 31%, of which 46.8% were located on the tongue or floor of the mouth, and OL in 27%, of which 59.2% were located in the same region. In addition, two cases (1%) of apparent OSCC were identified. Statistically significant increased OR (95% CI) of OL were (a) 6.91 (2.66-17.95) for an average duration of the respective shammah application >5min.; (b) 4.90 (1.99-12.08) for a daily frequency of those applications >10; and (c) 4.22 (1.43-12.43) for a daily duration >6h of chewing qat, also a traditional habit in Yemen. Likewise, decreased OR were (a) 0.39 (0.18-0.85) for rinsing the mouth after the shammah application; (b) 0.36 (0.17-0.78) for successful attempts to stop the use in the past; and (c) 0.26 (0.09-0.72) for existing knowledge about the carcinogenicity of shammah that was present in only 19% overall. In conclusion, evidence was shown for a significant association between the prevalence of OL and the daily duration of shammah application in a dose-dependent manner. An appropriate public health program might help to reduce this potential OSCC burden in shammah users. PMID:16759897
Malignancy Risk Models for Oral Lesions
Zarate, Ana M.; Brezzo, Mar�a M.; Secchi, Dante G.; Barra, Jos� L.
Objectives: The aim of this work was to assess risk habits, clinical and cellular phenotypes and TP53 DNA changes in oral mucosa samples from patients with Oral Potentially Malignant Disorders (OPMD), in order to create models that enable genotypic and phenotypic patterns to be obtained that determine the risk of lesions becoming malignant. Study Design: Clinical phenotypes, family history of cancer and risk habits were collected in clinical histories. TP53 gene mutation and morphometric-morphological features were studied, and multivariate models were applied. Three groups were estabished: a) oral cancer (OC) group (n=10), b) OPMD group (n=10), and c) control group (n=8). Results: An average of 50% of patients with malignancy were found to have smoking and drinking habits. A high percentage of TP53 mutations were observed in OC (30%) and OPMD (average 20%) lesions (p=0.000). The majority of these mutations were GC ? TA transversion mutations (60%). However, patients with OC presented mutations in all the exons and introns studied. Highest diagnostic accuracy (p=0.0001) was observed when incorporating alcohol and tobacco habits variables with TP53 mutations. Conclusions: Our results prove to be statistically reliable, with parameter estimates that are nearly unbiased even for small sample sizes. Models 2 and 3 were the most accurate for assessing the risk of an OPMD becoming cancerous. However, in a public health context, model 3 is the most recommended because the characteristics considered are easier and less costly to evaluate. Key words:TP53, oral potentially malignant disorders, risk factors, genotype, phenotype. PMID:23722122
Oral malignant melanoma--an unusual presentation.
Thomas, Priya Sara; Babu, Gogineni Subhas; Anusha, Rangare Laxman; Shetty, Shishir
Malignant melanoma is the least common but most deadly of all primary skin cancers. Oral malignant melanoma is a rare aggressive neoplasm usually seen in middle aged persons. This malignancy is more frequently seen on the hard palate and gingiva. Oral melanomas are associated with very poor prognosis because of the tendency to metastasise or invade tissues locally more readily than other malignant tumours of the oral cavity especially in the case of a geriatric patient. The surgical approach, combined with the chemotherapy, is the first choice treatment. This report highlights a case report of 71-year-old female patient diagnosed and treated surgically for an oral malignant melanoma of the pedunculated variety affecting the hard palate and gingiva with review of literature. PMID:22612841
Oral mucosal melanoma: a malignant trap
Emmanouil K Symvoulakis; Dionysios E Kyrmizakis; Emmanouil I Drivas; Anastassios V Koutsopoulos; Stylianos G Malandrakis; Charalambos E Skoulakis; John G Bizakis
Oral mucosal melanomas are highly malignant tumors. The 'chameleonic' presentation of a mainly asymptomatic condition, the rarity of these lesions, the poor prognosis and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health provider. We present the case of a 75-year-old man who was referred to the Ear, Nose and Throat
The clinical features, malignant potential, and systemic associations of oral lichen planus: A study of 723 patients
Drore Eisen
Background: Although oral lichen planus (OLP) is a relatively common disorder, reports comprising large numbers of patients with the disease are lacking in the dermatology literature. Objective and Methods: The purpose of this investigation was to describe the clinical characteristics of 723 patients with biopsy-proven OLP who were followed up from 6 months to 8 years (mean, 4.5 years). Results:
Noninvasive imaging of oral premalignancy and malignancy
NASA Astrophysics Data System (ADS)
Wilder-Smith, Petra; Krasieva, T.; Jung, W.; You, J. S.; Chen, Z.; Osann, K.; Tromberg, B.
Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES-86924, AFOSR FA 9550-04-1-0101.
Oral Lichen Planus and Malignant Transformation: Is a Recall of Patients Justified?
Ulf Mattsson; Mats Jontell; Palle Holmstrup
There has been a continuous debate regarding the possible malignant potential of oral lichen planus (OLP). Based on the results from follow-up studies, OLP is regarded by several authors as a pre-malignant condition, and patients with OLP have been recommended to have their lesions monitored two to four times annually. This recommendation needs reconsideration, because a recall system of all
Oral malignant melanoma: A case report with review of literature.
Manigandan, T; Sagar, G Vikram; Amudhan, A; Hemalatha, V T; Babu, N Aravinda
Oral mucosal melanoma is a rare malignancy with the tendency to metastasize and locally invade tissues more readily than other malignant tumor of the oral cavity. It occurs approximately four times more frequently in the oral mucosa of the upper jaw usually on the palate or alveolar gingiva. The chameleonic presentation of malignant melanoma, its asymptomatic condition, rarity of the lesion, poor prognosis and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health care provider. Herein we report a rare and interesting case of oral malignant melanoma of the maxillary anterior gingiva, which was clinically and histopathologically diagnosed with a brief review of literature, has been discussed. PMID:25191086
Oral malignant melanoma: A case report of an unusual clinical and histologic presentation.
Belgaumi, Uzma Iqbal; Shetty, Pushparaja; Shirlal, Shilpa
Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. The present case occurred in a 60-year-old female patient, as a pedunculated growth involving the palate and alveolar ridge and histologically showing a desmoplastic differentiation. The article discusses the distinct clinico-pathologic presentation of this case and emphasizes on the need to identify and report such cases for further understanding of their biologic behavior. PMID:24019813
Temperature-dependent terahertz imaging of excised oral malignant melanoma.
Sim, Yookyeong Carolyn; Ahn, Kang-Min; Park, Jae Yeon; Park, Chan-Sik; Son, Joo-Hiuk
We imaged a single case of oral malignant melanoma using terahertz (THz) reflection imaging at room temperature (20 �C) and below freezing (-20 �C). A malignant nodule beneath the oral tissue surface was visualized using 2-D and B-scan THz imaging techniques. The THz images were well correlated with the histological findings. The nodule was found to have lower water content than that of normal cells, and this water effect may have influenced the THz refractive index and absorption coefficient at 20 �C. The THz spectroscopic image of the frozen tissue at -20 �C showed better contrast because of the lack of liquid water; this implies that there are significant structural differences between malignant oral melanoma cells and normal mucosal cells. The better contrast in the frozen tissue images was due to the greater penetration of THz radiation into the sample. This temperature-dependent THz imaging approach demonstrated the feasibility of accurate imaging of the oral tumor tissue. PMID:25055305
Oral infections and septicemia in immunocompromised patients with hematologic malignancies.
Bergmann, O J
To estimate the role of oral infections during septicemic episodes in immunocompromised patients with hematologic malignancies, 78 febrile episodes in 46 patients were monitored with daily clinical and microbiological investigations. The 19 septicemic episodes did not differ from the 59 other febrile episodes in the qualitative composition of the aerobic and facultatively anaerobic oral microflora or in the presence of teeth or acute oral infections on day 1. The oral prevalence rates of members of the family Enterobacteriaceae were higher on days 10, 11, and 12 in the febrile episodes with septicemia when compared with those of febrile episodes without septicemia. The prevalence of a probable oral focus in septicemia was 10.5%, and the prevalence of a probable or possible oral origin in septicemia was 31.6%. The results suggest that prevention and elimination of oral infections may reduce the morbidity and perhaps even the mortality in these patients. PMID:3182997
Malignant melanoma of the oral cavity: Report of two cases.
Munde, Anita; Juvekar, Monica Vivek; Karle, Ravindra R; Wankhede, Pranali
Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female. PMID:24963252
Primary mucosal malignant melanoma of the oral cavity
Arif T�rkmen; Metin Temel; Mehmet Bekerecioglu
Mucosal malignant melanoma arising from the head and neck region is a rare entity, and it is more aggressive than cutaneous\\u000a melanoma. Furthermore, the complex anatomy of the oral cavity makes complete surgical excision difficult. Thus, early diagnosis\\u000a and treatment of a mucosal lesion are important. In this study, three mucosal malignant melanoma cases and the literature\\u000a have been reviewed.
Malignant tumors of the oral cavity
Henk, J.M.; Langdon, J.D.
This book discusses carcinomas of the oral cavity including the lymph nodes and salivary glands. Topics include; Epidemiology and etiology; Immunolgical and virological aspects; Basic principles of management; Surgery; Radiotherapy; Chemotherapy; and Cryosurgery.
Clinical behaviour of malignant transforming oral lichen planus
M. D. Mignogna; L. Lo Russo; S. Fedele; E. Ruoppo; L. Califano; L. Lo Muzio
Aims: At present oral lichen planus (OLP) is classified among precancerous conditions but very few data are available in literature regarding prognosis of OLP-related cancers. The aim of this paper is to evaluate clinical long-term behaviour of OLP-related oral squamous cell carcinomas (OSCCs).Methods: Clinical history and data from follow-up regarding 21 patients undergoing malignant transformation of OLP have been critically
II. Malignant potential of gastric polyps.
Ming, S C
The malignant potential of gastric polyps is correlated to their features. The vast majority can be divided into two types: hyperplastic polyp and ademona. Hyperplastic polyp is composed of well-differentiated glands and rarely becomes malignant. It is small, smooth-surfaced, often multiple, and randomly distributed. Adenoma is composed of dysplastic glands and often becomes malignant. The small adenoma is flat-surfaced and slightly raised. The large adenoma is papillary and broad-based. Adenoma is usually single and located in the antrum. In either case, a separate independent carcinoma may be present in the same stomach. PMID:1052453
A retrospective study of oral lichen planus patients with concurrent or subsequent development of malignancy
J. Hietanen; M.-R. Paasonen; M. Kuhlefelt; M. Malmstr�m
Oral lichen planus (OLP) carries a very small probability of becoming malignant. Our Finnish series comprised eight patients suffering from OLP and concurrent or subsequent oral squamous cell carcinoma over a 10-year period. The mean interval between the histologically suggested initial diagnosis of OLP and carcinoma was 3.4 years. An oral ulcer as a clinical manifestation of malignant change appeared
Malignant Epithelioid Schwannoma of the Oral Cavity in a Cat
BOONSRIROJ, Hassadin; KIMITSUKI, Kazunori; AKAGI, Tetsuya; PARK, Chun-Ho
ABSTRACT A malignant epithelioid schwannoma of the oral cavity was diagnosed in an 8-year-old domestic short-hair cat. The mass was located in the gingiva of the upper left premolar to molar region and showed multinodular growth patterns. The mass comprised epithelioid cells arranged in densely packed sheets. Tumor cells had large, round to oval nuclei with prominent nucleoli and an abundant eosinophilic cytoplasm. Immunohistochemically, most of the tumor cells were positive for S-100 protein, glial fibrillary acidic protein and vimentin, but all lacked melanoma-associated antigen and muscle and neuroendocrine markers. Stains for type IV collagen showed linear immunoreactivity around single cells and groups of cells. Ultrastructurally, tumor cells were separated by a well-defined basement membrane, and interdigitating cell processes were observed. To our knowledge, this is the first report of feline malignant epithelioid schwannoma. PMID:24632862
Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions
Onsongo, Getiria; Stone, Matthew D.; Chen, Xiao-Bing; Kooren, Joel A.; Refsland, Eric W.; Griffin, Robert J.; Ondrey, Frank G.; Wu, Baolin; Le, Chap T.; Rhodus, Nelson L.; Carlis, John V.; Griffin, Timothy J.
Background Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need. Methodology/Principal Findings To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p?=?0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells. Conclusions/Significance Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early. PMID:20567502
Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing PreMalignant and Malignant Oral Lesions
Ebbing P. de Jong; Hongwei Xie; Getiria Onsongo; Matthew D. Stone; Xiao-Bing Chen; Joel A. Kooren; Eric W. Refsland; Robert J. Griffin; Frank G. Ondrey; Baolin Wu; Chap T. Le; Nelson L. Rhodus; John V. Carlis; Timothy J. Griffin; Eric J. Bernhard
BackgroundOral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.Methodology\\/Principal FindingsTo discover such proteins, in a
Primary oral malignant melanoma: two case reports and review of literature.
Sharma, Neeraj
Primary malignant melanoma of the oral cavity is a rare neoplasm. The tumors tend to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. The survival of patients with mucosal melanomas is less than for those with cutaneous melanomas. Tumor size and metastases are related to the prognosis of the disease. Early detection, therefore, is important. PMID:22900212
Resection of a primary oral malignant melanoma and rehabilitative management using nasolabial flap: a case report
Ulrike Stephanie Beier; Thomas Salinas; Wolfgang Puelacher
Background��The primary malignant melanoma is a rare neoplasm of melanocytic origin in the oral cavity. Only about 1% of all melanomas\\u000a arise in the oral mucosa and these account for 0.5% of all oral malignancies\\u000a \\u000a \\u000a \\u000a \\u000a Case report��This report describes an oral malignant melanoma occurring in the right maxilla of a 73-year-old patient. The interdisciplinary\\u000a management using a nasolabial flap and
In vitro studies on erythrosine-based photodynamic therapy of malignant and pre-malignant oral epithelial cells.
Garg, Abhishek D; Bose, Muthiah; Ahmed, Mohammed I; Bonass, William A; Wood, Simon R
Photodynamic Therapy (PDT) involves the administration of a tumor localizing photosensitizing agent, which upon activation with light of an appropriate wavelength leads to the destruction of the tumor cells. The aim of the present study was to determine the efficacy of erythrosine as a photosensitizer for the PDT of oral malignancies. The drug uptake kinetics of erythrosine in malignant (H357) and pre-malignant (DOK) oral epithelial cells and their susceptibility to erythrosine-based PDT was studied along with the determination of the subcellular localization of erythrosine. This was followed by initial investigations into the mechanism of cell killing induced following PDT involving both high and low concentrations of erythrosine. The results showed that at 37 �C the uptake of erythrosine by both DOK and H357 cells increased in an erythrosine dose dependent manner. However, the percentage of cell killing observed following PDT differed between the 2 cell lines; a maximum of ~80% of DOK cell killing was achieved as compared to ~60% killing for H357 cells. Both the DOK and H357 cell types exhibited predominantly mitochondrial accumulation of erythrosine, but the mitochondrial trans-membrane potential (??(m)) studies showed that the H357 cells were far more resistant to the changes in ??(m) when compared to the DOK cells and this might be a factor in the apparent relative resistance of the H357 cells to PDT. Finally, cell death morphology and caspase activity analysis studies demonstrated the occurrence of extensive necrosis with high dose PDT in DOK cells, whereas apoptosis was observed at lower doses of PDT for both cell lines. For H357 cells, high dose PDT produced both apoptotic as well as necrotic responses. This is the first instance of erythrosine-based PDT's usage for cancer cell killing. PMID:22485174
Paraneoplastic pemphigus: two cases of intra-abdominal malignancy presenting solely as treatment refractory oral ulceration.
Kelly, Shane; Schifter, Mark; Fulcher, David A; Lin, Ming-Wei
Two patients with initial diagnoses of oral lichen planus and pemphigus vulgaris presented with refractory oral mucosal blistering. Subsequent positive serology results for paraneoplastic pemphigus led to the discovery of occult intra-abdominal malignancies in both, unicentric Castleman's and non-Hodgkin's lymphoma. The diagnosis of paraneoplastic pemphigus should be considered in patients with recalcitrant oral ulceration, even in the absence of clinical features of malignancy. PMID:25557248
Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors
Shin-ichi Ishioka; Satoru Sagae; Eiki Ito; Ryuichi Kudo
Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the
Detection of MAGE-A expression predicts malignant transformation of oral leukoplakia.
Ries, Jutta; Agaimy, Abbas; Vairaktaris, Elefterios; Gorecki, Patricia; Neukam, Friedrich W; Strassburg, Lei H; Nkenke, Emeka
The study aimed at checking if MAGE-A expression in oral leukoplakia (OLP) lesions is related to malignant transformation. The 48 samples of OLP that transformed to oral squamous cell carcinoma (OSCC) (group 1) and 50 samples of OLP that did not transform to OSCC (group 2) were included in the study. The expression of MAGE-A was restricted to group 1. The correlation between malignant transformation and MAGE-A occurrence in OLP was statistically significant (p < .0001). Detection of MAGE-A may allow identifying OLP with a high risk of malignant transformation giving a view to a new approach to prevention of oral cancer. PMID:22646284
Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study.
Ye, Y; Carlsson, G; Agholme, M Barr; Wilson, J A L; Roos, A; Henriques-Normark, B; Engstrand, L; Mod�er, T; P�tsep, K
The role of oral bacteria in the development of chemotherapy-related oral mucositis has not been fully elucidated. This study aimed to investigate oral bacterial community diversity and dynamics in paediatric patients with malignancies in relation to the occurrence of oral mucositis. Patients with malignancies (n = 37) and reference individuals without known systemic disorders (n = 38) were recruited. For patients, oral bacterial samples were taken from mucosal surfaces both at the time of malignancy diagnosis and during chemotherapy. If oral mucositis occurred, samples were taken from the surface of the mucositis lesions. Oral mucosal bacterial samples were also taken from reference individuals. All samples were assessed using a 16S ribosomal RNA gene 454 pyrosequencing method. A lower microbial diversity (p < 0.01) and a higher intersubject variability (p < 0.001) were found in patients as compared with reference individuals. At the time of malignancy diagnosis (i.e. before chemotherapy) patients that later developed mucositis showed a higher microbial diversity (p < 0.05) and a higher intersubject variability (p < 0.001) compared with those without mucositis. The change of bacterial composition during chemotherapy was more pronounced in patients who later developed mucositis than those without mucositis (p < 0.01). In conclusion, we found a higher microbial diversity at the time of malignancy diagnosis in patients who later develop oral mucositis and that these patients had a more significant modification of the bacterial community by chemotherapy before the occurrence of mucositis. These findings may possibly be of clinical importance in developing better strategies for personalized preventive management. PMID:23829394
Oral malignant melanoma diagnosed in an Iranian population over an 11-year period
Jahanfar Jahanbani; Aghdas Forouzandeh; Donya Sadri; Jila Mirlashari
Objective��The aim of this study was to determine the prevalence of oral malignant melanoma along with age range and site of presentation\\u000a over an 11-year period in Iran.\\u000a \\u000a \\u000a \\u000a Materials and methods��The files of Tehran Cancer Institute served as a source of material for this study. Files were systematically searched for\\u000a all malignant melanomas and oral malignant melanomas during an 11-year
Of Mice and Men (and Dogs): development of a xenogeneic DNA vaccine for canine oral malignant melanoma
Philip J. Bergman; Jedd D. Wolchok
Summary Melanoma is the most common oral malignancy in the dog. Oral and\\/or mucosal melanoma is generally considered an extremely malignant tumor with a high degree of local invasiveness and metastatic propensity. The WHO staging scheme for dogs with oral melanoma is based on size and metastasis, with stage I = < 2 cm. diameter tumor, stage II = 2
Spectrally resolved fluorescence lifetime imaging to investigate cell metabolism in malignant and nonmalignant oral mucosa cells
NASA Astrophysics Data System (ADS)
R�ck, Angelika; Hauser, Carmen; Mosch, Simone; Kalinina, Sviatlana
Fluorescence-guided diagnosis of tumor tissue is in many cases insufficient, because false positive results interfere with the outcome. Improvement through observation of cell metabolism might offer the solution, but needs a detailed understanding of the origin of autofluorescence. With respect to this, spectrally resolved multiphoton fluorescence lifetime imaging was investigated to analyze cell metabolism in metabolic phenotypes of malignant and nonmalignant oral mucosa cells. The time-resolved fluorescence characteristics of NADH were measured in cells of different origins. The fluorescence lifetime of bound and free NADH was calculated from biexponential fitting of the fluorescence intensity decay within different spectral regions. The mean lifetime was increased from nonmalignant oral mucosa cells to different squamous carcinoma cells, where the most aggressive cells showed the longest lifetime. In correlation with reports in the literature, the total amount of NADH seemed to be less for the carcinoma cells and the ratio of free/bound NADH was decreased from nonmalignant to squamous carcinoma cells. Moreover for squamous carcinoma cells a high concentration of bound NADH was found in cytoplasmic organelles (mainly mitochondria). This all together indicates that oxidative phosphorylation and a high redox potential play an important role in the energy metabolism of these cells.
Evaluation of MAGE-A expression and grade of dysplasia for predicting malignant progression of oral leukoplakia.
Ries, Jutta; Agaimy, Abbas; Vairaktaris, Elefterios; Kwon, Yeeun; Neukam, Friedrich W; Strassburg, Lei H; Nkenke, Emeka
The risk of the malignant transformation of oral leukoplakia (OLP) is difficult to predict by histopathology. Melanoma-associated antigen-A (MAGE-A) expression is restricted to malignant cells and may be useful for the more accurate estimation of the potential malignant transformation of pre-malignant lesions. The aim of the present study was to investigate whether the expression of MAGE-A can be used to predict the malignant transformation of OLP. Paraffin-embedded tissue samples of OLP from 74 patients followed-up for at least 5 years were included. A total of 24 progressing and 50 non-progressing OLP, 18 corresponding tumor and 30 healthy mucosa specimens were analysed for MAGE-A 1, 3, 4, 6 10 and 12 expression by nested real?time RT-PCR and graded for dysplasia. In total, 46% of the progressing lesions expressed at least 1 out of the examined MAGE-A antigens, whereas no expression was detected in any of the non-progressing OLP and normal specimens. The correlation between malignant transformation and MAGE-A expression was statistically significant (p=0.00001). Furthermore, 42% of the progressing OLPs without dysplasia (D0) expressed at least 1 antigen. The correlation between the grade of dysplasia and MAGE-A staining in the malignant transformation group was not significant (p=0.08). The detection of at least 1 MAGE-A antigen may allow the identification of high-risk lesions that may progress into carcinoma with time. Therefore, the investigation of MAGE-A expression should be assessed in order to obtain a more accurate evaluation of the potential cancer risk of OLP. PMID:22751922
Malignant melanomas of the oral cavity: Heterogeneity of pathological and clinical features
Kenichi Ohashi; Tsutomu Kasuga; Nobuyuki Tanaka; Syoji Enomoto; Junichi Horiuchi; Norihiko Okada
Summary Data on 35 patients with oral malignant melanomas were pooled and the pathological features and the clinical course were examined in detail. Of these 35 cases, 27 (77.1%) showed a two-phase growth pattern, with both a vertical and a radial growth phase. Moreover, these 27 cases were classified into three subtypes according to gross features of the vertical growth
Malignant melanoma of the oral cavity: report of 14 cases from a regional cancer centre
D. C. Doval; C. Rama Rao; K. S. Sabitha; M. Vigayakumar; S. Misra; K. Manie; P. P. Bapsy; S. V. Kumaraswamy
Fourteen patients with oral mucosal malignant melanomas seen at a regional cancer centre over a 10-year period were analysed. All the patients presented with symptoms of short duration, with extensive local disease at initial evaluation in 11 patients. The palate was the commonest site involved. Ten patients had regional nodal disease and of these four also had distant metastases to
Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas
Suzanne Shelly; May B. Chien; Becky Yip; Michael S. Kent; Alain P. Theon; Jennifer L. McCallan; Cheryl A. London
An activating mutation in codon 599 of BRAF has been identified in approximately 60% of human cutaneous nevi and melanomas, but not melanomas of mucosal origin. The purpose of this study was to determine if BRAF mutations occur in canine oral malignant melanomas. The canine BRAF gene was first cloned from normal canine testicular cDNA, and a novel previously unreported
Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions
Mehrotra, Ravi; Gupta, Anurag; Singh, Mamta; Ibrahim, Rahela
Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here. PMID:16556320
Erosive Potential of Oral Care Products
A. Lussi; E. Hellwig
Seven oral care products and orange juice as a positive control were tested for the erosive potential by immersing each enamel specimen (10 per group) into solutions of the various products for 10 and 20 min. Before and after the experiment Knoop surface hardness (SMH) was measured. The enamel microstructure before and after immersion was assessed by scanning electron microscopy
Oral pigmentation: case report and review of malignant melanoma with flow charts for diagnosis and treatment.
Pai, Anuradha; Prasad, Shesha; Patil, Bharati A; Dyasanoor, Sujatha; Hedge, Sushmini
The color of the human oral mucosa is not uniform. Chromatic variations can occur, depending on the degree of keratinization, melanogenic activity, number of melanocytes, vascularization, and type of submucosal tissue. If a pathological pigmentation is suspected, its benign or malignant nature will guide the treatment plan. This article presents a rare case of malignant melanoma of the anterior maxilla with asymptomatic palatal pigmentation and regional lymph node metastasis. Flow charts for the diagnosis and treatment of pigmented lesions (with special emphasis on treatment of primary and metastatic melanoma) are included. PMID:23032229
Large oncocytic adrenocortical tumor with uncertain malignant potential.
Lee, Chang Ki; Choi, Kyung Hwa; Cha, Yoon Jin; Bum, Jung Ha; Lee, Hyung Ho; Kim, Myung Soo; Park, Won Kyu; Yang, Seung Choul; Han, Woong Kyu
Oncocytoma is a neoplasm consisting of oncocytes that is found in the salivary gland, kidney, and thyroid. Adrenocortical oncocytoma is particularly uncommon, and most cases reported are benign and nonfunctioning. Here, we report a 20 cm adrenal mass associated with necrosis that was identified as an oncocytic adrenocortical tumor with uncertain malignant potential through histopathological evaluation after its resection. PMID:22025964
Large Oncocytic Adrenocortical Tumor with Uncertain Malignant Potential
Lee, Chang Ki; Choi, Kyung Hwa; Cha, Yoon Jin; Bum, Jung Ha; Lee, Hyung Ho; Kim, Myung Soo; Park, Won Kyu; Yang, Seung Choul
Oncocytoma is a neoplasm consisting of oncocytes that is found in the salivary gland, kidney, and thyroid. Adrenocortical oncocytoma is particularly uncommon, and most cases reported are benign and nonfunctioning. Here, we report a 20 cm adrenal mass associated with necrosis that was identified as an oncocytic adrenocortical tumor with uncertain malignant potential through histopathological evaluation after its resection. PMID:22025964
Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies
Ma, Jie; Frank, Markus H.
Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545
Tumor initiation in human malignant melanoma and potential cancer therapies.
Ma, Jie; Frank, Markus H
Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545
Prevalence of fungal hyphae in potentially malignant lesions and conditions�does its occurrence play a role in epithelial dysplasia?
Hongal, Bhagyalaxmi Praveen; Kulkarni, Venkatesh V; Deshmukh, Revati Shailesh; Joshi, Priya Shirish; Karande, Prasad Prakash; Shroff, Adil S
Background: Oral cancer is a major public health problem in India. A key factor that has led to lack of improvement in prognosis of oral cancer over the years, is delay in diagnosis and treatment. In many instances, a significant proportion of oral squamous cell carcinomas develop from premalignant lesions and conditions. Identification of such lesions and conditions is very important in order to prevent malignant transformation. The role of fungal infections has been studied and holds promise as an indicator to predict malignant transformation. So we designed a study to analyze the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of premalignant lesions and conditions. Aims and Objectives: To determine and compare the prevalence of fungal hyphae in biopsies of patients with clinically diagnosed cases of potentially malignant lesions and conditions and to assess the possible association between the degree of epithelial dysplasia and presence or absence of fungal hyphae. Materials and Methods: Clinically suspected and histopathologically diagnosed 70 cases of potentially malignant lesions and conditions (29 leukoplakia, 16 submucous fibrosis and 25 lichen planus) made up the study group. Three tissue sections (5?m) of each were stained with hematoxylin and eosin (H and E), periodic acid�Schiff's reagent (PAS) and Grocott's methenamine silver (GMS) and evaluated for fungal hyphae. The data collected was statistically analyzed by using Chi-square test and Statistical Package for Social Sciences (SPSS) software. Results: The estimated prevalence of fungal hyphae in cases with or without dysplasia in leukoplakia was 41.4%, lichen planus 36% and submucous fibrosis 25%. There was a significant association between degree of epithelial dysplasia with presence or absence of fungal hyphae in all the study groups. Conclusion: Presence of fungal hyphae in potentially malignant lesions and conditions may prove to be a useful indicator in predicting malignant transformation.
Endovascular Therapy for Management of Oral Hemorrhage in Malignant Head and Neck Tumors
Kakizawa, Hideaki, E-mail: email@example.com; Toyota, Naoyuki; Naito, Akira; Ito, Katsuhide [Graduate School of Biomedical Science, Hiroshima University, Department of Radiology, Division of Medical Intelligence and Informatics Programs for Applied Biomedicine (Japan)
Purpose. To evaluate the efficacy and safety of endovascular therapy in oral hemorrhage from malignant head and neck tumors. Methods. Ten patients (mean age 56 years) with oral hemorrhage caused by malignant head and neck tumors underwent a total of 13 emergency embolization procedures using gelatin sponge particles, steel and/or platinum coils, or a combination of these embolic materials. Angiographic abnormalities, technical success rate, clinical success rate, recurrence rate, complications, hemostatic period, hospital days, survival days, and patient outcome were all analyzed. Results. Angiographic abnormalities were identified during 85% of procedures (11/13). The technical success rate was 100% (13/13 procedures). The primary and secondary clinical success rates were 77% (10/13 procedures) and 67% (2/3 procedures), respectively. The overall clinical success rate was 92%, and the recurrence rate was 22% (2/9 procedures) in patients whom we were able to observe during the 1-month period after embolization. No major complications occurred. Several patients in whom gelatin sponge particles had been used complained of transient local pain after the procedure. The median hemostatic period was 71 days (range 0-518 days). Median hospital and survival days were 59 days (range 3-209 days) and 141 days (range 4-518 days), respectively. Three patients survived and 7 patients died during the observation period. Only 1 of these 7 patients died from hemorrhage. Conclusion. In conclusion, our findings suggest that endovascular therapy is an effective, safe, and repeatable treatment for oral hemorrhage caused by malignant head and neck tumors.
Oral malignant melanoma: A report of two cases with BRAF molecular analysis.
Soma, Pier Francesco; Pettinato, Angela; Agnone, Anna Maria; Donia, Claudio; Improta, Giuseppina; Fraggetta, Filippo
Primary oral malignant melanoma is a rare condition, accounting for 1.3-1.4% of all melanomas, usually presenting with an aggressive clinical behavior. The present study reports the clinicopathological findings of two cases of oral malignant melanoma and discusses the epidemiology, diagnosis and current therapeutic approaches for this uncommon condition. In the first case the patient presented with a pigmented lesion located on the lower mucosal lip. The patient showed no nodal metastases and therefore, underwent a wedge resection. After seven months, the patient presented with neck lymph nodes and multiple visceral metastases. Molecular analysis of BRAF, using a pyrosequencing approach, revealed the presence of BRAF V600E mutation. The patient developed multiple visceral metastases, but refused treatment and was lost to follow-up. In the second case, no BRAF V600E mutation was found, but the patient exhibited a pigmented patch in the lower gingival mucosa, which was excised by surgical treatment. The patient was followed up by an oncologist, but did not undergo an additional therapy and is currently alive with no evidence of visceral metastases at one year following the diagnosis. PMID:25120707
Incidental detection of an occult oral malignancy with autofluorescence imaging: a case report
Background Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. Case Description A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. Conclusion This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied. PMID:19863814
IL-1? promotes malignant transformation and tumor aggressiveness in oral cancer.
Lee, Chia-Huei; Chang, Jeffrey Shu-Ming; Syu, Shih-Han; Wong, Thian-Sze; Chan, Jimmy Yu-Wai; Tang, Ya-Chu; Yang, Zhi-Ping; Yang, Wen-Chan; Chen, Chiung-Tong; Lu, Shao-Chun; Tang, Pei-Hua; Yang, Tzu-Ching; Chu, Pei-Yi; Hsiao, Jenn-Ren; Liu, Ko-Jiunn
Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1?) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1? expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1? was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1? secretion in an inflammasome-dependent manner. IL-1? treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-? following IL-1? stimulation. The conditioned medium of IL-1?-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1? increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1? can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. PMID:25204733
Malignant rhabdoid tumor of the floor of mouth: first reported case in the oral cavity of an adult.
Wetzel, Stephanie L; Kerpel, Stanley; Reich, Renee F; Freedman, Paul D
Malignant rhabdoid tumors (MRTs) are exceedingly rare lesions. To our knowledge, only 2 cases have been reported in the oral cavity, with both examples occurring in infants. The current case is the third reported case of MRT of the oral cavity and the first reported case to occur in an adult at this location. The following report describes the clinical, histologic and immunohistochemical features of this tumor. PMID:24997629
Comparison of loss of heterozygosity patterns between ovarian tumors of low malignant potential and malignant ovarian tumors
Crawford, E.C.; Miller, D.M.; Finley, W.H. [Univ. of Alabama, Birmingham, AL (United States)] [and others
Ovarian tumors of low malignant potential (LMP) represent a pathologic subtype of ovarian tumor that possess many features common to malignant tumors including epithelial stratification, increased mitotic activity and atypical cellularity. These tumors, however, do not invade the ovarian stroma and have a much improved patient prognosis. Utilizing dinucleotide repeats, loss of heterozygosity (LOH) studies were performed on a total of 12 ovarian tumors of LMP in 5 regions found to have significant levels of LOH in malignant ovarian tumors. The regions chosen for study were 3p, 6q, 11p, 17p and 17q. LOH could be demonstrated in malignant ovarian tumors in loci from 3p, 11p and both chromosomal arms of 17 when compared to normal tissue from the same patient. Loss in malignant tumors was more common in loci mapped to 3p21 and to 11p15. OH was not noted in any samples for a repeat in the TP53 gene even though flanking markers on 17p were lost in 1 patient with a malignant tumor. Loss was not demonstrated in any of the loci examined from 6q in malignant ovarian tumors. LOH was not demonstrated in any of the 39 loci examined from any of the five chromosomal regions in the ovarian tumors of LMP. Cytogenetic analyses of these LMP tumors were consistent with lack of involvement in these chromosomal regions. These data suggest the mechanism of tumorigenesis is different in tumors of LMP from that in malignant ovarian tumors.
Toxicity of weekly oral topotecan in relation to dosage for gynecologic malignancies: a phase I study
von Gruenigen, Vivian E.; Frasure, Heidi E.; Smith, Deborah A.; Fusco, Nancy L.; Eaton, Susan M.; DeBernardo, Robert L.; Heugeland, Anne M.; Waggoner, Steven E.
The aim of this study was to determine the dose of weekly oral topotecan that allows safe administration and to evaluate the pharmacokinetics of this dose in patients with recurrent gynecologic malignancies. The first cohort of patients received oral topotecan 6 mg/week administered orally on days 1, 8, and 15 of a 28-day regimen. A standard 3 + 3 dose-escalating phase design was used for dose levels II�V (8, 10, 12 and 14 mg/week). Toxicity was scored according to the Common Terminology Criteria for Adverse Events. Cumulative toxicity was summarized in the 6�12 mg/week combined cohort and 14 mg/week cohort separately. Pharmacokinetic samples were obtained for day 1, cycle 1 only in the expansion cohort (dose level V). Twenty-five patients received a total of 88 cycles of therapy. Hematologic toxicities of grade 3 (6�12 mg dose) were neutropenia (25%) and anemia (8.3%). Gastrointestinal toxicities of grade 3 were diarrhea (16.7%) and obstruction (8.3%, disease-related). Grade 3 or 4 (14 mg/week) hematologic toxicities consisted of neutropenia (38.5%), platelets (15.4%), anemia (15.4%), infection with neutropenia (7.7%), and thrombosis (7.7%). Gastrointestinal toxicities of grade 3 were diarrhea (7.7%), obstruction (7.7%), and vomiting (7.7%). One patient died secondary to neutropenic sepsis. One patient (4%; 95% confidence interval: 2.1, 22.3) showed a partial response and five patients (20%; 95% confidence interval: 7.6, 41.3) had stable disease. An oral topotecan dose of 14 mg/week for 3 consecutive weeks out of 4 is mostly associated with acceptable toxicities and may be considered for use in future single-agent phase II trials. PMID:22555194
Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia
Nankivell, P; Williams, H; McConkey, C; Webster, K; High, A; MacLennan, K; Senguven, B; Rabbitts, P; Mehanna, H
Background: Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort. Methods: One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed. Results: Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability. Conclusion: This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition. PMID:24201754
[Classification and malignant potential of pancreatic cystic tumors].
Esposito, I; Schlitter, A M; Sipos, B; Kl�ppel, G
Cystic lesions of the pancreas are increasingly diagnosed with a reported prevalence of 10?% in 70-year-old individuals. Despite their broad spectrum, most resected cystic lesions can be attributed to one of the following entities: intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine cystic tumors (NECT), and solid pseudopapillary neoplasms (SPN). Among them, IPMN and MCN represent precursors of ductal adenocarcinoma, NECT and SPN are low-grade, potentially malignant lesions, and SCN are usually benign. Due to the not negligible morbidity and mortality rates in pancreatic surgery, even in highly specialized centers, an interdisciplinary preoperative stratification of pancreatic cystic lesions into high- and low-risk tumors is necessary in order to accurately select those cases that need to undergo immediate resection. The role of the pathologist is fundamental in both the preoperative assessment and in the postoperative classification, which determines prognosis, further treatment, and follow-up. PMID:25663186
Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity.
Su�rez Roa, M de Lourdes; Ruiz Godoy Rivera, L M; Vela Ch�vez, T; P�rez S�nchez, M; Meneses Garc�a, A
Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature. PMID:17462980
Recognizing and overcoming potential barriers to oral medications for MS.
Moses, Harold
Three FDA-approved oral medications are available for the treatment of relapsing forms of multiple sclerosis: fingolimod, teriflunomide, and dimethyl fumarate. While injection and IV treatments have proven to be beneficial, these newer oral agents also offer positive outcomes for patients. Numerous barriers exist, though, for these oral agents, including the unknown long-term efficacy and safety and potential side effects. Despite possible side effects, oral agents provide convenience, ease of use, and the elimination of injection/IV administration-site pain. To ensure MS patients receive the most appropriate individualized care, clinicians should present all of the available treatment options to both newly diagnosed and established patients. PMID:25373133
Current Aspects on Oral Squamous Cell Carcinoma
Markopoulos, Anastasios K
Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. This article overviews the essential points of oral squamous cell carcinoma, highlighting its risk and genomic factors, the potential malignant disorders and the therapeutic approaches. It also emphasizes the importance of the early diagnosis. PMID:22930665
Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review
Zabalza, Amaya; Gorosquieta, Ana; Equiza, Encarnaci�n P�rez
Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug�drug interactions given that voriconazole is metabolized through the P450 cytochrome system. PMID:23730499
Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review.
Zabalza, Amaya; Gorosquieta, Ana; Equiza, Encarnaci�n P�rez; Olavarria, Eduardo
Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug-drug interactions given that voriconazole is metabolized through the P450 cytochrome system. PMID:23730499
Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3)
Houssami, N; Ciatto, S; Bilous, M; Vezzosi, V; Bianchi, S
Breast core needle biopsy (CNB) is an accurate test but may result in borderline histology (lesions of uncertain malignant potential or B3). This is an evaluation of the largest series (to date) of B3 histology, which focusses on estimating positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a 10-year period in a single institution (N=372) from a series of 4035 consecutive needle biopsies. We describe the imaging findings, and report excision histology outcomes (N=279) and category-specific PPV for B3 lesions using two approaches including estimates based on subjects who had either excision or follow-up (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in 181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37 invasive carcinoma). Positive predictive value for malignancy (based on excision histology) was 35.1% (95% CI: 29.5�40.7) and PPV (based on excision or review) was 29.9% (95% CI: 24.9�34.8). Lesion-specific PPV (estimates in parentheses for excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%. Approximately one-third of CNB results classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between specific lesion groups. Whereas cases may be selectively managed without surgery, the majority warrant excision biopsy based on our estimates. Research is needed to improve differentiation between malignant and benign diseases in B3 lesions using diagnostic or predictive methods. PMID:17438578
Efficacy of Oral Cryotherapy on Oral Mucositis Prevention in Patients with Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Randomized Controlled Trials
Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji
Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT. PMID:26024220
Oral verrucous carcinoma arising from lichen planus and esophageal squamous cell carcinoma in a patient with hepatitis C virus-related liver cirrhosis-hyperinsulinemia and malignant transformation: A case report
Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral cancer. In Japan, the association of OLP with hepatitis C virus (HCV) infection is well documented. In the present study, a case of oral verrucous carcinoma arising from OLP coexisting vulvo-vaginal-gingival syndrome and esophageal squamous cell carcinoma (SCC) in a patient with HCV-related liver cirrhosis is reported. A 71-year old, non-smoking Japanese woman presented with lesions of OLP affecting the bilateral buccal mucosa, tongue, gingival, palate, oral floor and lower lip. Ten years later, an exophytic mass developed in the mandibular alveolar mucosa, the right buccal mucosa and the right lower lip. Pathological diagnosis confirmed the presence of verrucous carcinoma. However, she developed esophageal rather than oral cancer. The oral cancer was resected surgically three times and the patients underwent radiotherapy. The esophageal cancer was removed by endoscopic submucosal dissection. The risk of carcinogenesis increased as hyperinsulinemia continued. The results suggested that it is necessary to monitor for malignant changes in patients with OLP lesions and HCV infection. In addition, treatment requires the cooperation of various medical specialists, as well as an oral surgeon. PMID:24648893
Restricted expression and function of laminin 1-binding integrins in normal and malignant oral mucosal keratinocytes.
Zhang, K; Kim, J P; Woodley, D T; Waleh, N S; Chen, Y Q; Kramer, R H
Squamous cell carcinoma of the oral cavity spreads by initial invasion of the laminin-rich basement membrane. We examined the adhesion and motility of human oral SCC cells and normal mucosal keratinocytes and found that the SCC cells readily attached and migrated on laminin 1 substrates but migrated poorly on collagen type I and fibronectin. The normal keratinocytes, however, adhered poorly to and were non-motile on laminin 1 yet readily and preferentially attached and migrated on fibronectin and collagen type I. Analysis with blocking anti-integrin antibodies showed that the SCC cells used the alpha 6 beta 1 complex to attach and migrate on laminin 1 and that this activity was confined to the E8 long arm fragment of laminin. Affinity chromatography on laminin-Sepharose columns revealed that the SCC cells, but not normal keratinocytes, expressed high levels of the alpha 6 beta 1 laminin 1 receptor. Metabolic pulse-chase analysis indicated that in contrast to the SCC cells, keratinocytes did not have a stable pool of beta 1 subunit precursor. Preferential pairing of alpha 6 with beta 4 and the deficiency in pre-beta 1 levels appear to account for the failure of keratinocytes to form significant alpha 6 beta 1 complex. Additionally, the presence of laminin 1 in co-coating experiments blocked keratinocyte adhesion to other immobilized ligands, such as collagen type I or fibronectin. This anti-adhesive effect seemed to reflect a general paralysis of cell adhesive function, since laminin 1 also diminished the adhesion of keratinocytes to substrates coated with immobilized anti-integrin subunit antibody. The inhibitory activity of laminin 1 resided in the E1' and E8 fragments, and not in the E3, E4 or G domains. Collectively, our results indicate that laminin 1 is a restrictive ligand for normal keratinocytes, apparently because of their failure to assemble and express the alpha 6 beta 1 complex or other functional laminin receptors and their sensitivity to the anti-adhesive activity of laminin itself. The elevated expression of alpha 6 beta 1 following malignant conversion of muscosal keratinocytes promotes their migration on laminin, a process important during invasion and metastasis. PMID:8969862
Differential regulation of iron chelator-induced IL8 synthesis via MAP kinase and NF-?B in immortalized and malignant oral keratinocytes
Hwa-Jeong Lee; Jun Lee; Sun-Kyung Lee; Suk-Keun Lee; Eun-Cheol Kim
BACKGROUND: Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with
Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study.
Jaitley, Shweta; Agarwal, Pankaj; Upadhyay, Ramballabh
The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF) patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC) study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology). In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions. PMID:26148621
Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential.
Yazawa, Erika M; Geddes-Sweeney, Jenna E; Cedeno-Laurent, Filiberto; Walley, Kempland C; Barthel, Steven R; Opperman, Matthew J; Liang, Jennifer; Lin, Jennifer Y; Schatton, Tobias; Laga, Alvaro C; Mihm, Martin C; Qureshi, Abrar A; Widlund, Hans R; Murphy, George F; Dimitroff, Charles J
Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening antitumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity, and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely dysplastic nevi, as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by ?2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAM(KD)) or ST6GalNAc2-overexpressing (ST6(O/E)) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAM(KD) or ST6(O/E) melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1/melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy. PMID:25756799
Melanoma cell galectin-1 ligands functionally correlate with malignant potential*
Yazawa, Erika M.; Geddes-Sweeney, Jenna E.; Cedeno-Laurent, Filiberto; Walley, Kempland C.; Barthel, Steven R.; Opperman, Matthew J.; Liang, Jennifer; Lin, Jennifer Y.; Schatton, Tobias; Laga, Alvaro C.; Mihm, Martin C.; Qureshi, Abrar A.; Widlund, Hans R.; Murphy, George F.; Dimitroff, Charles J.
Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening anti-tumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely-dysplastic nevi as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by ?2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAMKD) or ST6GalNAc2-overexpressing (ST6O/E) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAMKD or ST6O/E melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1 � melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy. PMID:25756799
Polymerized liposomes as potential oral vaccine carriers: Stability and bioavailability
Hongming Chen; Vladimir Torchilin; Robert Langer
The potential of polymerized liposomes as oral vaccine carriers is evaluated. The stability of polymerized liposomes is demonstrated in mouse gastrointestinal tracts using dual-labeled liposomes. Similar transit kinetics displayed by the two labels of different hydrophobicity indicate the intactness of the polymerized liposomes inside the gastrointestinal tract. Uptake of liposomes from mouse gastrointestinal tract by Peyer's patches is quantified by
Immunohistochemical evaluation of oral epithelial dysplasia using cyclin-D1, p27 and p63 expression as predictors of malignant transformation
Ramasubramanian, Abilasha; Ramani, Pratibha; Sherlin, Herald J.; Premkumar, Priya; Natesan, Anuja; Thiruvengadam, Chandrasekar
Objective: To evaluate the degree of expression of cyclin-D1, p27 and p63 in mild, moderate and severe dysplasia using immunohistochemical evaluation in order to illustrate their prognostic value and attempt to propose a molecular grading system for oral epithelial dysplasia. Materials and Methods: The analysis included thirty cases of mild, moderate and severe dysplasia from Department of Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai after a critical review of the Hematoxylin and Eosin (H and E) stained sections. They were subjected to immunohistochemical evaluation using the markers cyclin-D1, p27 and p63. The assessment of the expression based on staining intensity and distribution of immunohistochemical staining of the various markers was analyzed followed by statistical analysis. Results: A highly significant increase in the expression of cyclin-D1 (P < 0.000) and p63 (P < 0.001) and a moderately significant decrease in the expression of p27 (P < 0.012) with the increasing severity of dysplasia was observed in our study. Conclusions: The result of our research affirms the fact that the increase in the expression of markers of cell cycle regulators such as cyclin D1, decrease in the expression of cell cycle inhibitors like p27 and increased expression of p63 in parallel with the increasing severity of dysplasia, emphasizes the use of immunohistochemical markers cyclin D1, p27 and p63 as prognostic markers for better understanding the behaviour of these potentially malignant disorders aiming towards proposing a molecular grading system for oral epithelial dysplasia to enable timely management prior to their possible malignant transformation. PMID:24082731
Oral squamous cell carcinoma of the maxilla, a second malignancy after a right ethmoido-maxillary chondrosarcoma.
Suciu, Mircea; Morariu, Silviu Horia; Ormeni?an, Alina; Grigora?, Radu Ionu?; Bostan, Radu Horia; Mocanu, Simona; Vartolomei, Mihai Dorin; Cotoi, Ovidiu Simion
Squamous cell carcinoma is defined as an invasive epithelial neoplasm, with variable degrees of squamous differentiation, with or without keratinization. It is origins stand at the level of the keratinized stratified squamous epithelium (skin) or non-keratinized (oral mucosa, esophageal mucosa, uterine exocervical mucosa), but it can also be found in squamous metaplasia areas (uterine endocervix or trachea-bronchial tree). This report presents the case of an oral squamous cell carcinoma as a second malignancy in the same anatomical territory, in a patient with prior treatment for chondrosarcoma, both surgical and radiotherapy. The tumor had appeared 5-6 months prior and had undergone a relatively rapid growth, this being the patient's main motive for addressing the doctors. The tumor was greyish, with imprecisely demarcated margins, of firm consistency, bleeding and with local necrotic deposits. The tumor extended from the incisive region to the maxillary tuberosity, towards the cheek mucosa and the soft palate. After a large excision, the histopathological diagnosis was infiltrative keratinizing squamous cell carcinoma, with moderate differentiation, with origins in the oral mucosa, infiltrating the whole of the maxilla and the maxillary sinus mucosa. Approximately three months after the surgery, a new tumor appeared in the oral cavity, on superior and inferior mucosa of the right cheek, extending towards the right buccal commissure, implying a relapse of the primary tumor. Postoperative oncological therapy included standard chemotherapy, which resulted in favorable postoperative evolution. This case is interesting by the association, of two metachronous malignant tumors, of different histological origin: a chondrosarcoma and a squamous cell carcinoma, at an interval of 25 years. PMID:25607415
The Potential Role of Aurora Kinase Inhibitors in Haematological Malignancies
Farag, Sherif S.
Summary Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers. PMID:21980926
W Parulekar; R Mackenzie; G Bjarnason; R. C. K Jordan
Oral mucositis is a common, dose limiting and potentially serious complication of both radiation and chemotherapy. Both these therapies are non-specific, interfering with the cellular homeostasis of both malignant and normal host cells. An important effect is the loss of the rapidly proliferating epithelial cells in the oral cavity, gut and in the bone marrow. Within the mouth, the loss
Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis.
Tang, Haikuo; Wu, Zhiyuan; Zhang, Jianping; Su, Bing
Oral squamous cell carcinoma (OSCC) is a common and lethal malignancy. Thus, improvement in current knowledge of molecular changes associated with OSCC is urgently needed to explore novel avenues of diagnostics and treatment of this disease. While aberrant expression of long non?coding RNAs (lncRNAs) has been functionally associated with certain types of cancer, including lung, breast and prostate carcinomas, their expression pattern and biological relevance in OSCC is currently unknown. In the present study, the relative abundance of a collection of lncRNAs in tissue or saliva samples from OSCC patients was investigated. It was shown that subsets of lncRNAs are expressed across non?tumor, tumor and metastatic tissue samples. Some detected lncRNAs were shown to be aberrantly expressed in cases of oral cancer and metastasis. Moreover, whole saliva contained a detectable amount of some lncRNAs, which appeared to be potential markers for OSCC. These findings suggest that the detection of lncRNAs in saliva may be used as a noninvasive and rapid diagnostic tool for the diagnosis of oral cancer. PMID:23292713
Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies.
Minden, Mark D; Hogge, Donna E; Weir, Scott J; Kasper, Jim; Webster, Debra A; Patton, Lavonne; Jitkova, Yulia; Hurren, Rose; Gronda, Marcela; Goard, Carolyn A; Rajewski, Lian G; Haslam, John L; Heppert, Kathleen E; Schorno, Kevin; Chang, Hong; Brandwein, Joseph M; Gupta, Vikas; Schuh, Andre C; Trudel, Suzanne; Yee, Karen W L; Reed, Gregory A; Schimmer, Aaron D
The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first-in-human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5-80 mg/m� oral ciclopirox olamine once daily for five days in 21-day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half-life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m� ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty-three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half-life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m�, demonstrating biological activity of the drug. Dose-limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m� four times daily, and no dose limiting toxicity was observed at 40 mg/m� once daily. Hematologic improvement was observed in two patients. Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population. PMID:24273151
Molecular Imaging of Oral Premalignant and Malignant Lesions Using Fluorescently Labeled Lectins
Baeten, John; Suresh, Amritha; Johnson, Alexander; Patel, Ketan; Kuriakose, Moni; Flynn, Anita; Kademani, Deepak
Aberrant glycosylation during carcinogenesis results in altered glycan expression on oral cancer cells. The objective of this study was to detect this atypical glycosylation via imaging of fluorophore-conjugated lectins. Paired normal and tumor tissue from seven patients with oral squamous cell carcinoma were investigated for sialic acid expression via the legume protein wheat germ agglutinin (WGA). Fluorophore (Alexa Fluor 350 and Alexa Fluor 647) conjugated WGA was topically applied to the tissue samples and imaged using a custom wide-field fluorescence imaging system. All seven patients had histologically confirmed disease with 6/7 exhibiting squamous cell carcinoma and 1/7 exhibiting dysplasia. Fluorescent data collected from all patients demonstrated that fluorophore conjugated WGA could distinguish between pathologically normal and diseased tissue with the average signal-to-noise ratio (SNR) among all patients being 5.88 (P = .00046). This SNR was statistically significantly higher than the SNR from differences in tissue autofluorescence (P = .0049). A lectin inhibitory experiment confirmed that lectin binding is molecularly specific to overexpressed tumor glycans and that fluorescence is not due to tissue optical properties or tissue diffusion differences. These results illustrate that changes in tumor glycan content of oral neoplasms can be detected with optical imaging using topically applied fluorescently labeled WGA. Lectin targeting of oral lesions using optical imaging may provide a new avenue for the early detection of oral cancers. PMID:24913673
A review of the recent literature regarding malignant transformation of oral lichen planus
Margot Van Dis; E. H. van der Meij; K. P. Schepman; L. E. Smeele; J. E. van der Wal; P. D. Bezemer; I. van der Waal
On the basis of a literature review of the period 1950-1976, Krutchkoff et al questioned the possible premalignant nature of oral lichen planus. Their criticism was largely based on insufficiencies of data in support of the initial diagnoses of the condition. In this article, a review of the literature from the period 1977-1999 has been described; the criteria used were
Australian management strategies for oral opioid use in non-malignant pain
C. Roger Goucke
Chronic non-cancer pain is a complex biopsychosocial phenomenon; as such it is unlikely that any one treatment modality will achieve relief. There is increasing availability of oral opioid preparations and an associated increased level of prescribing; consequently in 1997 the Australian Pain Society drew up some management strategies for their use. This paper reviews the principles of those strategies, stressing
Clinical study for classification of benign, dysplastic, and malignant oral lesions using autofluorescence
Duin, Robert P.W.
Sep. 16, 2003; revised manuscript received Jan. 20, 2004; accepted for publication Feb. 17, 2004. 1 Sciences Delft The Netherlands Max J. H. Witjes University Hospital Groningen Department of Oral University of Delft Pattern Recognition Group Faculty of Applied Sciences Delft The Netherlands Henricus J. C
Telomerase activity detected in oral lichen planus by RNA in situ hybridisation: not a marker for malignant transformation
O�Flatharta, C; Leader, M; Kay, E; Flint, S R; Toner, M; Robertson, W; Mabruk, M J E M F
Background: Oral lichen planus (OLP) is a chronic inflammatory condition. Clinically, it is characterised by the presence of a white lace-like lesion on the buccal mucosa, tongue, and gingivae, with erosions and ulceration. The World Health Organisation considers OLP to be a premalignant condition. Aims: To investigate expression of the telomerase RNA component (hTR) in OLP compared with normal control buccal mucosa and to assess the possibility of using hTR expression as a marker for malignant transformation in OLP. Methods: hTR expression was analysed in 40 cases of OLP and 18 normal control buccal mucosa samples using an RNA in situ hybridisation approach. Results: Strong hTR RNA expression was seen in the basal, suprabasal, and to a lesser extent in the upper epithelial layers in 36 of the 40 OLP lesions examined. Infiltrating subepithelial lymphocytes in OLP were also shown to express hTR RNA. Weak hTR RNA expression was seen in seven of the 18 normal control buccal mucosa specimens, with expression confined exclusively to the basal layer of the epithelium and absent in the suprabasal and upper layers. Conclusion: The telomerase RNA component hTR is found to be highly expressed in the epithelium of non-dysplastic OLP lesions. It is possible that this high expression is related to the increased cellular proliferation seen in OLP lesions rather than being an indicator of susceptibility to malignancy. Thus, hTR RNA expression may not be a suitable marker for predicting malignant transformation in OLP. PMID:12147655
Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling
V�ronique Ouellet; Diane M Provencher; Christine M Maugard; C�cile Le Page; Fengge Ren; Christian Lussier; Jaroslav Novak; Bing Ge; Thomas J Hudson; Patricia N Tonin; Anne-Marie Mes-Masson; A-M Mes-Masson
Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses
Hyalomma impeltatum (Acari: Ixodidae) as a potential vector of malignant theileriosis in sheep in Saudi Arabia
O. M. E. El-Azazy; T. M. El-Metenawy; H. Y. Wassef
Little is known about tick-borne diseases in Saudi Arabia, particularly regarding the prevalence of theileriosis in small ruminants. This survey studied the potential vectors of malignant theileriosis in Saudi Arabian sheep. Blood, lymph node and tick samples were collected from animals being treated or necropsied at the Veterinary Diagnostic Laboratory in Jeddah, Makkah (western region), and Bureida, Al-Qasim (central region).
The novel herbal cocktail MA128 suppresses tumor growth and the metastatic potential of highly malignant tumor cells.
Kim, Aeyung; Im, Minju; Yim, Nam-Hiu; Hwang, Youn-Hwan; Yang, Hye Jin; Ma, Jin Yeul
MA128, a novel herbal medicine, was previously identified and its effectiveness in the treatment of asthma and atopic dermatitis (AD) was demonstrated. In particular, post-inflammatory hyperpigmentation (PIH) in AD mice was improved by treatment with MA128. In addition, MA128 exhibited anti-melanogenic activity by inhibiting tyrosinase activity via the p38�MAPK and protein kinase�A signaling pathways in B16F10 cells. In the present study, we examined whether oral administration of MA128 suppressed the in�vivo tumor growth of HT1080 cells in athymic nude mice. The results showed that the daily oral administration of 75�and 150�mg/kg MA128 suppressed the tumorigenic growth of HT1080 cells efficiently. Since metastasis is a major cause of cancer-associated mortality and the greatest challenge during cancer treatment, we investigated the effect of non-toxic concentrations of MA128 on the metastatic potential of HT1080 cells. MA128 inhibited anchorage-independent colony formation, migration and invasion. Matrix metalloproteinase-9 (MMP-9) activity under resting and PMA-stimulated conditions was decreased in a dose-dependent manner by MA128 in HT1080 cells. In addition, the daily oral administration of MA128 at doses of 75�and 150�mg/kg efficiently blocked the lung metastasis of B16F10 cells that had been injected into the tail veins of C57BL/6 mice. In particular, none of the mice treated with MA128 exhibited systemic toxicity, such as body weight loss or liver and kidney dysfunction. MA128 also inhibited tumor?induced angiogenesis. Taken together, the results suggest that MA128 is a potential therapeutic agent and a safe herbal medicine for controlling malignant and metastatic cancer. PMID:26035620
Malignant conversion of florid oral and labial papillomatosis during topical immunotherapy with imiquimod
K. Wenzel; B. Saka; R. Zimmermann; K. K. H. Gundlach; M. Barten; G. Gross
We report a case of a 61-year-old woman suffering from florid oral papillomatosis with a squamous-cell cancer of the floor of the mouth, which was removed by scalpel surgery combined with a radical neck dissection in 1996. Between 1996 and 2000 several histologically benign papillomatous lesions of mouth and lips were removed with laser and electrosurgery. However, the lesions recurred.
Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity
M. de Lourdes Su�rez Roa; L. M. Ruiz Godoy Rivera; T. Vela Ch�vez; M. P�rez S�nchez; A. Meneses Garc�a
Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected\\u000a are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney\\u000a and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most\\u000a metastases to
Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review
Ajay Kumar Chaudhary; Mamta Singh; Shanthy Sundaram; Ravi Mehrotra
Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck
Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms
Hodges, Sally E.; Yagnik, Vivek; Mor�n, Fannie E.; Wu, Meng-Fen; Hilsenbeck, Susan G.; Raijman, Isaac L.; Charles Brunicardi, F.
Background. Cystic lesions of the pancreas are being identified more frequently. Deciding which asymptomatic lesions can be safely followed with serial imaging and which require resection due to malignant potential is an increasingly common question. Current clinical practice is to rely on characteristics of the lesions on CT scan, and additional information from endoscopic ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde pancreatography (ERCP) to assess malignant potential. Hypothesis. The malignant potential of pancreatic cystic lesions cannot be accurately predicted by CT scan. Methods. CT scans from 48 patients with cystic lesions of the pancreas were stripped of patient identifiers and retrospectively presented to two expert radiologists. The radiologists recorded specific characteristics of the lesions thought to be important in the differential diagnosis and their opinion of the likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists� diagnoses to the final pathologic diagnosis after resection. To determine if clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical records were retrospectively reviewed and scored as either supporting or not supporting malignant potential of the lesion. Results. Specific diagnoses based on CT findings alone were correct in an average of 39% of the cases. Even when diagnoses were dichotomized as benign (43%) or potentially malignant (57%, papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations based on CT alone were accurate in an average of 61% of cases. Accuracy rates were 60.4 and 62.5% for the two radiologists, although there was only fair agreement between them (Kappa=0.28, 95% CI=(0.01�0.55), p=0.05). When all clinical information available was considered together as a single dichotomous indicator of malignant potential, the indicator was accurate in 90% of the cases (Kappa=0.73, 95% CI=(0.51�0.95, p<0.0001)). Conclusion. Specific preoperative diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate. Complementary tests such as EUS-FNA with fluid analysis and ERCP should be recommended to improve diagnosis especially if nonoperative treatment is planned. PMID:19088937
Meurman, Jukka H.
Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion. PMID:21523227
Clinical guidelines in early detection of oral squamous cell carcinoma arising in oral lichen planus: a 5-year experience
M. D. Mignogna; L. Lo Muzio; L. Lo Russo; S. Fedele; E. Ruoppo; E. Bucci
In recent years, studies on the malignant potential of oral lichen planus (OLP) provided clinical evidence that patients affected by OLP have an increased risk to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still exist as to whether OLP has inherent predisposition to become malignant, or not. We believe extremely careful management of OLP patient is mandatory, and the
Casein/pectin nanocomplexes as potential oral delivery vehicles.
Luo, Yangchao; Pan, Kang; Zhong, Qixin
Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-?-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85�C for 30min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines. PMID:25800678
The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscopeTM) � a single blinded clinical evaluation
Objective The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope� using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. Materials and methods 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope�. Biopsies were obtained from all suspicious areas identified in both examination groups (n?=?52). The diagnostic strategies were compared regarding sensitivity and specificity. Results Based upon the result, use of the VELscope� leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope� is inferior (8.4%). Conclusion The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions. PMID:23967796
Chimeric adeno-associated virus and bacteriophage: a potential targeted gene therapy vector for malignant glioma.
Asavarut, Paladd; O'Neill, Kevin; Syed, Nelofer; Hajitou, Amin
The incipient development of gene therapy for cancer has fuelled its progression from bench to bedside in mere decades. Of all malignancies that exist, gliomas are the largest class of brain tumors, and are renowned for their aggressiveness and resistance to therapy. In order for gene therapy to achieve clinical success, a multitude of barriers ranging from glioma tumor physiology to vector biology must be overcome. Many viral gene delivery systems have been subjected to clinical investigation; however, with highly limited success. In this review, the current progress and challenges of gene therapy for malignant glioma are discussed. Moreover, we highlight the hybrid adeno-associated virus and bacteriophage vector as a potential candidate for targeted gene delivery to brain tumors. PMID:25375341
PARLATESCU, Ioanina; GHEORGHE, Carmen; COCULESCU, Elena; TOVARU, Serban
The main purpose of this paper was to assess the current state of science on oral leukoplakia. Although it is considered a potentially malignant disorder the overall malignant progression of oral leukoplakia is of the order of 5% and even more. Nowadays there are no currently accepted markers to distinguish those that may progress to cancer from those that may not. The current golden standard is considered the presence of epithelial dysplasia on the tissue biopsy of the lesion. Proliferative verrucous leukoplakia is a rare form of OL which has multiple recurrences, is refractory to treatment and has malignant transformation in a short period. It is considered a true premalignant lesion. The management of oral leukoplakia varies from a "wait and see" attitude and topical chemopreventive agents to complete surgical removal. PMID:25553134
Catheter ablation targeting Purkinje potentials controlled ventricular fibrillation in a patient with a malignant lymphoma occurring in the ventricular septum.
Nakabayashi, Keisuke; Sugiura, Ryo; Oka, Toshiaki
Malignant lymphoma is known to cause various types of arrhythmia, including ventricular fibrillation. However, radiofrequency catheter ablation of ventricular fibrillation associated with malignant lymphoma has never been reported. We describe the case of a 53-year-old man with refractory ventricular fibrillation that was associated with malignant lymphoma. Electrophysiological testing revealed that a Purkinje potential appeared before ventricular contraction at the tumour site. We successfully treated the ventricular fibrillation with radiofrequency catheter ablation, using the Purkinje potential as an indicator. Physicians should consider this treatment if ventricular fibrillation cannot be controlled using other strategies. PMID:26040826
A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies
Burris, Howard A.; Taylor, Charles W.; Jones, Suzanne F.; Koch, Kevin M.; Versola, Melissa J.; Arya, Niki; Fleming, Ronald A.; Smith, Deborah A.; Pandite, Lini; Spector, Neil; Wilding, George
Purpose This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies. Experimental Design Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments. The effect of a low-fat meal on lapatinib pharmacokinetics was assessed in a subset of patients. Results Lapatinib was well tolerated, such that dose escalation was limited at 1,800 mg once daily only by pill burden. Twice-daily dosing was implemented to further explore tolerability, and was limited by diarrhea to 500 mg twice daily. The most commonly reported adverse events with once-daily dosing were diarrhea (48%), nausea (40%), rash (40%), and fatigue (38%) and with twice-daily dosing were diarrhea (85%), rash (54%), and nausea (34%). Lapatinib serum concentrations accumulated upon repeated dosing, increasing nearly in proportion with dose, and were significantly increased when dosed with food or administered twice daily. One patient with head and neck cancer achieved a confirmed complete response and 22 patients had stable disease of ?8 weeks including three patients with stable disease of >10 months (renal, lung, and salivary gland cancers). Conclusion Lapatinib was well tolerated following once and twice daily administration. Systemic exposure to lapatinib was dependent on the dose, duration and frequency of dosing, and prandial state. Clinical activity was observed. PMID:19825948
COX-2 overexpression increases malignant potential of human glioma cells through Id1
Xu, Kaiming; Wang, Lanfang; Shu, Hui-Kuo G.
Increased COX-2 expression directly correlates with glioma grade and is associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also regulated by epidermal growth factor receptor signaling which is important in the pathogenesis of GBMs. However, COX-2 expression has not been previously shown to directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH) family of transcriptional repressors that act as dominant-negative inhibitors of basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast carcinoma cells and recent studies suggest that Id1 may also be involved in the genesis/progression of gliomas. We now show that COX-2 increases the aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma transformation/tumorigenesis. Furthermore, we find direct evidence of a role for Id1 with significant suppression of in vitro transformation and in vivo tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down. In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show greater migration/invasive potential and tumors that arise from these cells also display increased microvessel density, results in line with the increased malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of GBM cells through induction of Id1. PMID:24659686
Uterine smooth muscle tumors of uncertain malignant potential (STUMP): pathology, follow-up and recurrence
Dall�Asta, Andrea; Gizzo, Salvatore; Musar�, Andrea; Quaranta�, Michela; Noventa, Marco; Migliavacca, Costanza; Sozzi, Giulio; Monica, Michela; Mautone, Daniele; Berretta, Roberto
The term smooth uterine muscle of uncertain malignant potential (STUMPs) indicates a group of uterine smooth muscle tumors (SMTs) that cannot be diagnosed unequivocally as benign or malignant. Diagnosis, surgical management, and follow-up of this neoplasm remain controversial, especially in pre-menopausal women with fertility desire, due to the non aggressive behaviour and prolonged survival rate when compared to leiomyosarcomas. However, recurrence is estimated between 8.7% and 11% and may include delayed-recurrences. We reported five cases of uterine masses treated by surgical procedure diagnosed as STUMP on final pathology. Four patients underwent a total abdominal hysterectomy with or without salpingo-oophorectomy. One patient underwent excision of uterine mass and subsequent total abdominal hysterectomy plus bilateral salpingo-oophorectomy after the diagnosis of STUMP. All patients in our study remained recurrence-free to date (with a follow up period ranging from 6 to 81 months). Based on our experience and in consideration of the lack of consensus regarding the malignant potential, diagnostic criteria, gold-standard treatment and follow-up, we believe that close multidisciplinary management is mandatory in the event of STUMP. We suggest that gynaecologist, dedicated pathologist (with high level of expertize in gynaecological pathology) and oncologist should work as a team in the counselling and management of this neoplasm from detection till completion of follow up. Furthermore, we recommend immunohistochemistry to investigate the overexpression of p16 and p53 in order to identify the cohort of patients at increased risk of recurrence who may benefit from more aggressive surgical-oncological strategies. PMID:25550862
PDZ Domains and Viral Infection: Versatile Potentials of HPV-PDZ Interactions in relation to Malignancy
Kawana, Kei; Osuga, Yutaka; Fujii, Tomoyuki
Cervical cancer is caused by high-risk human papillomaviruses (HPVs), and a unique characteristic of these is a PDZ (P�SD-95/D�lg/Z�O-1-)binding motif in their E6 proteins. Through this motif HPV E6 interacts with a variety of PDZ domain-containing proteins and targets them mainly for degradation. These E6-PDZ interactions exhibit extraordinarily different functions in relation to HPV-induced malignancy, depending upon various cellular contexts; for example, Dlg and Scrib show different distribution patterns from what is seen in normal epithelium, both in localization and in amount, and their loss may be a late-stage marker in malignant progression. Recent studies show that interactions with specific forms of the proteins may have oncogenic potential. In addition, it is interesting that PDZ proteins make a contribution to the stabilization of E6 and viral episomal maintenance during the course of HPV life cycle. Various posttranslational modifications also greatly affect their functions. Phosphorylation of hDlg and hScrib by certain kinases regulates several important signaling cascades, and E6-PDZ interactions themselves are regulated through PKA-dependent phosphorylation. Thus these interactions naturally have great potential for both predictive and therapeutic applications, and, with development of screening tools for identifying novel targets of their interactions, comprehensive spatiotemporal analysis is currently underway. PMID:24093094
Estimation of malignant transformation rate in cases of oral epithelial dysplasia and lichen planus using immunohistochemical expression of Ki-67, p53, BCL-2, and BAX markers
Shailaja, G.; Kumar, J. Vijay; Baghirath, P. V.; Kumar, U.; Ashalata, G.; Krishna, A. Bhargavi
Background: The issue of a possible malignant transformation in the lesions like epithelial dysplasia and oral lichen planus (OLP) is a matter of serious controversy. The purpose of this study was to suggest the malignant transformation rate in OLP and oral epithelial dysplasia (OED) by using immunohistochemical expression of the tumor markers Ki-67, p53, BCL-2, and BAX. Materials and Methods: This was a cross-sectional study carried out among 70 samples, including 10 samples from normal healthy mucosa categorized into Group 1, Group 2 (30 OLP), and Group 3 (30 OED) samples. Five sections (4 ?m thick) were obtained and stained with monoclonal antibodies such as Ki-67, p53, BCL-2, and BAX and analyzed for number of positive cells and also for intensity of staining. Statistical analysis was done using Mann-Whitney U-test (P < 0.05). Results: Significant results were found only for expressions of Ki-67, p53, BCL-2 markers in both study groups (P < 0.05). In these groups, the intensity of staining was mostly mild to moderate for all studied tumor markers. In this study, subjects with an average positive IHC expression of Ki-67, p53, BCL-2, and BAX markers in normal mucosa was about 22.5%, which was significantly lower when compared with OLP (54.9%) and OED (64.9%). Conclusion: The high propensity for malignant transformation in OED followed by OLP suggests that a wide range of inherent and extrinsic factors contribute to the disease progression and malignant transformation. PMID:26005463
[Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)].
Nakata, Yoko; Hirashima, Tomonori; Kondou, Yoko; Tokuoka, Yoshie; Imazato, Hitomi; Iwata, Kaori; Oomori, Yukari; Yamato, Akihiro; Shimizu, Saburou; Nagao, Sadako; Matsui, Kaoru; Abe, Noriko
We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients. PMID:18633224
Juvenile polyposis of the stomach: clinicopathological features and its malignant potential.
Hizawa, K; Iida, M; Yao, T; Aoyagi, K; Fujishima, M
AIMS: To clarify a clinical entity of juvenile polyposis of the stomach compared with generalised juvenile gastrointestinal polyposis. METHODS: The clinicopathological features of juvenile polyposis dominantly involving the stomach at initial presentation were reviewed in 12 patients (three new patients and nine from the literature). These were compared with 29 cases of generalised juvenile gastrointestinal polyposis. RESULTS: There were three men and nine women with juvenile polyposis of the stomach, aged 10-63 years. Hypoproteinaemia was present in nine patients, anaemia in seven, and a family history of intestinal polyposis in seven. No patient presented with a congenital abnormality. During the observation period, two patients developed colonic juvenile polyps. Gastric polyps invariably affected the antrum and extended to the fundus, eventually becoming more numerous, larger, and more pedunculated. Ten patients required gastrectomy for associated malignancy or uncontrolled protein losing gastropathy. Histological examinations of the resected specimens demonstrated neoplastic tissue arising from juvenile polyps in four of the 12 patients. Atypism in these mixed polyps varied from adenoma to well or moderately differentiated adenocarcinoma. CONCLUSIONS: Juvenile polyposis of the stomach has malignant potential, and may be a separate entity from generalised juvenile gastrointestinal polyposis. Images PMID:9389980
mTOR Inhibitors and Their Potential Role in Therapy in Leukemia and Other Haematologic Malignancies
Teachey, David T.; Grupp, Stephan A.; Brown, Valerie I.
Summary The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, protein synthesis, and cell-cycle progression through interactions with a number of signaling pathways, including PI3K/AKT, ras, TCL1, and BCR/ABL. Many haematologic malignancies have aberrant activation of the mTOR and related signaling pathways. Accordingly, mTOR inhibitors, a class of signal transduction inhibitors that were originally developed as immunosuppressive agents, are being investigated in preclinical models and clinical trials for a number of haematologic malignancies. Sirolimus and second generation mTOR inhibitors such as temsirolimus and everolimus, are safe and relatively well-tolerated, making them potentially attractive as single agents or in combination with conventional cytotoxics and other targeted therapies. Promising early clinical data suggests activity of mTOR inhibitors in a number of haematologic diseases, including acute lymphoblastic leukemia, chronic myelogenous leukemia, mantle cell lymphoma, anaplastic large cell lymphoma, and lymphoproliferative disorders. This review describes the rationale for using mTOR inhibitors in a variety of haematologic diseases with a focus on their use in leukemia. PMID:19344392
Potential of 'flat' fibre evanescent wave spectroscopy to discriminate between normal and malignant cells in vitro.
Hammody, Z; Huleihel, M; Salman, A; Argov, S; Moreh, R; Katzir, A; Mordechai, S
The present study focuses on evaluating the potential of flattened AgClBr fibre-optic evanescent wave spectroscopy (FTIR-FEWS) technique for detection and identification of cancer cells in vitro using cell culture as a model system. The FTIR-FEWS results are compared to those from FTIR-microspectroscopy (FTIR-MSP) method extensively used to identify spectral properties of intact cells. Ten different samples of control and malignant cells were measured in parallel by the above two methods. Our results show a significant similarity between the results obtained by the two methodologies. The absorbance level of Amide I/Amide II, phosphates and carbohydrates were significantly altered in malignant compared to the normal cells using both systems. Thus, common biomarkers such as Amide I/Amide II, phosphate and carbohydrate levels can be derived to discern between normal and cancer cells. However, marked differences are also noted between the two methodologies in the protein bands due to CH3 bending vibration (1480-1350 cm(-1)). The spectral differences may be attributed to the variation in the penetration depth of the two methodologies. The use of flattened fibre rather than the standard cylindrical fibre has several practical advantages and is considered as an important step towards in vivo measurements in real time, such as that of skin nevi and melanoma using special designs of fibre-optic-based sensors. PMID:17970920
�Decoy� and �non-decoy� functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells
Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a �decoy� for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has �non-decoy� functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH. PMID:23817777
Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-?B in immortalized and malignant oral keratinocytes
Lee, Hwa-Jeong; Lee, Jun; Lee, Sun-Kyung; Lee, Suk-Keun; Kim, Eun-Cheol
Background Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-?B binding activity. Phosphorylation and degradation of the I-?B were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1? to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of I?B, and activation of NF-?B. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-?B, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions. PMID:17850672
Precancerous lesions of oral mucosa
Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin
Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862
Incidental prostatic stromal tumor of uncertain malignant potential (STUMP): histopathological and immunohistochemical findings.
De Berardinis, Ettore; Busetto, Gian Maria; Antonini, Gabriele; Giovannone, Riccardo; Di Placido, Mariarosaria; Magliocca, Fabio M; Di Silverio, Alessandro; Gentile, Vincenzo
Stromal prostate tumors are rare neoplastic proliferative lesions that have been classified into prostatic stromal tumor of uncertain malignant potential (STUMP) and prostatic stromal sarcoma (SS) based on these criteria: stromal cellularity, presence of mitotic figures, necrosis, and stromal overgrowth. A prostatic stromal tumor of uncertain malignant potential (STUMP) is a non-epithelial, mesenchymal spindle-cell tumor that can be classified as a specialized stromal tumor of the prostate. STUMPs have the capability to diffusely infiltrate the prostate gland and extend into adjacent tissues. Furthermore, they often recur and this is why they are considered as neoplastic entities. STUMPs usually tend to be not aggressive, but occasional cases have been reported with an extension into adjacent tissues. A few cases develop a sarcomatous dedifferentiation. A 67-year-old male referred to the Department of Urology, Sapienza Rome University, with acute urinary retention (AUR) and bladder overdistention. Digital rectal examination (DRE) showed the presence of a severe prostatic hyperplasia and a transvesical prostatic adenomectomy (TVPA) was performed. The pathological evaluation performed at the Department of Pathology, Sapienza Rome University, revealed an incidental diagnosis of prostatic STUMP. The patient's follow-up is made every year with transrectal ultrasonography and nuclear magnetic resonance with spectroscopy, and every two years with a transperineal prostate biopsy to exclude a progression to a stromal sarcoma. After 5 years of follow-up the STUMP is still detectable but there is no sign of sarcoma. As a result of its relative rarity and lack of long-term follow-up, the prognosis of STUMP is unclear. Therapy varies from a wait-and-see approach to a radical retropubic prostatectomy. PMID:22388992
Evaluation of an oral health scale of infectious potential using a telematic survey of visual diagnosis
Relvas, Marta; Limeres, Jacobo; Cabral, Cristina; Velazco, Corsina; Diz, Pedro
Objective: To compare the results of a subjective estimation of oral health through review of a set of intraoral photographs with those of an objective oral health scale of infectious potential. Method: The pool of patients was made up of 100 adults. Using an infectious-potential scale based on dental and periodontal variables, we assigned 1 of the 4 grades of the scale (range, 0 to 3; 0 corresponds to an excellent oral health status and 3 to the poorest oral health status) to each subject. A total of 20 representative subjects were selected from the pool of patients, 5 subjects for each one of the grades of the scale, and a standardized photographic record was made. One thousand dentists practicing in Spain were sent the survey by e-mail and 174 completed forms were received. We then calculated the concordance of the oral health status indicated by the respondents after visualising the photographs on comparison with the results of the oral health scale of infectious potential; concordance was termed correct grade allocation (CGA). Results: The majority of respondents (69.1%) achieved a CGA in 8 to 12 cases and none achieved more than 15 CGAs. The poorest CGA rates were found with grades 1 and 2, with a mean of 1.74 � 1.09 and 1.87 � 1.18, respectively, out of a maximum of 5. The concordance in terms of CGA was high for grade 0 (70.5%), very low for grade 1 (10.8%), low for grade 2 (37.3%), and moderate for grade 3 (42.6%). Conclusion: In comparison with visual examination of the oral cavity, the use of objective scale that establishes a reliable diagnosis of oral health in terms of infectious potential was found to be advantageous. Key words:Diagnosis, intraoral photographies, oral health scale, objective estimation, visual examination. PMID:23524432
Jurel, Sunit Kumar; Gupta, Durga Shanker; Singh, Raghuwar D.; Singh, Mrinalini; Srivastava, Shilpi
Oral cancers have been one of the leading causes of deaths particularly in the developing countries. Prime reason for this high mortality and morbidity is attributed to the delay in diagnosis and prompt treatment. Relentless research in the field of oncology has led to the advent of novel procedures for the early detection of oral cancers. Molecular biology is highly promising in this regard. It is a procedure that detects alterations at a molecular level much before they are seen under a microscope and much before clinical changes occur. Molecular studies serve as the basis by which we will eventually be able not only to augment clinical assessment and classification of oral lesions but also predict malignant potential of oral lesions, thus reducing the incidence and increasing the scope for early diagnosis and treatment of oral cancers. However, making such sophisticated tools available for the common man in developing countries is one of the most important challenges faced today. PMID:24959008
Combination therapy of potential gene to enhance oral cancer therapeutic effect
NASA Astrophysics Data System (ADS)
Yeh, Chia-Hsien; Hsu, Yih-Chih
The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.
Potential antidotes for reversal of old and new oral anticoagulants.
Suryanarayan, Deepa; Schulman, Sam
The prescription of new oral anticoagulants is on the rise. As opposed to vitamin K antagonists and heparins the new agents have single targets in the coagulation cascade, more predictable pharmacokinetics and they lack validated and available antidotes. In general, the new agents have similar or lower bleeding risk than vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for bleeding are typically the same for old and new anticoagulants. Old age, renal dysfunction and concomitant antiplatelet agents seem to be recurring risk factors. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. With the exception of vitamin K (for vitamin K antagonists) and protamine (for heparin) the same array of prohemostatic agents--unactivated or activated prothrombin complex concentrate, and activated factor VIIa--have been tried for almost all anticocoagulants in different models, and for some agents also in patients, with varying success. Hemodialysis can reduce the level of dabigatran efficiently and activated charcoal may be used for very recent oral ingestion of lipophilic agents. In view of the shorter half life of the new agents compared to warfarin the need for reversal agents may be less critical. Nevertheless, highly specific reversal agents for the thrombin- and factor Xa-inhibitors are under development and might be available within two years. PMID:24862137
Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence ?
Michele D Mignogna; Stefano Fedele; Lucio Lo Russo; Lorenzo Lo Muzio; Eduardo Bucci
The association of chronic inflammation with a variety of epithelial malignancies has been recognised for centuries. Well established examples include, among many others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel cancer associated with chronic inflammatory bowel diseases. By now no data, other than clinical observation, have been available in understanding the pathogenesis of these inflammation-related tumours. However, recent molecular
Antidotes for Novel Oral Anticoagulants: Current Status and Future Potential.
Crowther, Mark; Crowther, Mark A
The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies. PMID:26088576
HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST)
Lopez, Gonzalo; Bill, Kate Lynn J.; Bid, Hemant Kumar; Braggio, Danielle; Constantino, Dylan; Prudner, Bethany; Zewdu, Abeba; Batte, Kara; Lev, Dina; Pollock, Raphael E.
Introduction HDAC isoform-specific inhibitors may improve the therapeutic window while limiting toxicities. Developing inhibitors against class I isoforms poses difficulties as they share high homology among their catalytic sites; however, HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors are novel compounds and have affinity for class I HDAC isoforms demonstrating anti-cancer effects; little is known about their activity in malignant peripheral nerve sheath tumors (MPNST). Recently, we demonstrated anti-MPNST efficacy of HDAC8i in human and murine-derived MPNST pre-clinical models; we now seek to consider the potential therapeutic inhibition of HDAC8 in MPNST. Methods Four Human MPNST cell lines, a murine-derived MPNST cell line, and two HDAC8 inhibitors (PCI-34051, PCI-48012; Pharmacyclics, Inc. Sunnyvale, CA) were studied. Proliferation was determined using MTS and clonogenic assays. Effects on cell cycle were determined via PI FACS analysis; effects on apoptosis were determined using Annexin V-PI FACS analysis and cleaved caspase 3 expression. In vivo growth effects of HDAC8i were evaluated using MPNST xenograft models. 2D gel electrophoresis and mass spectrometry were used to identify potential HDAC8 deacetylation substrates. Results HDAC8i induced cell growth inhibition and marked S-phase cell cycle arrest in human and murine-derived MPNST cells. Relative to control, HDAC8i induced apoptosis in both human and murine-derived MPNST cells. HDAC8i exhibited significant effects on MPNST xenograft growth (p=0.001) and tumor weight (p=0.02). Four potential HDAC8 substrate targets were identified using a proteomic approach: PARK7, HMGB1, PGAM1, PRDX6. Conclusions MPNST is an aggressive sarcoma that is notoriously therapy-resistant, hence the urgent need for improved anti-MPNST therapies. HDAC8 inhibition may be useful for MPNST by improving efficacy while limiting toxicities as compared to pan-HDACis. PMID:26200462
Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer
Hoekstra, Elmer; Kodach, Liudmila L.; Das, Asha M.; Ruela-de-Sousa, Roberta R.; Ferreira, Carmen V.; Hardwick, James C.; van der Woude, C. Janneke; Peppelenbosch, Maikel P.; ten Hagen, Timo L.M.; Fuhler, Gwenny M.
Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease. PMID:25811796
Risk, Outcomes, and Costs of Radiation-Induced Oral Mucositis Among Patients With Head-and-Neck Malignancies
Elting, Linda S. [Section of Health Services Research, Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)]. E-mail: firstname.lastname@example.com; Cooksley, Catherine D. [Section of Health Services Research, Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Chambers, Mark S. [Department of Dental Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Garden, Adam S. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
Purpose: To study the risk, outcomes, and costs of radiation-induced oral mucositis (OM) among patients receiving radiotherapy (RT) to head and neck primary cancers. Methods and Materials: A retrospective cohort consisting of 204 consecutive head-and-neck cancer patients who received RT with or without chemotherapy during 2002 was formed; their records were reviewed for clinical and resource use information. Patients who had received prior therapy, had second primary cancers, or received palliative radiation therapy were excluded. The risk of OM was analyzed by multiple variable logistic regression. The cost of care was computed from the provider's perspective in 2006 U.S. dollars and compared among patients with and without OM. Results: Oral mucositis occurred in 91% of patients; in 66% it was severe (Grade 3-4). Oral mucositis was more common among patients with oral cavity or oropharynx primaries (odds ratio [OR], 44.5; 95% confidence interval [CI], 5.2 to >100; p < 0.001), those who received chemotherapy (OR = 7.8; 95% CI, 1.5-41.6; p 0.02), and those who were treated with altered fractionation schedules (OR 6.3; 95% CI, 1.1-35.1; p = 0.03). Patients with OM were significantly more likely to have severe pain (54% vs. 6%; p < 0.001) and a weight loss of {>=}5% (60% vs. 17%; p < 0.001). Oral mucositis was associated with an incremental cost of $1700-$6000, depending on the grade. Conclusions: Head-and-neck RT causes OM in virtually all patients. Oral mucositis is associated with severe pain, significant weight loss, increased resource use, and excess cost. Preventive strategies are needed.
The value of minimal access surgery in the staging of patients with potentially resectable peripancreatic malignancy.
Conlon, K C; Dougherty, E; Klimstra, D S; Coit, D G; Turnbull, A D; Brennan, M F
OBJECTIVE: The purpose of this study was to determine if an endosurgical approach that mimics open exploration would improve the accuracy of simple diagnostic laparoscopy. SUMMARY BACKGROUND DATA; Most patients with peripancreatic malignancy are found at exploration to be unable to undergo resection. Laparoscopy has been suggested as a sensitive method for detecting metastatic disease in this group of patients. However, the ability to assess resectability with simple diagnostic laparoscopy remains relatively low (<40%). METHODS: Between December 1992 and August 1994, 115 patients with radiologically resectable peripancreatic tumors underwent extended laparoscopy before undergoing a planned curative resection. This technique required assessment of the peritoneal cavity, liver, lesser sac, porta hepatis, duodenum, transverse mesocolon, and celiac and portal vessels. RESULTS: Sixty male and 55 female patients were included in the current study. The pancreatic head was involved in 74 patients (64%), followed by the body in 21 (18%), tail in 8 (7%), ampulla in 8 (7%), duodenum in 3 (3%), and distal bile duct in 1 (1%). An abdominal computed tomography (CT) scan was performed for all patients before laparoscopy, ultrasonography for 74 patients (64%), endoscopic retrograde choleangiopancreatography for 59 patients (51%), and mesenteric angiography for 9 patients (8%). Pneumoperitoneum was established successfully in all but 2 cases (98%). A complete examination of 108 patients was performed. Sixty-seven patients were considered to have resectable disease, and 61 resections were performed. Laparoscopy failed to identify hepatic metastases in 5 patients and portal venous encasement in 1 patient. Unresectable disease was identified in 41 patients. Hepatic metastases were observed in 20 patients, mesenteric vascular encasement in 14, extrapancreatic/peritoneal involvement in 16, and celiac or portal lymphatic metastases in 8. There were no intraoperative or postoperative complications related to the laparoscopic procedure. The positive predictive index, negative predictive index, and accuracy of laparoscopy were 100%, 91%, and 94%, respectively. CONCLUSIONS: This study demonstrates that extended laparoscopy is accurate and safe and makes exploration unnecessary in many patients with potentially resectable peripancreatic malignancy. In this series, 76% of patients explored were resected, compared with the authors' experience between 1983 and 1993 of 35%. The authors believe that laparoscopy is an important component in the staging of this group of patients and should be performed before exploration. PMID:8597506
Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations
Ilana Kaplan; Emmilia Hodak; Lehavit Ackerman; Daniel Mimouni; Grant J Anhalt; Shlomo Calderon
The review included 163 cases of paraneoplastic pemphigus (PNP) reported between 1990 and 2003, including a new unique case of PNP associated with occult breast cancer and an ovarian cyst of borderline malignancy.Hematologic-related neoplasms or disorders were associated with 84% of the cases, with non-Hodgkin lymphoma (38.6%) as the most frequent, followed by chronic lymphocytic leukemia (18.4%) and Castleman's disease
Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors
Sabine Wagner; Ove Peters; Christin Fels; Gisela Janssen; Anne-Kathrin Liebeskind; Axel Sauerbrey; Meinolf Suttorp; Peter Hau; Johannes E. A. Wolff
Background: The combination of topoisomerase I and II chemotherapeutic agents has shown promising preclinical synergistic effects in\\u000a the treatment of high-grade malignant brain tumors such as high-grade gliomas and choroid plexus carcinomas. To confirm the\\u000a effectiveness of this treatment combination and determine its possible toxicity, we conducted a retrospective review of the\\u000a charts of children who received the therapy. Methods:
Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry
Louise B Br�nden; Thomas Eriksen; Annemarie T Kristensen
BACKGROUND: Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral
Activated MET is a molecular prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumors
Torres, Keila E.; Zhu, Quan-Sheng; Bill, Katelynn; Lopez, Gonzalo; Ghadimi, Markus P.; Xie, Xianbiao; Young, Eric D.; Liu, Juehui; Nguyen, Theresa; Bolshakov, Svetlana; Belousov, Roman; Wang, Suizhau; Lahat, Guy; Liu, Jun; Hernandez, Belinda; Lazar, Alexander J.; Lev, Dina
Purpose: MET-signaling has been suggested a potential role in malignant peripheral nerve sheath tumors (MPNSTs). Here, MET function and blockade were preclinically assessed. Experimental Design: Expression levels of MET, its ligand HGF, and phosphorylated MET (pMET) were examined in a clinically annotated MPNST tissue microarray incorporating univariable and multivariable statistical analyses. Human MPNST cells were studied in vitro and in vivo; WB and ELISA were used to evaluate MET and HGF expression, activation, and downstream signaling. Cell culture assays tested the impact of HGF-induced MET activation and anti-MET-specific siRNA inhibition on cell proliferation, migration, and invasion; in vivo gelfoam assays were used to evaluate angiogenesis. Cells stably transduced with anti-MET shRNA constructs were tested for growth and metastasis in SCID mice. The effect of the tyrosine kinase inhibitor XL184 (Exelixis) targeting MET/VEGFR2 on local and metastatic MPNST growth was examined in vivo. Results: All three markers were expressed in MPNST human samples; pMET expression was an independent prognosticator of poor patient outcome. Human MPNST cell lines expressed MET, HGF, and pMET. MET activation increased MPNST cell motility, invasion, angiogenesis, and induced MMP2 and VEGF expression; MET knockdown had inverse effects in vitro and markedly decreased local and metastatic growth in vivo. XL184 abrogated human MPNST xenograft growth and metastasis in SCID mice. Conclusions: Informative prognosticators and novel therapies are crucially needed to improve MPNST management and outcomes. We demonstrate an important role for MET in MPNST, supporting continued investigation of novel anti-MET therapies in this clinical context. PMID:21540237
Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.
Yu, Miao; Wang, Yun-Hong; Abdalla, Ahmed M E; Liu, Wen-Qi; Mei, Fei; Wang, Jian; Ouyang, Chen-Xi; Li, Yi-Qing
A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9�17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, ?2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (?-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and ?2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and ?2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT. PMID:25318883
Study of feline oral squamous cell carcinoma: Potential target for cyclooxygenase inhibitor treatment
Lisa DiBernardi; Monique Dor�; John A. Davis; Jane G. Owens; Sulma I. Mohammed; Carolyn F. Guptill; Deborah W. Knapp
Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality. A potential target for OSCC treatment is cyclooxygenase-2 (cox-2). Pet cats with naturally occurring OSCC may offer the opportunity to study anticancer activity of cox inhibitors. Cox-2 expression in feline OSCC was determined by immunohistochemistry. High intensity cox-2 immunoreactivity was detected in 6 of 34 (18%) feline OSCC
FTIR microspectroscopic study of cell types and potential confounding variables in screening for cervical malignancies.
Wood, B R; Quinn, M A; Tait, B; Ashdown, M; Hislop, T; Romeo, M; McNaughton, D
FTIR microscopy was applied to the analysis of cell types and other variables present in Pap smears to ascertain the limitations of infrared spectroscopy in the diagnosis of cervical cancer and dysplasia. It was found that leukocytes, and in particular lymphocytes, have spectral features in the phosphodiester region (1300-900 cm[-1]) suggestive of what has previously been described as changes indicative of malignancy. Endocervical cells and fibroblasts have similar spectral features to HeLa cells and consequently could also confound diagnosis. The use of ethanol as a fixative and dehydrating agent results in retention of glycogen in cervical cell types and thus minimizes spectral changes in the glycogen region due to sampling technique. Spectra of seminal fluids exhibit strong bands in the phosphodiester/carbohydrate region; however, sperm contamination should be easily detectable by the presence of a distinctive doublet at 981/968 cm(-1). Erythrocyte spectra exhibit a reduction in glycogen band intensity, but can be discerned by a relatively low-intensity nu(s) PO2- band. Endocervical mucin spectra exhibit a reduction in glycogen bands and a very pronounced nu(s) PO2- band, which is similar in intensity to the corresponding band in HeLa cells. Thrombocytes have strong bands in the phosphodiester region, but thrombocytes can be discerned from other cell types by the presence of two small broad bands at 980 and 935 cm(-1). Candida albicans is characterized by strong bands in the polysaccharide region which could potentially obscure diagnostic bands if C. albicans is present in large numbers. Spectra of bacteria common to the female genital tract, in general, also have strong absorptions in the polysaccharide region; however, bacterial contamination is usually minimal and would not be expected to obscure cervical cell spectra. Nylon threads and bristles from cervical sampling implements produce characteristic IR profiles which allow for easy identification. Given the number of potential confounding variables associated with cervical cytology, a multivariate statistical or neural network analysis would appear to be necessary before the implementation of FTIR technology in clinical laboratories. PMID:9557903
Recent trends in prevention of oral cancer
Mangalath, Ummar; Aslam, Sachin Aslam; Abdul Khadar, Abdul Hafiz Kooliyat; Francis, Pulikkan George; Mikacha, Muhamed Shaloob Karimbil; Kalathingal, Jubin Hassan
Oral cancers often occurs out of long standing potentially malignant lesions and conditions so called premalignant lesions and conditions. Oral precancer is a intermediate state with increased cancer rate which can be recognized and treated obviously with much better prognosis than a full blown malignancy. Oral cancer risk can be lowered or even prevented by simply understanding basic oral hygiene, different bacteria found in the mouth, and how diet influences oral cancers. Currently, research is being done on the relationship between diet and oral cancer. Oral cancer is a very serious disease that can be prevented. Practicing good oral hygiene is key to help keep the oral cavity clean. Limiting the use of tobacco and alcohol products is also important because these are the causes of most oral cancers. Lastly, eating a well balanced diet that has protective affects can reduce the risk of oral cancer. This includes a diet high in fruits, vegetables, and fish and low in high fat and cholesterol meats, rice, and refined grains. PMID:25625069
Malignant Potential of Murine Stromal Cells after Transplantation of Human Tumors into Nude Mice
NASA Astrophysics Data System (ADS)
Goldenberg, David M.; Pavia, Rose A.
Human malignant cancer tumors grafted into nude mice produce tumors containing both human cancer cells and the host's stromal cells. After short-term propagation of these tumors in vitro, the murine mesenchymal cells appear transformed and are tumorigenic in nude mice. However, established human cancer cell lines fail to similarly alter adjacent murine stromal cells when used to produce tumors in nude mice. These experiments suggest that cancer cells may recruit normal cells to become malignant, qualifying the view of the clonal (unicellular) origin of cancer.
Evaluation of chronic oral toxicity and carcinogenic potential of lornoxicam in rats
G. Pohlmeyer-Esch; N. Mehdi; D. Clarke; S. Radhofer-Welte
As part of the preclinical development program for lornoxicam, a novel non-steroidal anti-inflammatory drug (NSAID), its chronic oral toxicity and carcinogenic potential was assessed in Sprague-Dawley rats. Male and female rats were administered lornoxicam by oral gavage at 0, 0.06, 0.16 or 0.40 mg\\/kg\\/day for 12 months or at 0, 0.01 or 0.06 mg\\/kg\\/day in a supplementary low-dose study of
Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies.
Ogura, Michinori; Uchida, Toshiki; Terui, Yasuhito; Hayakawa, Fumihiko; Kobayashi, Yukio; Taniwaki, Masafumi; Takamatsu, Yasushi; Naoe, Tomoki; Tobinai, Kensei; Munakata, Wataru; Yamauchi, Takeshi; Kageyama, Akiko; Yuasa, Miyuki; Motoyama, Masaaki; Tsunoda, Takeshi; Hatake, Kiyohiko
We carried out a multicenter dose-escalation phase I study of oral OPB-51602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with OPB-51602 at doses of 1, 2, 3, 4, and 6�mg in the "3�+�3" dose escalation design. The most common treatment-related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug-related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The MTD was 6�mg, with dose-limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1-2 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4�mg. OPB-51602 was rapidly absorbed, and exposure tended to increase in a dose-dependent manner. Accumulation of OPB-51602 was seen with 4�weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the MTD of OPB-51602 was 6�mg. OPB-51602 was safe and well tolerated in a dose range of 1-4�mg. However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of OPB-51602 for hematological malignancies with a daily dosing schedule was terminated. PMID:25912076
Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines.
Okamoto, Yoshihiko; Ohkubo, Tsuyako; Ikebe, Tetsuro; Yamazaki, Jun
Several members of the transient receptor potential (TRP)-channel family are expressed in cancer cells. One, cold/menthol-sensitive TRPM8, is reportedly an important player in carcinogenesis in human prostate cancer, although its involvement in oral squamous cell carcinoma (SCC) remains unclear. The present immunohistochemistry and RT-PCR results revealed intense TRPM8 expression in two SCC cell lines, HSC3 and HSC4, derived from the human tongue. Menthol, icilin, and a more specific TRPM8 agonist (WS-12) induced non-specific cation currents, with Ca2+ permeability being greater than that of Na+ or K+. The novel TRPM8 antagonist RQ-00203078 (RQ) profoundly reduced such agonist-induced cation currents. Intracellular Ca2+ imaging revealed that menthol induced both intracellular Ca2+ release and store-operated Ca2+ entry, with RQ inhibiting each effect. To assess the possible pathophysiological role of TRPM8 in oral SCC, we performed motility and invasion assays, and gelatin zymography. Menthol augmented the migration and invasion abilities of both HSC3 and HSC4 cells by potentiating MMP-9 activity. RQ suppressed all of these effects. These results may aid understanding of the pathophysiological implications of TRPM8 channels in the oral SCC cells, support TRP proteins as valuable targets for pharmaceutical intervention, and inform the targeting of oral SCC in which the prognosis is poor. PMID:22267123
Immunoregulatory T cells: Role and potential as a target in malignancy
Marc Beyer; Joachim L. Schultze
Regulatory T cells (Treg cells) are a highly specialized subset of immune cells capable of specifically suppressing autoreactive cells and thereby\\u000a preventing autoimmunity. Treg cells also play an important role in limiting the immune reaction in infectious diseases. In the context of malignancies,\\u000a however, accumulation of Treg cells occurs in the tumor microenvironment. Treg cells have been associated with prevention
The oral medicine clinic--what is its role?
Zakrzewska, J M; Downer, C; Lopes, V
The total number of new patients seen over a period of 12 months in an oral medicine department was 963. Of these 587 were seen by an oral physician, 168 by a liaison psychiatrist, 137 by an oral immunologist and 71 by a dermatologist with a special interest in diseases of the mouth. The broad categories of disease seen were: 364 with orofacial pain of non-dental origin; 263 with benign diseases of the oral mucosa; 149 with potentially malignant lesions, six with frank carcinomas; 100 with oral manifestations of a systemic disease; and 81 patients with conditions considered to be normal. PMID:8046724
Acute oral toxicity and bacterial translocation studies on potentially probiotic strains of lactic acid bacteria
J. S Zhou; Q Shu; K. J Rutherfurd; J Prasad; P. K Gopal; H. S Gill
Three potentially probiotic lactic acid bacteria (LAB) strains, Lactobacillus rhamnosus HN001 (DR20TM), Lb. acidophilus HN017 and Bifidobacterium lactis HN019 (DR10�), have recently been identified and characterized. The present study was designed to evaluate the acute oral toxicity of these strains to mice, and also to investigate bacterial translocation and gut mucosal pathology in BALB\\/c mice fed HN019, HN001 or HN017
Stage III ovarian tumors of low malignant potential treated with cisplatin combination therapy (a Gynecologic Oncology Group study).
Sutton, G P; Bundy, B N; Omura, G A; Yordan, E L; Beecham, J B; Bonfiglio, T
By serendipity we have had the opportunity to evaluate cis-platin-based chemotherapy in ovarian tumors of low malignant potential (LMP). Optimal (less than 1 cm residual disease) FIGO stage III ovarian carcinomas were randomly assigned to treatment with cisplatin plus cyclophosphamide with or without doxorubicin on a prospective Gynecologic Oncology Group Study. On review by the Gynecologic Oncology Group Pathology Committee, 32 of these cases were determined to represent low malignant potential tumors. Mean age of patients with these lesions was 48 years (range, 25-75 years). After initial cytoreduction, 19 patients had residual disease less than 1 cm and 13 had no residual. Twenty (62.5%) received cisplatin plus cyclophosphamide and 12 cisplatin, cyclophosphamide, and doxorubicin chemotherapy; 75% of patients received six or more courses. Second-look surgery was done in 15 cases; only six were negative. However, with a median follow-up of 31.7 months (range, 1-75), only 1 patient has died; no cancer was found at autopsy. The remaining patients are alive without clinical evidence of disease at a median of 30 months. The need for adjunctive therapy in patients with advanced LMP tumors remains speculative. PMID:1869100
Oral medicine and the ageing population.
Yap, T; McCullough, M
The oral cavity is subject to age related processes such as cellular ageing and immunosenescence. The ageing population bears an increased burden of intraoral pathology. In oral medicine, the majority of presenting patients are in their fifth to seventh decade of life. In this review, we discuss the ageing population's susceptibility to mucosal disorders and the increased prevalence of potentially malignant disorders and oral squamous cell carcinoma, as well as dermatoses including oral lichen planus and immunobullous conditions. We also address the ageing population's susceptibility to oral discomfort and explore salivary secretion, ulceration and the symptoms of oral burning. Finally, we will describe orofacial pain conditions which are more likely encountered in an older population. This update highlights clinical presentations which are more likely to be encountered in the ageing population in a general practice setting and the importance of screening both new and long-term patients. PMID:25762041
Certosimo, A J; O'Connor, R P
"Oral electricity," "electrogalvanism," or "galvanic currents" has long been recognized as a potential source of oral pain and discomfort. This phenomenon of oral galvanism results from the difference in electrical potential between dissimilar restorative metals located in the mouth. In this case report, the literature is reviewed, and an interesting case study'is presented. The patient's clinical presentation, and the duration and constancy of the oral symptoms, pose diagnostic challenges. A simple, yet effective treatment regimen is proposed. PMID:8957826
Depleted Uranium. Is it potentially involved in the recent upsurge of malignancies in populations exposed to war dust?
Shelleh, Hamdi H
Due to its extreme density, depleted Uranium (DU) has recently entered the warfare industry and became a major pollutant to the biosphere. Although DU is less radioactive than natural Uranium, it still retains all its chemical toxicity. Limited data exists regarding the long-term hazards of DU on humans, however, it is suspected to be a major toxic and mutagenic agent. Literature review reveals the scarcity of the World Health Organization's knowledge regarding related DU-malignancies. Battlefield reports documented a steady rise of malignancies and newborn malformations after war, that is, leukemia in the Balkans, and congenital anomalies and Kaposi sarcoma (KS) in Iraq. Kaposi sarcoma in Iraq has a quite aggressive behavior compared with the classic KS before, suggesting a potential relation with DU, and possibly a different DU related KS-type. Children are more susceptible to radiation than adults. This enlarges the responsibility of the medical communities for an evidence-based attitude towards DU, and to ban its use until proven otherwise. We, as medical bodies have a human approach - stand with man not to be mistreated, and with green norms, which veto all suspected pollutants of the planet. Until further notice, DU should be thoroughly checked for safety, before it kills. PMID:22588807
Patient self-monitoring of oral anticoagulant therapy: potential benefits and implications for clinical practice.
Douketis, J D
Coumarin derivatives are widely used oral anticoagulants for patients with chronic atrial fibrillation, venous thromboembolism, valvular heart disease, myocardial infarction or a mechanical prosthetic heart valve. Because of the narrow therapeutic window associated with coumarins and the potential for drug interactions, frequent monitoring of anticoagulation is required to maintain the International Normalized Ratio (INR) between 2.0 to 3.5 for most clinical indications. Monitoring of oral anticoagulant therapy is placing a considerable burden on healthcare providers because many patients require life-long treatment with coumarins, and because of an increasing number of elderly patients with conditions that are treated with coumarins. A novel approach that might, in part, address this healthcare need is patient self-monitoring of anticoagulation with a portable coagulometer. Several cohort studies and randomized controlled trials have found that anticoagulation self-monitoring is as good as, or better than, conventional monitoring in a specialized anticoagulation clinic or by a general practitioner. The advantages of anticoagulation self-monitoring include reduced patient inconvenience relating to anticoagulation clinic visits and laboratory monitoring of warfarin therapy, and fewer INR levels outside the therapeutic INR range if INR measurements are preformed more frequently with anticoagulation self-monitoring. Thus, anticoagulation self-monitoring has the potential to reduce the incidence of thromboembolic and bleeding episodes in patients who are receiving long term oral anticoagulant therapy. The potential drawbacks of anticoagulation self-monitoring include the costs of the portable coagulometer. Additionally, self-monitoring is limited to patients who have the cognitive and physical capabilities to perform the technique required for the portable coagulometer. PMID:14728024
Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies.
L�zot, Fr�d�ric; Chesneau, Julie; Battaglia, S�verine; Brion, R�gis; Castaneda, Beatriz; Farges, Jean-Christophe; Heymann, Dominique; R�dini, Fran�oise
High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption, are currently evaluated in phase III clinical trials in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton growth is a critical question in the context of patients with actively growing skeleton; in particular, in light of our previous studies evidencing that endochondral bone formation was transiently disturbed by high doses of ZOL. Two protocols adapted from pediatric treatments were developed for newborn mice (a total of 5 or 10 injections of ZOL 50?g/kg every two days). Their impact on skull bones and teeth growth was analyzed by X-rays, microCT and histology up to 3months after the last injection. ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption and root elongation. Other teeth were affected, but most were erupted by 3months. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in all mandibular incisors. High doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. These preclinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL. PMID:25193159
Persephin: A potential key component in human oral cancer progression through the RET receptor tyrosine kinase-mitogen-activated protein kinase signaling pathway.
Baba, Takao; Sakamoto, Yosuke; Kasamatsu, Atsushi; Minakawa, Yasuyuki; Yokota, Satoshi; Higo, Morihiro; Yokoe, Hidetaka; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro
Persephin (PSPN) is a neurotrophic factor of the glial cell line-derived neurotrophic factor (GDNF) family that promotes survival of multiple populations of neurons. Little is known about the relevance of PSPN in human malignancy including oral squamous cell carcinoma (OSCC). This study was undertaken to evaluate PSPN mRNA and protein expression by analyzing cellular proliferation and the cell cycle in PSPN knockdown cells in vitro. PSPN mRNA and protein were significantly (P?0.05) up-regulated in OSCC-derived cells compared with human normal oral keratinocytes (n?=?7). Cellular proliferation decreased significantly (P?0.05) in PSPN knockdown cells with reduced receptor tyrosine kinase (RTK) signaling, and cell-cycle arrest at the G1 phase resulted from up-regulation of the cyclin-dependent kinase inhibitors (p21(Cip1) , p27(Kip1) , p15(INK4B) , and p16(INK4A) ). Furthermore, the PSPN protein expression in 101 primary OSCCs was significantly (P?0.05) higher than in normal counterparts. Among the clinical variables analyzed, overexpression of PSPN also was related closely (P?0.05) to tumoral size. Our results suggested that PSPN is a possible key regulator of OSCC progression via PSPN-RET-mitogen-activated protein kinase activation and that PSPN overexpression may have diagnostic potential for OSCC. � 2013 Wiley Periodicals, Inc. PMID:24375483
Chemokines and Cytokines as Salivary Biomarkers for the Early Diagnosis of Oral Cancer
Prasad, Gareema; McCullough, Michael
Chemokines have been shown to be important in both inflammation and carcinogenesis and are able to be measured in saliva with relatively robust methods including enzyme-linked immunosorbent assays (ELISA). Thus it has been hypothesized that patients with oral cancer and oral potentially malignant lesions will have elevated levels of specific chemokines in oral fluids and that this may be used as a marker of both the early detection of malignant disease and progression to malignancy. The concept that salivary biomarkers can be easily measured and indicate disease states has profound consequences for clinical practice and may open up new strategies for the diagnosis, prognosis, and potential therapy of oral squamous cell carcinoma (OSCC). This review focuses on our understanding of cytokines and chemokines and the potential role that they may have in clinical practice. PMID:24376459
Malignant catarrhal fever in a Vietnamese pot-bellied pig. A potential threat to pigs in mixed-species exhibits?
Lapp, S; F�rster, C; Kummrow, M; Wohlsein, P; Haist, V
Malignant catarrhal fever (MCF) represents a sporadic and often fatal disease in various ungulate species including rarely swine. A close contact between susceptible and reservoir species of ovine herpesvirus-2 (OvHV-2) is a requirement for virus transmission. As in ruminants, a rapid course of disease with lymphohistiocytic meningoencephalitis and necrotizing vasculitis in multiple organs is frequently seen in porcine MCF. This report describes a case of MCF in a Vietnamese pot-bellied pig, which was kept in a zoological exhibit with direct contact to various ruminants. It represents the first description of porcine MCF with proven natural OvHV-2 infection in Germany. OvHV-2 should be considered as cause of fatalities among swine especially in mixed-species exhibits as present in many zoological gardens. Also farm pigs kept in free ranging husbandry systems with potential contact to sheep and other ruminant species may be at risk. PMID:25947878
Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.
Chamberland, John P; Moon, Hyun-Seuk
Omega-3 fatty acids (also called ?-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5�mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer. PMID:25336096
Primary malignant melanoma of maxillary gingiva.
Thakur, Sudhir Kumar; Jha, Somen; Singh, Sarabjeet; Yadav, Anubha
Malignant melanoma of maxillary gingiva is a rare clinical entity. Mucosal melanoma is more aggressive than cutaneous form and carries comparatively poorer prognosis. High index of suspicion is required for diagnosing malignant melanoma of oral cavity. Any pigmented lesion in the oral cavity should be taken seriously by the clinician. PMID:25177127
The Oral History Rating Scale�Revised: Preliminary Evaluation of a Clinician-Rated Measure of Divorce Potential
Amber L. Brewer; D. Eugene Mead
This study was a preliminary psychometric investigation of the Oral History Rating Scale�Revised (OHRS�R), a therapist-rated measure of married couples' divorce potential based a 90-min oral history interview. Findings suggest the OHRS�R shows promise as a clinical tool. Therapist and observing raters' total OHRS�R scores demonstrated high interrater reliability and discriminated from client reports of psychological functioning (Outcome Questionnaire-45.2) and
Rare variants of malignant melanoma
G. W. Milton; H. M. Shaw
The personal experience with 5 rare types of malignant melanoma is reviewed to point out some of the practical problems in the diagnosis and management of these tumors. The rare forms discussed are conjunctival, nasal, oral, vulvar, and penile melanomas. All pigmented lesions in the oral cavity, but not the penis or vulva, should be prophylactically excised as lesions in
High Expression of Wee1 Is Associated with Poor Disease-Free Survival in Malignant Melanoma: Potential for Targeted Therapy
Magnussen, Gry Irene; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Slipicevic, Ana; Fl�renes, Vivi Ann
Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15). Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p?=?0.001), p21Cip1/WAF1 (p?=?0.003), p53 (p?=?0.025). Furthermore, high Wee1 expression was associated with thicker primary tumors (p?=?0.001), ulceration (p?=?0.005) and poor disease-free survival (p?=?0.008). Transfections using siWee1 in metastatic melanoma cell lines; WM239WTp53, WM45.1MUTp53 and LOXWTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents. PMID:22719872
High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.
Magnussen, Gry Irene; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Slipicevic, Ana; Fl�renes, Vivi Ann
Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2)/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15). Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p = 0.001), p21(Cip1/WAF1) (p = 0.003), p53 (p = 0.025). Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001), ulceration (p = 0.005) and poor disease-free survival (p = 0.008). Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53), WM45.1(MUTp53) and LOX(WTp53), further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1)/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents. PMID:22719872
Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer
Silva, Dilson; Cortez, Celia M.; McKenzie, Edward A.; Bitu, Carolina C.; Salo, Sirpa; Nurmenniemi, Sini; Nyberg, Pia; Risteli, Juha; deAlmeida, Carlos E. B.; Brenchley, Paul E. C.; Salo, Tuula; Missailidis, Sotiris
Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use. PMID:25295847
Differences in Allergenic Potential of Food Extracts following Oral Exposure in Mice Reflect Differences in Digestibility: Potential Approaches to Safety Assessment
Christal C. Bowman; MaryJane K. Selgrade
An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to
The potential use of cell-based therapies in the treatment of oral diseases.
Kagami, H
A recent and exciting development in medicine is the use of living cells for patient treatment. The utility of living cells to treat diseases was first proved in hematopoietic stem cell transplantation for leukemia patients. This approach has been expanded for other diseases such as islet transplantation for diabetic patients. In those cases, the cells were isolated from donors or the patient and used without complex manipulation. Since the 1980s, cells have been expanded outside of the body for the treatment of burn patients' skin. This novel treatment strategy is designated 'tissue engineering' and has been successfully applied for treatment of skin, cartilage, and also bone defects. Due to the recent developments in stem cell science, this area has attracted much attention and the application has been expanding. In this review, the potential of cell-based therapy for oral diseases is discussed with a concise review of recent developments in this field. PMID:25652598
Oral Direct Renin Inhibition: Premise, Promise, and Potential Limitations of a New Class of Antihypertensive Drug
Shafiq, Moiz M.; Menon, Dileep V.; Victor, Ronald G.
The first oral direct renin inhibitor, aliskiren, recently received approval for the treatment of hypertension. This article addresses the premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor. While aliskiren adds to a list of > 100 drugs approved for the treatment of hypertension, its introduction into clinical medicine is of particular interest because of the novel mechanism of action� inhibition of renin�s catalytic activity, the most proximal and rate-limiting step in renin-angiotensin system activation. By producing more complete renin-angiotensin system inhibition than with existing agents, direct renin inhibitors may afford greater protection from hypertensive complications. Other potential advantages include additional blood pressure reduction when used in combination therapy, a placebo-like side-effect profile, avid renal concentration, and long duration of action. Potential limitations include modest levels of blood pressure reduction that are equivalent to but not greater than angiotensin receptor blockers, reduced gastrointestinal absorption with a high fat meal, and large reactive increases in renin secretion�the functional importance of which is under intense investigation. The results of outcomes trials are eagerly awaited. PMID:18374681
Traditional Medicinal Plant Extracts and Natural Products with Activity Against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases
Enzo A. Palombo
Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The associ- ation between oral diseases and the oral microbiota is well established. Of the more than 750 species of
Lysophosphatidic acid receptor 4 signaling potentially modulates malignant behavior in human head and neck squamous cell carcinoma cells
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer worldwide. Despite improvement in therapeutic strategies, the prognosis of advanced HNSCC remains poor. The extacellular lipid mediators known as lysophosphatidic acids (LPAs) have been implicated in tumorigenesis of HNSCC. LPAs activate G-protein-coupled receptors not only in the endothelial differentiation gene (Edg) family (LPA1, LPA2, LPA3) but also in the phylogenetically distant non-Edg family (LPA4, LPA5, LPA6). The distinct roles of these receptor isoforms in HNSCC tumorigenesis have not been clarified. In the present study, we investigated the effect of ectopic expression of LPA4 in SQ-20B, an HNSCC cell line, expressing a trivial level of endogenous LPA4. LPA (18:1) stimulated proliferation of SQ-20B cells, but did not affect proliferation of HEp-2, an SCC cell line expressing higher levels of LPA4, comparable to those of with LPA1. LPA-stimulated proliferation of SQ-20B cells was attenuated by Ki16425 and Rac1 inhibitor, but not by Y-27632. Infection with doxycycline-regulatable adenovirus vector expressing green fluorescent protein-tagged LPA4 (AdvLPA4G) abolished LPA-stimulated proliferation in SQ-20B cells with the accumulation of G2/M-phasic cells. Ectopic LPA4 induction further downregulated proliferation of Ki16425-treated SQ-20B cells, of which downregulation was partially recovered by LPA. Ectopic LPA4 induction also downregulated proliferation of Rac1 inhibitor-treated SQ-20B cells, however, LPA no longer recovered it. Finally, LPA-induced cell motility was suppressed by ectopic LPA4 expression as well as by Ki16425, Rac1 inhibitor or Y-27632. Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. LPA signaling, which is mediated by both Edg and non-Edg receptors, may be a determinant of malignant behavior of HNSCC and could therefore be a promising therapeutic target. PMID:23467751
Potential Therapeutic Targets for Oral Cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70
Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.
In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13), chemokine (C-X-C motif) ligands (IL8, CXCL-10/-11), PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78), SERPINB11 and serine peptidase inhibitors (SPINK-5/7). XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70. PMID:25029526
Potential impact of new oral anticoagulants on the management of atrial fibrillation-related stroke in primary care
Harris, K; Mant, J
Aim Anticoagulant prophylaxis with vitamin K antagonists (such as warfarin) is effective in reducing the risk of stroke in patients with atrial fibrillation (AF). New oral anticoagulants have emerged as potential alternatives to traditional oral agents. The purpose of this review was to summarise the effectiveness and safety of rivaroxaban, dabigatran and apixaban in stroke prevention in patients with AF in phase III trials, evaluate their cost-effectiveness and consider the implications for primary care. Methodology A literature search was performed between 2007 and 2012, selecting all phase III trials (ROCKET AF, RE-LY and ARISTOTLE) of new oral anticoagulants and relevant cost�benefit studies. Results Evidence shows that all three agents are at least as effective as warfarin in the prevention of stroke and systemic emboli, with similar safety profiles. Cost�benefit studies of rivaroxaban and dabigatran further confirm their potential use as alternatives to warfarin in clinical practice. These observations may allow stratification of the general practice AF population, to help prioritise which patients may benefit from receiving a new oral anticoagulant. Conclusion The clinical and economic benefits of the new oral anticoagulants, along with appropriate risk stratification, may enable a higher number of patients with AF to receive effective and convenient prophylaxis for stroke prevention. PMID:23621153
Benefit cost scenarios of potential oral rabies vaccination for skunks in California.
Shwiff, Stephanie A; Sterner, Ray T; Hale, Robert; Jay, Michele T; Sun, Ben; Slate, Dennis
Scenario-based analyses were computed for benefits and costs linked with hypothetical oral rabies vaccination (ORV) campaigns to contain or eliminate skunk-variant rabies in skunks (Mephitis mephitis) in California, USA. Scenario 1 assumed baiting eight zones (43,388 km(2) total) that comprised 73% of known skunk rabies locations in the state. Scenario 2 also assumed baiting these eight zones, but further assumed that added benefits would result from preventing the spread of skunk-variant rabies into Los Angeles County, USA. Scenarios assumed a fixed bait cost ($1.24 each) but varied campaigns (one, two and three annual ORV applications), densities of baits (37.5/km(2), 75/km(2) and 150/km(2)), levels of prevention (50%, 75%, and 100%), and contingency expenditures if rabies recurred (20%, 40%, and 60% of campaign costs). Prorating potential annual benefits during a 12-yr time horizon yielded benefit-cost ratios (BCRs) between 0.16 and 2.91 and between 0.34 and 6.35 for Scenarios 1 and 2, respectively. Economic issues relevant to potentially managing skunk-variant rabies with ORV are discussed. PMID:19204355
Three long-term studies were performed to evaluate the carcinogenic potential of the pesticide rotenone in hamsters and rats. Rotenone was administered orally to Wistar rats and by intraperitoneal injection to Sprague-Dawley rats, which were maintained and observed for 14 and 18 ...
Type of presentation: Oral IT-11-O-1669 Electrostatic potential of single-layer graphene measured using
Dunin-Borkowski, Rafal E.
Type of presentation: Oral IT-11-O-1669 Electrostatic potential of single-layer graphene measured-corrected TEM (Pico), operated at 80kV, was used to take holograms of graphene. The biprism voltage was set of a typical region of a graphene sheet. Fig. 2: Phase of the hologram of the single-layer graphene. Inset
Prevalence of potential respiratory pathogens in the mouths of elderly patients and effects of professional oral care
Shu Abe; Kazuyuki Ishihara; Katsuji Okuda
To evaluate the effectiveness of professional oral health care in reducing the risk of aspiration pneumonia, we examined the prevalence of potential respiratory pathogens in gargled samples from elderly persons. Samples were obtained from 54 elderly subjects over 65 years of age who required daily nursing care, from 21 healthy elderly subjects over 65 years old, and from 22 healthy
Babburi, Suresh; Subramanyam, R V; Aparna, V; Sowjanya, P
Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2-8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and biologically unpredictable of all human neoplasms, having the worst prognosis. In this article, we report a case of oral melanoma in a 52-year-old female patient with a chief complaint of black discolouration of the maxillary gingiva and palate. PMID:24249959
Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin
Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-?B function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-?B function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601
Caffeic Acid phenethyl ester is a potential therapeutic agent for oral cancer.
Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin
Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-?B function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-?B function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601
The effect of oral prednisolone on visual evoked potential latencies in acute optic neuritis monitored in a prospective, randomized, controlled study
Susanne Trauzettel-Klosinski; Hans-Christoph Diener; Klaus Dietz; Eberhart Zrenner
The T�bingen study of optic neuritis treatment was started in 1980 to apply new and sensitive tests for monitoring a potential therapeutical steroid effect on the course of acute optic neuritis. Visual evoked potentials were used to assess an effect of oral methylprednisolone in a randomized, controlled trial. Forty-eight patients with acute optic neuritis were treated orally either with methylprednisolone
Oral tolerance in neonates: from basics to potential prevention of allergic disease
V Verhasselt
Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the
1�-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations
Background Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1�S-1�-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Methods Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. Results We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-?B through suppression of IKK?/? activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-?B regulated gene (FasL and Bim), including proinflammatory (NF-?B and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Conclusion Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger. PMID:23043547
Experimental oral inoculations in birds to evaluate potential definitive hosts of Neospora caninum.
Baker, D G; Morishita, T Y; Brooks, D L; Shen, S K; Lindsay, D S; Dubey, J P
Experimental oral inoculations to evaluate potential definitive hosts of Neospora caninum were conducted by feeding infected rodent tissues to 9 carnivorous birds of 4 species. Birds included 2 red-tailed hawks (Buteo jamaicensis), 2 turkey vultures (Cathartes aura), 2 barn owls (Tyto alba), and 3 American crows (Corvus brachyrhynchus). The rodents (mice or rats) had been inoculated with 100,000 culture-derived tachyzoites of N. caninum 1-6 mo before feeding to the birds. Fecal samples were collected from each bird daily for 1 mo after feeding rodents and examined for oocysts by fecal flotation. In addition, processed aliquots from all avian fecal samples were fed to BALB/c mice. Five weeks after feeding, mice were bled and sera were tested for antibodies against N. caninum. One to two months later, mice were killed and brain tissue was examined microscopically for protozoal cysts. While occasional oocysts were found in avian fecal samples, these were likely not N. caninum because they were not infective to BALB/c mice. It was concluded that the bird species tested are not likely to be definitive hosts of N. caninum. PMID:7472875
Lymphoid Proliferations of Indeterminate Malignant Potential arising in Adults with Common Variable Immunodeficiency Disorders: Unusual Case Studies and Immunohistological Review in the Light of Possible Causative Events
Sara Pereira da Silva; Elena Resnick; Mary Lucas; Jennifer Lortan; Smita Patel; Charlotte Cunningham-Rundles; Kevin Gatter; Qingyan Liu; Elaine S. Jaffe; Helen Chapel
Patients with common variable immunodeficiency disorders (CVIDs) who developed B cell lymphoproliferation of indeterminate\\u000a malignant potential are described in order to raise a discussion of the relationship between infection and lymphoproliferation\\u000a in infection prone patients. Those with CVID are at risk of developing either polyclonal or monoclonal lymphoproliferation\\u000a in part due to the dysregulation of their adaptive immune systems. The
In vivo native fluorescence spectroscopy and nicotinamide adinine dinucleotide\\/flavin adenine dinucleotide reduction and oxidation states of oral submucous fibrosis for chemopreventive drug monitoring
Shanmugam Sivabalan; C. Ponranjini Vedeswari; Sadaksharam Jayachandran; Dornadula Koteeswaran; Chidambaranathan Pravda; Prakasa Rao Aruna; Singaravelu Ganesan
Native fluorescence spectroscopy has shown potential to characterize and diagnose oral malignancy. We aim at extending the native fluorescence spectroscopy technique to characterize normal and oral submucous fibrosis (OSF) patients under pre- and post-treated conditions, and verify whether this method could also be considered in the monitoring of therapeutic prognosis noninvasively. In this study, 28 normal subjects and 28 clinically
Long-term low-dose ?-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway.
Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin
Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy ?-particles for 8 times in total and then further cultured for 1-2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1-2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of ?-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway. PMID:24746471
Design of Estradiol Loaded PLGA Nanoparticulate Formulations: A Potential Oral Delivery System for Hormone Therapy
S. Hariharan; V. Bhardwaj; I. Bala; J. Sitterberg; U. Bakowsky; M. N. V. Ravi Kumar
\\u000a Abstract��Estradiol (E2), a highly lipophilic molecule with good oral absorption but poor oral bioavailability, was incorporated into\\u000a poly(lactide-co-glycolide) (PLGA) nanoparticles to improve its oral bioavailability. Nanoparticles were prepared by using polyvinyl alcohol\\u000a (PVA) or didodecyldimethylammonium bromide (DMAB) as stabilizer, leading to negatively (size 410.9 39.4�nm) and positively\\u000a (size 148.3 10.7�nm) charged particles, respectively. Both preparations showed near zero order release
Second malignancies after prostate brachytherapy: Incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up
Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Sylvester, John E. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States) and Swedish Cancer Center at Stevens Hospital, Edmonds, WA (United States)]. E-mail: email@example.com; Morris, Christopher G. [Department of Radiation Oncology, University of Florida, College of Medicine, Gainesville, FL (United States); Blasko, John C. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States); Grimm, Peter D. [Seattle Prostate Institute at Swedish Hospital, Seattle, WA (United States)
Purpose: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy. Methods and Materials: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data. Results: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment. Conclusions: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.
Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sj�gren's syndrome
Pedersen, Anne Marie Lynge; Bardow, Allan; Nauntofte, Birgitte
Background the classification criteria for primary Sj�gren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. Methods in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. Results in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. Conclusion the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption. PMID:15740617
Epigenetics in the hematologic malignancies.
Fong, Chun Yew; Morison, Jessica; Dawson, Mark A
A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952
Potential beneficial effects of oral administration of isoflavones in patients with chronic mountain sickness.
Cui, Jianhua; Gao, Liang; Yang, Haijun; Wang, Fuling; Jiang, Chunhua; Gao, Yuqi
Soy isoflavones (Ifs), which are natural phytoestrogens, have beneficial effects in cardiovascular disease. We have previously shown that genistein, the most active component of Ifs, inhibits pulmonary vascular structural remodeling and right ventricular hypertrophy induced by chronic hypoxia in male Wistar rats. This study aimed to evaluate the effects of Ifs on right ventricular and pulmonary hemodynamics in individuals with chronic mountain sickness (CMS). Twenty-eight male patients living on the Qinghai-Tibetan plateau (5,200 m) who were suffering from CMS were treated orally with Ifs (20 mg, twice daily) for 45 days. Physiological and plasma biochemical indices, hematology and echocardiography were investigated. It was observed that 45 days of treatment with Ifs significantly increased blood oxygen saturation and markedly decreased the CMS score and heart rate (all P<0.05) of the subjects. Following treatment with Ifs, hematocrit (P<0.05), hemoglobin concentration (P<0.01) and plasma levels of malondialdehyde (P<0.05) were significantly decreased, while plasma levels of nitric oxide (P<0.01) and the plasma activity of nitric oxide synthase (P<0.01) and superoxide dismutase (P<0.01) were markedly increased compared with the respective values obtained prior to treatment with Ifs. The echocardiography results showed that Ifs significantly decreased the main pulmonary artery diameter (P<0.05), right ventricular end-diastolic anteroposterior diameter (P<0.01), right ventricular end-diastolic trans diameter (P<0.01), right ventricular anterior wall (P<0.01) and right ventricular outflow tract (P<0.01). These results indicate the potential beneficial effects of Ifs in the reduction of excessive erythrocytosis, the alleviation of oxidative damage and the amelioration of right ventricular index and pulmonary hemodynamics in CMS. PMID:24348805
MCP-1 as a potential target to inhibit the bone invasion by oral squamous cell carcinoma.
Quan, Jingjing; Morrison, Nigel A; Johnson, Newell W; Gao, Jin
Bone invasion is a common complication of oral squamous cell carcinoma (OSCC), and this study sought to explore whether suppressed expression of monocyte chemotactic protein-1 (MCP-1) can be used to inhibit the bone invasion by OSCC. Strong staining of MCP-1 protein was observed from 10 archival blocks of OSCC by immunohistochemistry (IHC). Real-time PCR showed MCP-1 mRNA was highly expressed by OSCC cell lines (SCC25, HN5, and Tca8113), and SCC25 cells had the highest expression. An expression construct of a dominant negative variant of MCP-1 with 7 amino acids truncated (7ND), in the vector pcDNA was used to transfect SCC25 cells, and resultant stabilized SCC25 cells (SCC25-7ND) were generated by antibiotic selection. 10% conditioned media (CM, supernatant) of SCC25-7ND cells efficiently inhibited the formation of human osteoclasts grown from CD14(+) monocyte subpopulation, comparing with 10% CM of SCC25 cells. Further, cells of SCC25 or SCC25-7ND were injected onto the surface of calvariae of nude mice to establish an animal model of bone invasion by OSCC. H&E staining showed well-differentiated OSCC was formed in both groups, tumour cells invading the bone while osteoclasts locating in typical resorption lacunae. TRAP staining indicated significantly fewer osteoclasts were found in calvariae with cells of SCC25-7ND in comparison to cells of SCC25. These data demonstrate the relevance of MCP-1 with research on bone invasion by OSCC, and suggest the potential value of MCP-1 as a target to inhibit this common complication. PMID:24905457
p53 expression in oral lichenoid lesions and oral lichen planus.
Arreaza, A; Rivera, H; Correnti, M
The aim of this article was to compare the expression of p53 protein in oral lichen planus (OLP) and oral lichenoid reaction (OLR). The study population consisted of 65 patients--31 diagnosed with OLP and 34 with OLR. The results showed more p53 positive cases in the OLP group than in the OLR group. However, the difference between the 2 groups was not statistically significant (P = 0.114). The most common immunolocalization was observed at the basal cell layer. Due to the chance of potential future malignancy, follow-up for all cases is recommended. PMID:25574723
Oral Lichenoid Lesions - A Review and Update
Kamath, Venkatesh Vishwanath; Setlur, Krishnanand; Yerlagudda, Komali
Background: Oral lichenoid lesions or reactions (OLLs/OLRs) are clinical and histological contemporaries of the classical oral lichen planus (OLP) that have generated a lot of debate in literature. In contrast to the idiopathic nature of OLP, OLLs are often associated with a known identifiable inciting factor. A superficial examination of these lesions clinically and histologically often reveals many similarities with OLP, but recent data indicate that distinguishable features do exist and form the basis of most classifications. Aims and Objectives: This paper attempts to collate available data in English literature on OLLs, highlight distinguishing features clinically and histologically and reflect on the malignant transformation potential and treatment modalities of the condition. Materials and Methods: A comprehensive search of medical and dental databases including PubMed, Ovid, Cochrane, Pubget, Researchgate, and non-medical search engines were utilized for the review. The search words included �oral lichen planus�, �oral lichenoid lesions�, �oral drug reactions�, �lichenoid dysplasia�, and �adverse effects of dental materials�. Review Results: OLLs seem to grossly underrated and most cases were clubbed as OLP. Definite clinical and histological features were uncovered to establish the identity of this lesion. Associations with dental restorative materials, drugs, and medications have been conclusively proven in the etiology of this condition. Specific markers are being utilized to diagnose the condition and monitor its progress. Conclusion: Substantial differentiating features were uncovered to delineate OLLs as a separate entity with definite etiology, pathogenesis, and a high malignant transformation rate compared with OLP. PMID:25657414
Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias
Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo
High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549
Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.
Sales, K U; Friis, S; Konkel, J E; Godiksen, S; Hatakeyama, M; Hansen, K K; Rogatto, S R; Szabo, R; Vogel, L K; Chen, W; Gutkind, J S; Bugge, T H
The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)?B through G?i. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NF?B inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis. PMID:24469043
Diagnostic aids in the screening of oral cancer
Fedele, Stefano
The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required. PMID:19284694
Primary Malignant Melanoma of the Tongue
Tien-Tse Chiu; Hsin-Ching Lin; Chih-Ying Su; Chao-Cheng Huang
The oral cavity is a rare location for the development of primary malignant melanoma. The most common primary lesion sites are the palate and gingiva. Melanoma of the tongue is specifically uncommon. A 66-year-old woman was referred to our clinic with a complaint of a huge, painless, black, discolored mass on the right side of the oral tongue for 7
Prevalence and potential influencing factors of non-nutritive oral behaviors of veal calves on commercial farms.
Leruste, H; Brscic, M; Cozzi, G; Kemp, B; Wolthuis-Fillerup, M; Lensink, B J; Bokkers, E A M; van Reenen, C G
Veal calves raised under intensive conditions may express non-nutritive oral behaviors. When expressed in an abnormal way, these behaviors can be a sign of mental suffering and reduced welfare due to a mismatch between environmental or management features and the animal's needs. The aims of this study were to estimate the prevalence of non-nutritive oral behaviors in a large sample of veal farms in Europe and to determine the potential influencing factors present at farm level. Data were collected on 157 commercial veal farms in the 3 main veal-producing countries in Europe (the Netherlands, France, and Italy). Observations of 3 non-nutritive oral behaviors (manipulating substrates, tongue rolling, and manipulating a penmate) were performed when calves were aged 14 wk, and the prevalence of these behaviors was calculated. Information on management practices and characteristics of the building and equipment were collected on all farms to assess potential influencing factors for each of the 3 behaviors. Odds ratios and 95% confidence intervals were calculated to evaluate the effect of each individual factor within a generalized linear model. The mean percentage of calves per farm performing manipulating substrates was 11.0 � 0.46%, performing tongue rolling 2.8 � 0 .18%, and manipulating a penmate 2.7 � 0.09%, with a high range between farms. Allowing more space for calves than the legal minimum requirement of 1.8 m(2)/ calf and housing them in groups of >10 calves/pen reduced the incidences of manipulating substrates and tongue rolling. Incidence of manipulating substrates was lower for calves fed maize silage compared with calves fed cereal grain, pellets, or muesli. A higher risk of tongue rolling was found when baby-boxes (i.e., single housing during the first 5 to 8 wk) were not used. Risk of calves manipulating a penmate was higher for calves of milk- or meat-type breeds compared with dual-purpose breeds and for calves fed with 280 to 380 kg compared with those fed >380 kg of milk powder in total for the fattening period. The study allowed assessment of multiple factors across farms that showed variety in terms of conditions and level of non-nutritive oral behaviors. Identification of the factors influencing non-nutritive oral behavior is helpful to define potential actions that could be taken on farms to improve the welfare of calves and reduce the prevalence of these behaviors. PMID:25218744
Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation
Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei
Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% � 2% and a particle size of 154 � 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and ?-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379
Potentiality of double liposomes containing salmon calcitonin as an oral dosage form
Kenji Yamabe; Yoshinori Kato; Hiraku Onishi; Yoshiharu Machida
The hypocalcemic effects of salmon calcitonin (SCT) after oral administration in rats by means of SCT-loading double liposomes (DL) which consist of liposomes containing small liposomes were investigated. SCT-loading DL consisted of four types of the inner liposomes such as neutral liposomes (NL) and cationic charged liposomes (CL) prepared using Coatsome�, and neutral (VET) and cationic charged (c-VET) liposomes prepared
Oral Viscous Budesonide: A Potential New Therapy for Eosinophilic Esophagitis in Children
Seema S. Aceves; John F. Bastian; Robert O. Newbury; Ranjan Dohil
BACKGROUND:Eosinophilic esophagitis (EE) is a disorder characterized typically by pan-esophageal eosinophilia. We evaluate a palatable, long-acting topical corticosteroid preparation for the treatment of EE.STUDY DESIGN:This is a retrospective analysis of symptoms, endoscopic and histologic findings, efficacy, and safety of treatment in children with EE receiving oral viscous budesonide. Response to therapy was determined histologically by the number of eos\\/hpf. Patients
Potential for use of retinoic acid as an oral vaccine adjuvant.
Mwanza-Lisulo, Mpala; Kelly, Paul
Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of ?4?7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology. PMID:25964457
Oral Grape Seed Extract Inhibits Prostate Tumor Growth and Progression in TRAMP Mice
Komal Raina; Rana P. Singh; Rajesh Agarwal; Chapla Agarwal
Prostate cancer chemoprevention is an alternative and potential strategy to control this malignancy. Herein, we evaluated the chemopreventive efficacy of grape seed extract (GSE) against prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice where animals were fed with GSE by oral gavage at 200 mg\\/kg body weight dose during 4 to 28 weeks of age. Our results
Traditional Medicinal Plant Extracts and Natural Products with Activity against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases
Palombo, Enzo A.
Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Of the more than 750 species of bacteria that inhabit the oral cavity, a number are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse affects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, plant extracts or phytochemicals that inhibit the growth of oral pathogens, reduce the development of biofilms and dental plaque, influence the adhesion of bacteria to surfaces and reduce the symptoms of oral diseases will be discussed further. Clinical studies that have investigated the safety and efficacy of such plant-derived medicines will also be described. PMID:19596745
Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas.
Yang, Cuihua; Wang, Cheng; Chen, Xi; Chen, Sidi; Zhang, Yanni; Zhi, Feng; Wang, Junjun; Li, Limin; Zhou, Xiaojun; Li, Nanyun; Pan, Hao; Zhang, Junfeng; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni
The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome-wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III-IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II-IV astrocytomas. In addition, paired serum samples before and after operation were collected from 14 malignant astrocytomas to determine the effect of surgery on the miRNAs' levels. A marked difference in serum miRNA profile was observed between high-grade astrocytomas and normal controls. Seven miRNAs were validated by RT-qPCR assay to be significantly decreased in grades II-IV patients (p < 0.001), including miR-15b*, miR-23a, miR-133a, miR-150*, miR-197, miR-497 and miR-548b-5p, and the seven-miRNA panel demonstrated a high sensitivity (88.00%) and specificity (97.87%) for malignant astrocytomas prediction. These identified miRNAs also exhibited a global decrease in tumor tissues relative to normal tissues. Furthermore, these miRNAs in serum were markedly elevated after operation (p < 0.001). In addition, some of these serum miRNAs were significantly different between malignant and benign cases, astrogliosis and other primary brain tumors. The seven serum miRNAs identified in our study hold potential as noninvasive biomarker for malignant astrocytomas. PMID:22674182
Exciting new advances in oral cancer diagnosis: avenues to early detection
The prognosis for patients with oral squamous cell carcinoma remains poor in spite of advances in therapy of many other malignancies. Early diagnosis and treatment remains the key to improved patient survival. Because the scalpel biopsy for diagnosis is invasive and has potential morbidity, it is reserved for evaluating highly suspicious lesions and not for the majority of oral lesions which are clinically not suspicious. Furthermore, scalpel biopsy has significant interobserver and intraobserver variability in the histologic diagnosis of dysplasia. There is an urgent need to devise critical diagnostic tools for early detection of oral dysplasia and malignancy that are practical, noninvasive and can be easily performed in an out-patient set-up. Diagnostic tests for early detection include brush biopsy, toluidine blue staining, autofluorescence, salivary proteomics, DNA analysis, biomarkers and spectroscopy. This state of the art review critically examines these tests and assesses their value in identifying oral squamous cell carcinoma and its precursor lesions. PMID:21798030
Moore, Alastair J; Parker, Robert J; Wiggins, John
Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10�20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560
Potentiating Effect of Morphine on Oral Salmonella enterica serovar Typhimurium Infection is ?-Opioid Receptor Dependent
Breslow, Jessica M.; Feng, Pu; Meissler, Joseph J.; Pintar, John E.; Gaughan, John; Adler, Martin W.; Eisenstein, Toby K.
Previous studies from our laboratory demonstrated that mice treated with morphine pellets are sensitized to Salmonella enterica, serovar Typhimurium infection. However, the opioid receptor antagonist, naltrexone, only partially blocked the effect of morphine, raising the possibility that the opioid might have some of its effects through a nonopioid receptor. To further clarify whether sensitization to infection is an opioid receptor-dependent phenomenon, ?-opioid receptor knock-out (MORKO) mice were used in the present study. Wild type (WT) and MORKO mice were treated with morphine and their sensitivity to oral Salmonella infection assessed by mortality, bacterial burdens in gut associated lymphoid tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory cytokines in plasma. MORKO animals treated with morphine were refractory to a sublethal dose of Salmonella, while similar treatment of WT animals resulted in 100% mortality. WT animals treated with morphine had high bacterial loads in all organs tested, while morphine-treated MORKO animals had no culturable Salmonella in any organs. Pro-inflammatory cytokine levels were elevated in morphine treated WT but not MORKO mice infected with Salmonella. These results provide definitive evidence that the morphine-mediated enhancement of oral Salmonella infection is dependent on the ?-opioid receptor. PMID:20688146
Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation
Haverman, T. M.; Raber-Durlacher, J. E.; Rademacher, W. M. H.; Vokurka, S.; Epstein, J. B.; Huisman, C.; Hazenberg, M. D.; de Soet, J. J.; de Lange, J.; Rozema, F. R.
Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis. PMID:24817792
Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials
Holpuch, Andrew S.; Desai, Kashappa-Goud H.; Schwendeman, Steven P.; Mallery, Susan R.
Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have assessed the therapeutic efficacy of diverse chemopreventive agents. The standard of care for more advanced oral dysplastic lesions entails surgical excision and close clinical follow-up due to the potential (~33%) for local recurrence at a similar or more advanced histological stage. The purpose of this review was to identify prominent oral cancer chemoprevention clinical trials, assess their overall therapeutic efficacy, and delineate effects of local versus systemic drug administration. In addition, these compiled clinical trial data present concepts for consideration in the design and conduction of future clinical trials. PMID:22013393
Adisa, A O; Olawole, W O; Sigbeku, O F
Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399
Pande, A K
We present an interesting case of paroxysmal hypertension in a young male caused by malignant pheochromocytoma. This patient, who had history of paroxysms of abdominal pain with severe hypertension, developed osseous metastasis in the first lumbar vertebra resulting in collapse of the vertebra and it caused paraplegia. The diagnosis of pheochromocytoma was confirmed on histopathology. PMID:1563860
Zhu, Qing; Berzofsky, Jay A.
Oral vaccines are safe and easy to administer and convenient for all ages. They have been successfully developed to protect from many infectious diseases acquired through oral transmission. We recently found in animal models that formulation of oral vaccines in a nanoparticle-releasing microparticle delivery system is a viable approach for selectively inducing large intestinal protective immunity against infections at rectal and genital mucosae. These large-intestine targeted oral vaccines are a potential substitute for the intracolorectal immunization, which has been found to be effective against rectogenital infections but is not feasible for mass vaccination. Moreover, the newly developed delivery system can be modified to selectively target either the small or large intestine for immunization and accordingly revealed a regionalized immune system in the gut. Future applications and research endeavors suggested by the findings are discussed. PMID:23493163
Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma
Pinton, Giulia; Manente, Arcangela Gabriella; Angeli, Giovanni
Background PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials. Methods We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy. Results We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin. Conclusions This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe. PMID:22590625
Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review
Carreras-Torras, Cl�udia
Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words �squamous cell carcinoma�, �early diagnosis� �oral cavity�, �Potentially Malignant Disorders� y �premalignant lesions�. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554
Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs.
Kleppe, Mary S; Forney-Stevens, Kelly M; Haskell, Roy J; Bogner, Robin H
Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closed-form analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort. PMID:25851513
Evaluation of the mutagenic potential and acute oral toxicity of standardized extract of Ocimum sanctum (OciBest�).
Chandrasekaran, C V; Srikanth, H S; Anand, M S; Allan, J Joshua; Viji, M M Hipolith; Amit, A
Ocimum sanctum L. (Lamiaceae) is found throughout India and in many parts of world. O. sanctum is used for the treatment of various health indications. In this lieu, it is of prime importance to investigate the safety aspects of the plant. Hence, the present study was conducted to investigate the possible genotoxic potential and acute oral toxicity of the extract of O. sanctum (OciBest�). The standard battery of in vitro genotoxicity tests, namely bacterial reverse mutation, chromosome aberration and micronucleus (MN) tests were employed to assess the possible mutagenic activity. The results showed that OciBest� (7.9-2500.0 �g/mL) did not increase the number of histidine revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with and without exogenous metabolic activation (S9). OciBest� (10.0-100.0 �g/mL) did not show structural chromosomal aberrations or increase in MN induction, with and without S9, at the tested dose range in both 4-h and 18-h exposure cell cultures. Thus, OciBest� is not genotoxic in bacterial reverse mutation, chromosomal aberration and MN tests. In an acute oral toxicity test, rats were treated with 5 g/kg of OciBest� and observed for signs of toxicity for 14 days and the results did not show any treatment-related toxic effects to Wistar rats. PMID:23424203
Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection.
Chen, Hsiao-Ling; Huang, Jiun-Yan; Chu, Te-Wei; Tsai, Tung-Chou; Hung, Che-Ming; Lin, Chih-Cheng; Liu, Fang-Chueh; Wang, Li-Chung; Chen, Yi-Ju; Lin, Ming-Fong; Chen, Chuan-Mu
Enterovirus 71 (EV71) is the most common etiological agent detected in cases of hand-foot-and-mouth disease (HFMD) resulting in incidences of neurological complications and fatality in recent years. The clinical data have already shown the significant increase in recent EV71 epidemic activity throughout the Asia-Pacific region. Due to the lack of an effective antiviral agent, primary prevention of the disease, including the development of an effective vaccine, has been the top priority in terms of control strategies. In this study, we first generated a transgenic animal system to produce the EV71 VP1 capsid protein under the control of alpha-lactalbumin promoter and alpha-casein leader sequences. A high level of recombinant VP1 protein (2.51 mg/ml) was expressed and secreted into the milk of transgenic mice. Mouse pups that received VP1-transgenic milk orally demonstrated relatively better health conditions after challenge with the respective virus as compared with the non-transgenic milk fed group; moreover, the mice fed with the VP1-milk had body weights similar to those of the PBS placebo control groups. According to the serum-neutralization assay and serum antibody detection, the littermates suckling VP1-milk generated antibodies specific to EV71. Our data suggest that EV71 VP1-containing milk is suitable for development as a potential oral vaccine. PMID:18450335
Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS).
Pettit, Marie W; Dyer, Paul D R; Mitchell, John C; Griffiths, Peter C; Alexander, Bruce; Cattoz, Beatrice; Heenan, Richard K; King, Stephen M; Schweins, Ralf; Pullen, Frank; Wicks, Stephen R; Richardson, Simon C W
An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (?15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120-160 �. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 �C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology. PMID:24680960
Formulating SLMs as oral pulsatile system for potential delivery of melatonin to pediatric population.
Albertini, Beatrice; Di Sabatino, Marcello; Melegari, Cecilia; Passerini, Nadia
The formulation development of melatonin (MLT) for infants and children with neurodevelopmental difficulties was fully investigated. This population have a higher prevalence of sleep disorders and present special challenges for drug administration and swallowing. To solve these issues, solid lipid microparticles (SLMs) were designed to obtain an oral flexible dosage form constituted by GRAS excipients and a free flow pulsatile delivery system for MLT, able to maintain its release through 8h. Three groups of SLMs were produced by spray congealing and characterized as regards particle size, morphology, flowability, solid state, drug content and release behavior. The SLMs manipulation with milk and yogurt and the MLT stability in these foods were also investigated. Microparticles with different excipient composition were selected to obtain a pulsatile release pattern over 8h. The final delivery platform displayed a prompt release from group I SLMs together with a lag phase of groups II and III SLMs, followed by a repeated MLT release from group II and a prolonged MLT release related to the last group. Finally, MLT was compatible and stable in milk and yogurt suggesting that microparticles sprinkled into food is acceptable for MLT administration to children unable to swallow capsules or tablets. PMID:24768728
Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development
The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development. PMID:24900784
Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence
Chaidos, Aristeidis; Caputo, Valentina
Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID:26137204
Two-year survival of patients screened for transcatheter aortic valve replacement with potentially malignant incidental findings in initial body computed tomography
Stachon, Peter; Kaier, Klaus; Milde, Simone; Pache, Gregor; Sorg, Stefan; Siepe, Matthias; von zur M�hlen, Constantin; Zirlik, Andreas; Beyersdorf, Friedhelm; Langer, Mathias; Zehender, Manfred; Bode, Christoph; Rein�hl, Jochen
Aims Recently, transcatheter aortic valve replacement (TAVR) has evolved as the standard treatment in patients with inoperable aortic valve stenosis. According to TAVR guidelines, body computed tomography (CT) is recommended for pre-procedural planning. Due to the advanced age of these patients, multiple radiological potentially malignant incidental findings (pmIFs) appear in this cohort. It is unknown how pmIFs influence the decision by the heart team to intervene and the mortality. Methods and results We evaluated in a retrospective single-centre observational study 414 participants screened for TAVR with dual-source CT between October 2010 and December 2012. pmIFs are common and appeared in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart team and the role of pmIF in decision-making and time to treatment with TAVR or SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835] or time to treatment (91 � 152 vs. 61 � 109 days, respectively). Several findings, which are highly suspicious for malignancy, were less likely associated with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for at least 2 years until January 2014. Two-year survival of patients after TAVR or SAVR, treated according to the heart team decision, was ?75% and independent from the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF. Conclusion The study indicates that frequently occurring radiologic pmIF did not influence 2-year survival after a decision to intervene was made by an interdisciplinary heart team. PMID:25759083
Pailler, J L; Vicq, P; Jancovici, R; Essoussi, J; Seigneuric, A
A case of metastatic malignant pheochromocytoma which was operated on is discussed. The benefits derived from the most recent localizing techniques such as CT scan and MIBG scintigraphic scanning are stressed. In the case presented these enabled the adrenal tumor to be detected but also demonstrated the presence of a costal metastasis and two metastases in the axial skeleton. A therapeutic trial with MIBG at doses of 100 mCi per treatment only enabled a survival of a little more than one year to be achieved. PMID:2794545
Histological patterns in orbital malignant tumors.
Ibric-Cioranu, Viorel; Nicolae, Vasile; Iorgulescu, Daniel; F?ge?an, Iulian Mihai; Petrescu Seceleanu, Vlad; Cernu?c?-Mi?ariu, Mihaela; Nicolae, Silviu; Ibric-Cioranu, Sorin
There is a wide variety of tumors affecting the orbit. The most encountered histological type of malignant orbital tumor is the basal cell carcinoma followed by the malignant melanoma and the squamous cell carcinoma. The authors conducted a retrospective review of the malignant orbit tumors from the Department of Oral and Maxillofacial Surgery, University Emergency Hospital of Sibiu, Romania. The main surgical methods implied were tumor resection, exenteration and extended exenteration. The reconstruction was performed with the help of local flaps using different techniques: advancement, translation or rotation. The use of local flaps allowed for a good esthetic outcome and a decrease in the healing time. PMID:25178348
Patients� perspectives regarding long-term warfarin therapy and the potential transition to new oral anticoagulant therapy
Gebler-Hughes, Elizabeth S.; Kemp, Linda
Objectives: To examine patients� perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions. Design, setting and participants: Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July�September 2013. Main outcome measures: Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought. Results: Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (�4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (�4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001). Conclusion: When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area. PMID:25436104
Expression of the Pituitary Tumor Transforming Gene (PTTG1) in Pheochromocytoma as a Potential Marker for Distinguishing Benign Versus Malignant Tumors.
Haji Amousha, Mohamad Reza; Sabet Kish, Nastaran; Heshmat, Ramin; Rajabiani, Afsaneh; Saffar, Hiva; Haghpanah, Vahid; Tavangar, Seyed Mohammad
The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study. PMID:25871022
Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs.
Lindeblad, Matthew; Kapetanovic, Izet M; Kabirov, Kasim K; Detrisac, Carol J; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V
2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN upward arrow and PT downward arrow) and hyperkeratosis of the nonglandular stomach in the 2000mg/kg/day dose group (in one or both sexes). In the 500mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800mg/kg/day (four male dogs/dose group). PMCol treatment at 800mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100mg/kg/day and 50mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 500mg/kg/day, which correlated to the higher plasma drug levels in female rats. It appeared that dogs were generally more sensitive than rats to oral administration of PMCol. Further examination of the potential toxic effects of PMCol in longer term studies is required prior to understanding the full risks of PMCol administration as a chemopreventative agent. PMID:20430063
Assessment of Oral Toxicity and Safety of Pentamethylchromanol (PMCol), A Potential Chemopreventative Agent, in Rats and Dogs
Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.
2,2,5,7,8-pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN?and PT?) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (4 male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-hour recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 500 mg/kg/day, which correlated to the higher plasma drug levels in female rats. It appeared that dogs were generally more sensitive than rats to oral administration of PMCol. Further examination of the potential toxic effects of PMCol in longer term studies is required prior to understanding the full risks of PMCol administration as a chemopreventative agent. PMID:20430063
Graft-versus-host disease affecting oral cavity. A review
Margaix-Mu�oz, Maria; Bag�n, Jos� V.; Jim�nez, Yolanda; Sarri�n, Mar�a-Gracia; Poveda-Roda, Rafael
Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival. PMID:25810826
Oral Lactoferrin Treatment of Experimental Oral Candidiasis in Mice
Natsuko Takakura; Hiroyuki Wakabayashi; Hiroko Ishibashi; Susumu Teraguchi; Yoshitaka Tamura; Hideyo Yamaguchi; Shigeru Abe
We assessed the potential of lactoferrin (LF), a multifunctional milk protein, for treatment of oral candi- diasis with immunosuppressed mice, which have local symptoms characteristic of oral thrush. Oral adminis- tration of bovine LF in drinking water starting 1 day before the infection significantly reduced the number of Candida albicans in the oral cavity and the score of lesions on
Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas
Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase �II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high. PMID:24550969
Bafl-boyun mukozal malign melanomlu �� olgunun sunumu
T. Balam; M. Sar; Z. M. Yaz; N. �zdemir; C. �neri
38 Mucosal melanoma of the head and neck: report of three cases Primary malignant mucosal melanoma of the head and neck is a rare and usually lethal disease, accounting for only 0.5-2% of all malignant melanomas. Of lesions arising in head and neck, the most frequent location is the nasal cavity followed by the oral mucosa. In general, suspicious lesions
The application of vizilite in oral cancer.
Sambandham, Thirugnana; Masthan, K M K; Kumar, M Sathish; Jha, Abhinav
This article depicts the various applications of Vizilite plus in oral cancer. The oral cavity demonstrates a variety of red and white, pigmented and vesiculo- bullous lesions. Oral cancer still happens to carry the highest mortality worldwide, especially in India. In India, the prime focus is on the downstreaming of oral cancer from an advanced stage to an early diseased state. The techniques that are promoted to facilitate an earlier detection and diagnosis of an oral malignancy include Toluidine blue, ViziLite Plus with TBlue, ViziLite, Microlux DL, Orascoptic DK, VEL scope, Oral CDx and brush biopsy. PMID:23450083
The Application of Vizilite in Oral Cancer
Sambandham, Thirugnana; Masthan, K. M. K.; Kumar, M. Sathish; Jha, Abhinav
This article depicts the various applications of Vizilite plus in oral cancer. The oral cavity demonstrates a variety of red and white, pigmented and vesiculo- bullous lesions. Oral cancer still happens to carry the highest mortality worldwide, especially in India. In India, the prime focus is on the downstreaming of oral cancer from an advanced stage to an early diseased state. The techniques that are promoted to facilitate an earlier detection and diagnosis of an oral malignancy include Toluidine blue, ViziLite Plus with TBlue, ViziLite, Microlux DL, Orascoptic DK, VEL scope, Oral CDx and brush biopsy. PMID:23450083
Development and characterization of a novel nanoemulsion drug-delivery system for potential application in oral delivery of protein drugs
Sun, Hongwu; Liu, Kaiyun; Liu, Wei; Wang, Wenxiu; Guo, Chunliang; Tang, Bin; Gu, Jiang; Zhang, Jinyong; Li, Haibo; Mao, Xuhu; Zou, Quanming; Zeng, Hao
Background: The stability of protein drugs remains one of the key hurdles to their success in the market. The aim of the present study was to design a novel nanoemulsion drug-delivery system (NEDDS) that would encapsulate a standard-model protein drug � bovine serum albumin (BSA) � to improve drug stability. Methods: The BSA NEDDS was prepared using a phase-inversion method and pseudoternary phase diagrams. The following characteristics were studied: morphology, size, zeta potential, drug loading, and encapsulation efficiency. We also investigated the stability of the BSA NEDDS, bioactivity of BSA encapsulated within the NEDDS, the integrity of the primary, secondary, and tertiary structures, and specificity. Results: The BSA NEDDS consisted of Cremophor EL-35, propylene glycol, isopropyl myristate, and normal saline. The average particle diameter of the BSA NEDDS was about 21.8 nm, and the system showed a high encapsulation efficiency (>90%) and an adequate drug-loading capacity (45 mg/mL). The thermodynamic stability of the system was investigated at different temperatures and pH levels and in room-temperature conditions for 180 days. BSA NEDDS showed good structural integrity and specificity for the primary, secondary, and tertiary structures, and good bioactivity of the loaded BSA. Conclusions: BSA NEDDS showed the properties of a good nanoemulsion-delivery system. NEDDS can greatly enhance the stability of the protein drug BSA while maintaining high levels of drug bioactivity, good specificity, and integrity of the primary, secondary, and tertiary protein structures. These findings indicate that the nanoemulsion is a potential formulation for oral administration of protein drugs. PMID:23118537
A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed m�llerian tumors with evaluation of potential molecular targets
Lois M Ramondetta; Thomas W Burke; Anuja Jhingran; Rosemarie Schmandt; Michael W Bevers; Judith K Wolf; Charles F Levenback; Russell Broaddus
ObjectiveThe aim of this study was to determine the efficacy of cisplatin, ifosfamide, and mesna in uterine malignant mixed m�llerian tumor (MMMT) and to evaluate the expression of clinically relevant molecular markers.
An insight into salivary markers in oral cancer.
Krishna Prasad, Ramnarayan Belur; Sharma, Akhilesh; Babu, Harsha Mysore
Salivary diagnostics has fascinated many researcheres and has been tested as a valuable tool in the diagnosis of many systemic conditions and for drug monitoring. Advances in the field of molecular biology, salivary genomics and proteomics have led to the discovery of new molecular markers for oral cancer diagnosis, therapeutics and prognosis. Oral cancer is a potentially fatal disease and the outcome of the treatment and prognosis largely depends on early diagnosis. Abnormal cellular products elucidated from malignant cells can be detected and measured in various body fluids including saliva and constitute tumor markers. This article discusses the various salivary tumor markers and their role in oral pre-cancer and cancer. PMID:24019794
Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma
Elsherbiny, Marwa E.; Emara, Marwan; Godbout, Roseline
Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal. Polyunsaturated fatty acids are abundant in brain, particularly ?-6 arachidonic acid (AA) and ?-3 docosahexaenoic acid (DHA). Although the levels of ?-6 and ?-3 polyunsaturated fatty acids are tightly regulated in brain, the ?-6:?-3 ratio is dramatically increased in malignant glioma, suggesting deregulation of fundamental lipid homeostasis in brain tumor tissue. The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium. This fatty acid-dependent effect on cell migration is dependent on expression of the brain fatty acid binding protein (FABP7) previously shown to bind DHA and AA. Increased levels of enzymes involved in eicosanoid production in FABP7-positive malignant glioma cells suggest that FABP7 is an important modulator of AA metabolism. We provide evidence that increased production of eicosanoids in FABP7-positive malignant glioma growing in an AA-rich environment contributes to tumor infiltration in the brain. We discuss pathways and molecules that may underlie FABP7/AA-mediated promotion of cell migration and FABP7/DHA-mediated inhibition of cell migration in malignant glioma. PMID:23981365
FOXC2 Expression is Associated with Tumor Proliferation and Invasion Potential in Oral Tongue Squamous Cell Carcinoma.
Imayama, Naomi; Yamada, Shin-Ichi; Yanamoto, Souichi; Naruse, Tomofumi; Matsushita, Yuki; Takahashi, Hidenori; Seki, Sachiko; Fujita, Shuichi; Ikeda, Tohru; Umeda, Masahiro
Forkhead box protein C2 (FOXC2) is a gene encoding a transcription factor that controls the generation of mesodermal tissue including vascular and lymphatic tissues. FOXC2 has previously been associated with EMT and tumor angiogenesis in various cancers. Moreover, a relationship between the expression of FOXC2 and poor prognosis has been reported in various cancers. We herein examined the clinicopathological significance of FOXC2 in oral tongue squamous cell carcinoma (OTSCC) and attempted to clarify the function of FOXC2 in OTSCC cell lines in vitro. The overexpression of FOXC2 was more frequent in cancers with higher grades according to the pattern of invasion (grade 4 vs. 1-3; p?0.05). A correlation was observed between the expression of FOXC2 and that of VEGF-A and -C (VEGF-A; p?0.05, VEGF-C; p?0.001). The high-FOXC2 expression group had a significantly poorer prognosis than that of the low-expression group (p?0.001). Multivariate analysis indicated that the overexpression of FOXC2 may also be an independent prognostic factor, similar to N classification (N0 vs 1/2; p?0.05), stage classification (stage I/II vs III/IV; p?0.05), pattern of invasion (grade 1-3vs 4; p?0.05), local recurrence (local recurrence (+) vs (-); p?0.01), and the overexpression of FOXC2 (FOXC2 overexpression (-) vs.(+); p?0.05). In the OTSCC cell line analysis, the expression of FOXC2 was also associated with proliferation and invasion potential. These results strongly suggest that the overexpression of FOXC2 may be a potent predictor of survival in OTSCC patients. PMID:25573594
Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug
Yi, Chengxue; Zhong, Hui; Tong, Shanshan; Cao, Xia; Firempong, Caleb K; Liu, Hongfei; Fu, Min; Yang, Yan; Feng, Yingshu; Zhang, Huiyun; Xu, Ximing; Yu, Jiangnan
Purpose To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. Methods Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. Results The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC50] = 11.99 ?g � mL?1) and the standard anticancer drug, 5-fluorouracil (IC50 = 0.88 ?g � mL?1) exhibited strong in vitro antiproliferative activity against SGC cells, with IC50 > 30.0 ?g � mL?1; but the FVS performed poorly against LoVo cells (IC50 > 40.0 ?g � mL?1). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg � mL?1 as compared to free FVS (0.67 ?g � mL?1). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ~ 22.9 nm) as against free FVS were greatly enhanced. Conclusion These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations. PMID:23049254
Preservation of high phenylalanine ammonia lyase activities in roots of Japanese Striped corn: a potential oral therapeutic to treat phenylketonuria.
L�pez-Villalobos, Arturo; L�cker, Joost; L�pez-Quir�z, Ana Angela; Yeung, Edward C; Palma, Kristoffer; Kermode, Allison R
Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, the enzyme responsible for the disposal of excess amounts of the essential amino acid phenylalanine (Phe). Phenylalanine ammonia-lyase (PAL, EC 188.8.131.52) has potential to serve as an enzyme substitution therapy for this human genetic disease. Using 7-day-old Japanese Striped corn seedlings (Japonica Striped maize, Zea mays L. cv. japonica) that contain high activities of PAL, we investigated a number of methods to preserve the roots as an intact food and for long-term storage. The cryoprotectant effects of maple syrup and other edible sugars (mono- and oligosaccharides) were evaluated. Following thawing, the preserved roots were then examined to determine whether the rigid plant cell walls could protect the PAL enzyme from proteolysis during simulated (in vitro) digestion comprised of gastric and intestinal phases. While several treatments led to retention of PAL activity during freezing, upon thawing and in vitro digestion, root tissues that had been previously frozen in the presence of maple syrup exhibited the highest residual PAL activities (?50% of the initial enzyme activity), in marked contrast to all of the treatments using other edible sugars. The structural integrity of the root cells, and the stability of the functional PAL tetramer were also preserved with the maple syrup protocol. These results have significance for the formulation of oral enzyme/protein therapeutics. When plant tissues are adequately preserved, the rigid cell walls constitute a protective barrier even under harsh (e.g. gastrointestinal-like) conditions. PMID:24657198
Adjuvant potential of low dose all-trans retinoic acid during oral typhoid vaccination in Zambian men.
Lisulo, M M; Kapulu, M C; Banda, R; Sinkala, E; Kayamba, V; Sianongo, S; Kelly, P
There is an urgent need to identify ways of enhancing the mucosal immune response to oral vaccines. Rotavirus vaccine protection is much lower in Africa and Asia than in industrialized countries, and no oral vaccine has efficacy approaching the best systemic vaccines. All-trans retinoic acid (ATRA) up-regulates expression of ?4?7 integrin and CCR9 on lymphocytes in laboratory animals, increasing their gut tropism. The aim of this study was to establish the feasibility of using ATRA as an oral adjuvant for oral typhoid vaccination. In order to establish that standard doses of oral ATRA can achieve serum concentrations greater than 10?nmol/l, we measured ATRA, 9-cis and 13-cis retinoic acid in serum of 14 male volunteers before and 3?h after 10?mg ATRA. We then evaluated the effect of 10?mg ATRA given 1?h before, and for 7 days following, oral typhoid vaccine in eight men, and in 24 men given various control interventions. We measured immunoglobulin (Ig)A directed against lipopolysaccharide (LPS)and protein preparations of vaccine antigens in whole gut lavage fluid (WGLF) and both IgA and IgG in serum, 1 day prior to vaccination and on day 14. Median [interquartile range (IQR)] C(max) was 26�2 (11�7-39�5) nmol/l, with no evidence of cumulation over 8 days. No adverse events were observed. Specific IgA responses to LPS (P?=?0�02) and protein (P?=?0�04) were enhanced in WGLF, but no effect was seen on IgA or IgG in serum. ATRA was well absorbed, well tolerated and may be a promising candidate oral adjuvant. PMID:24237035
Exploring the potential of self-assembled mixed micelles in enhancing the stability and oral bioavailability of an acid-labile drug.
Zhang, Xingwang; Wang, Huan; Zhang, Tianpeng; Zhou, Xiaotong; Wu, Baojian
Oral delivery of many drugs is plagued with limited solubility and/or poor stability. This paper aimed to explore the performance of polymeric mixed micelles on solubilization, stabilization and bioavailability enhancement with stiripentol as model drug. Stiripentol-loaded mixed micelles were prepared by solvent-diffusion method: rapid dispersion of an ethanol solution containing stiripentol, monomethoxy poly(ethylene glycol)-b-poly(?-caprolactone) and sodium oleate into water. Stiripentol micelles were characterized by the particle size, entrapment efficiency, in vitro drug release, TEM, DSC and FTIR. The pharmacokinetic profile of stiripentol was determined in rats after oral administration of stiripentol micelles. The obtained stiripentol micelles were 44.2 nm in size with an entrapment efficiency over 90%. It was shown that micelles substantially improved the solubility and gastric stability of stiripentol. The oral absorption of stiripentol was also enhanced to a great extent with a relative bioavailability of 157% and 444% to the commercial formulation (Diacomit�) and in-house suspensions. Mixed micelles assembled by di-block copolymer/sodium oleate exhibited a good potential in the improvement of drug stability and bioavailability. It should be a promising carrier for oral delivery of therapeuticals with solubility and stability issues. PMID:24956461
HIV/AIDS associated malignancies of the head and neck.
Bunn, B K; van Heerden, W F P
Patients with HIV/AIDS are at increased risk for the development of malignancy. Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma in women are regarded as AIDS-defining malignancies. The spectrum of malignancy is, however, changing, particularly where patients receive highly active antiretroviral therapy (HAART). South Africa has the highest number of HIV-infected individuals globally. The possibility of the oral health care worker encountering HIV/AIDS-related pathology therefore seems inevitable. The aim of this article is to heighten the awareness of head and neck malignancies occurring in HIV/AIDS whilst highlighting some of the clinical features in order to facilitate early recognition and diagnosis. It is of clinical significance that in many instances, identification of these malignancies precedes HIV/AIDS diagnosis. Optimal patient management requires close co-operation between the oral health care practitioner and the extended health care team. PMID:23957103
Kirsten I. Black; Ali Kubba
Non-oral contraception is increasingly being promoted by contraceptive experts as a more convenient and, in many cases, safer and more efficacious alternative to oral contraception. Injectables, implants and intrauterine methods offer the advantage of being long-acting and less user dependent, factors which may potentially improve contraceptive compliance. Combined contraceptive methods in non-oral delivery forms offer a choice for women who
The microflora associated with human oral carcinomas
K. N. Nagy; I. Sonkodi; I. Sz�ke; E. Nagy; H. N. Newman
Both local and systemic infections may complicate the morbidity of patients with oral malignant neoplasms, particularly those presenting intraorally. This study investigated the microbial contents of the biofilms present on the surfaces of oral squamous cell carcinomas. Biofilm samples were obtained from the central surface of the lesions in 21 patients (20 male, 1 female) aged 52.8 (� 8.2) years,
The potential role of oral pH in the persistence of Trichomonas gallinae in Cooper's Hawks (Accipiter cooperii).
Urban, Elizabeth H; Mannan, R William
Trichomoniasis, caused by the protozoan Trichomonas gallinae, affects a variety of species worldwide including avivorious raptors. Existing information suggests that the disease is most prevalent in young birds, and differential susceptibility to trichomoniasis among individuals in different age groups was documented in Cooper's Hawks (Accipiter cooperii) nesting in Tucson, Arizona. In that population, 85% of nestling Cooper's Hawks had T. gallinae in their oral cavity, compared to only 1% of breeding-age hawks. Trichomonads generally are sensitive to environmental pH and we explored the possibility that differences in oral pH may contribute to the differential prevalence of infection between age groups. We measured the pH of the fluid in the oral cavity in 375 Cooper's Hawks from three age groups (nestlings, fledglings, and breeding age) in Tucson, Arizona, in 2010 and 2011 and clinically tested for T. gallinae in a subsample of hawks. Oral pH of nestlings (? 6.8) was 7.3 times less acidic than in fledgling or breeding Cooper's Hawks (? 6.1). The incidence of T. gallinae was higher in nestlings (16%) than in either fledglings or breeding hawks (0%). Our findings indicate that oral pH becomes more acidic in Cooper's Hawks soon after they leave the nest. Trichomonas gallinae thrives when pH is between 6.5 and 7.5 (optimum 7.2), but is less viable in more acidic conditions. Higher levels of acidity in the oral cavity of fledglings and breeding Cooper's Hawks may reduce their susceptibility to trichomoniasis, and play a role in the differential prevalence of infection among age groups. PMID:24171574
Preventable and potentially preventable serious adverse reactions induced by oral protein kinase inhibitors through a database of adverse drug reaction reports.
Egron, Adeline; Olivier-Abbal, Pascale; Gouraud, Aurore; Babai, Samy; Combret, Sandrine; Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle
Antineoplastic drugs are one of the pharmacological classes more frequently involved in occurrence of "serious" adverse drug reactions. However, few epidemiological data are available regarding the preventability of adverse drug reactions with ambulatory cancer chemotherapy. We assessed the rate and characteristics of "preventable" or "potentially preventable" "serious" adverse drug reactions induced by oral protein kinase inhibitors (PKIs). We performed a retrospective study with all "serious" adverse drug reactions (ADRs) recorded from 1 January 2008 to 31 December 2009 in the French Pharmacovigilance Database with the eight oral protein kinase inhibitors marketed in France: sorafenib, imatinib, erlotinib, sunitinib, dasatinib, lapatinib, nilotinib and everolimus (Afinitor�) using the French adverse drug reactions preventability scale. This study was carried out on 265 spontaneous notifications. Most of adverse drug reactions were "unpreventable" (63.8�%). Around one third were "unevaluable" due to notifications poorly documented (medical history, dosage, use of drugs as first or second intention, concomitant drugs). One (0.4�%) adverse drug reaction was "preventable" with dasatinib (subdural hematoma) and three (1.1�%) were "potentially preventable" (hepatic adverse drug reactions): two with imatinib and one with sorafenib. For these four cases, we identified some characteristics: incorrect dosages, drug interactions and off-label uses. An appropriate prescription could avoid the occurrence of 1.5�% "serious" adverse drug reactions with oral PKIs. This rate is low and further studies are needed to compare our results by using other preventability instruments and to improve the French ADRs Preventability Scale. PMID:25056801
Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem
Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196
Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67
Kannan, S; Chandran, G Jagadeesh; Pillai, K Raveendran; Mathew, Babu; Sujathan, K; Nalinakumary, K R; Nair, M Krishnan
Aim�To study p53 expression in relation to proliferative status in normal and nondysplastic, dysplastic and malignant lesions of the oral mucosa. Method�The standard avidin-biotin complex (ABC) immunohistochemical staining method was used to study the expression of p53 and Ki67 on frozen sections of oral leukoplakias and carcinomas. Results�Of the leukoplakia and carcinoma samples, 70% expressed p53 in over 5% of cells. In normal mucosa less than 5% of cells expressed p53. The proliferation index, as assessed by expression of Ki67, was highest in the malignant lesions (43%) and lowest in normal mucosa (11%). Statistical analysis revealed that expression of both p53 and Ki67 was correlated significantly with the histopathological stage of the tumour. However, expression of p53 was not correlated with that of Ki67. In leukoplakia lesions with proliferative features p53 immunostaining was less intense than in non-proliferative lesions; this difference was statistically significant. Conclusions�These results emphasise the potential of Ki67 and p53 as biomarkers of carcinogenesis in oral cancer and may also serve as intermediate points for cancer prevention programmes, such as the oral chemopreventive trials. Factors other than p53 may have a more important role in the deregulation of proliferation in pre-malignant oral lesions. Images PMID:16696067
Iron chelation studies using desferrioxamine and the potential oral chelator, 1,2-dimethyl-3-hydroxypyrid-4-one, in normal and iron loaded rats.
Kontoghiorghes, G J; Sheppard, L; Hoffbrand, A V; Charalambous, J; Tikerpae, J; Pippard, M J
A novel iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one, and desferrioxamine were compared for their ability to remove iron and for their site of action in iron release in rats. Repeated intraperitoneal injections of the chelators in rats with widespread tissue labelling by 59Fe derived from transferrin showed comparable 59Fe mobilisation by each chelator in normal and iron loaded rats. Specific labelling of a chelatable "cold" iron pool in hepatocytes by 59Fe derived from ferritin showed this pool to be equally accessible to parenteral doses of both chelators and also to oral 1,2-dimethyl-3-hydroxypyrid-4-one, which is an effective oral iron chelating agent that removes iron from parenchymal cells. This and other alpha-ketohydroxypyridines need further development as potential therapeutic agents in human iron overload. PMID:3584483
Malignant melanoma of lingual gingiva with ipsilateral submandibular lymph node metastasis: a case report
L. Krishna Prasad; P. Srinivasa Chakravarthi; K. Naga Neelima Devi; M. Sridhar; Y. Ram Kumar; D. Yesuratnam
Malignant melanoma is a neoplasm of epidermal melanocytes. It is one of the most biologically unpredictable and deadly of\\u000a all human neoplasms. However, malignant melanoma in the oral cavity is a rare malignancy, accounting for 0.2% to 8% of all\\u000a melanomas. It has a grave prognosis, with a 5 year survival of 10�20%. We present a case of malignant melanoma
Expression of MMP-1/PAR-1 and patterns of invasion in oral squamous cell carcinoma as potential prognostic markers
Fan, Hai-Xia; Chen, Yan; Ni, Bo-Xiong; Wang, Shan; Sun, Miao; Chen, Dong; Zheng, Jin-Hua
Background Matrix metalloproteinase (MMP)-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR)-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD) and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC) specimens with different patterns of invasion (POI) and to evaluate their association with clinical outcomes. Methods Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry. Results Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I�II and POI types III�IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III�IV was shorter than that of patients with POI types I�II. Conclusion POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC. PMID:26170698
Abstract : Abstract : Abstract : Abstract : Momordica charantia (MC) fruit was subjected to phytochemical and pharmacological interaction studies with oral hypoglycemis in NIDDM patients. Phytochemical, chromatographical analysis and extraction of methanolic MC fruit soft (semi-solid form) in CCl 4 + C 6 H 6 solvent system yielded 15 diverse chemical constituents - alkaloids, glycosides, aglycone, tannin, sterol, phenol
Oral lichen planus: An overview.
Krupaa, R Jayasri; Sankari, S Leena; Masthan, K M K; Rajesh, E
Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment. PMID:26015696
[Transvaginal ultrasound-guided core needle biopsy for residual potentially malignant ovarian tumors in cases with severe peritoneal adhesion and frozen pelvis requiring polysurgery].
Kitayama, Rie; Nishizawa, Minako; Tasaka, Reiko; Mita, Ikuko; Tokuyama, Osamu; Miyama, Masato; Kawamura, Naoki
A multiparous woman in her 40s had advanced peritoneal adhesions and frozen pelvis from 3 previous surgeries. Endometrial ovarian cysts also remained. After the last surgery, imaging showed cysts with a septum and enhanced moieties in the Douglas pouch. Highly invasive surgery was anticipated, and the patient underwent a transvaginal ultrasound-guided core needle biopsy(TVCNB, 16-gauge needle)with full awareness of the risks involved. The histopathological diagnosis was adenocarcinoma. We inserted a ureteral stent and performed an S-shaped colon resection and standard ovarian cancer surgery after preoperative chemotherapy. TVCNB in this case was less invasive and easier to perform than other exploratory procedures, and has a low risk of iatrogenic intraperitoneal dissemination even if the tumor is malignant. Chemotherapy can be administered before surgery if malignancy is detected. In summary, TVCNB is a useful alternative method for conducting exploratory operations. PMID:25981664
[Malignant keratoma: Harlequin fetus].
Largu�che, K; L�arif, Z; Ajroud, C; Oueslati, H
Harlequin fetus, with an incidence of about 1 in 300.000 births, is an extremely severe form of congenital ichtyosis. We report a case of malignant keratoma: a male infant was born at 40 weeks' gestational age. The parents were first cousins. This infant was covered with massive thick, waxy, plate-like scales and deep fissures. There was striking facial distortion including severe eclabium and ectropion. The baby was transferred to the Neonatal Intensive Care Unit but he died at 2 days of age. There is limited information regarding the course and prognosis of neonates affected with Harlequin ichthyosis because most affected patients die within the first days or weeks of life. However, it is now evident that these infants, may have extended survival potential with intensive supportive measures as well as the addition of retinoids. Prenatal diagnosis for malignant keratoma had been performed by fetal skin biopsy and electron microscopic observation at 19-23 weeks estimated gestational age. In 2005, ABCA12 was identified as the causative gene for this disease. It has now become possible to make DNA-based prenatal diagnosis for Harlequin ichthyosis by chorionic villus or amniotic fluid sampling procedures in the earlier stages of pregnancy with a lower risk to fetal health and with a reduced burden on the mothers. PMID:19353943
CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models
W Schneiderhan; M Scheler; K-H Holzmann; M Marx; J E Gschwend; M Bucholz; T M Gress; T Seufferlein; G Adler; F Oswald
Background:CD147 (basigin, EMMPRIN) is a multifunctional, highly conserved glycoprotein enriched in pancreatic ductal adenocarcinomas (PDACs) which is associated with poor prognosis in many malignancies. The role of CD147 in pancreatic cancer, however, remains elusive.Methods and Results:Silencing of CD147 by RNA interference (RNAi) reduced the proliferation rate of MiaPaCa2 and Panc1 cells. CD147 is required for the function and expression of
The cutaneous manifestations of metastatic malignant melanoma.
Reed, Kurtis B; Cook-Norris, Robert H; Brewer, Jerry D
Cutaneous metastases are common sequelae of primary malignant melanoma. Because patients with melanoma are examined frequently after diagnosis, it is important that dermatologists are aware of the range of findings that may represent metastatic disease. Many case reports and a few retrospective series have been published detailing the wide variety of clinical presentations of cutaneous metastatic melanoma. This article reviews the various manifestations of metastatic melanoma of the skin and oral mucous membranes and summarizes treatment options for metastatic disease. PMID:22348556
Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation
Purpose Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. Methods A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7�days after potential extraction). The majority of patients (n?=?74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients� general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. Results The patients� dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4�years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. Conclusion The occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature. PMID:24088270
EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells
Cho, Min Chul; Cho, Sung Yong; Yoon, Cheol Yong; Lee, Seung Bae; Kwak, Cheol; Kim, Hyeon Hoe; Jeong, Hyeon
Objectives To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells. Methods Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively. Results In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation. Conclusions Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of malignant progression of non-metastatic RCC. PMID:26177500
Phase I clinical trial to determine maximum tolerated dose of oral albendazole in patients with advanced cancer
Mohammad H. Pourgholami; Michael Szwajcer; Melvin Chin; Winston Liauw; Jonathan Seef; Peter Galettis; David L. Morris; Matthew Links
Purpose��Albendazole is a potential anticancer agent that is currently under development for the treatment of cancer. We carried out\\u000a a dose-finding phase I study of oral albendazole in patients with advanced malignancies.\\u000a \\u000a \\u000a \\u000a Patients and methods��Thirty-six patients with refractory solid tumors were enrolled. Albendazole was given orally on a day 1�14 of a 3�weekly cycle,\\u000a starting at 400�mg BD with dose
Unusual variants of malignant melanoma
Cynthia M Magro; A Neil Crowson; Martin C Mihm
A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called �minimal-deviation melanoma,� melanoma with prominent pigment synthesis or �animal-type melanoma,� and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase
Discrimination of premalignant conditions of oral cancer using Raman spectroscopy of urinary metabolites
NASA Astrophysics Data System (ADS)
Elumalai, Brindha; Rajasekaran, Ramu; Aruna, Prakasarao; Koteeswaran, Dornadula; Ganesan, Singaravelu
Oral cancers are considered to be one of the most commonly occurring malignancy worldwide. Over 70% of the cases report to the doctor only in advanced stages of the disease, resulting in poor survival rates. Hence it is necessary to detect the disease at the earliest which may increase the five year survival rate up to 90%. Among various optical spectroscopic techniques, Raman spectroscopy has been emerged as a tool in identifying several diseased conditions, including oral cancers. Around 30 - 80% of the malignancies of the oral cavity arise from premalignant lesions. Hence, understanding the molecular/spectral differences at the premalignant stage may help in identifying the cancer at the earliest and increase patient's survival rate. Among various bio-fluids such as blood, urine and saliva, urine is considered as one of the diagnostically potential bio-fluids, as it has many metabolites. The distribution and the physiochemical properties of the urinary metabolites may vary due to the changes associated with the pathologic conditions. The present study is aimed to characterize the urine of 70 healthy subjects and 51 pre-malignant patients using Raman spectroscopy under 785nm excitation, to know the molecular/spectral differences between healthy subjects and premalignant conditions of oral malignancy. Principal component analysis based Linear discriminant analysis were also made to find the statistical significance and the present technique yields the sensitivity and specificity of 86.3% and 92.9% with an overall accuracy of 90.9% in the discrimination of premalignant conditions from healthy subjects urine.
Anti-inflammatory potential of Rikkosan based on IL-1? network through macrophages to oral tissue cells.
Horie, Norio; Hashimoto, Ken; Hino, Shunsuke; Kato, Takao; Shimoyama, Tetsuo; Kaneko, Tadayoshi; Kusama, Kaoru; Sakagami, Hiroshi
Rikkosan is a traditional Kampo medicine using the control of oral pain caused by dental caries, pulpitis, periodontitis and stomatitis. In order to provide evidence for its clinical effects, we herein investigated whether Rikkosan inhibits the production of pro-inflammatory substances in human and mouse models of inflammation. Rikkosan alone did not induce prostaglandin E2 (PGE2) production, but inhibited interleukin-1? (IL-1?) (5 ng/ml)-stimulated PGE2 production in human gingival fibroblasts and human periodontal ligament fibroblasts, with a selectivity index higher than 4.0 and 4.3, respectively. Rikkosan alone dose-dependently stimulated tumor necrosis factor-? (TNF-?) production, reaching a peak level slightly lower than that attained by lipopolysaccharide (LPS) at 0.4 mg/ml in mouse macrophage-like RAW264.7 cells. At a higher concentration of Rikkosan (4 mg/ml), TNF-? production, however, declined significantly regardless of the presence or absence of LPS. Rikkosan dose-dependently inhibited IL-1? production by LPS-stimulated RAW264.7 cells, with a selective index of 7.6. Five constituent extracts of Rikkosan, either alone or in combination, showed similar effects on TNF-? and IL-1? productions in activated RAW264.7 cells, but to lower extents than that of Rikkosan. These results demonstrated that Rikkosan inhibited both IL-1? production by LPS-activated macrophages and PGE2 production by IL-1?-stimulated human gingival fibroblasts and human periodontal ligament fibroblasts, suggesting that anti-inflammatory effects of Rikkosan may partially be generated by the inhibition of these pro-inflammatory substances via the IL-1? network through macrophages to oral tissue cells. PMID:24982223
Rheumatic Diseases and Malignancies
BOJINCA, Violeta; JANTA, Iustina
ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881
The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer
Warner, Margaret [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden) [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden); Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX (United States); Gustafsson, Jan-Ake, E-mail: email@example.com [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden) [Center for BioSciences, Department of BioSciences and Nutrition, Karolinska Institutet, Stockholm (Sweden); Center for Nuclear Receptors and Cell Signaling, Department of Biochemistry and Cell Biology, University of Houston, Houston, TX (United States)
The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role of ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.
Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome
Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K.; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D.
Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. PMID:23616410
Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome.
Diaz, Patricia I; Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna
Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. PMID:23616410
Salivary biomarkers for detection of oral squamous cell carcinoma - current state and recent advances.
Yakob, Maha; Fuentes, Laurel; Wang, Marilene B; Abemayor, Elliot; Wong, David T W
Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional "omics", including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261
Cancer associated fibroblasts in hematological malignancies
Raffaghello, Lizzia; Vacca, Angelo; Pistoia, Vito; Ribatti, Domenico
Tumor microenvironment plays an important role in cancer initiation and progression. In hematological malignancies, the bone marrow represents the paradigmatic anatomical site in which tumor microenvironment expresses its morphofunctional features. Among the cells participating in the composition of this microenvironment, cancer associated fibrobasts (CAFs) have received less attention in hematopoietic tumors compared to solid cancers. In this review article, we discuss the involvement of CAFs in progression of hematological malignancies and the potential targeting of CAFs in a therapeutic perspective. PMID:25474039
Oral premalignant lesions: epidemiological and clinical analysis in the northern Polish population
Paw?owska, Anita; Renkielska, Dorota; Michaj?owski, Igor; Sobjanek, Micha?; B?a?ewicz, Izabela
Introduction Leukoplakia is the most common potentially malignant condition of the oral cavity. Aim Epidemiological and clinical analysis of patients with oral leukoplakia (OL) diagnosed and treated in the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk. Material and methods The study was retrospective and prospective. Among 55 911 patients diagnosed and treated in the Department in 1999�2009, 204 people with OL were selected. The material includes 104 women and 100 men with an average age of 58.1. Most of the patients were in the age group of 50�70 years, average age was 58.1. Results The most common concomitant disease was diabetes. More than 88% of the patients declared occurrence of OL predisposing development factors (50.49% � cigarette smoking). Three hundred and twenty foci of OL were found among patients. Homogeneous OL dominated (72.05%). Multifocal OL was diagnosed in 58.3% of patients. The most common location of lesions was buccal mucosa (52.2%). Cancers developed on the basis of OL in 7 patients (3.43%). The percentage of malignant transformation was 12.19% for untreated patients and 1.41% for treated patients. The floor of the oral cavity was proven to be the location of the highest risk of oral squamous cell carcinoma. Patients with diabetes may be more likely to develop OL. The risk of malignant transformation is relatively high. In our material it was equal to 3.43%. Conclusions Cigarette smoking is the most important factor, which can influence the effectiveness of treatment. PMID:25610347
[Oral medicine 10. Pigmented lesions of the oral mucosa].
de Visscher, J G A M; van der Meij, E H; Schepman, K P
Pigmented oral lesions may be due to the most diverse disorders. A distinction can be made between non-melanin-associated and melanin-associated pigmentations. Some lesions may be diagnosed on the basis of medical history and clinical research. In focal pigmented lesions, histological examination is necessary to establish a definitive diagnosis. Most disorders are benign but some may be malignant melanomas. PMID:25026743
Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration.
Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik; Jain, Sanyog
The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin entrapped within the freeze-dried formulation was found stable both chemically as well as conformationally and developed formulation exhibited excellent stability in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies revealed higher uptake of folic acid functionalized layersomes in comparison with their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution. Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery. PMID:24283460
Spatiotemporal Trends in Oral Cancer Mortality and Potential Risks Associated with Heavy Metal Content in Taiwan Soil
Chiang, Chi-Ting; Lian, Ie-Bin; Su, Che-Chun; Tsai, Kuo-Yang; Lin, Yu-Pin; Chang, Tsun-Kuo
Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972�2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran�s I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology. PMID:21139868
Heparanase expression correlates with poor survival in oral mucosal melanoma.
Wang, Xin; Wen, Weiwei; Wu, Heming; Chen, Yi; Ren, Guoxin; Guo, Wei
Oral mucosal melanoma (OMM) is a lethal cancer with a poor prognosis. Despite the great interest in heparanase (HPSE) as a potential anticancer therapy target, the prognostic role of HPSE in oral mucosal melanoma has not been elucidated. In this study, we investigated HPSE expression in OMM tissues and examined its association with clinical outcome. A total of 81 patients with OMM were enrolled in this study. We examined the expression of HPSE in OMM, and its staining extent, intensity and cellular localization were analyzed for clinical significance. HPSE staining was positive in 81�% of tumors (66 of 81 patients) and was negative in the remaining 19�% (15 patients). The median survival time and the 5-year survival rate were 12�months and 7.0�% in the high-heparanase group, 35�months and 36.4�% in the low-heparanase group and 62�months and 53.3�% in the none-heparanase group (P�=�0.001). In univariate survival analysis of oral mucosal melanoma, AJCC Stage, heparanase level, heparanase location and tumor size were the clinical parameters related to overall survival. In Cox analysis, overall survival time was significantly dependent on AJCC stage and heparanase level, but not tumor size and heparanase location. Heparanase is frequently expressed in oral mucosal melanoma, and its expression levels inversely correlate with the survival rates of OMM patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy and an attractive target for anticancer drug development. PMID:23794232
Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study
Andreas B. Eisingerich; Ana Wheelock; Gabriela B. Gomez; Geoffrey P. Garnett; Mark R. Dybul; Peter K. Piot
BackgroundThe use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to
The Evaluation of Hydroxyethyl Starch (6% HES 130/0.4) Solution�s Potential Preventive Effects on Coagulation Status in Women with Gynecologic Malignancies Using Rotation Thromboelastography
Akay, Meltem Olga; Bilir, Ayten; �ge, Tufan; Ku?, G�khan; Mutlu, Fezan ?ahin
Objective: The aim of this study was to determine the effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) 130/0.4 solution on the coagulation status of women with gynecologic malignancies by using rotation thromboelastogram (ROTEM�). Materials and Methods: Twenty-two patients with gynecological tumors scheduled for anesthesia were enrolled. Blood samples were diluted by 20% with 6% HES (130/0.4) solution. Results: In the INTEM assay, clotting time (CT) (p<0.01) and clot formation time (CFT) (p<0.001) were significantly increased and maximum maximum clot formation (MCF) (p< 0.001) was significantly decreased in HES hemodilution compared with the undiluted control samples. In the EXTEM assay, there was a similar significant increase in increase in CFT (p<0.01) and a decrease in maximum a decrease in MCF (p<0.01) in HES hemodilution when compared with control samples. Conclusion: HES 130/0.4 solution causes significant hypocoagulable changes in the thromboelastographic profile of gynecologic cancer patients in vitro. PMID:25330518
Hydroxypropyl-?-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs
Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo
The objective of the present study was to demonstrate that a novel hydroxypropyl-?-cyclodextrin functionalized calcium carbonate (HP-?-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-?-CD/CC matrix using an immersion method. The IRB-loaded HP-?-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-?-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-?-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-?-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (Cmax) and the area under the mean plasma concentration�time curve (AUC[0?48]) of IRB-loaded HP-?-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-?-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-?-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB. PMID:25995635
Hydroxypropyl-?-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.
Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo
The objective of the present study was to demonstrate that a novel hydroxypropyl-?-cyclodextrin functionalized calcium carbonate (HP-?-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-?-CD/CC matrix using an immersion method. The IRB-loaded HP-?-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-?-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-?-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-?-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C max) and the area under the mean plasma concentration-time curve (AUC[0?48]) of IRB-loaded HP-?-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-?-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-?-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB. PMID:25995635
Prevalence of oral mucosal lesions in a brazilian military police population
Ara�jo, Viviani-Silva; Godinho, Eliane-Lopes; Farias, Lucyana-Concei��o; Marques-Silva, Luciano; Santos, S�rgio-Henrique-Sousa; Rodrigues-Neto, Jo�o-Fel�cio; Ferreira, Raquel-Concei��o; De-Paula, Alfredo-Maur�cio-Batista; Martins, Andr�a-Maria-Eleut�rio-de Barros-Lima
Background Data obtained from oral health surveys are very important for identifying disease-susceptible groups and for developing dental care and prevention programs. So, the purpose of the current article was to investigate the prevalence of oral mucosa lesions (OMLs) in a population of Brazilian police. Material and Methods Interviews and oral cavity examinations were performed on a sample of 395 police officers who were randomly selected by the calibrated researcher. The number of individuals was obtained by a sample calculation using the finite population correction. The diagnostic criteria were based on the WHO (1997) criteria and adapted to Brazilian surveys. Results In total, 8.61% of the population presented some OML. Traumatic injuries and benign migratory glossitis (BMG) were the most prevalent lesions. Conclusions The prevalence of potentially malignant disorders was lower than among the Brazilian population.The most prevalent lesion among the police officers was related to trauma. Patients dissatisfied with oral health had a higher risk of presenting OMLs. Key words:Mouth disease, mouth mucosa, military personnel, public health, oral pathology, oral leukoplakia.
[Prognostic and predictive markers of malignant melanoma].
R�s�, Erzs�bet; Barbai, Tam�s; Gy�rffy, Bal�zs; T�m�r, J�zsef
Malignant melanoma biologically can be divided into non-metastatic and metastatic forms which cannot be predicted precisely using classical clinicopathological parameters, therefore studies on novel genetic or protein markers are abundant in the literature. These studies did not result in clinically useful markers because mostly ignored the results of studies on the genetic basis of metastatic potential of malignant melanoma. Accordingly, the list of promising novel markers is short (BCL2, CDK2, MART-1, OPN). Similar to other solid malignancies, introduction of targeted therapy into clinical practice of melanoma turned the attention toward the genetic basis of resistance to chemo- and targeted therapies. These novel data could lead to the development of molecular diagnostics which can help in designing more effective therapeutic strategies of malignant melanoma. PMID:23795352
Gabapentin in the Treatment of Persistent Hiccups in Advanced Malignancy
Menon, Mahesh
Hiccups are a distressing symptom in advanced malignancies in the setting of palliative care. A case of persistent hiccups treated with oral Gabapentin is presented to highlight the clinical and ethical dilemmas in patients with advanced malignancy. A 70-year-old male with non-small cell cancer of the lung with widespread metastases presented with persistent hiccups. The patient and family sought only symptom relief from home, without hospitalization or further investigations. The hiccups were dramatically relieved by oral Gabapentin, highlighting the recent reports that mention this molecule as being useful for hiccups. Gabapentin is a simple tool that may be utilized by palliative care physicians to relieve hiccups in advanced malignancies. PMID:23093831
Gabapentin in the treatment of persistent hiccups in advanced malignancy.
Menon, Mahesh
Hiccups are a distressing symptom in advanced malignancies in the setting of palliative care. A case of persistent hiccups treated with oral Gabapentin is presented to highlight the clinical and ethical dilemmas in patients with advanced malignancy. A 70-year-old male with non-small cell cancer of the lung with widespread metastases presented with persistent hiccups. The patient and family sought only symptom relief from home, without hospitalization or further investigations. The hiccups were dramatically relieved by oral Gabapentin, highlighting the recent reports that mention this molecule as being useful for hiccups. Gabapentin is a simple tool that may be utilized by palliative care physicians to relieve hiccups in advanced malignancies. PMID:23093831
Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.
Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Hara, Kieko; Suehara, Yoshiyuki; Takagi, Tatsuya; Mitani, Keiko; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi
The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion on the biological behavior and the mechanism of acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic alterations of tumor protein p53 (TP53),, platelet-derived growth factor receptor, ? polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT) promoters. These gene variations were compared with the clinicopathological features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and 83%, respectively. All 40 samples demonstrated nuclear staining for STAT6, including CD34-negative cases. Moreover, p53-positive staining was associated with a lower DFSR and was significantly associated with higher Ki-67 label index, higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which was associated with thoracic tumor location and the less aggressive phenotype. In contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases respectively, and these occurred in a mutually exclusive fashion. TERT promoter hot spot mutations were observed in 5 cases, which were associated with shorter DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter mutations. TP53 mutations, which result in its overexpression, in combination with TERT promoter mutations seem to play an important role in the dedifferentiation process. PMID:25582503
Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study
Gomez, Gabriela B.; Garnett, Geoffrey P.; Dybul, Mark R.; Piot, Peter K.
Background The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. Methods and findings Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. Conclusions Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development. PMID:22247757
Oral complications in cancer patients
Carl, W.
Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications.
Imaging malignant and apparent malignant transformation of benign gynaecological disease.
Lee, A Y; Poder, L; Qayyum, A; Wang, Z J; Yeh, B M; Coakley, F V
Common benign gynaecological diseases, such as leiomyoma, adenomyosis, endometriosis, and mature teratoma, rarely undergo malignant transformation. Benign transformations that may mimic malignancy include benign metastasizing leiomyoma, massive ovarian oedema, decidualization of endometrioma, and rupture of mature teratoma. The aim of this review is to provide a contemporary overview of imaging findings in malignant and apparent malignant transformation of benign gynaecological disease. PMID:21070909
Mucosal malignant melanomas in head and neck surgery: a retrospective study of six patients and review of the literature
Astrid L. D. Kruse; Marc O. Riener; Klaus W. Graetz; Heinz-Theo Luebbers
Introduction��Of all malignant processes of the oral mucosa, 0.5% are malignant melanomas. Because of late diagnosis, pattern of growth,\\u000a close proximity to the bone (particularly in palatinal localizations), and the correlated infiltration, malignant melanomas\\u000a have a bad prognosis.\\u000a \\u000a \\u000a \\u000a \\u000a Patients and methods��In this retrospective study, six cases of patients with oral mucosal malignant melanoma are evaluated, and a critical review\\u000a of
Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma
Sekine, Joji; Kanno, Takahiro; Nariai, Yoshiki; Urano, Takeshi
Background Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC. Methods and Findings The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients� pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11�1.28], p < 0.001) and NAC1 IRI (0.78 [0.68�0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ? 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC. Conclusions NAC1 has potential as a marker for distinguishing OED from CIS/OSCC. PMID:26172271
Chemoembolization of hepatic malignancy
Carin F. Gonsalves; Daniel B. Brown
Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component\\u000a of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated\\u000a with transarterial chemoembolization.
Chemoembolization of hepatic malignancy
Carin F. Gonsalves; Daniel B. Brown
Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential\\u000a component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications\\u000a associated with TACE.
Brain Malignancies Steering Committee
The Brain Malignancy Steering Committee evaluates and prioritizes concepts for phase 3 and large phase 2 therapeutic clinical trials to be conducted in the NCI National Clinical Trials Network (NCTN).
Gynecologic malignancy in pregnancy
Ji, Yong Il
Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis and treatment of malignancy during pregnancy, a multidisciplinary approach is needed. Patients should be advised about the benefits and risk of treatment. When selecting a treatment for malignancy during pregnancy, the physiologic changes that occur with the pregnancy should be considered. Various diagnostic procedures that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be safely performed. The staging approach and treatment should be standard. Systemic chemotherapy during the first trimester should be delayed if possible. Radiation therapy should preferably start postpartum. Although delivery should be delayed preferably until after 35 weeks of gestation, termination of pregnancy may be considered when immediate treatment is required. Subsequent pregnancies do not increase the risk of malignancy recurrence. PMID:24328018
Neuroleptic Malignant Syndrome
... to be useful. What is the prognosis? Early identification of and treatment for individuals with neuroleptic malignant ... http://www.rarediseases.org Tel: 203-744-0100 Voice Mail 800-999-NORD (6673) Fax: 203-798- ...
Antmann, K.; Aisner, J.
This book contains 20 chapters. Some of the chapter titles are: The Radiology of Asbestosis and Related Neoplasms; Computed Tomography and Malignant Mesothelioma; Radiation Therapy for Pleural Mesothelioma; and Radiation Therapy of Peritoneal Mesothelioma.
Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies
A. Bonnie; G. Just-N�bling; L. Bergmann; P. M. Shah; W. Stille; D. Hoelzer
The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of systemic mycoses was investigated in granulocytopenic patients with haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic efficacy, and 214 for adverse events. Patients with similar characteristics receiving oral amphotencin B as antifungal prophylaxis, observed over 15 months before introduction of itraconazole, served as control
Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite.
Hasegawa, H; Uchiyama, M
The antimetastatic effects of orally administered ginsenoside Rb1 (Rb1) and an active metabolite by intestinal bacteria, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (I), were studied, by using a spontaneous metastasis model produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by intestinal bacteria) was first done and the data found were positively correlated to the antimetastatic effect of Rb1 through the medium of I. The transformation rate by 41% fecal specimens was less than 10% and consecutive Ginseng administrations were ineffective for the mice with hydrolyzing potential of less than 10%, which limited the antimetastatic efficacy of Rb1- In contrast, the efficacy of I was greater than that of Rb1 and at least comparable to that of S-FU. No effect of I on the primary tumor growth was found, indicating a specific antimetastatic activity. In a leg amputation model with the LLC-line, an effect on survival time of I (8 mg/kg/day) equal to that of 5-FU (10 mg/kg/day) was seen and 38% mice were cured as compared with 13% cured by amputation alone. These findings suggest that the active drug is the bacterial metabolite I which should be administered rather than Rb1. PMID:9933987
Galectin-7 as a potential predictive marker of chemo-and/or radio-therapy resistance in oral squamous cell carcinoma
Matsukawa, Sho; Morita, Kei-ichi; Negishi, Ayako; Harada, Hiroyuki; Nakajima, Yusuke; Shimamoto, Hiroaki; Tomioka, Hirofumi; Tanaka, Kae; Ono, Masaya; Yamada, Tesshi; Omura, Ken
Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches. The aim of this study was to identify predictors of tumor sensitivity to preoperative radiotherapy/chemotherapy for OSCC in order to allow oncologists to determine optimum therapeutic strategies without the associated adverse effects. Here, the protein expression profiles of formalin-fixed paraffin-embedded (FFPE) tissue samples from 18 OSCC patients, termed learning cases, who received preoperative chemotherapy and/or radiotherapy followed by surgery were analyzed by quantitative proteomics and validated by immunohistochemistry in 68 test cases as well as in the 18 learning cases. We identified galectin-7 as a potential predictive marker of chemotherapy and/or radiotherapy resistance, and the sensitivity and specificity of the galectin-7 prediction score (G7PS) in predicting this resistance was of 96.0% and 39.5%, respectively, in the 68 test cases. The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction. In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line. Therefore, our findings suggest that galectin-7 is a potential predictive marker of chemotherapy and/or radiotherapy resistance in patients with OSCC. Identification of proteins differentially expressed in OSSC samples from patients sensitive or resistant. The samples were processed by LC-MS and analyzed with 2DICAL. PMID:24515895
Levy, Angela D
The primary hepatic malignancies are a diverse group of neoplasms with distinctive clinical and pathologic features. Imaging of the primary hepatic malignancies continues to be challenging. Ultrasonography, CT scanning, and MR imaging play complementary roles in the evaluation of these patients. Many [figure: see text] of these neoplasms have distinctive imaging features that may permit diagnosis. In most instances, however, biopsy is required for definitive diagnosis and treatment planning. PMID:11933586
Malignant mixed mullerian tumors
J. Ruiz Tovar; M. E. Reguero Callejas; J. I. Arano Bermejo; L. F. Capote Armas; F. Gonz�lez-Palacios Mart�nez; L. Caba�as Navarro
Malignant mixed mullerian tumours (MMMTs) are rare neoplasms, highly aggressive and with an extremely poor prognosis, usually\\u000a arising in elderly postmenopausal women and presenting at an advanced stage. MMMTs derive from the mullerian mesodermus that\\u000a differentiates in epithelial and stromal elements, both malignant elements.\\u000a \\u000a The clinic pathological features of 3 uterine MMMTs are reported here. The patients ranged in age
... be caused by several things, including: Poor oral hygiene Some foods Dentures Gum disease Dry mouth Tobacco use Respiratory, ... other health problems Some medicines Practicing good oral hygiene and avoiding tobacco and some foods often helps people with bad-smelling breath. You ...
Haneke, E
Because of the large number of different tissues making up the distal phalanx of fingers and toes, a large variety of malignant tumors can be found in and around the nail apparatus. Bowen disease is probably the most frequent nail malignancy. It is usually seen as a verrucous plaque of the nail fold and nail bed in persons above the age of 40 years. It slowly grows over a period of years or even decades before degenerating to an invasive squamous cell carcinoma. The latter may also occur primarily often as a weeping onycholysis. The next most frequent nail malignancy is ungual melanoma. Those arising from the matrix are usually pigmented and often start with a longitudinal melanonychia whereas those originating from the nail bed remain amelanotic, are often nodular and mistaken for an ingrown nail in an elderly person. The treatment of choice for in situ and early invasive subungual melanomas is generous extirpation of the nail apparatus whereas distal amputation is only indicated for advanced melanomas. In addition to these frequent nail malignancies, nail-specific carcinomas, malignant vascular and osseous tumors, other sarcomas, nail involvement in malignant systemic disorders and metastases may occur. In most cases, they cannot be diagnosed accurately on clinical grounds. Therefore, a high degree of suspicion is necessary in all isolated or single-digit proliferations that do not respond to conservative treatment. PMID:24718507
Urban legends series: oral manifestations of HIV infection.
Patton, L L; Ramirez-Amador, V; Anaya-Saavedra, G; Nittayananta, W; Carrozzo, M; Ranganathan, K
Human immunodeficiency virus-related oral lesions (HIV-OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV-OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy-to-use diagnostic techniques have been recently introduced likely restricting the importance of HIV-OLs in diagnosis. (iii) The 1993 EC-Clearinghouse classification of HIV-OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV-OL case definitions were updated in 2009 to facilitate the accuracy of HIV-OL diagnoses by non-dental healthcare workers in large-scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV-OLs has been reported for OC and OHL. PMID:23517181
Endoscopic treatment of malignant biliary strictures.
Rustagi, Tarun; Jamidar, Priya A
Endoscopic stenting is a widely accepted strategy for providing effective drainage in both extrahepatic and intrahepatic malignant strictures. In patients with extrahepatic malignancies, uncovered self-expanding metal stents (SEMS) provide excellent palliation. Hilar malignancies are probably best palliated by placement of uncovered SEMS although some disagreement exists among experts regarding the type and number of stents for optimal palliation. Preoperative biliary drainage (PBD) is commonly performed although a higher risk of complications and the lack of clear benefit raise questions about this practice. Certain groups of patients such as those with markedly elevated bilirubin levels, and in those in whom neoadjuvant therapy is planned, are good candidates for PBD. Considerable controversy exists regarding the optimal method as well as type of stent for PBD in patients with hilar malignancies. Novel endoscopic therapies, including photodynamic therapy and radiofrequency ablation, have emerged as potential adjuvant therapies in the management of malignant bile duct strictures but need further long-term evaluation to establish survival benefit. This review focuses on the current status of endoscopic therapies for malignant biliary obstructions. PMID:25613178
Oral and systemic photoprotection.
Chen, Andrew C; Damian, Diona L; Halliday, Gary M
Photoprotection can be provided not only by ultraviolet (UV) blockers but also by oral substances. Epidemiologically identified associations between foods and skin cancer and interventional experiments have discovered mechanisms of UV skin damage. These approaches have identified oral substances that are photoprotective in humans. UV inhibits adenosine triphosphate (ATP) production causing an energy crisis, which prevents optimal skin immunity and DNA repair. Enhancing ATP production with oral nicotinamide protects from UV immunosuppression, enhances DNA repair and reduces skin cancer in humans. Reactive oxygen species also contribute to photodamage. Nontoxic substances consumed in the diet, or available as oral supplements, can protect the skin by multiple potential mechanisms. These substances include polyphenols in fruit, vegetables, wine, tea and caffeine-containing foods. UV-induced prostaglandin E2 (PGE2 ) contributes to photodamage. Nonsteroidal anti-inflammatory drugs and food substances reduce production of this lipid mediator. Fish oils are photoprotective, at least partially by reducing PGE2 . Orally consumed substances, either in the diet or as supplements, can influence cutaneous responses to UV. A current research goal is to develop an oral supplement that could be used in conjunction with other sun protective strategies in order to provide improved protection from sunlight. PMID:24313740
Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise
Bernard, M. P.; Bancos, S.; Sime, P. J.; Phipps, R. P.
There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin�s lymphoma, non-Hodgkin�s lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastases. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies. PMID:18691115
The potential of organic-based amylose-ethylcellulose film coatings as oral colon-specific drug delivery systems.
Siew, L F; Basit, A W; Newton, J M
Amylose-ethylcellulose film coatings obtained from organic-based solvents were investigated as potential vehicles for colonic drug delivery. Amylose, in the form of an amylose-butan-1-ol dispersion, and ethylcellulose, dissolved in either ethyl lactate, ethanol, or propanol and plasticized with dibutyl sebacate, were mixed in various proportions and applied using a fluidized bed coater to achieve a range of film thicknesses on 5-aminosalicylic acid pellets. Drug release from the coated pellets was assessed under gastric and small intestinal conditions in the presence and absence of pepsin and pancreatin using dissolution methodology, and also within a simulated colonic environment involving fermentation testing with human feces in the form of a slurry. Under upper gastrointestinal tract conditions, the rate and extent of drug release were found to be related to the thickness of the coating and the ratio of amylose to ethylcellulose within the film. Modeling of the drug release data revealed that the ratio was more important than coat thickness in controlling drug release, irrespective of the solvent used for coating. Coatings with a thick film and/or low amylose content were relatively impermeable and able to delay drug release under conditions mimicking the upper gastrointestinal tract. Furthermore, drug release was unaffected by the presence of pepsin and pancreatin and by long-term storage. Under simulated colonic conditions, drug release was more pronounced from coating formulations containing higher proportions of amylose. Colon-specificity can therefore be achieved using such systems by judicious choice of the appropriate ratio of amylose to ethylcellulose and coat thickness. PMID:14727908
Feasibility of using gold nanorods for optical contrast in two photon microscopy of oral carcinogenesis
NASA Astrophysics Data System (ADS)
Motamedi, Saam; Shilagard, Tuya; Koong, Luke; Vargas, Gracie
Gold nanorods (GNRs) combined with two-photon microscopy were explored for potential application in imaging of oral carcinogenesis. GNRs have been shown to be effective contrast agents for two photon luminescence in that excitation laser powers required for imaging are low compared to traditional fluorophores. Imaging of cells, ex vivo tissues, and in vivo oral mucosa labeled with GNRs was performed to evaluate potential advantages of these agents in molecular imaging of epithelial carcinogenesis. Powers required to elicit a two-photon luminescence signal from GNRs were determined for cells as well as normal and malignant transformed lesions, 24 hours following injection of GNRs in a hamster model for oral cancer. The strength of the detected emission as the function of the average incident laser power was measured in tissues with and without GNRs to compare the sensitivity of GNRs against tissue autofluorescence. Finally, in vivo imaging was performed immediately following GNR injection to establish the ability to image microvasculature at low incident powers. The pilot study demonstrated uptake of GNRs by cells and in tissues yielding bright fluorescence signals using significantly lower incident powers than those needed to excite tissue autofluorescence. The in vivo imaging aspect of the study demonstrated the localization of GNRs within the microvasculature of the oral cancer model. These preliminary studies demonstrated the ability of GNRs to function as photostable, high contrast imaging agents and suggest that GNRs and multi-photon imaging have great potential for applications in the field of molecular imaging and early detection of cancer.
Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration.
Suresh, Shruthy; Raghu, Dinesh; Karunagaran, Devarajan
Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells. PMID:24175842
Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy.
Ries, Jutta; Schultze-Mosgau, Stefan; Neukam, Friedrich; Diebel, Elke; Wiltfang, Joerg
MAGE genes are silent in normal tissues except testis but are expressed in a variety of neoplastic lesions, and therefore represent ideal targets for immunotherapy. We analysed the expression of 6 MAGE-A genes (MAGE-A1 to -A6) to determine potential implications of these antigens as targets for immunotherapy in oral squamous cell carcinoma (OSCC). Oral tumor specimens (n=21) and non-neoplastic tissue samples (n=10) of oral mucosa from healthy patients were examined by a highly sensitive reverse transcription-nested polymerase chain reaction (MAGE-1- to -6 assay) which detect any cancer cells that express at least one of six MAGE subtype genes and allows also the identification of individual MAGE isotypes (M1 to M6). MAGE expression was restricted to neoplastic specimens. No expression of MAGE was observed in the non-neoplastic normal oral mucosal tissues. Fifteen of 21 (71%) oral carcinomas expressed at least one of MAGE-A1 to -6. The expression pattern of subtypes was heterogeneous: 62% of the tumor patients were positive for MAGE-3, 57% for MAGE-4, 48% for MAGE-6, 43% for MAGE-1, 38% for MAGE-2 and 24% for MAGE-5. Also coexpression of the genes could be determined: 13 (62%) coexpressed two, 10 (48%) coexpressed three, 8 (38%) coexpressed four, 6 (29%) coexpressed five and 5 coexpressed six of the 6 subtypes tested. The high incidence of MAGE expression in oral cancer indicates that monitoring of MAGE-A subtype expression in OSCC may be of potential interest to determine new immunotherapeutic targets and may be a possibility of specific immunotherapy with polyvalent anti-genes for this disease. PMID:15703841
Virtual bronchoscopy for evaluation of malignant tumors of the thorax
Steven E. Finkelstein; Ronald M. Summers; Dao M. Nguyen; John H. Stewart; Jean A. Tretler; David S. Schrump
Objective: Virtual bronchoscopy is a novel technique making use of 3-dimensional reconstruction of 2-dimensional helical computed tomographic images for noninvasive evaluation of the tracheobronchial tree. This study was undertaken to evaluate the diagnostic potential of virtual bronchoscopy by comparing virtual bronchoscopic images with fiberoptic bronchoscopic findings in patients with thoracic malignant disease. Methods: Thirty-two consecutive patients with thoracic malignant tumors
Urokinase Plasminogen Activator Receptor (uPAR) and Plasminogen Activator Inhibitor-1 (PAI-1) Are Potential Predictive Biomarkers in Early Stage Oral Squamous Cell Carcinomas (OSCC)
Hadler-Olsen, Elin; Uhlin-Hansen, Lars; Svineng, Gunbj�rg
Oral squamous cell carcinoma (OSCC) is often associated with metastatic disease and a poor 5 year survival rate. Patients diagnosed with small tumours generally have a more favourable outcome, but some of these small tumours are aggressive and lead to early death. To avoid harmful overtreatment of patients with favourable prognosis, there is a need for predictive biomarkers that can be used for treatment stratification. In this study we assessed the possibility to use components of the plasminogen activator (PA) system as prognostic markers for OSCC outcome and compared this to the commonly used biomarker Ki-67. A tissue-micro-array (TMA) based immunohistochemical analysis of primary tumour tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC was conducted. The expression of the biomarkers was compared with clinicopathological variables and disease specific death. The statistical analyses revealed that low expression of uPAR (p?=?0.031) and PAI-1 (p?=?0.021) in the tumour cells was significantly associated with low disease specific death in patients with small tumours and no lymph node metastasis (T1N0). The commonly used biomarker, Ki-67, was not associated with disease specific death in any of the groups of patients analysed. The conclusion is that uPAR and PAI-1 are potential predictive biomarkers in early stage tumours and that this warrants further studies on a larger cohort of patients. PMID:24999729
Nateglinide comes as a tablet to take by mouth. It is usually taken three times daily. Take ... that contain alcohol or sugar; mesoridazine (Serentil); niacin; oral contraceptives (birth control pills); perphenazine (Trilafon); phenelzine (Nardil); ...
... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...
... High School and College Students Recent College Graduates Dental and Medical Students See All Careers & Training Opportunities Job Openings Loan Repayment Programs Careers in Dental Research See All Continuing Education Practical Oral Care ...
... High School and College Students Recent College Graduates Dental and Medical Students See All Careers & Training Opportunities Job Openings Loan Repayment Programs Careers in Dental Research See All Continuing Education Practical Oral Care ...
... High School and College Students Recent College Graduates Dental and Medical Students See All Careers & Training Opportunities Job Openings Loan Repayment Programs Careers in Dental Research See All Continuing Education Practical Oral Care ...
... virus type 2 (HSV-2) most often causes genital herpes . However, sometimes HSV-2 is spread to the ... the virus to the genitals. Both oral and genital herpes viruses can sometimes be spread, even when you ...
Malignant peritoneal mesothelioma
Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D
Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade. PMID:21160794
Alv�rez-Falc�n, Ana; Ruiz-Santana, Sergio
Early nutrition can help to improve energy and protein intake and decrease the negative impact of the metabolic response to surgery. A key goal is to identify patients who exhibit increased respiration risk before beginning oral alimentation. Once a simple bedside 3-oz (90 ml) challenge, or early intervention in the oral care, administered by a trained provider is passed, specific diet recommendations can be made safely and confidently without the need for further objective dysphagia testing. Gastrointestinal motility disorders occur as part of the pathophysiology of diseases and critical illness, or are a result of medication therapies or enteral feeding complications. Inadequate energy intake in the first 7 days following extubation have recently been described. It would be highly beneficial to determine when it is best to initiate timely oral alimentation for recovering extubated intensive care unit (ICU) and more specifically surgical ICU patients to support the maintenance and rebuilding of lean body mass, maintain hydration, and permit the ingestion of oral medications. In a cross-sectional multicenter study conducted in 18 Spanish ICUs, within the scope of the 2007 European Nutrition Day, only 95 of 348 investigated patients (27.3%) received oral nutritional support. Constipation and diarrhea were common adverse effects. Unexpectedly, however, constipation episodes were more frequent than diarrhea in the patients not receiving oral nutritional support. PMID:23075585
Surveillance for gastrointestinal malignancies
Tiwari, Ashish K; Laird-Fick, Heather S; Wali, Ramesh K; Roy, Hemant K
Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal prognoses. Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions, therefore, is recognized as an effective cancer prevention strategy. In order to efficiently detect these lesions, systemic application of screening tests (surveillance) is needed. However, most of the currently used non-invasive screening tests for GI malignancies (for example, serum markers such as alpha-fetoprotein for hepatocellular carcinoma, and fecal occult blood test, for colon cancer) are only modestly effective necessitating the use of highly invasive endoscopy-based procedures, such as esophagogastroduodenoscopy and colonoscopy for screening purposes. Even for hepatocellular carcinoma where non-invasive imaging (ultrasonography) has become a standard screening tool, the need for repeated liver biopsies of suspicious liver nodules for histopathological confirmation can�t be avoided. The invasive nature and high-cost associated with these screening tools hinders implementation of GI cancer screening programs. Moreover, only a small fraction of general population is truly predisposed to developing GI malignancies, and indeed needs surveillance. To spare the average-risk individuals from superfluous invasive procedures and achieve an economically viable model of cancer prevention, it�s important to identify cohorts in general population that are at substantially high risk of developing GI malignancies (risk-stratification), and select suitable screening tests for surveillance in these cohorts. We herein provide a brief overview of such high-risk cohorts for different GI malignancies, and the screening strategies that have commonly been employed for surveillance purpose in them. PMID:22969223
Integrating the Diagnosis of Childhood Malignancies
Significant progress has been made in understanding the molecular basis of pediatric malignancies. Mechanisms of pediatric acute leukemia induction include hyperdiploidy, aberrant expression of proto-oncogenes, and activation of trans- cription factors or kinases by aberrant fusion genes. Molecular analysis of these alterations has facilitated the recognition of distinct groups with different sensitivity to therapy, and identified potential targets for antileukemic
Detection and diagnosis of human oral cancer using hypericin fluorescence endoscopic imaging interfaced with embedded computing
NASA Astrophysics Data System (ADS)
Thong, Patricia S. P.; Olivo, Malini; Lin, Feng; Seah, Hock-Soon; Tandjung, Stephanus S.; Qian, Kemao; Chin, William W. L.; Bhuvaneswari, Ramaswamy; Mancer, Kent; Soo, Khee-Chee
Oral cancers are currently diagnosed using white light endoscopy and histopathology. However, oral tumours are mostly superficial and can be difficult to visualise. Here we present the use of hypericin with fluorescence endoscopy and laser confocal fluorescence endomicroscopy interfaced with embedded computing for the diagnosis of oral cancers. Fluorescence imaging of oral lesions was carried out in the clinic using a fluorescence endoscope. The images were analyzed to extract the red to blue (R/B) ratios to discriminate between tissue types. The results showed that the R/B ratio is a good image parameter to discriminate between normal, hyperplastic and malignant oral tissue. We are also developing an embedded, real-time computing system interfaced to a fluorescence endomicroscope for 3D visualization of tumors, where synchronization of cross-sectional image grabbing and Z-depth scanning is realized through programming a Field-Programmable Gate Array. In addition to the programming task, a proprietary control circuit has been developed for the automated 3D reconstruction of fluorescence sections; and preliminary results from fluorescent samples have demonstrated the potential of this system for real-time in vivo 3D visualization of tumours. This will ultimately enable same-day clinical diagnosis to be achieved and further enhance the clinical usefulness of fluorescence diagnostic imaging.
Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis
Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993
Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis; Karavias, Dionissios
Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993
Chemokine function in periodontal disease and oral cavity cancer.
Sahingur, Sinem Esra; Yeudall, W Andrew
The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides with a wide range of activities that include recruitment of immune cells to sites of infection and inflammation, as well as stimulation of cell proliferation. As such, they function as antimicrobial molecules and play a central role in host defenses against pathogen challenge. However, their ability to recruit leukocytes and potentiate or prolong the inflammatory response may have profound implications for the progression of oral diseases such as chronic periodontitis, where tissue destruction may be widespread. Moreover, it is increasingly recognized that chronic inflammation is a key component of tumor progression. Interaction between cancer cells and their microenvironment is mediated in large part by secreted factors such as chemokines, and serves to enhance the malignant phenotype in oral and other cancers. In this article, we will outline the biological and biochemical mechanisms of chemokine action in host-microbiome interactions in periodontal disease and in oral cancer, and how these may overlap and contribute to pathogenesis. PMID:25999952
Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis
Sonis, Stephen T
Purpose: Oral mucositis is a significant toxicity of cytotoxic chemo- and radiation-therapy used to treat cancer. Palifermin is the first pharmaceutical/biological agent approved for the intervention of oral mucositis. The major objective of this review is to evaluate the evidence supporting the use of palifermin. Methods: A literature search was performed using an appropriate keyword search in MEDLINE and PubMed databases. Results: Of 100 full papers and 4 abstracts identified, 12 papers and 3 abstracts were appropriate for analysis. Level 2 evidence supporting palifermin use in patients with hematologic malignancies being treated with autologous hematopoietic stem cell transplantation (HSCT) is clear. Level 2 evidence also exists for the use of palifermin in the prevention of oral mucositis in patients with solid tumors (colorectal cancer, head and neck cancer), but is incomplete. Level ? 3 data support the use of palifermin in allogeneic HSCT recipients and cycled chemotherapy. A single health economic study concluded that palifermin is essentially cost neutral in the autologous HSCT population. Conclusion: Data supporting the use of palifermin in autologous HSCT recipients with hematologic malignancies is clear. Some data exist demonstrating its efficacy in other oncologic indications. Additional studies are needed to broaden the potential applications of palifermin and to ascertain its economic, but not symptomatic, effectiveness. PMID:20694076
Oral cysticercosis: a clinical dilemma
Wanjari, Sangeeta Panjab; Patidar, Kalpana A; Parwani, Rajkumar N; Tekade, Satyajitraje A
Cysticercosis is a potentially fatal parasitic disease caused by cysticercus cellulosae, the larval stage of Taenia solium. Oral cysticercosis is a rare entity and represents difficulty in clinical diagnosis. This article reports two cases of oral cysticercosis involving buccal and labial mucosa. Both the cases presented with solitary, nodular swelling that had been clinically diagnosed as a mucocele. Histopathology of excisional biopsy revealed it to be cysticercosis. Single, cystic nodular swelling of oral cavity may be the only evidence of cysticercosis and may present first to dentist. These cases emphasise the role of dentist and thorough histopathological examination in the early diagnosis of disease that can prevent potential systemic complication. PMID:23580668
New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.
Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucaf�, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Mar�n, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; N��ez, Luis; Macor, Paolo
Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders. PMID:24098639
[Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 2: cytodiagnosis, pathogenesis, therapy, and prognostic aspects].
Suter, Val�rie G A; Morger, Reto; Altermatt, Hans J�rg; Spieler, Peter; Bornstein, Michael M
The second part of the present review article presents and discusses the current literature regarding cytodiagnostic aspects, pathogenesis, therapy, incidence of recurrence, and malignant transformation rate of oral erythroplakia (OE) and oral erythroleukoplakia (OEL). Oral cytopathology, eventually in combination with DNA cytometry, can add valuable information to conventional histopathology, but is not able yet to replace the aforementioned. Numerous molecular genetic variants have been studied in precancerous lesions to gain knowledge about the prognosis of these lesions. Still, there are no evidence-based parameters available to safely detect precursor lesions that will undergo malignant transformation in the future. Excision of OE and OEL should be performed with a margin of safety using the CO2 laser or a scalpel. Data about incidence of recurrence and malignant tranformation rates of OE are mostly based upon case reports or case series. The OEL has a significantly higher risk of malignant transformation than oral leukoplakias. PMID:18619138
RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer.
Imaoka, Hiroki; Toiyama, Yuji; Saigusa, Susumu; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Junichiro; Tanaka, Koji; Inoue, Yasuhiro; Mohri, Yasuhiko; Kusunoki, Masato
Rac GTPase-activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration and metastasis. This study investigated the function and clinical significance of RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time PCR. Finally, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa and increased according to tumor node metastasis stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC. PMID:25568185
Gynaecological malignancies in Qatar.
Ejeckam, G C; Abdulla, F; el-Sakka, M; Dauleh, W; Haseeb, F
Gynaecological malignancies constitute 6.88% (144 of 2092) of all malignant lesions in Qatar over a 15 year period (1979-1993). Cancer of the cervix was the most common with 54.86% followed by ovarian cancer 22.91%, endometrium 15.97%, vulva and vagina 2.75% and 2.08% respectively. Malignancies of the corpus uteri were rare. No tumours of the Fallopian tubes were registered during the study period. Early marriage, frequent coitus started early in life and increasing number of pregnancies were predisposing factors for the genesis of cancer of the cervix. As in some other developing countries, cervical and ovarian neoplasms tend to occur in the younger age group. Germ cell and gonadal stromal tumours were rare in Qatar and this may suggest rarity of these tumours in women of Arab and Indian subcontinent descent. Increasing number of pregnancies seems to protect against ovarian cancer. Abortions and age at menarche do not influence the incidence of gynaecological malignancies. Our findings provide an adequate data base for planning of gynaecological cancer education, screening programmes and resource allocation in Qatar. PMID:7705247
Technology Transfer Automated Retrieval System (TEKTRAN)
Malignant catarrhal fever (MCF) is a frequently fatal viral disease of ruminant species, particularly cattle, bison, and deer. Clinical signs vary between species. Two major epidemiologic types of MCF exist, and are defined by the ruminant species that serve as natural reservoir hosts for infection...
Brooks, B.J.
This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.
Pigmented oral carcinoma in situ: a case report and literature review.
Matsumoto, Naoyuki; Kitano, Taiichi; Oki, Hidero; Omagari, Daisuke; Matsue, Yasuyoshi; Okudera, Michisato; Yamamura, Takashi; Nishikawa, Yohichi; Nishimura, Satoshi; Asano, Masatake; Komiyama, Kazuo
Oral melanotic lesions, including melanin pigmentation, melanocytic nevus, and malignant melanoma, are well-recognized pathologic entities. However, melanocytic proliferation within malignant oral mucosal lesions is not well documented. We report the unusual case of a 53-year-old Japanese man who developed oral carcinoma in situ (CIS) with melanocytic proliferation and melanin pigmentation in the epithelial layer. The patient, a nonsmoker and an opportunistic drinker, presented with a brown tongue lesion. Initial examination found a large brown pigmented area and multiple small white patchy areas on the right tongue border. The pigmentation had an ill-defined border with uneven color distribution. Physical examination found no abnormalities. Ultrasonography did not find a deeply infiltrating lesion. Oral mucosal malignant melanoma in situ was diagnosed, and partial tongue resection was performed. Histopathologic examination found oral pigmented CIS. To the best of our knowledge, this is only the third reported case of oral pigmented CIS. PMID:24746807
The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective study
Erik H van der Meij; Kees-Pieter Schepman; Isa�c van der Waal
ObjectivesThe possible malignant transformation of oral lichen planus (OLP) is the subject of an ongoing and controversial discussion in the literature. The main criticism of studies on this subject relates to the lack of sufficient data to support the initial diagnosis of OLP in cases that finally developed into squamous cell carcinoma. We describe the possible premalignant character of OLP
Despotov, O; Ficheva, M; Avramov, T
The pleomorphism of the tussies taking part in the formation of oral cavity is basis for the great majority of benign and malignant tumors. They often have similar clinical manifestations macroscopic view. Histological investigations help us for exact diagnosis and adequate treatment. Authors present a clinical case of 67 years old female treated in II ORL clinic of a tumour, originating from the floor of oral cavity, displacing tongue to the left. First complaints of the pathient a dating from 23 years. During that period the tumour gradually increased its dimensions and obstructed swallowing. The weight of the pathient of the time of the admitance at the hospital was 47 Kg. After operative removal of the tumour, the woman was in very good condition. The histological result--fibrolipoma. At the control examination (3 and 6 months after operation) she had increase her weight by 17 and 21 Kg respectively. This case present the conclusion that even benign tumours should be removed in shortes possible terms after the diagnoses. PMID:15587749
Oral manifestations of plummer-vinson syndrome: a classic report with literature review.
Samad, Abdul; Mohan, N; Balaji, R V Suresh; Augustine, Dominic; Patil, Shankar Gouda
Plummer-Vinson syndrome (PVS) is a triad of microcytic hypochromic anemia, atrophic glossitis, and esophageal webs or strictures. It is one of the syndromes associated with iron deficiency anemia. Symptoms resulting from anemia predominates the clinical picture, apart from the additional features such as glossitis, angular cheilitis, and dysphagia. Dysphagia is main clinical feature of PVS. PVS carries an increased risk of development of squamous cell carcinoma of esophagus and pharynx. A classic case report of PVS with clinical features, oral manifestations, malignant potential, differential diagnosis, investigation, dental implication, and treatment is discussed here with the literature review from the dentist's point of view. The article carries a message that dental surgeons have to be familiar with the oral manifestations of anemia and be able to suspect PVS to aid in early diagnosis and prompt treatment. PMID:25878483
Hyperbaric Oxygen Therapy�A Novel Treatment Modality in Oral Submucous Fibrosis: A Review
Kumar, M. Ashwini; Radhika, Besta; Reddy, Satya Prakash; Yaga, Uday Shankar
Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level.
Oral Manifestations of Plummer-Vinson Syndrome: A Classic Report with Literature Review
Samad, Abdul; Mohan, N; Balaji, R V Suresh; Augustine, Dominic; Patil, Shankar Gouda
Plummer-Vinson syndrome (PVS) is a triad of microcytic hypochromic anemia, atrophic glossitis, and esophageal webs or strictures. It is one of the syndromes associated with iron deficiency anemia. Symptoms resulting from anemia predominates the clinical picture, apart from the additional features such as glossitis, angular cheilitis, and dysphagia. Dysphagia is main clinical feature of PVS. PVS carries an increased risk of development of squamous cell carcinoma of esophagus and pharynx. A classic case report of PVS with clinical features, oral manifestations, malignant potential, differential diagnosis, investigation, dental implication, and treatment is discussed here with the literature review from the dentist�s point of view. The article carries a message that dental surgeons have to be familiar with the oral manifestations of anemia and be able to suspect PVS to aid in early diagnosis and prompt treatment. PMID:25878483
Impact of Hormone-Associated Resistance to Activated Protein C on the Thrombotic Potential of Oral Contraceptives: A Prospective Observational Study
M�ller, Jens; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C.; Oldenburg, Johannes; Rudlowski, Christian; P�tzsch, Bernd
Introduction The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Patients and Methods Blood samples were collected prospectively from healthy women (n?=?21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. Results All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p?=?0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. Conclusions In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk. PMID:25121606
Malignant melanoma...133 Chapter 12
Paxton, Anthony T.
NICR/NCRI Malignant melanoma...133 Chapter 12: Malignant melanoma (C43) KEY FINDINGS - INCIDENCE During 2000-2004 incidence rates for melanoma increased with increasing affluence. o Male incidence rates and 60 female deaths from malignant melanoma in Ireland. o Among males mortality rates increased
Pembrolizumab in Treating Patients With Malignant Mesothelioma
Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma
Transforming growth factor-?1 and TGF-?2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation
Kamath, Venkatesh Viswanath; Krishnamurthy, Shruti; Satelur, Krishnanand P.; Rajkumar, Komali
Background and objectives: Oral Submucous Fibrosis (OSF) is a potentially malignant oral disorder which leads to fibrosis of the oral mucosa and has a high rate of malignant transformation. The consumption of various forms of areca nut is causatively linked to the condition. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor-?1, ?2, which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-?1, ?2 probably represent the major pathway in the deposition of collagen fibres in this condition. The present study aims to identify and correlate the expressions of TGF-?1 and TGF-?2 immunohistochemically on paraffin sections of various stages of OSF. A comparison was also made between normal oral mucosa and scar tissue and OSF to judge the mode, extent and type of expression of TGF ?1, ?2. Methods: The expression of TGF-?1 antibody (8A11, NovusBio, USA) and TGF-?2 antibody (TB21, NovusBio, USA) was detected immunohistochemically on paraffin sections of 58 and 70 cases of OSF respectively, 10 cases of normal oral mucosal tissue and 4 cases of scar tissue. A mapping of the positivity of the two cytokines was done using JenOptik camera and ProReg image analysis software. The results were statistically analysed using one way ANOVA and students �t� test. Results: Expression of TGF-?1 and TGF-?2 was more in OSF as compared with normal oral mucosa, scar/keloid tissue showing highest values. Positivity for both the markers was seen in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. TGF-?1 expression was higher and more intense than that of TGF-?2 in all the cases. TGF-?2 was restricted in its expression to submucosal area with minimal involvement of the epithelium and the deeper muscle tissue. Conclusion: TGF-?1 is the most prominent cytokine in the fibrotic pathway and TGF-?2 plays a contributory role.
MIEN1 promotes oral cancer progression and implicates poor overall survival.
Rajendiran, Smrithi; Kpetemey, Marilyne; Maji, Sayantan; Gibbs, Lee D; Dasgupta, Subhamoy; Mantsch, Rebecca; Hare, Richard J; Vishwanatha, Jamboor K
Oral squamous cell carcinoma is a highly malignant tumor with the potential to invade local and distant sites and promote lymph node metastasis. Major players underlying the molecular mechanisms behind tumor progression are yet to be fully explored. Migration and invasion enhancer 1 (MIEN1), a novel protein overexpressed in various cancers, facilitates cell migration and invasion. In the present study we investigated the expression and role of MIEN1 in oral cancer progression using an in vitro model, patient derived oral tissues and existing TCGA data. Expression analysis using immortalized normal and cancer cells demonstrated increased expression of MIEN1 in cancer. Assays performed after MIEN1 knockdown in OSC-2 cells showed decreased migration, invasion and filopodia formation; while MIEN1 overexpression in DOK cells increased these characteristics and also up-regulated some Akt/NF-?B effectors, thereby suggesting an important role for MIEN1 in oral cancer progression. Immunohistochemical staining and analyses of oral tissue specimens, collected from patients over multiple visits, revealed significantly more staining in severe dysplasia and squamous cell carcinoma compared to mildly dysplastic or hyperplastic tissues. Finally, this was corroborated with the TCGA dataset, where MIEN1 expression was not only higher in intermediate and high grade cancer with significantly lower survival but also correlated with smoking. In summary, we demonstrate that MIEN1 expression not only positively correlates with oral cancer progression but also seems to be a critical molecular determinant in migration and invasion of oral cancer cells, thereby, playing a possible role in their metastatic dissemination. PMID:25996585
Nano-bio-chip sensor platform for examination of oral exfoliative cytology
Weigum, Shannon E.; Floriano, Pierre N.; Redding, Spencer W.; Yeh, Chih-Ko; Westbrook, Stephen D.; McGuff, H. Stan; Lin, Alan; Miller, Frank R.; Villarreal, Fred; Rowan, Stephanie D.; Vigneswaran, Nadarajah; Williams, Michelle D.; McDevitt, John T.
Oral cancer is a deadly and disfiguring disease which could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a non-invasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the EGFR biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (p < 0.0001), the nuclear-to-cytoplasmic ratio (p < 0.0001), and EGFR biomarker expression (p < 0.03). Further examination using logistic regression and receiver operating characteristic (ROC) curve analysis identified morphologic features as the best predictors of disease (AUC ? 0.93) individually, while a combination of all features further enhanced discrimination of oral cancer and pre-cancerous conditions (AUC = 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival. PMID:20332305
The clinical effectiveness of reflectance optical spectroscopy for the in vivo diagnosis of oral lesions
Messadi, Diana V; Younai, Fariba S; Liu, Hong-Hu; Guo, Gao; Wang, Cun-Yu
Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green�amber light at 545?nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi� system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi� device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green�amber light at 545?nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions. PMID:25059250
Touch imprint cytology: a rapid diagnostic tool for oral squamous cell carcinoma.
Geetha, L; Astekar, M; Ashok, K N; Sowmya, G V
Techniques for intraoperative pathologic examination of oral squamous cell carcinoma are rare in the literature. We evaluated the advantages and limitations of touch imprint cytology for intraoperative diagnosis of oral squamous cell carcinoma. We used 30 incisional biopsies of clinically diagnosed oral squamous cell carcinoma and compared touch imprint cytology to histopathological sections. Touch imprint cytology showed 24 specimens positive for malignancy, two suspicious for malignancy and four inadequate specimens. The accuracy of the test was 93.2%. Touch imprint cytology is an accurate, simple, rapid and cost-effective method that aids diagnosis of oral squamous cell carcinoma during operation, but it does not replace incisional biopsy. PMID:25801179
Ancient neurilemmoma: A rare oral tumor.
Muruganandhan, J; Prasad, T Srinivasa; Selvakumar, T; Kumar, S Nalin
Neurilemmomas are benign tumors of neural origin composed of Schwann cell proliferation in characteristic patterns. Ancient neurilemmomas are usually longstanding growths that exhibit degenerative features that could be mistaken for malignancy. They are extremely rare in the oral cavity and present in older individuals of long duration. The authors report a case of ancient neurilemmoma in a young patient with short duration of growth. This unique case presented with remarkable histopathological features with respect to vascularity and atypia associated with degenerative change. It is essential to not mistake these features as malignant transformation so as to avoid radical procedures. PMID:24574671
Ancient neurilemmoma: A rare oral tumor
Muruganandhan, J; Prasad, T Srinivasa; Selvakumar, T; Kumar, S Nalin
Neurilemmomas are benign tumors of neural origin composed of Schwann cell proliferation in characteristic patterns. Ancient neurilemmomas are usually longstanding growths that exhibit degenerative features that could be mistaken for malignancy. They are extremely rare in the oral cavity and present in older individuals of long duration. The authors report a case of ancient neurilemmoma in a young patient with short duration of growth. This unique case presented with remarkable histopathological features with respect to vascularity and atypia associated with degenerative change. It is essential to not mistake these features as malignant transformation so as to avoid radical procedures. PMID:24574671
... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...
Ir�ne Hitz Lindenm�ller; J. Thomas Lambrecht
Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing\\/recovering from chemo-\\/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases.
[Isolated malignant mediastinal lymphadenopathy].
Riquet, M; Bagan, P; Fabre-Guillevin, E; Scott�, F; Cazes, A; Le Pimpec-Barthes, F
Mediastinal adenopathies without pulmonary disease may be benign, lymphomatous or the metastases from intra- or extrathoracic malignancy or more rarely metastases with unknown primary site. We observed 507 patients with isolated mediastinal adenopathies: benign, lymphomatous and metastatic disease represented 41.4% (210/507), 26.8% (136/507), 31.8% (161/507) of them, respectively. Management of the latter was the most challenging. Surgery was generally diagnostic, restricted to confirming the metastatic process, because of too numerous and disseminated or unresectable lymph nodes in 84% of patients (135/161). However, radical surgery consisting in lymphadenectomy proved effective in case of mediastinal lymph node malignancy without other extra- and intrathoracic disease. We observed long-term good results in such cases, which also was demonstrated by case reports in the literature. We suggest that including surgery in the multimodality treatment of mediastinal metastatic lymph nodes may be advisable in selected patients. PMID:20207295
Hyaluronan in human malignancies
Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland)] [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)] [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: firstname.lastname@example.com [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)
Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.
Esophageal tuberculosis mimicking malignancy.
Geusens, E; Verschakelen, J A; Flamaing, J; Bogaert, J; Ponette, E; Decramer, M; Baert, A L
A case of pulmonary and esophageal tuberculosis in an 82-year-old female is presented. Esophageal tuberculosis is very rarely seen in Europe and the United States, but the disease is still endemic in India. The major differential diagnosis is esophageal malignancy. Findings that can suggest the diagnosis are tracheo-esophageal fistula formation, enlarged, centrally necrotizing lymph nodes, and a micronodular lung pattern. PMID:8797957
Stents in Tracheobronchial Malignancy
H.-J. Wagner
\\u000a Malignant obstructions of the tracheobronchial system usually derive from cancer of the trachea or bronchus. However, infiltration\\u000a from tumors arising from adjacent organs (e.g., lymph nodes, esophageal cancer) can cause airway stenosis as well. For non-small\\u000a cell lung cancer the only curative approach is resection. However, many bronchial cancers are not resectable at the time of\\u000a diagnosis. Therefore, palliative measures
Malignant spinal cord compression
Madhuri Yalamanchili; Glenn J. Lesser
Opinion statement��Malignant spinal cord compression is one of the most dreaded complications of cancer. If untreated, it can lead to worsening\\u000a neurologic function culminating in paralysis and sphincter incontinence. The most challenging aspect in the management of\\u000a this complication is early diagnosis because the single most important factor determining outcome is the level of neurologic\\u000a function at initiation of therapy.
Primary malignant melanoma of the upper aero-digestive tract
Manoj Pandey; Elizabeth K. Abraham; Aleyamma Mathew; Iqbal M. Ahamed
Malignant mucosal melanoma represents 0.3 to 10% of all melanomas. The majority of these lesions arise in the oral cavity or paranasal sinuses. Very few authors report reliable treatment results, however all suggest a uniformly poor outcome. A retrospective analysis of all cases of upper aero-digestive tract melanoma (UADT) treated since 1982 at our centre are presented. During the 15-year
Malignant Catatonia Mimicking Pheochromocytoma
Li, Dailin
Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752?nmol/day (normal, 89�470?nmol/day), epinephrine at 1045?nmol/day (normal, <160?nmol/day), and dopamine at 7.9??mol/day (normal, 0.4�3.3??mol/day). The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features. PMID:24251048
Talcott, J.A.; Antman, K.H.
Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. 179 references.
[Clinical outcomes of stenting for malignant bowel obstruction in terminally ill cancer patients].
Sawatsubashi, Takahiro; Morioka, Nobuhiro; Shimizu, Takao; Kanda, Tatsuo; Nakatsuka, Hideki
We evaluated the effects of stenting for malignant bowel obstruction in terminally ill cancer patients. Six terminally ill cancer patients with malignant bowel obstruction underwent gastrointestinal stenting at our department from November 2010 to October 2012. Stent insertion was successful and abdominal symptoms improved in all cases. Oral intake improved in 4 cases. Descending colon perforation occurred in 1 case. The survival time ranged between 10 and 184 days( median, 71.5 days). The palliative performance status (PPS) improved in 4 cases, and the survival time was extended as assessed by the palliative prognostic index (PPI). In cases with a PPI of were more than 6.0, namely cases for which the estimated survival time was less than 3 weeks, survival time and oral intake did not change. These findings suggest that gastrointestinal stenting is clinically useful for malignant obstruction and improving the PPS and prognosis in terminally ill patients with malignant bowel obstruction. PMID:24394138
Malignant degeneration of pulmonary juvenile-onset recurrent respiratory papillomatosis.
Knepper, Benjamin R; Eklund, Meryle J; Braithwaite, Kiery A
Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare disease associated with the human papilloma virus (HPV) in which papillomas form along the aerodigestive tract in children. Pulmonary involvement is uncommon, but associated with worse clinical outcomes, including the rare complication of malignant transformation. We present a patient with JORRP in which lung disease underwent malignant transformation during adolescence. Our goal is to raise awareness of the potential for malignant transformation in children, as well as to familiarize pediatric radiologists with imaging features of malignant lung disease in JORRP. We advocate for the identification of the subgroup of JORPP patients with pulmonary disease who, due to increased risk for malignant transformation, may benefit from closer clinical and imaging surveillance by a multidisciplinary team. PMID:25487719
The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies.
Chon, Hae J; Bae, Kyoung J; Lee, Yura; Kim, Jiyeon
The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past 2 years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies. PMID:25873900
The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies
Chon, Hae J.; Bae, Kyoung J.; Lee, Yura; Kim, Jiyeon
The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past 2 years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies. PMID:25873900
Dionne, R
"I fear a trip to the dentist more than I fear death" is the response one person gave in a national survey recently cited in USA Today. While clearly representing an extreme, the results of many surveys suggest that fear of dentistry is still prevalent and is a measure of the failure of current therapeutic approaches to reduce pain and anxiety sufficiently to enable people, especially those with special needs, to visit the dentist. Patients who are fearful would likely seek oral health care more regularly if anesthesia and sedation were more readily available. Taking into consideration that the safety of anxiolytic drugs is highly dependent on the drug, dose, and route of administration used, oral premedication should be the sedative technique used by most dentists because it is efficacious, requires little monitoring when appropriate doses are used, and is unlikely to result in serious morbidity. PMID:9852800
Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections
Background A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects. Methods Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression. Results CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm. Conclusions Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response. PMID:24063298
Estimation of serum lipids in patients with Oral Submucous Fibrosis in India
Panat, Sunil R.; Aggarwal, Ashish; Agarwal, Nupur; Upadhyay, Nitin; Joshi, Anuja
Objectives: Oral submucous fibrosis (OSMF) is the most prevalent precancerous condition in India. Low levels of lipids serves as a marker and prognostic indicator in the early detection of oral precancerous and cancerous states. In spite of the high prevalence and its potential to undergo malignant transformation, this condition has not widely been investigated with respect to the serum lipid levels. In the present study, an attempt was made to analyze the complete serum lipid profile, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol in OSMF and controls. Material and Methods: The study was conducted in 45 clinically and histopathologically diagnosed cases of OSMF and 45 age and sex matched controls. The complete lipid profile including TC, TG, HDL cholesterol, LDL cholesterol and VLDL cholesterol was analyzed. Results: The serum lipid levels were significantly lower in the patients with OSMF than in the controls. When the values were compared between different disease stages, the maximum reduction of lipids was evident for stage 3 OSMF. From the present results, it is evident that the level of serum lipids decreases with progression of the disease. Conclusions: From these findings, it appears that the decrease in the lipid levels may be considered as a useful marker in the early diagnosis of oral premalignant condition like OSMF. Key words:Oral submucous fibrosis, lipids, premalignant condition. PMID:25136423
The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer
Huang, Bin; Shieh, Tien-Yu; Wang, Yan-Hsiung; Chen, Yuk-Kwan; Wu, Ju-Hui; Huang, Jhen-Hao; Chen, Chun-Chia; Lee, Ka-Wo
Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS. PMID:25389533
Antiangiogenic Agents in Myeloid Malignancies
Magda Melchert; Alan F. List
The role of angiogenesis in the development and progression of solid tumors has been well established over the 1980s and 1990s.\\u000a Through more recent investigations, it has become increasingly clear that neovascularization within the bone marrow of patients\\u000a with hematologic malignancies is of primary importance in the development and progression of these disorders. Evidence of\\u000a malignant angiogenesis in myeloid malignancies
Cancer Stem Cells and Oral Cavity Cancer Metastasis
Mark Prince
\\u000a Oral cavity squamous cell carcinoma is a common malignancy with a high propensity for the development of metastasis. Even\\u000a early stage oral cavity tumors are frequently associated with metastasis to regional lymph nodes. Cancer stem cells have recently\\u000a been isolated from head and neck squamous cell cancer and represent the critical population of cancer cells responsible for\\u000a primary tumor growth.
Cancer and oral lichen planus in a Swedish population
Per-Olof R�dstr�m; Mats Jontell; Ulf Mattsson; Erik Holmberg
Oral lichen planus (OLP) is generally regarded as a premalignant condition. The objective of the present study was to assess the number of oral malignant tumours in a retrospective analysis of 1028 patients (mean age=55 years; range=18�86; female, n=667; men, n=351) who between 1978 to end of 1993 were diagnosed with OLP at the Faculty of Odontology, G�teborg University, Sweden.
Gynaecological Malignancies from Palliative Care Perspective
Mishra, Kamlesh
Of the approximately 80,000 new cases of all cancers detected every year in India, 10�15% are gynecological malignancies. As per population-based registries under the National Cancer Registry Program, the leading sites of cancer among women are the cervix uteri, breast, and oral cavity. About 50�60% of all cancers among women in India are mainly of the following four organs: cervix uteri, breast, corpus uteri, and ovaries. Over 70% of these women report for diagnostic and treatment services at an advanced stage of disease, resulting in poor survival and high mortality rates. Among all gynecological cancers, ovarian cancer is the deadliest one and, in 2/3rd of the cases, is detected in an advanced stage. But, in India and in other developing countries, due to inadequate screening facilities for the preventable cancer cervix, this kills more women than any other cancer in females. Gynecology Oncologist as a sub-specialist has an immensely important role in curtailing the menace of gynecological malignancies by providing comprehensive preventive, curative, palliative and follow-up services, with the aim of assuring a good quality of life to women as a cornerstone of cancer management. PMID:21811372
Risk Factors for Second Malignancies Following Stem Cell Transplant
Debra L. Friedman
\\u000a Hematopoietic cell transplantation (HCT) offers potentially curative therapy for numerous malignancies, as well as immunologic,\\u000a hematologic and metabolic disorders. While many patients are cured of their primary disease, a proportion develops posttransplant\\u000a (secondary) malignant neoplasms (SMN) [2, 19, 29]. Individuals treated with HCT may have been exposed to pre-transplant chemotherapy or radiotherapy, then to additional cytotoxic\\u000a therapy as part of
Rare Malignant Tumors of Clitoris-a Case Report.
Venugopal, P R; Ramachandran, Padma
Tumors of the clitoris are very rare. Isolated case reports are available in literature. This case report highlights the importance of this disease, due to its high malignant potential and treatment options. We had come across a rare tumor of the clitoris in a young girl, reported to be malignant extrarenal rhabdoid tumor and patient had a short life span of 6�months. PMID:25177123
Evans, Ginger; Sutton, Eliza L
Oral contraception (OC) remains a popular noninvasive, readily reversible approach for pregnancy prevention and, largely off label, for control of acne, hirsutism, dysmenorrhea, irregular menstruation, menorrhagia, and other menstrual-related symptoms. Many OC formulations exist, with generics offering lower cost and comparable efficacy. Certain medical conditions, including hypertension, migraine, breast cancer, and risk of venous thromboembolism (VTE), present contraindications. Blood pressure measurement is the only physical examination or testing needed before prescription. Although no OC is clearly superior to others, OCs containing the second-generation progestin levonorgestrel have been associated with lower VTE risk than those containing other progestins. PMID:25841596
Use of Transgenic Mouse Models to Understand the Oral Disposition and Drug-Drug Interaction Potential of Cobimetinib, a MEK Inhibitor.
Choo, Edna F; Woolsey, Sarah; DeMent, Kevin; Ly, Justin; Messick, Kirsten; Qin, Ann; Takahashi, Ryan
Data from the clinical absolute bioavailability (F) study with cobimetinib suggested that F was lower than predicted based on its low hepatic extraction and good absorption. The CYP3A4 transgenic (Tg) mouse model with differential expression of CYP3A4 in the liver (Cyp3a(-/-)Tg-3A4Hep) or intestine (Cyp3a(-/-)Tg-3A4Int) and both liver and intestine (Cyp3a(-/-)Tg-3A4Hep/Int) were used to study the contribution of intestinal metabolism to the F of cobimetinib. In addition, the effect of CYP3A4 inhibition and induction on cobimetinib exposures was tested in the Cyp3a(-/-)Tg-3A4Hep/Int and PXR-CAR-CYP3A4/CYP3A7 mouse models, respectively. After i.v. administration of 1 mg/kg cobimetinib to wild-type [(WT) FVB], Cyp3a(-/-)Tg-3A4Hep, Cyp3a(-/-)Tg-3A4Int, or Cyp3a(-/-)Tg-3A4Hep/Int mice, clearance (CL) (26-35 ml/min/kg) was similar in the CYP3A4 transgenic and WT mice. After oral administration of 5 mg/kg cobimetinib, the area under the curve (AUC) values of cobimetinib in WT, Cyp3a(-/-)Tg-3A4Hep, Cyp3a(-/-)Tg-3A4Int, or Cyp3a(-/-)Tg-3A4Hep/Int mice were 1.35, 3.39, 1.04, and 0.701 ?M?h, respectively. The approximately 80% lower AUC of cobimetinib in transgenic mice when intestinal CYP3A4 was present suggested that the intestinal first pass contributed to the oral CL of cobimetinib. Oxidative metabolites observed in human circulation were also observed in the transgenic mice. In drug-drug interaction (DDI) studies using Cyp3a(-/-)Tg-3A4Hep/Int mice, 8- and 4-fold increases in oral and i.v. cobimetinib exposure, respectively, were observed with itraconazole co-administration. In PXR-CAR-CYP3A4/CYP3A7 mice, rifampin induction decreased cobimetinib oral exposure by approximately 80%. Collectively, these data support the conclusion that CYP3A4 intestinal metabolism contributes to the oral disposition of cobimetinib and suggest that under certain circumstances the transgenic model may be useful in predicting clinical DDIs. PMID:25813936
Micronuclei Frequencies and Nuclear Abnormalities in Oral Exfoliated Cells of Nuclear Power Plant Workers
Babannavar, Roopa; Lohra, Abhishek; Kodgi, Ashwin; Bapure, Sunil; Rao, Yogesh; J., Arun; Malghan, Manjunath
Aim: Biomonitoring provides a useful tool to estimate the genetic risk from exposure to genotoxic agents. The aim of this study was to evaluate the frequencies of Micronuclei (MN) and other Nuclear abnormalities (NA) from exfoliated oral mucosal cells in Nuclear Power Station (NPS) workers. Materials and Methods: Micronucleus frequencies in oral exfoliated cells were done from individuals not known to be exposed to either environmental or occupational carcinogens (Group I). Similarly samples were obtained from full-time Nuclear Power Station (NPS) workers with absence of Leukemia and any malignancy (Group II) and workers diagnosed as leukemic patients and undergoing treatment (Group III). Results: There was statistically significant difference between Group I, Group II & Group III. MN and NA frequencies in Leukemic Patients were significantly higher than those in exposed workers &control groups (p < 0.05). Conclusion: MN and other NA reflect genetic changes, events associated with malignancies. Therefore, there is a need to educate those who work in NPS about the potential hazard of occupational exposure and the importance of using protective measures. PMID:25654022
Application of Lateral Arm Free Flap in Oral and Maxillofacial Reconstruction following Tumor Surgery
Xiao-meng Song; Ye Yuan; Zhen-jiang Tao; He-ming Wu; Hua Yuan; Yu-nong Wu
Objective: To describe the application of lateral arm free flap (LAFF) in reconstruction of defects in the oral and maxillofacial regions following ablative oncological surgery. Subjects and Methods: The study included 16 patients (13 male, 3 female, mean age 56, range 35�69 years). Sixteen LAFF were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral
Tuberose sclerosis with malignant astrocytoma.
Brown, J M
A case is described of a recurrent malignant gemistocytic astrocytoma in which a diagnosis of tuberose sclerosis was made at post-mortem examination, when "rhabdomyomata" were found in the cardiac muscle and tubers in the cerebral hemispheres. Malignant degeneration of a cerebral lesion has not been described in association with tuberose sclerosis. PMID:1152773
Das maligne Lymphom des Hodens
M. Raute; K. Wurster
Malignant lymphoma of the testis is rare, accounting for only about 3�8% of all testicular neoplasms. The most common type of these tumors is the reticulum cell sarcoma. Its histopathological features are described. Malignant lymphoma tends to occur after the age of 60, as opposed to germ cell tumors: occurrence in children is rarely reported. The right testicle is more
Expression of Ki-67 in normal oral epithelium, leukoplakic oral epithelium and oral squamous cell carcinoma
Birajdar, Smita Shrishail; Radhika, MB; Paremala, K; Sudhakara, M; Soumya, M; Gadivan, Mohsin
Aims and Objective: To demonstrate the presence, location and pattern of cell proliferation in different histological grades of oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC) and normal oral epithelium (NOE) using an antibody directed against the Ki-67 antigen and its intensity of staining evaluated respectively. Materials and Methods: A total number of 100 archival paraffin embedded blocks obtained from Department of Oral and Maxillofacial Pathology were studied. The case details were retrieved which consisted of histopathologically diagnosed cases of OSCC (n = 20), low risk OED (n = 30), high risk OED (n = 30) and normal appearing mucosa (n = 20) were taken as standard for comparison. Ki-67 immunostaining was detected. Ki-67 positive cells were counted in the five random high power fields in each case. Results: Ki-67 labeling Index (LI) was restricted to the basal and parabasal layers of the normal oral epithelium irrespective of age, sex and site whereas it was seen in the basal, suprabasal and spinous layers in OED. Ki-67 LI is increased in high risk cases than the low risk cases of OED. Ki-67 positive cells in OSCC were located in the periphery of the tumor nests than the center, where frequent mitoses were observed. Conclusion: The architectural alteration evaluated by Ki-67 antibody in proliferating cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of OED. Ki-67 LI increased in high risk cases than low risk cases of OED. This study showed that over expression of Ki-67 antigen between well-differentiated and poorly differentiated OSCC was in accordance with histologic grade of malignancy but not in accordance with moderately differentiated OSCC. PMID:25328294
Neuroleptic Malignant Syndrome
Berman, Brian D.
Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Although uncommon, NMS remains a critical consideration in the differential diagnosis of patients presenting with fever and mental status changes because it requires prompt recognition to prevent significant morbidity and death. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases. Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early, however, remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes. PMID:23983836
Malignant fibrous histiocytoma
Mohan, Ravi Prakash Sasankoti; Verma, Sankalp; Siddhu, Vivek Kumar; Agarwal, Neha
Malignant fibrous histiocytoma (MFH) is a type of histiocytoma and is the most common soft tissue sarcoma of late adult life. However, it is relatively uncommon in the head and neck area. It usually occurs/develops in the lower extremities and in the retroperitonium. This tumour is difficult to distinguish histologically from other sarcomas and carcinomas. Surgery is the only treatment option. Prognosis is fairly poor; recurrence and local metastasis are common. In comparison with MFH of the extremities and the trunk, the 5-year survival rate for cases of this tumour in the head and neck is low. It is important to consider MFH in differential diagnosis of head and neck tumours because of its poor prognosis. We report a rare case of MFH in an 11-year-old girl. PMID:23729703
[Malignant vasovagal syncope].
Halmai, L�szl�; Avramov, Katalin; Rudas, L�szl�
The diagnosis of epilepsy is complicated by various conditions that can mimic an epileptic seizure. Many patients with abnormal seizure activity during loss of consciousness may have cardiovascular syncope with global cerebral hypoxia (convulsive syncope), which may be difficult to differentiate from epilepsy on clinical grounds. The differentiation is, however, important because they need quite different treatment modalities. In addition, long-term anticonvulsant therapy is expensive and can cause serious morbidity. The authors present a case of a patient thought to have treatment-resistant epilepsy for years with recurrent seizure-attacks, who were subsequently found to have a malignant vasovagal reaction of 24s-asystole as a cause for the so called convulsive syncope. A simple, non-invasive evaluation of circulatory responses to acute orthostasis, the head-up tilt table test, can identify cardiovascular reflex abnormalities in patients with recurrent idiopathic seizure-like episodes. The authors could also reproduce the symptoms of the spontaneous attacks in their patient by this way, to confirm an alternative diagnosis of malignant vasovagal reaction and convulsive syncope in this patient with "refractory epilepsy". This rare cardioinhibition can be safely treated by dual-chamber pacemaker implantation, alleviating for the convulsive attacks, this therapeutic option was advised to this patient as well. Orthostatic stress tests should be considered early in the diagnostic workup of patients with convulsive blackouts. Cardiac causes of loss of consciousness should be considered in patients with presumed epilepsy, atypical premonitory symptoms, non-diagnostic electroencephalograms and failure to respond to anticonvulsant therapy. PMID:12901179
Primary intrahepatic malignant epithelioid mesothelioma
Perysinakis, Iraklis; Nixon, Alexander M.; Spyridakis, Ioannis; Kakiopoulos, George; Zorzos, Charalampos; Margaris, Ilias
INTRODUCTION Primary malignant hepatic mesotheliomas are extremely rare. We report the case of a patient with primary intrahepatic malignant mesothelioma who was treated in our department. PRESENTATION OF CASE A 66-year old male patient was admitted to our department for the evaluation of anemia. An abdominal computed tomography scan revealed a large space occupying lesion in the right liver lobe. DISCUSSION The tumor was subsequently resected and a diagnosis of primary intrahepatic malignant mesothelioma was made after pathologic examination. The patient did not receive adjuvant therapy and is currently alive and free of disease, 36 months after the resection. CONCLUSION To our knowledge this is the eighth adult case of primary intrahepatic malignant mesothelioma reported in the literature. These tumors are rarely diagnosed preoperatively. Absence of previous asbestos exposure does not exclude malignant mesothelioma from the differential diagnosis. Proper surgical treatment may offer prolonged survival to the patient, without adjuvant therapy. PMID:25460485
Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a smoking ... Nicotine oral inhalation comes as a cartridge to inhale by mouth using a special inhaler. Follow the directions on ...
Urban legends series: oral leukoplakia.
Arduino, P G; Bagan, J; El-Naggar, A K; Carrozzo, M
To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis. PMID:23379968
Malignant Sweat Gland Tumors: An Update.
Brenn, Thomas
Sweat gland carcinomas represent an important and somewhat contentious group of tumors in diagnostic skin pathology. Although their overall incidence is rare, they show a wide range of histologic features, and reliable classification is often challenging. Awareness and recognition of these tumors is, however, important as they may be associated with significant morbidity and even disease-related mortality, especially if left untreated. According to their behavior, sweat gland carcinomas are traditionally separated into tumors with low-grade and high-grade malignant behavior. This article is aimed at increasing awareness and providing an overview of malignant sweat gland tumors with emphasis on recently reported and novel findings and diagnostically challenging and potentially underrecognized entities. It further aims to illustrate the wide morphologic range of these tumors and provides a discussion of the relevant immunohistochemistry, disease-specific behavior, and differential diagnosis. PMID:26050261
Malignant tumours of the kidney: imaging strategy
de Kraker, Jan
Primitive malignant renal tumours comprise 6% of all childhood cancers. Wilms tumour (WT) or nephroblastoma is the most frequent type accounting for more than 90%. Imaging alone cannot differentiate between these tumours with certainty but it plays an important role in screening, diagnostic workup, assessment of therapy response, preoperative evaluation and follow-up. The outcome of WT after therapy is excellent with an overall survival around 90%. In tumours such as those where the outcome is extremely good, focus can be shifted to a risk-based stratification to maintain excellent outcome in children with low risk tumours while improving quality of life and decreasing toxicity and costs. This review will discuss the imaging issues for WT from the European perspective and briefly discuss the characteristics of other malignant renal tumours occurring in children and new imaging techniques with potential in this matter. PMID:20432020
Megakaryocytes, Malignancy and Bone Marrow Vascular Niches
Psaila, Bethan; Lyden, David; Roberts, Irene
Summary Dynamic interactions between haematopoietic cells and their specialised bone marrow microenvironments, namely the vascular and osteoblastic �niches� regulate haematopoiesis. The vascular niche is conducive for thrombopoiesis, and megakaryocytes may, in turn, regulate the vascular niche, especially in supporting vascular and haematopoietic regeneration following irradiation or chemotherapy. A role for platelets in tumour growth and metastasis is well established and, more recently, the vascular niche has also been implicated as an area for preferential homing and engraftment of malignant cells. This article aims to provide an overview of the dynamic interactions between cellular and molecular components of the bone marrow vascular niche and the potential role of megakaryocytes in bone marrow malignancy. PMID:22122829
Potential use of chitosan nanoparticles for oral delivery of DNA vaccine in black seabream Acanthopagrus schlegelii Bleeker to protect from Vibrio parahaemolyticus.
Li, L; Lin, S-L; Deng, L; Liu, Z-G
To develop an effective and easy-to-administer vaccine against vibriosis of fish, the chitosan nanoparticles-loaded DNA vaccine against Vibrio parahaemolyticus was studied. A DNA vaccine was constructed using the outer membrane protein K (ompK) gene of V.�parahaemolyticus strain (OS4) and pEGFP-N2 , a eukaryotic expression vector, and the construct was named pEGFP-N2 -OMPK (pDNA). The pDNA was encapsulated in chitosan particles (chitosan/pDNA). The effective diameter, mean diameter and polydispersity of the particles were 284.4�nm, 218.9�nm and 0.160, respectively. Scanning electron microscopy showed that the particles are dispersed as individual nanoparticles with spherical shape of around 200�nm and are homogeneously distributed. Encapsulation efficiency and loading percentage of nanoparticles were 91.5% and 2.08%, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) showed that RNA-containing information of the ompK gene existed in mid-intestine, liver, kidney and muscle 3�weeks after oral administration in black seabream Acanthopagrus schlegelii Bleeker. Expression of the reporter gene, green fluorescent protein (GFP), was observed in the above-mentioned tissues by fluorescence microscopy. Expression of the ompK gene within 3�weeks evoked an immune response. Black seabream was protected from V.�parahaemolyticus (OS4), with 72.3% relative percentage survival (RPS) 3�weeks post-vaccination with chitosan/pDNA. The direct agglutination test indicated that oral administration with chitosan/pDNA induced an antibody immune response in fish against V.�parahaemolyticus (OS4). Data obtained, here and in other related studies, suggest that chitosan nanoparticles are promising carriers for an oral pDNA vaccine. PMID:24093149
Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence.
Vrijens, Bernard; Heidbuchel, Hein
Suboptimal medication adherence is a widespread problem in ambulatory care of chronic diseases, with deviations in either direction from the prescribed dosing regimen. For the non-vitamin K antagonist oral anticoagulants (NOACs), such deviations occur and can lead to bleeding or clotting, as suboptimal adherence involves temporary periods of either overdosing or underdosing. In this expert review, we discuss: (a) the proper definition of adherence in terms of its three elements: initiation, implementation, and discontinuation; (b) how adherence is reliably and accurately measured and (c) successfully enhanced, to achieve and maintain safe and effective levels of NOAC-based anticoagulation. We also discuss the comparative effects of prescribing the same total daily dose, given either once-daily or as half-strength twice-daily doses. Because NOACs have plasma half-lives of ?12 h, the twice-daily dosing regimen is less prone than the once-daily dosing regimen to hazardously high peaks or hazardously low troughs in anticoagulant concentrations and associated actions. As in other fields of oral drug treatment, the continuity of drug action is greater with twice-daily than with once-daily dosing, despite the fact that a few more doses are skipped with twice-daily than with once-daily dosing. This paradox is explained by the disproportionately greater impact on drug action of skipping a once-daily than a twice-daily dose. Integration of these principles into real-world medication management is the next step in the improvement of oral anticoagulation. PMID:25694538
Oral hairy leukoplakia in a patient with multiple myeloma.
Blomgren, J; B�ck, H
The first case of oral hairy leukoplakia in an HIV-negative patient with multiple myeloma is reported. The patient is a 56-year old man who has had monoclonal gammopathy of undetermined significance since 1986 and has been treated for a symptomatic multiple myeloma since 1993. The clinical and histopathologic findings are typical for oral hairy leukoplakia, and Epstein-Barr virus was demonstrated with polymerase chain reaction technique. Although a relatively large number of cases of oral hairy leukoplakia has been reported in HIV-negative patients, both immunocompromised and immunocompetent, only a few of these patients have had a malignant hematologic disease. PMID:8899778
Plaque-Type Blue Nevus of the Oral Cavity
Susanna K. Fistarol; Peter H. Itin
Background: The blue nevus of the oral cavity is a rare lesion with important differential diagnoses. The plaque-type blue nevus is an uncommon variant of the blue nevus. Because of its particular clinical appearance, it can easily be confused with satellite metastases from malignant melanoma. The diagnosis usually requires a biopsy. Objectives: To describe the clinical and histological features of
Oral mucosal melanoma: a series of case reports
Paolo Garzino-Demo; Massimo Fasolis; Gian Marco La Terra Maggiore; Marco Pagano; Sid Berrone
Introduction: Due to the rarity of oral malignant melanomas case reports are a necessary source of information. Ten new cases are reported with a minimum follow-up of 3 years. Patients and methods: Patients were treated during a period of 10 years. Clinical, demographic and pathologic findings were examined. Results: In 6 males (60%) and 4 females with a mean age
Global Oral Health Inequalities
Pitts, N.; Amaechi, B.; Niederman, R.; Acevedo, A.-M.; Vianna, R.; Ganss, C.; Ismail, A.; Honkala, E.
The IADR Global Oral Health Inequalities Task Group on Dental Caries has synthesized current evidence and opinion to identify a five-year implementation and research agenda which should lead to improvements in global oral health, with particular reference to the implementation of current best evidence as well as integrated action to reduce caries and health inequalities between and within countries. The Group determined that research should: integrate health and oral health wherever possible, using common risk factors; be able to respond to and influence international developments in health, healthcare, and health payment systems as well as dental prevention and materials; and exploit the potential for novel funding partnerships with industry and foundations. More effective communication between and among the basic science, clinical science, and health promotion/public health research communities is needed. Translation of research into policy and practice should be a priority for all. Both community and individual interventions need tailoring to achieve a more equal and person-centered preventive focus and reduce any social gradient in health. Recommendations are made for both clinical and public health implementation of existing research and for caries-related research agendas in clinical science, health promotion/public health, and basic science. PMID:21490233
A cadherin switch underlies malignancy in high-grade gliomas.
Appolloni, I; Barilari, M; Caviglia, S; Gambini, E; Reisoli, E; Malatesta, P
Although the infiltrative behavior of malignant gliomas is one of their most critical aspects, the mechanisms underlying it have not yet been elucidated. To migrate in the brain parenchyma, malignant glioma cells need to bypass the cell-cell contact inhibitory signals. Here we propose that the blinding of cell-cell contact sensing in gliomas is caused by an unusual mechanism of cadherin switch, involving the replacement of N-cadherin with R-cadherin (Rcad) at the cell-cell junctions and the activation of ERK and p27. In our model of malignant glioma, we found that Rcad expression is necessary and sufficient to release cells from contact inhibition of proliferation, and is necessary, although not sufficient, for overriding contact inhibition of migration and for tumorigenicity. Altogether, these observations suggest that Rcad is a potential target for malignant glioma therapies. PMID:24858041
Retooling Manganese(III) Porphyrin-Based Peroxynitrite Decomposition Catalysts for Selectivity and Oral Activity: A Potential New Strategy for Treating Chronic Pain
Rausaria, Smita; Ghaffari, Mahsa M.E.; Kamadulski, Andrew; Rodgers, Kenny; Bryant, Leesa; Chen, Zhoumou; Doyle, Tim; Shaw, Michael J.; Salvemini, Daniela; Neumann, William L.
Redox-active metalloporphyrins represent the most well characterized class of catalysts capable of attenuating oxidative stress in vivo through the direct interception and decomposition of superoxide and peroxynitrite. While many interesting pharmacological probes have emerged from these studies, few catalysts have been developed with pharmaceutical properties in mind. Herein we describe our efforts to identify new Mn(III)-porphyrin systems with enhanced membrane solubilizing properties. To this end seven new Mn(III)-tetracyclohexenylporphyin (TCHP) analogues 7, 10, 12, 15, 16a�c have been prepared in which the beta-fused cyclohexenyl rings provide a means to shield the charged metal center from the membrane during passive transport. Compounds 7, 15, and 16a�c have been shown to be orally active and potent analgesics in a model of carrageenan-induced thermal hyperalgesia. In addition oral administration of compound 7 (10�100 mg/kg, n = 5) has been shown to dose dependently reverse mechano-allodynia in the CCI model of chronic neuropathic pain. PMID:22082008
Occupational exposure and malignant lymphoma.
Persson, B
The incidence of malignant lymphoma, especially non-Hodgkin's lymphoma has increased over the last few decades. This statement is true despite the fact that methods for diagnosing malignant lymphoma have changed and misclassification has become a problem. The present review is mainly concerned with occupational aspects of malignant lymphoma. Several subsequent studies have dealt with malignant lymphoma among woodworkers and pulp and paper mill workers pointing to increased risks. Exposure to phenoxy herbicides have provided reasonable evidence to be connected with an increased risk of non-Hodgkin's lymphoma, whereas there is limited information regarding Hodgkin's disease. The relationship between solvent exposure and malignant lymphoma has been observed in a great number of studies. It is, however, still hard to identify specific solvent compounds responsible for the increased risk. Other occupational exposures i.e. wood preservatives, welding, asbestos, hair dyes and exposure to animal viruses among meatworkers and veterinarians have also been studied in relation to malignant lymphoma. This review shows that occupational factors, especially exposure to solvents and phenoxy herbicides and also to wood, play a role in the epidemiology of malignant lymphoma. PMID:9117190
Malignancy and chronic renal failure.
Peces, Ramon
Increased incidence of cancer at various sites is observed in patients with end-stage renal disease (ESRD). Certain malignant diseases, such as lymphomas and carcinomas of the kidney, prostate, liver and uterus, show an enhanced prevalence compared with the general population. In particular, renal cell carcinoma (RCC) shows an excess incidence in ESRD patients. A multitude of factors, directly or indirectly associated with the renal disease and the treatment regimens, may contribute to the increased tumor formation in these patients. Patients undergoing renal replacement therapy (RRT) are prone to develop acquired cystic kidney disease (ACKD), which may subsequently lead to the development of RCC. In pre-dialysis patients with coexistent renal disease, as in dialysis and transplant patients, the presence of ACKD may predispose to RCC. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse, are additional risk factors for malignancy. Malignancy following renal transplantation is an important medical problem during the follow-up. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. The type of malignancy is different in various countries and dependent on genetic and environmental factors. Finally, previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and post-malignancy screening. PMID:17657083
Hyperthermic treatment of cutaneous malignancies.
Draelos, Z K; Levine, N
Malignant cells are susceptible to high temperatures, and recent technical advances have allowed heat to be concentrated at the site of the neoplasm in vivo. The mechanism(s) of hyperthermic cytotoxicity is(are) unclear but may involve cellular accumulation of nuclear proteins, plasma membrane damage, and/or lysosomal effects. Three methods of localized hyperthermia delivery have been described: ultrasound, radiofrequency, and microwave. All involve production of high-energy save forms which are produced by passing electrical energy through an oscillator that produces heat of sufficient magnitude to cause tumor necrosis. Temperatures of at least 42 degrees C are necessary, but other factors, such as tissue pH, metabolic depletion, tissue hypoxia, and tumor vascularity, also influence cell killing. Hyperthermic treatment of cutaneous neoplasms may have great potential usefulness. Animal studies show high cure rates for squamous cell carcinoma with the use of radiofrequency hyperthermia. Human trials are needed before this technic can be considered suitable for clinical use. PMID:6355221
Noncoding RNAs in Endocrine Malignancy
Kentwell, Jessica; Gundara, Justin S.
Only recently has it been uncovered that the mammalian transcriptome includes a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. Among numerous kinds of ncRNAs, short noncoding RNAs, such as microRNAs, have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. Long noncoding RNAs (lncRNAs) have only recently been implicated in playing a key regulatory role in cancer biology. The deregulation of ncRNAs has been demonstrated to have important roles in the regulation and progression of cancer development. In this review, we describe the roles of both short noncoding RNAs (including microRNAs, small nuclear RNAs, and piwi-interacting RNAs) and lncRNAs in carcinogenesis and outline the possible underlying genetic mechanisms, with particular emphasis on clinical applications. The focus of our review includes studies from the literature on ncRNAs in traditional endocrine-related cancers, including thyroid, parathyroid, adrenal gland, and gastrointestinal neuroendocrine malignancies. The current and potential future applications of ncRNAs in clinical cancer research is also discussed, with emphasis on diagnosis and future treatment. PMID:24718512
Hypocalcaemia following thyroidectomy unresponsive to oral therapy.
Etheridge, Zac C; Schofield, Christopher; Prinsloo, Peter J J; Sturrock, Nigel D C
Hypocalcaemia due to hypoparathyroidism following thyroidectomy is a relatively common occurrence. Standard treatment is with oral calcium and vitamin D replacement therapy; lack of response to oral therapy is rare. Herein we describe a case of hypoparathyroidism following thyroidectomy unresponsive to oral therapy in a patient with a complex medical history. We consider the potential causes in the context of calcium metabolism including: poor adherence, hungry bone syndrome, malabsorption, vitamin D resistance, bisphosphonate use and functional hypoparathyroidism secondary to magnesium deficiency. Malabsorption due to intestinal hurry was likely to be a contributory factor in this case and very large doses of oral therapy were required to avoid symptomatic hypocalcaemia. PMID:24776629
Clinical diagnosis of oral erosive lichen planus by direct oral microscopy
Drogoszewska, Barbara; Polcyn, Adam; Michcik, Adam
Introduction Direct oral microscopy is a novel, non-invasive diagnostic technique that aids clinical examination of the oral cavity. The basic principles of this method derive from colposcopy and dermoscopy. The principle is to reveal precancerous lesions of oral mucosae in their subclinical phase in order to begin their treatment as early as possible and prevent malignant transformation. Oral lichen planus (OLP) is an autoimmune, inflammatory, chronic disease affecting oral mucous membranes. Buccal mucosae are most often affected. Aim To describe the in vivo picture of erosive OLP in direct oral microscopy in terms of the pattern and density of subepithelial blood vessels, surface texture, color, transparency and borders of the lesions. The study also demonstrates the utility of the method in the selection of the most appropriate biopsy site. Material and methods A total of 30 patients with erosive OLP were examined. Clinical examination of the oral cavity with the naked eye was performed, followed by direct oral microscopy. The most appropriate biopsy sites based on both examinations were chosen for every individual and biopsies were taken for histopathological evaluation. Results Biopsies obtained based on direct oral microscopy revealed dysplasia in 16 patients (53.3%). Biopsies obtained based on clinical examination with the naked eye revealed dysplasia in 3 cases (10%). Conclusions Direct oral microscopy makes it possible to obtain a repeated picture of erosive OLP and constitutes an alternative to the clinical examination with the naked eye in election of the most appropriate biopsy site. Thus, introduction of the most accurate and early therapy is possible. PMID:25254007
Malignant sigmoidoduodenal fistula
Shapey, I.M.; Mahmood, K.; Solkar, M.H.
INTRODUCTION Duodenocolic fistula is a rare complication of malignant colonic disease especially when involving and originating from the sigmoid colon. We aim to discuss the unusual clinical presentation of this case as well as the investigation and management of duodenocolic fistulas. PRESENTATION OF CASE A 91 year old lady presented as an emergency to a general surgical service at a District General Hospital with diarrhoea, vomiting and weight loss. Computed Tomography (CT) reported a large ovarian cyst elevating the sigmoid colon into immediate proximity of the duodenum. Adenocarcinoma was confirmed on histology obtained by colonoscopy. A classic apple core lesion with fistulating tract from the sigmoid colon to the duodenum was synchronously demonstrated on barium enema. DISCUSSION Sigmoido-duodenal fistulae represent a complex manifestation of gastrointestinal pathologies. CONCLUSION Management options must be considered in the context of patient wishes, their co-morbidities, and predicted post-operative outcome. In most cases this is likely to represent a non-operative approach, however surgical resection may benefit selected cases on occasion. PMID:25460456
DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia
Saintigny, Pierre; El-Naggar, Adel K.; Papadimitrakopoulou, Vali; Ren, Hening; Fan, You-Hong; Feng, Lei; Lee, J. Jack; Kim, Edward S.; Hong, Waun Ki; Lippman, Scott M.; Mao, Li
Purpose The risk of malignant transformation of oral preneoplastic lesion (OPL) is difficult to assess. DeltaNp63 is an early oncoprotein associated with mucosal tumorigenesis. The purpose of this study was to assess deltaNp63 expression in OPL and its role as a marker of oral cancer risk. Experimental Design DeltaNp63 expression was determined using immunohistochemistry in 152 OPL patients included in a clinical trial comparing retinyl palmitate alone or plus beta-carotene with low dose 13-cis retinoic acid. The associations between deltaNp63 expression as well as deltaNp63 expression with other potential risk factors for oral cancer development were analyzed. Results deltaNp63 expression was positive in 41 (27%) patients, clusters of intraepithelial inflammatory cells (EIC) were noted in 37 (26%) patients, and podoplanin (previously reported), was positive in 56 (37%) patients. Significantly more patients whose lesions were deltaNp63 positive or exhibited EIC developed oral cancers. In the multicovariate analysis including age, treatment, and histologic status as cofactors, positive deltaNp63 expression was associated with an increased hazard ratio of 3.308 (95% CI, 1.663 to 6.580; P=0.0007). Patients whose lesions showed positive deltaNp63, podoplanin, and EIC had the highest oral cancer risk with a hazard ratio of 4.372 (95% CI, 1.912 to 9.992; P=0.0005) and 61% oral cancer development rate at 5 years compared to 15% of other OPL patients (P<0.0001). Conclusion deltaNp63 overepression in OPL is associated with increased oral cancer risk. Together, deltaNp63, podoplanin, and EIC may be used as biomarkers to identify OPL patients with substantially high oral cancer risk. PMID:19773378
Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice
Liu, Menghua; Li, Panlin; Zeng, Xuan; Wu, Huanxian; Su, Weiwei; He, Jingyu
Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development. PMID:25751722
Oral lesions associated with human immunodeficiency virus disease.
Patton, Lauren L
Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications. PMID:24034072
Bruce F Barker; William M Carpenter; Troy E Daniels; Michael A Kahn; Alan S Leider; Francina Lozada-Nur; Denis P Lynch; Raymond Melrose; Philip Merrell; Thomas Morton; Edmund Peters; Joseph A Regezi; Susan D Richards; Gordon M Rick; Michael D Rohrer; Lee Slater; Jeffery C. B Stewart; Charles E Tomich; Robert A Vickers; Norman K Wood; Stephen K Young
A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in
James R. Marshall; Peter Boyle
Epidemiologic evidence on the relationship between nutrition and oral cancer is reviewed. Ecologic and case-control studies provide most of the evidence regarding the nutritional epidemiology of oral cancer. The ecologic evidence is that the considerable geographic variation in the incidence of oral cancer is consistent with variation in nutrition. Because incipient oral cancer is likely to affect the diets of
Drugs Approved for Malignant Mesothelioma
This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.
Development of a widefield reflectance and fluorescence imaging device for the detection of skin and oral cancer
NASA Astrophysics Data System (ADS)
Pratavieira, S.; Santos, P. L. A.; Bagnato, V. S.; Kurachi, C.
Oral and skin cancers constitute a major global health problem that cause great impact in patients. The most common screening method for oral cancer is visual inspection and palpation of the mouth. Visual examination relies heavily on the experience and skills of the physician to identify and delineate early premalignant and cancer changes, which is not simple due to the similar characteristics of early stage cancers and benign lesions. Optical imaging has the potential to address these clinical challenges. Contrast between normal and neoplastic areas may be increased, distinct to the conventional white light, when using illumination and detection conditions. Reflectance imaging can detect local changes in tissue scattering and absorption and fluorescence imaging can probe changes in the biochemical composition. These changes have shown to be indicatives of malignant progression. Widefield optical imaging systems are interesting because they may enhance the screening ability in large regions allowing the discrimination and the delineation of neoplastic and potentially of occult lesions. Digital image processing allows the combination of autofluorescence and reflectance images in order to objectively identify and delineate the peripheral extent of neoplastic lesions in the skin and oral cavity. Combining information from different imaging modalities has the potential of increasing diagnostic performance, due to distinct provided information. A simple widefiled imaging device based on fluorescence and reflectance modes together with a digital image processing was assembled and its performance tested in an animal study.
Physiological Approaches to the Control of Oral Biofilms
Philip D. Marsh; David J. Bradshaw
Evidence that physiological strategies may be potential routes for oral biofilm control has come from (i) observations of the variations in the intra-oral distribution of members of the resident oral microflora, (ii) changes in plaque composition in health and disease, and (iii) data from laboratory model systems. Key physiological factors that were identified as significant in modulating the microflora included
Mobile microbiome: oral bacteria in extra-oral infections and inflammation.
Han, Y W; Wang, X
The link between oral infections and adverse systemic conditions has attracted much attention in the research community. Several mechanisms have been proposed, including spread of the oral infection due to transient bacteremia resulting in bacterial colonization in extra-oral sites, systemic injury by free toxins of oral pathogens, and systemic inflammation caused by soluble antigens of oral pathogens. Mounting evidence supports a major role of the systemic spread of oral commensals and pathogens to distant body sites causing extra-oral infections and inflammation. We review here the most recent findings on systemic infections and inflammation complicated by oral bacteria, including cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, respiratory tract infections, and organ inflammations and abscesses. The recently identified virulence mechanisms of oral species Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Campylobacter rectus are also reviewed. A pattern emerges indicating that only select subtype(s) of a given species, e.g., F. nucleatum subspecies animalis and polymorphum and S. mutans non-c serotypes, are prone to extra-oral translocation. These findings advocate the importance of identification and quantification of potential pathogens at the subtype levels for accurate prediction of disease potential. PMID:23625375
Chapter Oral Health Advocates: A Nationwide Model for Pediatrician Peer Education and Advocacy about Oral Health
Lewis, Charlotte W.; Barone, Lauren; Quinonez, Rocio B.; Boulter, Suzanne; Mouradian, Wendy E.
Objective. (1) To describe an innovative program training US pediatricians to be Chapter Oral Health Advocates (COHAs). (2) To provide insight into COHAs' experiences disseminating oral health knowledge to fellow pediatricians. Patients and Methods. Interviews with 40 COHAs who responded to an email request, from a total of 64 (62% response). Transcripts were analyzed for common themes about COHA activities, facilitators, and barriers. Results. COHAs reported positive experiences at the AAP oral health training program. A subset of academic COHAs focused on legislative activity and another on resident education about oral health. Residents had an easier time adopting oral health activities while practicing pediatricians cited time constraints. COHAs provided insights into policy, barriers, and facilitators for incorporating oral health into practice. Conclusions. This report identifies factors influencing pediatricians' adoption of oral health care into practice. COHAs reported successes in training peers on integrating oral health into pediatric practice, identified opportunities and challenges to oral health implementation in primary care, and reported issues about the state of children's oral health in their communities. With ongoing support, the COHA program has a potential to improve access to preventive oral health services in the Medical Home and to increase referrals to a Dental Home. PMID:24228032
Basic and clinical aspects of malignant melanoma
Nathanson, L. (Health Sciences Center, State Univ. of New York at Stony Brook, Stony Brook, NY (US))
This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.
Malignant melanoma of breast: a unique case with diagnostic dilemmas.
Vasudevan, Jayasudha A; Somanathan, Thara; Mathews, Anitha; Kattoor, Jayasree
Melanomas arising in the skin, mucous membranes, and eye are encountered commonly than melanomas involving the breast. Melanomas in the breast are usually metastatic. Primary melanoma of the breast is extremely rare. We report a case of malignant melanoma of breast (primary/metastatic) that presented as a breast lump in a patient with no detectable cutaneous, mucosal or ocular lesion and who is a known case of squamous cell carcinoma of the oral cavity and had relapsed twice. The unexpected challenges faced during the diagnosis prompted us to report this case. PMID:24943768
Prognostic factors in malignant pleural mesothelioma.
Davidson, Ben
Malignant pleural mesothelioma (MPM) is a clinically aggressive tumor originating from mesothelial cells, which line the serosal cavities. Recent years have seen extensive research aimed at identifying new therapeutic targets, predictive markers and prognostic factors in this disease. These include both serum and tissue markers, and are related to multiple cellular pathways which affect cell survival, proliferation, apoptosis, angiogenesis, interaction with the immune response and DNA repair. Several of these molecules may become relevant for pathologists as part of the effort to select patient sub-populations for targeted therapy in the future. This review summarizes current data in this area and discusses their potential clinical relevance. PMID:25824607
Metastatic potential of melanoma cells is not affected by electrochemotherapy
Ljubljana, University of
Metastatic potential of melanoma cells is not affected by electrochemotherapy Vesna Todorovica in the treatment of malignant melanoma. However, the effect of electrochemotherapy on the metastatic potential of human malignant melanoma cells. Cells treated by electrochemotherapy with cisplatin were tested
Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
Ramage, Gordon; Milligan, Steven; Lappin, David F.; Sherry, Leighann; Sweeney, Petrina; Williams, Craig; Bagg, Jeremy; Culshaw, Shauna
Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and ?-terpineol, with an MIC50 of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and ?-terpineol displayed rapid kill kinetics. For all three compounds, 1?�?MIC50 effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2?h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1?�?MIC50, whereas at 0.5?�?MIC50 T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration. PMID:22719736
Expression of Proliferating Cell Nuclear Antigen (PCNA) in Oral Submucous Fibrosis: An Immunohistochemical Study
Keshav, Roopavathi
Background and objectives Expression of Proliferating Cell Nuclear Antigen (PCNA) well-correlates with the cell division. The suprabasal expression of PCNA is considered to be a marker of dysplastic oral mucosa indicating a special proliferative cellular state in those lesions. Oral submucous fibrosis (OSMF) is considered to be a premalignant condition with potential to get transformed into oral squamous cell carcinoma (OSCC). The present study was done to assess the PCNA expression in different grades and in different layers of epithelium of OSMF and to compare the expression of PCNA in OSMF with OSCC. Materials and Methods A group of 40 histopathologically diagnosed, formalin fixed, paraffin embedded tissue samples were included in study. The study group was further divided into 2 groups; 30 OSMF and 10 OSCC. Theses samples were collected from Department of Oral and Maxillofacial Pathology, Government Dental College and Research Institute, Bangalore. The samples were subjected to immunohistochemical method using indirect immunoenzyme LSAB method. Results All 40 cases showed positivity for PCNA. The percentage of positive cells was more in basal and suprabasal layer both in OSMF and OSCC, whereas the greater percentage of positive cells was seen in the superficial layer of OSCC. All OSMF cases showed positive expression in basal and suprabasal layer and only 77% of cases showed positive PCNA expression in the superficial layer with variable immunoreactivity and 23% did not show any positive staining in the superficial layer. The percentage of positive cells and the intensity of staining increased as the disease severity increased in OSMF. Conclusion Increased proportion of cells expressed PCNA staining which are in proliferative layers of OSMF. This biomarker provides an insight into the biological behaviour of the condition that substantiates its potentially malignant nature and may also provide an intermediate end point in chemotherapeutic trials.
Comparative evaluation of eosinophils in normal mucosa, dysplastic mucosa and oral squamous cell carcinoma with hematoxylin-eosin, Congo red, and EMR1 immunohistochemical staining techniques
kargahi, Neda; Razavi, Sayyed Mohammad; Deyhimi, Parviz; Homayouni, Solmaz
Background: Oral squamous cell carcinoma is the most common malignant lesion of the oral cavity, and it involves various molecular mechanisms. The development of oral squamous cell carcinoma is influenced by the host immune cells, such as eosinophils. The present study was conducted to compare the presence of eosinophils in normal mucosa, dysplastic mucosa, and oral squamous cell carcinoma by -hematoxylin- eosin staining, Congo red staining, and epidermal growth factor-like (EGF-like) module containing a mucin�like hormone receptor1 (EMR1) immunohistochemical marker. Methods: In this cross-sectional study, 60 paraffinized samples were selected, consisting of 20 normal mucosae, 20 dysplastic mucosae, and 20 squamous cell carcinoma samples. After confirmation of the diagnosis, the mean number of eosinophils was evaluated by hematoxylin-eosin, Congo red, and immunohystochemical staining techniques. The data were analyzed by SPSS-10 software using the Kruskal-Wallis and Friedman tests. Results: The results showed that the number of eosinophils in dysplastic mucosa was significantly higher than the number in normal mucosa, and the number of eosinophils in squamous cell carcinoma was significantly higher than the number in dysplastic mucosa in all staining techniques (p<0.001). Moreover, the comparison of staining techniques showed a significantly higher number of eosinophils in EMR1immunohistochemicalmarker than were observed when Congo red and hematoxylin - eosin (H&E) staining techniques were used (p<0.001). Conclusion: It can be argued that eosinophil contributes to the identification of lesions that have a higher potential of malignant transformation. Moreover, eosinophil can be suggested as an indicator in the differentiation of oral lesions in cases with borderline diagnosis and in targeted molecular therapy. PMID:26120409
Current concepts in malignant hyperthermia.
Finsterer, Josef
Malignant hyperthermia (MH) is a rare, potentially lethal, clinically and genetically heterogeneous pharmacogenic myopathy, which during or after general anesthesia manifests as MH crisis (MHC) in genetically predisposed, but otherwise mostly normal, individuals (MH susceptibles) in response to anesthetic-triggering agents. MHC can also occur in patients with central core disease. MCH-like crises have been reported in those with Duchenne/Becker muscular dystrophy, myotonic dystrophy, mitochondriopathy, and various other conditions. MH susceptibility is diagnosed if there is an MHC in the individual or family history or by the in vitro caffeine-halothane contracture test. Although screening for mutations in the ryanodine-receptor-1 gene and the dihydropyridine-receptor gene, respectively, could further substantiate the diagnosis, the caffeine-halothane-contracture test still remains the gold standard for diagnosing MH susceptibility. The most well-known triggers of an MHC are depolarizing muscle relaxants and volatile anesthetics. Therapy of an MHC comprises discontinuation of triggering agents, oxygenation, and correction of the acidosis and electrolyte disturbances, treatment of arrhythmias, cooling, and dantrolene. If MH susceptibility is not known preoperatively and an MHC unexpectedly interrupts anesthesia, consultation by a specialist in MH susceptibility after anesthesia is essential to investigate the patient for MH susceptibility or subclinical myopathy, guide laboratory investigations, manage therapy, and counsel the family on further risk. To further reduce morbidity and mortality of those with MHC, anesthesiologists and neurologists should be well educated and should strengthen their clinical vigilance. Research should be intensified and extended with regard to the development of new in vitro tests to further elucidate the heterogeneous genetic background of MH susceptibility. PMID:19078692
Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf
Jothy, Subramanion L.; Chen, Yeng; Kanwar, Jagat R.; Sasidharan, Sreenivasan
Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of???OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100??g/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000?mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats. PMID:23878610
Febrile neutropenia in hematologic malignancies.
Keng, Michael K; Sekeres, Mikkael A
Febrile neutropenia (FN) can occur at any time during the course of a malignancy, especially hematologic malignancies, from diagnosis to end-stage disease. The majority of FN episodes are typically confined to the period of initial diagnosis and active treatment. Because of suppressed inflammatory responses, fever is often the sole sign of infection. As FN is a true medical emergency, prompt identification of and intervention in FN can prolong survival and improve quality of life. This article reviews FN in the setting of hematologic malignancies, specifically myelodysplastic syndromes and acute leukemias, providing an overview of the definition of fever and neutropenia, diagnostic approach, categories of risk/risk assessment, management in patients at low and high risk, and prophylaxis of infections. PMID:23990311
Pollen grains for oral vaccination.
Atwe, Shashwati U; Ma, Yunzhe; Gill, Harvinder Singh
Oral vaccination can offer a painless and convenient method of vaccination. Furthermore, in addition to systemic immunity it has potential to stimulate mucosal immunity through antigen-processing by the gut-associated lymphoid tissues. In this study we propose the concept that pollen grains can be engineered for use as a simple modular system for oral vaccination. We demonstrate feasibility of this concept by using spores of Lycopodium clavatum (clubmoss) (LSs). We show that LSs can be chemically cleaned to remove native proteins to create intact clean hollow LS shells. Empty pollen shells were successfully filled with molecules of different sizes demonstrating their potential to be broadly applicable as a vaccination system. Using ovalbumin (OVA) as a model antigen, LSs formulated with OVA were orally fed to mice. LSs stimulated significantly higher anti-OVA serum IgG and fecal IgA antibodies compared to those induced by use of cholera toxin as a positive-control adjuvant. The antibody response was not affected by pre-neutralization of the stomach acid, and persisted for up to 7 months. Confocal microscopy revealed that LSs can translocate into mouse intestinal wall. Overall, this study lays the foundation of using LSs as a novel approach for oral vaccination. PMID:25151980
Environmental risk factors for primary malignant brain tumors: A review
Margaret Wrensch; Melissa L. Bondy; John Wiencke; Michael Yost
Conclusions This review suggests that existing theories of carcinogenesis provide much of the necessary framework for understanding the etiologies of malignant gliomas. Most of the environmental risk factors associated with brain tumors involve exposures to infectious, chemical, or physical agents capable of inflicting genetic damage. It is equally important to recognize that some potential risk factors for brain tumors, if
Metastases in the oral cavity. Case reports.
Bu?in, E; Andr�asson, L; Bj�rlin, G
4 cases of metastases in the oral cavity are described. They were seen in patients with carcinoma of the renal pelvis, renal carcinoma, breast carcinoma and malignant melanoma. In 3 of the cases, the metastases were situated distally to the canines in the mandible, where Roentgen examination had revealed a radiolucent area, and in the 4th case, in the soft tissue in the upper jaw. The initial symptoms in all 4 cases were swelling, pain or decreased sensitivity. The metastases were diagnosed, on average, 7 years after diagnosis of the primary tumour. PMID:6818172
Polichemotherapy of advanced head and neck malignancies.
Fazio, M; Cavallero, P; Minetto, E; Rattalino, P G; Sartoris, S
The favorable results obtained by other authors with polichemotherapy encouraged us to employ therapeutic scheme using a combination of 4 drugs. Treatment envolved the administration of 300 mg/mz cyclophosphamide, 350 mg/m2 5-fluorouracil, 10 mg/mw2 methotrexate i.v. on alternate days 6-8 times, and 15 mg bleomycin on alternate days until a total dose of 150-200 mg is reached. Thirty-five out of 37 patients treated with this protocol (30 previously treated and 5 not) qualified for analysis; the site of the neoplasm, mostly squamous cell carcinoma, was different; for the most part it was in the larynx (18/35) and the oral cavity (10/35). Complete remission was achieved in 9/35 patients (25.7%), varying from 5 to 33 months (median 22); partial remission was achieved in 15/35 cases (42.8%), varying from 1 to 14 months (median 3); and there was no success in 11/35 cases (31.5%). Overall, a total remission greater than 50% was observed in 24/35 patients (68.5%). The most serious side effects both ascribed to BLM were observed in the central nervous system (increasing drowsiness and coma) and the lung. This study has shown that in the ultra head and neck malignancies medical treatment can achieve satisfactory results. PMID:67688
Tissue engineering of oral mucosa: a shared concept with skin.
Kinikoglu, Beste; Damour, Odile; Hasirci, Vasif
Tissue-engineered oral mucosa, in the form of epithelial cell sheets or full-thickness oral mucosa equivalents, is a potential solution for many patients with congenital defects or with tissue loss due to diseases or tumor excision following a craniofacial cancer diagnosis. In the laboratory, it further serves as an in vitro model, alternative to in vivo testing of oral care products, and provides insight into the behavior of the oral mucosal cells in healthy and pathological tissues. This review covers the old and new generation scaffold types and materials used in oral mucosa engineering; discusses similarities and differences between oral mucosa and skin, the methods developed to reconstruct oral mucosal defects; and ends with future perspectives on oral mucosa engineering. PMID:25326194
Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K
Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment. PMID:26125159
[Pigmented lesions of the oral mucosa].
Beck-Mannagetta, J; Hutarew, G
The oral mucosa contains melanocytes, even though one might not suspect this when examining white subjects. Drug-induced pigmentation is usually irregularly distributed over the oral mucosa; typical causes are contraceptives and tetracyclines. Localized traumatic pigmentation can be due to injuries contaminated by foreign material (dust). Not infrequently an amalgam tattoo can be seen, caused by introduction of amalgam during dental treatment with rotating instruments. Focal melanosis is harmless. Neoplastic pigmentation is rare. Melanotic nevi are small with indistinct borders. Malignant melanoma occurs predominantly on the maxilla or hard palate. Frequently it has already metastasized by the time of diagnosis. Verification by biopsy is essential if a lesion has suddenly appeared, is extensive, elevated, with irregular pigmentation and has no obvious cause. PMID:22956033
Floyd E. Dewhirst; Erin A. Klein; Emily C. Thompson; Jessica M. Blanton; Tsute Chen; Lisa Milella; Catherine M. F. Buckley; Ian J. Davis; Marie-Lousie Bennett; Zoe V. Marshall-Jones
Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S
The Consequences of Tongue Piercing on Oral and Periodontal Tissues
Sakellari, Dimitra
This paper is discussing the potential consequences that may arise by the implementation of piercing in the oral cavity and is also categorizing the consequences according to their extent and severity. Furthermore, this paper is reviewing some possible oral hygiene methods that can prove to be auxiliary in decreasing the potential complications arising from oral piercing. This literature review is based on articles published from 1985 to 2012. PMID:24616814
Oral and sublingual immunotherapy
Burks, Wesley
Allergic diseases have continued to increase throughout the developed world. Subcutaneous immunotherapy has been a mainstay of treatment for allergic rhinitis and asthma, however, some patients are precluded from treatment. On the other hand, in the case of food allergy, treatments simply do not exist. Oral and sublingual immunotherapy, with its superior safety and ease of administration, offers an alternative for patients with allergic rhinitis and asthma and has also been promising as a potential treatment for food allergy. The review summarizes significant advances from the past year including further data on the effectiveness of existing treatments, preliminary data on novel treatments, and further understanding of the mechanisms of these new therapies. PMID:25133094
Rapid-developed primary malignant myoepithelioma in the cavernous sinus: a case report
Background Malignant myoepithelioma is a relatively rare malignant tumor occurring most frequently in the salivary glands. A few isolated cases have been described in other locations, including soft tissue, bone, lung, bronchus, oral cavity, nasopharynx, larynx, and maxillary sinus. Malignant myoepithelioma, however, is uncommonly involved within the cavernous sinus. To the best of our knowledge, this is the first report of malignant myoepithelioma arising from within the cavernous sinus. Case presentation Herein, we report a case of a 48-year-old woman who presented a 1-month history of diplopia and blepharoptosis as well as radiological evidence of a rapidly developing cavernous sinus tumor. The patient underwent a trans-sphenoidal biopsy and a histological diagnosis indicated a malignant myoepithelioma. After diagnosis, the tumor grew rapidly and her clinical condition deteriorated progressively. Therefore, a pterional craniotomy with partial tumor removal was performed. The patient�s clinical state was worsened, and she died two months after the initial operation. Because the malignant myoepithelioma could not be traced to an organ of origin, other than the cavernous sinus, this case was diagnosed as a primary intracranial malignant myoepithelioma. Conclusion The purpose of presenting this case report is to raise awareness among clinicians to consider malignant myoepithelioma as a differential diagnosis when a cavernous sinus mass is identified. Furthermore, an ideal management strategy for malignant myoepithelioma is not known and the prognosis seems to be unfavorable; therefore, more cases are needed to enhance our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion. PMID:23642050
Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies
Blumel, Susan; Broadway-Duren, Jackie
Lenalidomide is an oral immunomodulatory agent approved in relapsed multiple myeloma with dexamethasone, for transfusion-dependent anemia in myelodysplastic syndrome associated with deletion 5q, and in relapsed/progressive mantle cell lymphoma following bortezomib. In recent clinical trials, lenalidomide has shown promising activity in hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Starting doses and dosing schedules vary by malignancy, with lenalidomide started at a lower dose for CLL than for NHL or multiple myeloma. Certain adverse events (AEs) are common across tumor types (e.g., neutropenia, thrombocytopenia, fatigue), whereas others are more often associated with CLL patients (e.g., tumor lysis syndrome and tumor flare reaction). Effective management requires awareness of these differences as well as appropriate prophylaxis, monitoring, and treatment of AEs. This article reviews the efficacy and safety of lenalidomide in CLL and NHL, focusing on approaches for the advanced practitioner to improve patient quality of life through optimal management of side effects. With these steps, lenalidomide can be administered safely, at the best starting doses and with minimal dose interruptions or reductions across hematologic malignancies.
Malignant mesothelioma of the pleura
A. Calavrezos; G. Koschel; H. Hfisselmann; A. Taylessani; H.-P. Heilmann; H. Fabel; H.-J. Schmoll; H. Dietrich; E. Hain
Summary Between March 1981 and February 1985, 93 out of 132 patients with a histologically confirmed diagnosis of malignant pleural mesothelioma were eligible for therapy and were prospectively assigned to receive either combined therapy or best supportive care, according to their personal preferences. Fifty-seven patients underwent multimodal therapy including surgical resection where possible, polychemotherapy, and radiation therapy in case of
Management of paranasal sinus malignancy.
Day, Terry A; Beas, Ricardo A; Schlosser, Rodney J; Woodworth, Bradford A; Barredo, Julio; Sharma, Anand K; Gillespie, M Boyd
Malignancies of the nasal cavity and paranasal sinuses represent a wide spectrum of histologies, tissues of origin, and anatomic primary sites. The inherent difficulty in generalizing treatment approaches is obvious, given the numerous variables associated with the broadly-based term, paranasal sinus malignancy (PNSCa). Nevertheless, the majority of epithelial and salivary malignancies of this region (ie, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, sinonasal undifferentiated carcinoma, and esthesioneuroblastoma) require surgical intervention as part of any treatment regimen. Recent trends have broadened the indications for chemotherapeutic and radiotherapeutic options in the management of advanced PNSCa. Nonepithelial malignancies, including the wide variety of sarcomas arising in this region, most commonly require multimodality treatment including chemotherapy, radiation, and/or surgery for definitive treatment. Moreover, the proximity of the nasal cavity and paranasal sinuses to structures including the orbit, dura, brain, cranial nerves, and carotid arteries mandates careful radiologic and neurologic evaluations throughout the course of the disease. Surgical advances now permit complex tumor removal and reconstruction surrounding these structures resulting in functional and cosmetic improvements when compared to earlier techniques. However, additional clinical trials are necessary to systematically evaluate the locoregional control, organ-preservation strategies, and survival related to the variety of treatments currently available. PMID:15610711
Skin Manifestations of Internal Malignancy
Donsky, Howard J.
Although some of the skin manifestations of internal malignancy are relatively rare, their identification may often be made at a crucial time, when intervention may save a life. This article classifies such signs and describes those which may be seen in family practice. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:21301498
The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis
Sun, Xiao-Jian; Man, Na; Tan, Yurong; Nimer, Stephen D.; Wang, Lan
Histone, and non-histone, protein acetylation plays an important role in a variety of cellular events, including the normal and abnormal development of blood cells, by changing the epigenetic status of chromatin and regulating non-histone protein function. Histone acetyltransferases (HATs), which are the enzymes responsible for histone and non-histone protein acetylation, contain p300/CBP, MYST, and GNAT family members. HATs are not only protein modifiers and epigenetic factors but also critical regulators of cell development and carcinogenesis. Here, we will review the function of HATs such as p300/CBP, Tip60, MOZ/MORF, and GCN5/PCAF in normal hematopoiesis and the pathogenesis of hematological malignancies. The inhibitors that have been developed to target HATs will also be reviewed here. Understanding the roles of HATs in normal/malignant hematopoiesis will provide the potential therapeutic targets for the hematological malignancies. PMID:26075180
Serologic laboratory findings in malignancy.
Madrid, F�lix Fern�ndez; Maroun, Marie-Claire
Autoantibodies are extremely promising diagnostic and prognostic biomarkers of cancer, and have the potential to promote early diagnosis and to make a large impact by improving patient outcome and decreasing mortality. Moreover, autoantibodies may be useful reagents in the identification of subjects at risk for cancer, bearing premalignant tissue changes. Great efforts are being made in many laboratories to validate diagnostic panels of autoantibodies with high sensitivity and specificity that could be useful in a clinical setting. It is likely that prospective studies of sufficiently large cohorts of patients and controls using high-throughput technology may allow the identification of biomarkers with diagnostic significance, and perhaps of discrete antigen phenotypes with clinical significance. The identification of TAAs may also be essential for the development of anticancer vaccines, because autoantibodies found in cancer sera target molecules involved in signal transduction, cell-cycle regulation, cell proliferation, and apoptosis, playing important roles in carcinogenesis. On this basis, molecular studies of antigenantibody systems in cancer promise to yield valuable information on the carcinogenic process. TAAs identified by serum antibodies in cancer sera can be natural immunogenic molecules, useful as targets for cancer immunotherapy. An important problem encountered in the practice of medicine is the identification of healthy individuals in the general population who unknowingly are at high risk of developing cancer. For the rheumatologist, a related problem is the identification of those patients with rheumatic diseases who are at high risk for developing a malignant process. These problems encountered in the fields of cancer and the rheumatic diseases can in the future be helped by new diagnostic instruments based on antibodies. The need for promoting the early diagnosis of cancer is a recognized major public health problem in need of significant research support for the validation of multiple promising but inconclusive studies, with the intention of producing diagnostic panels of autoantibodies in various types of cancers. Cancer developing in patients with rheumatic diseases is also an important problem requiring prospective longterm follow-up studies of patients with rheumatic diseases, particularly because some of the new biologic therapies seem to increase the cancer risk. It is possible that a panel of autoantibodies common to patients with cancer and the rheumatic diseases may prove to be of value in the identification of those patients with ADs at high risk for neoplasms. PMID:22075195
Inhibition of autophagy overcomes glucocorticoid resistance in lymphoid malignant cells.
Jiang, Lei; Xu, Lingzhi; Xie, Jiajun; Li, Sisi; Guan, Yanchun; Zhang, Yan; Hou, Zhijie; Guo, Tao; Shu, Xin; Wang, Chang; Fan, Wenjun; Si, Yang; Yang, Ya; Kang, Zhijie; Fang, Meiyun; Liu, Quentin
Glucocorticoid (GC) resistance remains a major obstacle to successful treatment of lymphoid malignancies. Till now, the precise mechanism of GC resistance remains unclear. In the present study, dexamethasone (Dex) inhibited cell proliferation, arrested cell cycle in G0/G1-phase, and induced apoptosis in Dex-sensitive acute lymphoblastic leukemia cells. However, Dex failed to cause cell death in Dex-resistant lymphoid malignant cells. Intriguingly, we found that autophagy was induced by Dex in resistant cells, as indicated by autophagosomes formation, LC3-I to LC3-II conversion, p62 degradation, and formation of acidic autophagic vacuoles. Moreover, the results showed that Dex reduced the activity of mTOR pathway, as determined by decreased phosphorylation levels of mTOR, Akt, P70S6K and 4E-BP1 in resistant cells. Inhibition of autophagy by either chloroquine (CQ) or 3-methyladenine (3-MA) overcame Dex-resistance in lymphoid malignant cells by increasing apoptotic cell death in vitro. Consistently, inhibition of autophagy by stably knockdown of Beclin1 sensitized Dex-resistant lymphoid malignant cells to induction of apoptosis in vivo. Thus, inhibition of autophagy has the potential to improve lymphoid malignancy treatment by overcoming GC resistance. PMID:25778879
Liver transplantation for malignancy: Current treatment strategies and future perspectives
Hackl, Christina; Schlitt, Hans J; Kirchner, Gabriele I; Knoppke, Birgit; Loss, Martin
In 1967, Starzl et al performed the first successful liver transplantation for a patient diagnosed with hepatoblastoma. In the following, liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic malignancies. Several reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon dismissed. In 1996, Mazzaferro et al introduced the Milan criteria, offering liver transplantation to patients diagnosed with limited hepatocellular carcinoma. Since then, liver transplantation for malignant disease is an ongoing subject of preclinical and clinical research. In this context, several aspects must be considered: (1) Given the shortage of deceased-donor organs, long-term overall and disease free survival should be comparable with results obtained in patients transplanted for non-malignant disease; (2) In this regard, living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice; and (3) Ongoing research focusing on perioperative therapy and anti-proliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall survival. The present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease. PMID:24833863
Successful oral acyclovir desensitization.
Henry, R E; Wegmann, J A; Hartle, J E; Christopher, G W
A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy. Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity. Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity. Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens. Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity. This report is an example of acyclovir hypersensitivity and successful oral desensitization. PMID:8498729
Animal models of malignant mesothelioma.
Kane, Agnes B
Animal models of diffuse malignant mesothelioma have historically been used to assess carcinogenicity of various fiber types and to study the pathogenesis of this unusual neoplasm. Pleural and peritoneal mesotheliomas have been induced in rodents following exposure to erionite or asbestos fibers, radionuclides, particulate nickel compounds, and chemicals such as 3-methylcholanthrene. The role of SV40 virus as a cofactor with asbestos fibers in the development of diffuse malignant mesotheliomas in humans has been explored in animal models. SV40 virus alone induces mesotheliomas in hamsters. Generation of new transgenic mouse strains with targeted expression of SV40 large T and small t antigens in the mesothelium would be very useful for mechanistic studies. Human malignant mesotheliomas frequently show hypermethylation or deletions at the Cdkn2a/Arf and Cdkn2b gene loci and deletions or mutations at the NF2 gene locus. Heterozygous Nf2 (+/-) mice exposed to crocidolite asbestos fibers exhibited accelerated development of malignant mesotheliomas compared to wild-type littermates. Loss of the wild-type Nf2 allele, leading to biallelic inactivation, was observed in nine mesothelioma cell lines derived from Nf2 (+/-) mice. Similar to human malignant mesotheliomas, tumors from Nf2 (+/-) mice showed frequent homozygous deletions of the Cdkn2a/Arf locus and adjacent Cdkn2b tumor suppressor gene. As in the human disease, murine mesotheliomas also showed constitutive activation of Akt. This murine model of asbestos carcinogenesis recapitulates the molecular and histopathological features of the human disease and has significant implications for preclinical testing of novel preventive or therapeutic modalities. PMID:16920675
Prebiotics and Probiotics and Oral Health
NASA Astrophysics Data System (ADS)
Meurman, J. H.
The first part of this chapter describes the unique characteristics of the mouth with special emphasis on the oral microbiota. Next, the highly prevalent dental diseases are briefly described together with more rare but still important diseases and symptoms of the mouth. Prevention and treatment of oral and dental diseases are also discussed focusing on aspects considered important with respect to the potential application of prebiotics and probiotics. The second part of the chapter then concentrates on research data on prebiotics and probiotics in the oral health perspective, ending up with conclusions and visions for future research.
Sensitivity of Malignant Peripheral Nerve Sheath Tumor Cells to TRAIL Is Augmented by Loss of NF1 through Modulation of MYC/MAD and Is Potentiated by Curcumin through Induction of ROS
Reuss, David E.; Mucha, Jana; Hagenlocher, Christian; Ehemann, Volker; Kluwe, Lan; Mautner, Victor; von Deimling, Andreas
Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS. PMID:23437333
The Malignant Cell and Its Membranes
Warren, Leonard
In this brief review the hypothesis that altered membrane proteins and glycoproteins may be critical mediators of malignant expression is discussed. Examples of alterations of membrane proteins in malignancy are presented. Data is summarized showing changes in the carbohydrate components of glycoproteins of surface and internal membranes of malignant cells in culture as compared to their normal counterparts. PMID:4374888
Renal cell carcinoma presenting with malignant ascites
Wathuge, Gayathri W; Gorard, David A
Lesson It is rare for renal cell carcinoma to involve the peritoneum and cause malignant ascites. Furthermore, it is uncommon for malignant ascites to be a presenting feature of this cancer. An unusual case of renal cell carcinoma presenting with malignant ascites is reported, and its response to sunitinib described. PMID:25973217
Congenital malignant rhabdoid tumor of the orbit
D. Brian Stidham; Richard A. Burgett; Mary M. Davis; David A. Plager
Malignant rhabdoid tumor is a rare and highly malignant renal tumor of infancy. Extrarenal tumors involving the orbit have been reported, but never at birth.1-5 The authors describe a primary malignant rhabdoid tumor of the orbit in a neonate who had massive unilateral proptosis at birth. Clinical, radiographic, and histologic features of the tumor are discussed.
Oral cancer detection using diffuse reflectance spectral ratio R540/R575 of oxygenated hemoglobin bands
NASA Astrophysics Data System (ADS)
Subhash, N.; Mallia, J. R.; Thomas, S. S.; Mathews, A.; Sebastian, P.; Madhaven, J.
A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of oral mucosa based on diffuse reflectance spectral signatures is presented. In this technique, output of a tungsten halogen lamp is guided to the tissue through the central fiber of a reflection probe whose surrounding six fibers collects tissue reflectance. Ex vivo diffuse reflectance spectra in the 400 to 600-nm region is measured from surgically removed oral cavity lesions using a miniature fiber optic spectrometer connected to a computer. Reflectance spectral intensity is higher in malignant tissues and shows dips at 542 and 577 nm owing to absorption from oxygenated hemoglobin (HbO2). Measurements carried out, within an hour of surgical excision, on malignant lesion and adjoining uninvolved mucosa show that these absorption features are more prominent in neoplastic tissues owing to increased microvasculature and blood content. It is observed that reflectance intensity ratio of hemoglobin bands, R540/R575, from malignant sites are always lower than that from normal sites and vary according to the histological grade of malignancy. The diffuse reflectance intensity ratio R540/R575 of the hemoglobin bands appears to be a useful tool to discriminate between malignant lesions and normal mucosa of the oral cavity in a clinical setting.
Malignant Mucosal Melanoma of the Head and Neck Diagnosed in an Iranian Population over an 11Year Period
Maryam Assadat Hashemi Pour; M. Rad; M. R. Zarei; G. Chamani
Problem statement: Mucosal Melanoma of the Head and Neck (MMHN) is a rare lethal disease. This malignancy accounts for half of all m ucosal melanomas, occurring mainly in the nasal cavity, oral cavity and pharynx. They appear with e qual gender distribution and with a peak incidence in the age range 60-80 years. The aim of this study was to
Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer
Sharma, Neha; Om, Hari
In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN) for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer. PMID:26171415
Oralidad, narraci�n oral y narraci�n oral esc�nica
Garzó n Cé spedes, Francisco
narrador oral esc�nico y del p�blico como interlocutores. Tambi�n analizan la narraci�n oral como una de las formas de hipnosis alternativa. Y se detienen en la T�cnica: C�mo seleccionar el cuento, C�mo analizarlo, C�mo interiorizarlo y apropi�rselo para..., sabidur�a, estimulaci�n, provocaci�n, humildad, indefensi�n, transparencia; un acto de hipnosis alternativa, de belleza, audacia, pureza, indagaci�n, lealtad, justicia, libertad, dignificaci�n, solidaridad, amistad y amor. La oralidad, por tanto...
A Computer-Aided Distinction Method of Borderline Grades of Oral Cancer
NASA Astrophysics Data System (ADS)
Sami, Mustafa M.; Saito, Masahisa; Muramatsu, Shogo; Kikuchi, Hisakazu; Saku, Takashi
We have developed a new computer-aided diagnostic system for differentiating oral borderline malignancies in hematoxylin-eosin stained microscopic images. Epithelial dysplasia and carcinoma in-situ (CIS) of oral mucosa are two different borderline grades similar to each other, and it is difficult to distinguish between them. A new image processing and analysis method has been applied to a variety of histopathological features and shows the possibility for differentiating the oral cancer borderline grades automatically. The method is based on comparing the drop-shape similarity level in a particular manually selected pair of neighboring rete ridges. It was found that the considered similarity level in dysplasia was higher than those in epithelial CIS, of which pathological diagnoses were conventionally made by pathologists. The developed image processing method showed a good promise for the computer-aided pathological assessment of oral borderline malignancy differentiation in clinical practice.
Oral Melanoacanthoma of a Rare Intraoral Site: Case Report and Review of Literature
Ramesh, V; Balamurali, PD; Singh, Namrata
ABSTRACT Oral melanoacanthoma is rare pigmented mucosal lesion that presents most commonly on the buccal mucosa, characterized by sudden appearance and rapid radial growth, thus clinically mimicking malignant melanoma. It was originally described as a mixed tumor of melanocytes and keratinocytes, but appears to be a reactive process; formed in areas prone to trauma, and regressing after the removal of trauma or incomplete excision. The clinical appearance of oral melanoacanthoma is nondiagnostic, and biopsy is mandatory to rule out malignancy. We report a case of melanoacanthoma of a rarer oral mucosal site in a 12-year-old Asian male. A brief review of the current literature is also presented. How to cite this article: Rohilla K, Ramesh V, Balamurali PD, Singh N. Oral Melanoacanthoma of a Rare Intraoral Site: Case Report and Review of Literature. Int J Clin Pediatr Dent 2013;6(1):40-43. PMID:25206187
Colposcopy - A Novel Diagnostic Technique for Oral Mucosal Lesions
Shankar, Y Uday; Prakash, Sathya; Radhika, B; Fatima, Nikhat
The incidence of premalignant lesions and oral cancers is steadily increasing globally. In spite of advancement in early detection, there is increased mortality and morbidity related to oral cancers. The diagnosis of a dysplastic premalignant lesion of the oral mucosa cannot be based solely on clinical findings. Therefore histologic evaluation of a representative biopsy specimen is necessary. Therefore, the selection for a biopsy site is highly significant. In this article, we present a current review of the colposcope and oral application of the colposcopy technique and its use as an adjunct in the early diagnosis of premalignant and malignant lesions of the oral mucosa. We stress upon the fact that colposcopy (direct oral microscopy) of oral mucosal lesions helps in selecting more representative sites for biopsy than routine clinical examination alone. Because of its precision, versatility, ease of use, and being a non-invasive technique, colposcopy might prove to be a useful step toward continuing to learn and improve the care for our patients. PMID:25478477
Colposcopy - a novel diagnostic technique for oral mucosal lesions.
Kumar, Ashwini; Shankar, Y Uday; Prakash, Sathya; Radhika, B; Fatima, Nikhat
The incidence of premalignant lesions and oral cancers is steadily increasing globally. In spite of advancement in early detection, there is increased mortality and morbidity related to oral cancers. The diagnosis of a dysplastic premalignant lesion of the oral mucosa cannot be based solely on clinical findings. Therefore histologic evaluation of a representative biopsy specimen is necessary. Therefore, the selection for a biopsy site is highly significant. In this article, we present a current review of the colposcope and oral application of the colposcopy technique and its use as an adjunct in the early diagnosis of premalignant and malignant lesions of the oral mucosa. We stress upon the fact that colposcopy (direct oral microscopy) of oral mucosal lesions helps in selecting more representative sites for biopsy than routine clinical examination alone. Because of its precision, versatility, ease of use, and being a non-invasive technique, colposcopy might prove to be a useful step toward continuing to learn and improve the care for our patients. PMID:25478477
Biomarkers and chemopreventives in oral carcinogenesis and its prevention
Shah, Sonalee; Kaur, Manpreet
Squamous cell carcinoma is the predominant type of oral malignancy and is a result of oral carcinogenesis. Oral carcinogenesis is a mutifactorial and complex process related to the sequential occurrence of alterations in genetic structures, promoting inhibitory or excitatory effects of the tumor oncogenes and gene suppressors, compromising the histophysiology of the division, differentiation and cell death; and therefore, methods to prevent, detect, or treat it in the best way is constantly being searched for. Biomarkers reveal the genetic and molecular changes related to early, intermediate and late endpoints in the process of oral carcinogenesis. Thereby, they are likely to not only refine our ability to predict the biologic course of oral cancer and distinguish individuals at high and/or low risk of oral cancer development; but, also they will also reveal the genetic and molecular changes related to various endpoints of oral carcinogenesis. Chemopreventives are chemicals of natural or synthetic origin, which reduce the incidence of fatal diseases such as cancer before clinical symptoms occur. Chemopreventives are agents whose curative capacity is defined with help of biomarkers, as the later determine the effectiveness and safety of chemopreventives. PMID:24959040
Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; a potential graft-polymeric carrier for oral delivery of 5-fluorouracil
Background of the Study The propose of the present work was to develop chemically cross-linked polyvinyl alcohol-co-poly(methacrylic acid) hydrogel (PVA-MAA hydrogel) for pH responsive delivery of 5-Fluorouracil (5-FU). Methods PVA based hydrogels were prepared by free radical copolymerization. PVA has been cross-linked chemically with monomer (methacrylic acid) in aqueous medium, cross-linking agent was ethylene glycol di-methacrylate (EGDMA) and benzoyl peroxide was added as reaction initiator. 5-FU was loaded as model drug. FTIR, XRD, TGA and DSC were performed for characterization of copolymer. Surface morphology was studied by SEM. pH sensitive properties were evaluated by swelling dynamics and equilibrium swelling ratio at low and higher pH. Results FTIR, XRD, TGA and DSC studies confirmed the formation of new copolymer. Formulations with higher MAA contents showed maximum swelling at 7.4 pH. High drug loading and higher drug release has been observed at pH 7.4. Conclusions The current study concludes that a stable copolymeric network of PVA was developed with MAA. The prepared hydrogels were highly pH responsive. This polymeric network could be a potential delivery system for colon targeting of 5-FU in colorectal cancers. PMID:23721569
A Review of the Nonsurgical Treatment of Oral Leukoplakia
Ribeiro, Adriana Spinola; Salles, Patr�cia Ribeiro; da Silva, Tarc�lia Aparecida; Mesquita, Ricardo Alves
The aim of this paper was to assess the nonsurgical treatment of oral leukoplakia (OL). A medline search from 1983 to 2009 was conducted. The topical or systemic nonsurgical treatments or combination of both was reviewed. The primary outcomes of interest were clinical resolution, malignant transformation, follow-up, and recurrence of OL. Studies showed a rate higher than 50% of clinical resolution with photodynamic therapy, beta-carotene, lycopene, or vitamin A. Few studies reported rates of recurrence from 5 to 67% and of malignant transformation from 8 to 23%. There is a lack of randomized clinical trials that assess the effectiveness of nonsurgical treatment of OL. At this time, randomized controlled trials for nonsurgical treatment of OL demonstrate no evidence of effective treatment in preventing malignant transformation and recurrence. It reinforces that even after clinical resolution, OL should be regularly followed. PMID:20339486
Gene therapy for hematological malignancies
G. D. Schmidt-Wolf; I. G. H. Schmidt-Wolf
.�� Since cancer is the result of genetic mutations, it should be well suited for correction through gene therapy. Hematological\\u000a malignancies in which human gene transfer has been performed are leukemias, lymphomas, graft-versushost disease after allogeneic\\u000a bone marrow transplantation in leukemia, and multiple myeloma. Gene therapy may be used to induce or enhance an antitumor\\u000a immunological reaction, to correct a
Comparative study between the Hybrid Capture II test and PCR based assay for the detection of human papillomavirus DNA in oral submucous fibrosis and oral squamous cell carcinoma
Ajay Kumar Chaudhary; Shruti Pandya; Ravi Mehrotra; Alok C Bharti; Mangal Singh; Mamta Singh
BACKGROUND: Oral malignancy is a major global health problem. Besides the main risk factors of tobacco, smoking and alcohol, infection by human papillomavirus (HPV) and genetic alterations are likely to play an important role in these lesions. The purpose of this study was to compare the efficacy of HC-II assay and PCR for the detection of specific HPV type (HPV
High dose fraction radiotherapy for mucosal malignant melanoma of the head and neck
Xiuying Liu; Huiling Li; Tianrong Zheng; Xiangsong Lin
Objective: To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck\\u000a (HNMM). Methods: From 1984�1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the\\u000a nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6�8 Gy\\/fraction)\\u000a with the
Silibinin Inhibits Invasion of Oral Cancer Cells by Suppressing the MAPK Pathway
P.-N. Chen; Y.-S. Hsieh; C.-L. Chiang; H.-L. Chiou; S.-F. Yang; S.-C. Chu
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Here, we provide molecular evidence associated with the anti-metastatic effect of silibinin by showing a marked inhibition of the invasion and motility of SCC-4 tongue cancer cells, with 89% and 66.4% of inhibition, respectively, by 100 ?M of silibinin. This effect was associated with a reduced
Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model
A. Monti Hughes; ECC Pozzi; S. Thorp; M. A. Garabalino; R. O. Farias; S. J. Gonzalez; E. M. Heber; M. E. Itoiz; R. F. Aromando; A. J. Molinari; M. Miller; D. W. Nigg; P. Curotto; V. A. Trivillin; A. E. Schwint
Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.
Blood cells transcriptomics as source of potential biomarkers of articular health improvement: effects of oral intake of a rooster combs extract rich in hyaluronic acid.
S�nchez, Juana; Bonet, M Luisa; Keijer, Jaap; van Schothorst, Evert M; M�lller, Ingrid; Chetrit, Carles; Martinez-Puig, Daniel; Palou, Andreu
The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65�%) from rooster comb (Mobilee� as commercial name) for 90�days. Effects on functional quality-of-life parameters related to joint health were assessed. Whole-genome microarray analysis of peripheral blood samples from a subset of 20 subjects (10 placebo and 10 supplemented) collected pre- and post-intervention was performed. Mobilee� supplementation reduced articular pain intensity and synovial effusion and improved knee muscular strength indicators as compared to placebo. About 157 coding genes were differentially expressed in blood cells between supplemented and placebo groups post-intervention, but not pre-intervention (p�<�0.05; fold change ?1.2). Among them, a reduced gene expression of glucuronidase-beta (GUSB), matrix metallopeptidase 23B (MMP23B), xylosyltransferase II (XYLT2), and heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) was found in the supplemented group. Correlation analysis indicated a direct relationship between blood cell gene expression of MMP23B, involved in the breakdown of the extracellular matrix, and pain intensity, and an inverse relationship between blood cell gene expression of HS6ST1, responsible for 6-O-sulfation of heparan sulfate, and indicators of knee muscular strength. Expression levels of specific genes in blood cells, in particular genes related to GAG metabolism and extracellular matrix dynamics, are potential biomarkers of beneficial effects on articular health. PMID:25024048
Comparative effectiveness in hepatic malignancies.
Page, Andrew J; Cosgrove, David; Pawlik, Timothy M
The benefits of applying comparative effectiveness research (CER) strategies to the management of cancer are important. As the incidence of cancer increases both in the United States and worldwide, accurate analysis of which tests and treatments should be applied in which situations is critical, both in terms of measurable and meaningful clinical outcomes and health care costs. In the last 20 years alone, multiple controversies have arisen in the diagnosis and treatment of primary and metastatic tumors of the liver, making the management of liver malignancies a prime example of CER. Contributing factors to the development of these controversies include improvements in molecular characterization of these diseases and technological advances in surgery and radiology. The relative speed of these advances has outpaced data from clinical trials, in turn making robust data to inform clinical practice lacking. Indeed, many of the current treatment recommendations for the management of liver malignancies are based primarily on retrospective data. We herein review select CER issues concerning select decision-making topics in the management of liver malignancies. PMID:25677025
Immunotherapy of malignant brain tumors
Mitchell, Duane A.; Fecci, Peter E.; Sampson, John H.
Summary Despite aggressive multi-modality therapy including surgery, radiation, and chemotherapy, the prognosis for patients with malignant primary brain tumors remains very poor. Moreover, the non-specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissues. Thus, there is an urgent need for the development of therapeutic strategies that precisely target tumor cells while minimizing collateral damage to neighboring eloquent cerebral cortex. The rationale for using the immune system to target brain tumors is based on the premise that the inherent specificity of immunologic reactivity could meet the clear need for more specific and precise therapy. The success of this modality is dependent on our ability to understand the mechanisms of immune regulation within the central nervous system (CNS), as well as counter the broad defects in host cell-mediated immunity that malignant gliomas are known to elicit. Recent advances in our understanding of tumor-induced and host-mediated immunosuppressive mechanisms, the development of effective strategies to combat these suppressive effects, and a better understanding of how to deliver immunologic effector molecules more efficiently to CNS tumors have all facilitated significant progress toward the realization of true clinical benefit from immunotherapeutic treatment of malignant gliomas. PMID:18363995
Malignant cancer and invasive placentation
D'Souza, Alaric W.; Wagner, G�nter P.
Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971;47:1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490
Integrative therapies for children with hematological malignancies.
Kelly, Kara M
Evidence for integrative therapies (IT) in children with hematological malignancies is slowly evolving. The ideal model of integrative pediatric oncology would offer IT modalities that are deemed safe and effective in conjunction with effective conventional medical treatments. Because of potential interactions, herbs and other dietary supplements should be used with caution, especially during active therapy. Health and wellness should be the emphasis, with IT therapies supporting health promotion and key disease prevention strategies for childhood cancer survivors. All uses, responses, and effects of IT therapies should be carefully documented. A desire to use IT therapies may be an effort to become an active participant in the healing process. Health care providers should encourage, not discourage, this partnership. PMID:20008215
Cancer stem cells in haematological malignancies
Golab, Jakub
At least several types of human haematological malignancies can now be seen as �stem-cell diseases�. The best-studied in this context is acute myeloid leukaemia (AML). It has been shown that these diseases are driven by a pool of �leukaemia stem cells (LSC)�, which remain in the quiescent state, have the capacity to survive and self-renew, and are responsible for the recurrence of cancer after classical chemotherapy. It has been understood that LSC must be eliminated in order to cure patients suffering from haematological cancers. Recent advances in LSC research have allowed for description of LSC phenotype and identification of potential targets for anti-LSC therapies. This concise review summarises the current view on LSC biology and targeted approaches against LSC. PMID:25691816
Cancer stem cells in haematological malignancies.
Zagozdzon, Radoslaw; Golab, Jakub
At least several types of human haematological malignancies can now be seen as 'stem-cell diseases'. The best-studied in this context is acute myeloid leukaemia (AML). It has been shown that these diseases are driven by a pool of 'leukaemia stem cells (LSC)', which remain in the quiescent state, have the capacity to survive and self-renew, and are responsible for the recurrence of cancer after classical chemotherapy. It has been understood that LSC must be eliminated in order to cure patients suffering from haematological cancers. Recent advances in LSC research have allowed for description of LSC phenotype and identification of potential targets for anti-LSC therapies. This concise review summarises the current view on LSC biology and targeted approaches against LSC. PMID:25691816
Honkala, Eino
The aim of this review was to describe the background and evolution of primary oral health care (POHC), including the development of an oral health policy, by identifying the resources necessary for oral health services, reviewing the evidence of the effectiveness of oral health promotion and education, providing essential oral health care, and establishing evidence of the benefits of regular dental visits for effective POHC. At present, evidence for the effectiveness of oral health education and regular dental visits is very weak. Nevertheless, POHC needs to be developed as an integral part of primary health care (PHC). Therefore, a need exists to increase financial investment, resources and workforce in PHC to lower the prevalence of dental caries and periodontal disease in the Middle-East using the POHC approach. PMID:24503932
Oral health and elite sport performance.
Needleman, Ian; Ashley, Paul; Fine, Peter; Haddad, Fares; Loosemore, Mike; de Medici, Akbar; Donos, Nikos; Newton, Tim; van Someren, Ken; Moazzez, Rebecca; Jaques, Rod; Hunter, Glenn; Khan, Karim; Shimmin, Mark; Brewer, John; Meehan, Lyndon; Mills, Steve; Porter, Stephen
While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies. PMID:25263651
Oral health and elite sport performance
Needleman, Ian; Ashley, Paul; Fine, Peter; Haddad, Fares; Loosemore, Mike; de Medici, Akbar; Donos, Nikos; Newton, Tim; van Someren, Ken; Moazzez, Rebecca; Jaques, Rod; Hunter, Glenn; Khan, Karim; Shimmin, Mark; Brewer, John; Meehan, Lyndon; Mills, Steve; Porter, Stephen
While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies. PMID:25263651
Identifying predictive morphologic features of malignancy in eyelid lesions
Leung, Christina; Johnson, Davin; Pang, Renee; Kratky, Vladimir
Abstract Objective To determine features of eyelid lesions most predictive of malignancy, and to design a key to assist general practitioners in the triaging of such lesions. Design Prospective observational study. Setting Department of Ophthalmology at Queen�s University in Kingston, Ont. Participants A total of 199 consecutive periocular lesions requiring biopsy or excision were included. Main outcome measures First, potential features suggestive of malignancy for eyelid lesions were identified based on a survey sent to Canadian oculoplastic surgeons. The sensitivity, specificity, and odds ratios (ORs) of these features were then determined using 199 consecutive photographed eyelid lesions of patients who presented to the Department of Ophthalmology and underwent biopsy or excision. A triage key was then created based on the features with the highest ORs, and it was pilot-tested by a group of medical students. Results Of the 199 lesions included, 161 (80.9%) were benign and 38 (19.1%) were malignant. The 3 features with the highest ORs in predicting malignancy were infiltration (OR = 18.2, P < .01), ulceration (OR = 14.7, P < .01), and loss of eyelashes (OR = 6.0, P < .01). The acronym LUI (loss of eyelashes, ulceration, infiltration) was created to assist in memory recall. After watching a video describing the LUI triage key, the mean total score of a group of medical students for correctly identifying malignant lesions increased from 46% to 70% (P < .001). Conclusion Differentiating benign from malignant eyelid lesions can be difficult even for experienced physicians. The LUI triage key provides physicians with an evidence-based, easy-to-remember system for assisting in the triaging of these lesions. PMID:25756148
Christopher Draven Oral History
Draven, Christopher; Albin, Tami
Under the Rainbow: Oral Histories of Gay, Lesbian, Bisexual, Transgender, Intersex and Queer People in Kansas Christopher Draven Oral History Interviewed by Tami Albin February 9, 2008 http...://hdl.handle.net/1808/5684 This interview was made possible by the generous support of the University of Kansas Libraries and the University of Kansas grants 2302114, 2301283, 2301334. � Under the Rainbow: Oral Histories of Gay, Lesbian, Bisexual...
A scoring system for the prognosis and treatment of malignant bowel obstruction
Henry, Jon C.; Pouly, Severin; Sullivan, Rachael; Sharif, Suhail; Klemanski, Dori; Abdel-Misih, Sherif; Arradaza, Nicole; Jarjoura, David; Schmidt, Carl; Bloomston, Mark
Background Malignant bowel obstruction is a common result of end-stage abdominal cancer that is a treatment dilemma for many physicians. Little has been reported predicting outcomes or determining the role of surgical intervention. We sought to review our experience with surgical and nonsurgical management of malignant bowel obstruction to identify predictors of 30-day mortality and of who would most likely benefit from surgical intervention. Methods A chart review of 523 patients treated between 2000 and 2007 with malignant bowel obstruction were evaluated for factors present at admission to determine return to oral intake, 30-day mortality, and overall survival. Propensity score matching was used to homogenize patients treated with and without surgery to identify those who would benefit most from operative intervention. Results Radiographic evidence of large bowel obstruction was predictive of return to oral intake. Hypoalbuminemia and radiographic evidence of ascites or carcinomatosis were all predictive of increased 30-day mortality and overall survival. A nomogram of 5 identified risk factors correlated with increased 30-day mortality independent of therapy. Patients with large bowel or partial small bowel obstruction benefited most from surgery. A second nomogram was created from 4 identified risk factors that revealed which patients with complete small bowel obstruction might benefit from surgery. Conclusion Two nomograms were created that may guide decisions in the care of patients with malignant bowel obstruction. These nomograms are able to predict 30-day mortality and who may benefit from surgery for small bowel obstruction. PMID:22929404
Serum lipid profile in oral precancer and cancer: a diagnostic or prognostic marker?
Garg, Deepanshu; Sunil, M K; Singh, Param Pal; Singla, Neetu; Rani, S R Ashwini; Kaur, Beant
Background: Changes in lipid profile have been associated with malignancy because of their key role in the maintenance the integrity of the cell membrane. This study evaluated the alterations in serum lipid profile in untreated patients of oral submucus fibrosis (OSMF), oral leukoplakia, and oral lichen planus and proven cases of oral cancer with respect to healthy controls. Materials & Methods: In this case control study, 20 clinically and histopathologically proven patients of oral precancer and oral cancer each were compared with 20 healthy controls. In these groups, serumlipids including: (i) Total cholesterol. (ii) Triglycerides (TGL). (iii) High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) were analyzed. Results: Decrease in plasma total cholesterol, triglycerides, HDL, LDL, VLDL in the subjects with the oral precancer and oral cancer as compared to the controls was statistically significant. There was also decrease in plasma levels of TGL and VLDL in oral cancer subjects as compared to precancer subjects. Thus, it was found that there is an inverse relationship between plasma lipid levels and patients. Conclusion: Post operative morbidity was increasing along with more operating time and increase in the depth of mandibular third molar impaction. How to cite the article: Garg D, Sunil MK, Singh PP, Singla N, Rani SR, Kaur B. Serum lipid profile in oral precancer and cancer: a diagnostic or prognostic marker? J Int Oral Health 2014;6(2):33-9. PMID:24876700
Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans
Tamura, Akitoshi, E-mail: firstname.lastname@example.com; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi
It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: � We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. � The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. � Some of allergic drugs increased inflammatory cells and IgE, but the others did not. � The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. � Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.
Envisioning an oral healthcare workforce for the future.
Nash, David A
Health is critical to human well-being. Oral health is an integral component of health. One is not healthy without oral health. As health is essential to human flourishing, it is important that an oral healthcare delivery system and workforce be developed and deployed which can help ensure all citizens have the potential to access oral health care. As such access does not generally exist today, it is imperative to advance the realization of this goal and to develop a vision of an oral healthcare workforce to functionally support access. Public funding of basic oral health care is an important element to improving access. However, funding is only economically feasible if a workforce exists that is structured in a manner such that duties are assigned to individuals who have been uniquely trained to fulfill specific clinical responsibilities. An essential element of any cost-effective organizational system must be the shared responsibility of duties. Delegation must occur in the oral health workforce if competent, cost-effective care is to be provided. Desirable members of the oral health team in an efficient and effective system are as follows: generalist dentists who are educated as physicians of the stomatognathic system (oral physicians), specialist dentists, dental therapists, dental hygienists, dually trained hygienists/therapists (oral health therapists), oral prosthetists (denturists), and expanded function dental assistants (dental nurses). PMID:22998319
Laser Raman detection for oral cancer based on a Gaussian process classification method
NASA Astrophysics Data System (ADS)
Du, Zhanwei; Yang, Yongjian; Bai, Yuan; Wang, Lijun; Zhang, Chijun; Chen, He; Luo, Yusheng; Su, Le; Chen, Yong; Li, Xianchang; Zhou, Xiaodong; Jia, Jun; Shen, Aiguo; Hu, Jiming
Oral squamous cell carcinoma is the most common neoplasm of the oral cavity. The incidence rate accounts for 80% of total oral cancer and shows an upward trend in recent years. It has a high degree of malignancy and is difficult to detect in terms of differential diagnosis, as a consequence of which the timing of treatment is always delayed. In this work, Raman spectroscopy was adopted to differentially diagnose oral squamous cell carcinoma and oral gland carcinoma. In total, 852 entries of raw spectral data which consisted of 631 items from 36 oral squamous cell carcinoma patients, 87 items from four oral gland carcinoma patients and 134 items from five normal people were collected by utilizing an optical method on oral tissues. The probability distribution of the datasets corresponding to the spectral peaks of the oral squamous cell carcinoma tissue was analyzed and the experimental result showed that the data obeyed a normal distribution. Moreover, the distribution characteristic of the noise was also in compliance with a Gaussian distribution. A Gaussian process (GP) classification method was utilized to distinguish the normal people and the oral gland carcinoma patients from the oral squamous cell carcinoma patients. The experimental results showed that all the normal people could be recognized. 83.33% of the oral squamous cell carcinoma patients could be correctly diagnosed and the remaining ones would be diagnosed as having oral gland carcinoma. For the classification process of oral gland carcinoma and oral squamous cell carcinoma, the correct ratio was 66.67% and the erroneously diagnosed percentage was 33.33%. The total sensitivity was 80% and the specificity was 100% with the Matthews correlation coefficient (MCC) set to 0.447?213?595. Considering the numerical results above, the application prospects and clinical value of this technique are significantly impressive.
Gene profiling analysis for patients with oral verrucous carcinoma and oral squamous cell carcinoma
Wang, Yue-Hong; Tian, Xin; Liu, Ou-Sheng; Fang, Xiao-Dan; Quan, Hong-Zhi; Xie, Shang; Gao, Shan; Tang, Zhan-Gui
Oral verrucous carcinoma (OVC) is one malignant tumor which was carved out from the oral squamous cell carcinoma (OSCC). However, the clinical and pathological features as well as the treatment strategies of OVC are different from OSCC. Here, global transcript abundance of tumor tissues from five patients with primary OVC and six patients with primary OSCC including their matched adjacently normal oral mucosa were profiled using the Affymetrix HGU133 Plus 2.0. Ingenuity Systems IPA software was used to analyse the gene function and biological pathways. There were 109 differentially expressed genes (more than 2-fold) between OVC and the adjacently normal tissue, among them 66 were up-regulated and 43 were down-regulated; 1172 differentially expressed genes (more than 2-fold) between OSCC and the adjacently normal tissue, among them 608 were up-regulated and 564 were down-regulated. There were 39 common differentially expressed genes in OVC and OSCC compared with their matched normal oral mucosa, among them 22 up-regulated and 17 down-regulated, and 8 of them different between OVC and OSCC. In addition, the gene expression profile was further validated by quantitative real-time PCR (Q-RT-PCR) analysis for four of those 39 selected genes. PMID:25126189
American Academy of Oral Medicine
... Fall Meeting AAOM: Representing the Discipline of Oral Medicine Oral Medicine is the discipline of dentistry concerned with the ... offers credentialing, resources and professional community for oral medicine practitioners. Our membership provides care to thousands We ...
signal processing and oral communication
Penn, Gerald
SPOClab signal processing and oral communication Computational Linguistics, 5 December 2012 Frank University of Toronto #12;SPOClab signal processing and oral communication An introduction to SPOClab � SPOClab (Signal Processing and Oral Communication) is a new lab intersecting Computer Science
Cho, Hokwon
GRADUATE COLLEGE ORAL DEFENSE RESULTS THESIS, DISSERTATION/MUSIC DOCUMENT, PROFESSIONAL: Phone: MEANS OF PUBLICIZING ORAL DEFENSE Department email Posted flyer UNLV Today Department website GPSA/GPSA Lounge Other (specify): Date: ORAL DEFENSE
Joseph, Benny; Vyloppilli, Suresh; Ahsan, Auswaf; Anirudhan, Anroop
Extreme oral myiasis is a rare condition, mostly affecting bedridden patients whose oral health care measures are neglected. Single stage manual removal of the maggots along with the necrotic tissue, debridement, and suturing under general anesthesia is the most effective way to treat the condition. Preventive measures are also equally important to eliminate the cause and recurrence.� PMID:25228190
The malignant lymphomas in Africa.
Jacobs, P
Africa, the "dark continent" and the source of such wonderful tales as King Solomon's Mines and Jock of the Bushveld, has an equally enthralling story to tell about malignant disease in general and the lymphomas in particular as they occur among its varied people. It is uncertain how far back in history contact existed with the rest of the world, primarily in the form of slave trading and colonization by, among others, the Portuguese and the British. Until recent times, however, Africa's secrets have remained largely undisturbed. Fragments of medical information are recorded in the diaries of those early, intrepid explorers, such as Albert Cook, Henry Stanley, David Livingstone, and Albert Schweitzer. However, it is only in recent years that the great natural experiments that have for so long been underestimated, and very much less understood, belatedly started to attract attention. Examples are the systematic studies by Denis Burkitt, who through perseverance unraveled the lymphoma that now bears his name, and the thought-provoking description of the immunoproliferative small intestinal disease carried out by the Cape Town group, with both illustrating the axiom that "the study of man is man." Despite such occasional outstanding achievements, there is still considerable paucity of data pertaining to the various lymphoreticular malignancies, so that only limited conclusions are possible. Certainly, lymphoma in Africa differs from that elsewhere in the world. In part, this may reflect a background of immunologic disturbance attributable to parasitic infestation, viral infection, rampant malnutrition, and the impact of a wide variety of vectors, such as mosquitoes, in disease transmission. Striking differences exist in the distribution of these tumors as the incidence and pattern are followed from the equator to the milder climates in the south. This confirmed phenomenon gives rise to the tantalizing suggestion that, to some significant extent, the changes reflect the influence of geography. Thus, there may be associated alterations in the fauna and flora that determine the presence of intermediary hosts that have an impact on the eventual expression of the malignant clone. Many questions remain unanswered. For example, how can the lower incidence of Hodgkin's disease and the predominance of high-grade malignancies in the tropics and subtropics be explained? To what extent does the lymphocytic and plasmacytic hyperplasia, ascribed to intense antigenic stimulus in Burkitt's lymphoma and myeloma--perhaps even other lymphomas, such as IPSID--predispose the host to a mutational event that leads to the emergence of each distinctive neoplasm?(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1938763
Management of spermatic cord tumors: a rare urologic malignancy
Rodr�guez, Dayron
Primary spermatic cord tumors are rare yet clinically significant urologic lesions that affect patients of all ages. They are the most common tumors of the paratesticular region and generally present as asymptomatic, slow growing, firm, palpable paratesticular masses. Although most of them are benign comprised primarily of lipomas, approximately 25% are potentially life-threatening malignant tumors. The most common reported malignant histological types include liposarcomas, leiomyosarcomas, rhabdomyosarcomas, malignant fibrous histiocytoma, and fibrosarcomas. Management of these malignant tumors has been difficult because of their rarity, therefore there is little consensus regarding optimal surgical and adjunctive treatment strategies. It is recommended that radiological techniques such as scrotal ultrasound (US), computed tomography, and magnetic resonance be used to evaluate these masses before surgery. The curative treatment of choice is radical orchiectomy with high cord ligation and wide excision of surrounding soft tissue structures within the inguinal canal. Patients with inadequately resected disease should undergo a reoperative procedure for wide inguinal re-resection. Retroperitoneal lymphadenectomy is recommended when there is preoperative evidence of retroperitoneal lymph node metastasis and as an adjuvant treatment for rhabdomyosarcomas since they have a higher propensity for lymphatic spread. Adjuvant treatments, such as radiotherapy and chemotherapy, have shown little efficacy, except in the management of patients with local recurrence or high-grade rhabdomyosarcomas. Long-term follow up is recommended given their high recurrence rates. PMID:23205059
Laparoscopic approach to gastrointestinal malignancies: toward the future with caution.
Bencini, Lapo; Bernini, Marco; Farsi, Marco
After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district. PMID:24587655
Laparoscopic approach to gastrointestinal malignancies: Toward the future with caution
Bencini, Lapo; Bernini, Marco; Farsi, Marco
After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district. PMID:24587655
Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma.
Cioce, M; Ganci, F; Canu, V; Sacconi, A; Mori, F; Canino, C; Korita, E; Casini, B; Alessandrini, G; Cambria, A; Carosi, M A; Blandino, R; Panebianco, V; Facciolo, F; Visca, P; Volinia, S; Muti, P; Strano, S; Croce, C M; Pass, H I; Blandino, G
We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed. PMID:24240684
Mycoplasmas and Oncogenesis: Persistent Infection and Multistage Malignant Transformation
Shien Tsai; Douglas J. Wear; James Wai-Kuo Shih; Shyh-Ching Lo
Oncogenic potential of human mycoplasmas was studied using cultured mouse embryo cells, C_3H\\/10T1\\/2 (C_3H). Mycoplasma fermentans and Mycoplasma penetrans, mycoplasmas found in unusually high frequencies among patients with AIDS, were examined. Instead of acute transformation, a multistage process in promotion and progression of malignant cell transformation with long latency was noted; after 6 passages (1 wk per passage) of persistent
Galectins as therapeutic targets for hematological malignancies: a hopeful sweetness
Pena, Camilo; Mirandola, Leonardo; Figueroa, Jose A.; Hosiriluck, Nattamol; Suvorava, Natallia; Trotter, Kayley; Reidy, Adair; Rakhshanda, Rahman; Payne, Drew; Jenkins, Marjorie; Grizzi, Fabio; Littlefield, Lauren; Cobos, Everardo
Galectins are family of galactose-binding proteins known to play critical roles in inflammation and neoplastic progression. Galectins facilitate the growth and survival of neoplastic cells by regulating their cross-talk with the extracellular microenvironment and hampering anti-neoplastic immunity. Here, we review the role of galectins in the biology of hematological malignancies and their promise as potential therapeutic agents in these diseases. PMID:25405162
Palliative Noninvasive Mechanical Ventilation in Patients with Hematological Malignancies
Anne-Pascale Meert; Thierry Berghmans; Jean-Paul Sculier
\\u000a Treatment with noninvasive ventilation (NIV) is feasible and effective in cancer patients. However, virtually no data are\\u000a available on the role for NIV as a component of palliative care for patients with hematological malignancies. NIV can be used\\u000a in patients with reversible causes of acute respiratory failure for whom potentially life-extending treatments are available.\\u000a In patients with treatment-limitation decisions, NIV
Incidence and predictive factors for malignancies in 136 Japanese patients with dermatomyositis, polymyositis and clinically amyopathic dermatomyositis.
Azuma, Kohei; Yamada, Hidehiro; Ohkubo, Michiko; Yamasaki, Yoshioki; Yamasaki, Masaomi; Mizushima, Machiko; Ozaki, Shoichi
The aim of this study was to define the standardized incidence ratio (SIR) of malignancy and the potential risk factors of concomitant malignancies in patients with inflammatory myopathies, including clinically amyopathic dermatomyositis (CADM). A total of 145 patients diagnosed with either dermatomyositis/polymyositis (DM/PM) or CADM at our institute between 1984 and 2002 were enrolled in the study. The demographic, clinical and laboratory features of the patients at the time of DM/PM or CADM diagnosis were compared between patients with and without malignancies, respectively. Multivariate analysis by logistic regression was used to determine the independent risk factors for the development of malignancies in DM/PM patients. Malignancy was found in 17 of 70 patients with DM (24%), three of 15 patients with CADM (20%), and three of 51 patients with PM (6%). Gastric cancer (8/23) was the most common malignancy. Compared with general population, the SIR of malignancies was 13.8 (range 9.0-21.1). The patients who developed malignancies were older (61.5 vs. 51.1 years; P < 0.005), presented more often with dysphagia (61 vs. 15%; P < 0.0001) and were less likely to have the complication of interstitial lung disease (30 vs. 60%; P < 0.05). These features were independent predictive factors for developing malignancies in multiple logistic regression analysis. The results of our study confirm that CADM in addition to DM was associated with high rates of malignancy among our patient cohort. PMID:20922453
Malignant Leydig cell tumour of the testis.
Powari, Manish; Kakkar, Nandita; Singh, S K; Rai, R S; Jogai, Sanjay
A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed. PMID:11803271
Hematopoietic cell transplantation and cellular therapeutics in the treatment of childhood malignancies.
Mallhi, Kanwaldeep; Lum, Lawrence G; Schultz, Kirk R; Yankelevich, Maxim
Hematopoietic cell transplantation (HCT) represents the most common and effective form of immunotherapy for childhood malignancies. The role of the graft-versus-leukemia effect in allogeneic HCT has been well established in childhood malignancies, but is also associated with short-term and long-term morbidity. HCT may be ineffective in some settings at obtaining control of the malignancy, and as such, cannot be used as a universal cancer immunotherapy. Novel therapies using dendritic cell vaccinations, tumor-infiltrating lymphocytes, and chimeric antigen receptor T cells are being evaluated as potential adjuvants to HCT. PMID:25435122
Malignant hyperthermia in a 3-year-old child with microstomia.
Evans, Tyler A; Flores, Roberto L; Tholpady, Sunil S; Dierdorf, Stephen
Freeman-Sheldon syndrome is a congenital disorder that has been suggested to be associated with malignant hyperthermia. Clinical features of the Freeman-Sheldon syndrome include flexion contractures and characteristic facial features, including microstomia and a whistling shape to the lips. We report a case of malignant hyperthermia in a 3-year-old girl with microstomia but no other features of Freeman-Sheldon syndrome. The purpose of this report was to review the diagnosis and treatment of malignant hyperthermia as craniofacial surgeons have an increased exposure to this rare and potentially fatal condition. PMID:25478978
Malignant gastric lymphoma with spontaneous perforation
Shimada, Satoko; Gen, Tokichi; Okamoto, Hiroyuki
Malignant gastric lymphoma, accounting only for 1% of primary gastric carcinoma, is usually a diffuse large B-cell lymphoma. Toyota et al reported that 37% of gastric perforations involved malignancy, generally gastric carcinoma. Fukuda et al found that less than 5% of malignant gastric lymphomas perforate. While it is relatively well known that perforations often take place during chemotherapy, they are rare in patients not receiving chemotherapy. To our knowledge, spontaneous perforation is rare in gastric malignant lymphoma, having been reported in the Japanese literature only 26 times, including this case, in the last 25?years. PMID:23329705
Rationale for Proton Therapy in Pediatric Malignancies
NASA Astrophysics Data System (ADS)
Woo, Shiao Y.
Proton therapy (PT) is being applied with increasing frequency in the treatment of pediatric malignancies. The principal rationale, selected published clinical results, and remaining challenges will be presented.
Indwelling pleural catheters for malignant pleural effusion.
McPhillips, Dympna; Breen, David
Pleural effusions are a common cause of symptoms in patients with malignancy and can adversely affect quality of life. However, not all effusions in the setting of malignancy are due to the cancer itself and therefore it is essential to perform an extensive assessment to diagnose the underlying aetiology. There are a number of treatment options available to manage a malignant effusion and reduce the associated symptomatology. The choice of intervention depends on a number of factors and, in particular, patient preference. In this paper, we will discuss the role of an indwelling pleural catheter in the outpatient management of individuals with malignant effusions. PMID:26126674
Radiotherapy-Induced Malignancies: Review of Clinical Features, Pathobiology, and Evolving Approaches for Mitigating Risk
Braunstein, Steve; Nakamura, Jean L.
One of the most significant effects of radiation therapy on normal tissues is mutagenesis, which is the basis for radiation-induced malignancies. Radiation-induced malignancies are late complications arising after radiotherapy, increasing in frequency among survivors of both pediatric and adult cancers. Genetic backgrounds harboring germline mutations in tumor suppressor genes are recognized risk factors. Some success has been found with using genome wide association studies to identify germline polymorphisms associated with susceptibility. The insights generated by genetics, epidemiology, and the development of experimental models are defining potential strategies to offer to individuals at risk for radiation-induced malignancies. Concurrent technological efforts are developing novel radiotherapy delivery to reduce irradiation of normal tissues, and thereby, to mitigate the risk of radiation-induced malignancies. The goal of this review is to discuss epidemiologic, modeling, and radiotherapy delivery data, where these lines of research intersect and their potential impact on patient care. PMID:23565507