interacts_with DB01278?
Andrographolide induces apoptosis of P13671 glioma cells via the P29323 -p53-caspase 7-PARP pathway . BACKGROUND : Glioma is the most malignant tumor of the central nervous system . Efforts on the development of new chemotherapy are mandatory . Andrographolide ( AND ) , a diterpenoid lactone isolated from the Andrographis paniculata , has been shown to have antitumor activities in several types of cancer cells . Whether AND can exert its antitumor activity in glioblastoma cells remains unknown . This study examined the anticancer effects of AND , both in vitro and in vivo . METHODS : Cell apoptosis was assayed by flow cytometry and nuclear staining . The signaling pathway for AND was determined by western blotting . The effects of AND on tumor growth was evaluated in a mouse model . RESULTS AND CONCLUSION : In vitro , with application of specific inhibitors and siRNA , AND-induced apoptosis was proven through ROS- P29323 - P04637 -caspase 7-PARP signaling pathway . In vivo , AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo . Furthermore , AND did not induce apoptosis or activate P29323 and p53 in primary cultured astrocyte cells , and it may serve as a potential therapeutic candidate for the treatment of glioma . P62158 and troponin C : affinity chromatographic study of divalent cation requirements for troponin I inhibitory peptide ( residues 104-115 ) , mastoparan and fluphenazine binding . The different conformations induced by the binding of Mg2+ or Ca2+ to troponin C ( TnC ) and calmodulin ( P62158 ) results in the exposure of various interfaces with potential to bind target compounds . The interaction of TnC or P62158 with three affinity columns with ligands of either the synthetic peptide of troponin I ( TnI ) inhibitory region ( residues 104-115 ) , mastoparan ( a wasp venom peptide ) , or fluphenazine ( a phenothiazine drug ) were investigated in the presence of Mg2+ or Ca2+ . TnC and P62158 in the presence of either Ca2+ or Mg2+ bound to the TnI peptide 104-115 . The cation specificity for this interaction firmly establishes that the TnI inhibitory region binds to the high affinity sites of TnC ( most likely the N-terminal helix of site III ) and presumably the homologous region of P62158 . Mastoparan interacted strongly with both proteins in the presence of Ca2+ but , in the presence of Mg2+ , did not bind to TnC and only bound weakly to P62158 . DB00623 bound to TnC and P62158 only in the presence of Ca2+ . When the ligands interacted with either proteins there was an increase in cation affinity , such that TnC and P62158 were eluted from the TnI peptide or mastoparan affinity column with 0.1 M DB00974 compared with the 0.01 M DB00974 required to elute the proteins from the fluphenazine column . The interaction of these ligands with their receptor sites on TnC and P62158 require a specific and spatially correct alignment of hydrophobic and negatively charged residues on these proteins. ( ABSTRACT TRUNCATED AT 250 WORDS ) Modeling of Q14654 and inhibition mechanism of the natural ligand , ellagic acid , using molecular docking . Diabetes mellitus is a disorder in which blood sugar ( glucose ) levels are abnormally high because the body does not produce enough insulin to meet its needs . Post-prandial hyperglycemia ( PPHG ) is an independent risk factor for the development of macro vascular complications . It is now recognized that normalizing post-prandial blood glucose is more difficult than normalizing fasting glucose . DB01345 channels are the most widely distributed type of ion channel and are found in virtually all living organisms . The function of KATP channels is best understood in pancreatic beta cells , the membrane potential of which is responsive to external glucose concentration . Beta cells show a remarkably complex electrical bursting behavior in response to an increase in glucose level . DB00731 and DB00222 are a class of insulin secretagog agents that lowers blood glucose levels by stimulating insulin secretion from the pancreas . These compounds interact with the DB00171 -sensitive potassium ( K+ DB00171 ) channel in pancreatic beta cells . However , the side effects of these drugs overpass their uses , and the need to identify compounds with less adverse effects is exigent . In our research study , we used the natural compound ellagic acid , which is an already proven anti-carcinogen , anti-mutagen , and anticancer initiator , for its anti-diabetic activity in comparison to the two commercial drugs ( DB00731 and DB00222 ) . The drugs and the compounds were docked to the DB00171 -dependent potassium channel and their energy value showed that the compound had higher binding value than the commercial drugs . Then an ADME/Tox analysis for the compound was carried out which showed that ellagic can be a possible lead molecule . Molecular weight and biochemical profile of a chemically modified heparin derivative , Suleparoide . Recently , a new chemically modified derivative of heparin ( Suleparoide , Syntex Laboratories Buenos Aires , Argentina ) was introduced for the prophylaxis of thrombosis and treatment of vascular disorders . This agent is claimed to contain a depolymerized , chemically modified , heparin derivative with similar biologic actions as heparan sulfate . To study the pharmacologic profile of this agent , we have defined its molecular weight distribution profile , utilizing a computerized gel permeation chromatographic system equipped with ultraviolet and refractive index detectors . Suleparoide exhibited a normal molecular distribution profile with no contaminants . It exhibited a weight average of 9.3 K DA and an apparent peak MW of 8.0 K DA . Approximately 50 % of the molecular components were < 5.0 K DA and 40 % > 5.0 K DA . The results from these studies on the mechanisms show that Suleparoide has anticoagulant activity primarily mediated through DB01109 Cofactor-II ( P05546 ) and because of its novel mechanism of action , further investigations on the biochemical profile of Suleparoide are carried out . Global clotting tests such as Activated Partial P13726 Time ( APTT ) , Heptest and Thrombin Time ( TT ) revealed a concentration dependent effect in all assays . Plasma samples supplemented with Suleparoide exhibited no significant anti-Xa and anti-IIa activities . However , in the P05546 mediated inhibitory assay for IIa , Suleparoide exhibited significant activity . In contrast , the P01008 ( DB11598 ) mediated inhibition of IIa was much weaker . Q15070 -mir-125b-2 is highly expressed in childhood P41212 / Q01196 ( P41212 / Q01196 ) leukemias and confers survival advantage to growth inhibitory signals independent of p53 . MicroRNAs ( miRNAs ) regulate the expression of multiple proteins in a dose-dependent manner . We hypothesized that increased expression of miRNAs encoded on chromosome 21 ( chr 21 ) contribute to the leukemogenic function of trisomy 21 . The levels of chr 21 miRNAs were quantified by qRT-PCR in four types of childhood acute lymphoblastic leukemia ( ALL ) characterized by either numerical ( trisomy or tetrasomy ) or structural abnormalities of chr 21 . Suprisingly , high expression of the hsa-mir-125b-2 cluster , consisting of three miRNAs , was identified in leukemias with the structural P41212 / Q01196 abnormality and not in ALLs with trisomy 21 . Manipulation of P41212 / Q01196 expression and chromatin immunoprecipitation studies showed that the high expression of the miRNA cluster is an event independent of the P41212 / Q01196 fusion protein . Overexpression of hsa-mir-125b-2 conferred a survival advantage to Ba/ P13726 cells after P08700 withdrawal or a broad spectrum of apoptotic stimuli through inhibition of caspase 3 activation . Conversely , knockdown of the endogenous miR-125b in the P41212 / Q01196 leukemia cell line P23141 increased apoptosis after Doxorubicin and DB02010 treatments . P04637 protein levels were not altered by miR-125b . Together , these results suggest that the expression of hsa-mir-125b-2 in P41212 / Q01196 ALL provides survival advantage to growth inhibitory signals in a p53-independent manner . [ Signal transduction inhibitor -- STI571 -- a new treatment for chronic myeloid leukemia ( CML ) , which opens a new targeted approach to cancer therapy ] . Chronic myeloid leukemia ( CML ) , in most of the cases , is the molecular consequence of the t(9,22) translocation , resulting in the Philadelphia ( Ph ) chromosome and the creation of the fusion gene P11274 - P00519 . The fusion gene is translated to the protooncogen P11274 - P00519 , a constitutively activated tyrosine kinase that is linked to the malignant transformation . Thus , this tyrosine kinase became an attractive target for drug design . The development of the novel investigational drug DB00619 is based on its potent and selective ability to inhibit this fusion tyrosine kinase . In preclinical studies , DB00619 selectively inhibited the growth of CML cells that carry the Ph chromosome . In this review we discuss the drug development and design , its mechanism of action , the preclinical studies and the results of phase I and II clinical trials . Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis . Endometriosis displays some features that resemble malignant processes , including invasive growth , resistance to apoptosis and distant implantation . The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis . Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score stage 1 ( n= 1 ) , 2 ( n= 10 ) , 3 ( n= 11 ) or 4 ( n= 1 ) endometriosis . Six genes ( P25054 , CDKN2A , Q9ULZ3 , P10826 , Q9NS23 and P03372 ) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis , and 9 genes ( P15056 , P01112 , P01111 , P35222 , P11802 , P22607 , P42336 , P04637 and P60484 ) were analyzed for mutations using denaturing gradient gel electrophoresis and direct sequencing . An oncogenic mutation in P01116 ( c.34G > T ; p.G12C ) was detected in a single lesion . No gene alterations were found in the remaining samples . Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis . However , other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation . Renal medullary carcinoma : clinical , pathologic , immunohistochemical , and genetic analysis with pathogenetic implications . OBJECTIVES : To investigate the pathologic , clinical , and genetic features of renal medullary carcinomas ( RMCs ) in search of clues to their pathogenesis . METHODS : We analyzed 40 RMCs for clinical features , for immunohistochemical expression using a panel of markers , and for genetic changes using comparative genomic hybridization . RESULTS : Patients presented at 5 to 32 years of age , and 82 % were African American . All patients tested had sickle cell trait or disease . Seven patients presented with suspected renal abscess or urinary track infection without a clinically recognizable mass . Of the 15 tumors able to be analyzed , all were positive for epithelial markers P62158 5.2 and epithelial membrane antigen . All were negative for high-molecular-weight cytokeratin 34betaE12 . Cytokeratins 7 and 20 and carcinoembryonic antigen were heterogeneous and variable . Ulex was focally positive in a minority of cases . Eight of 12 tumors showed significant positivity for P04637 protein ( greater than 25 % nuclear positivity ) . All tumor tested ( n = 8 ) were strongly positive for vascular endothelial growth factor and hypoxia inducible factor . Of nine tumors analyzed for genetic gains and losses using comparative genomic hybridization , eight showed no changes and one showed loss of chromosome 22 . Survival ranged from 2 weeks to 15 months ( mean 4 months ) . CONCLUSIONS : These findings suggest that RMC is clinically and pathologically distinct from collecting duct carcinoma . The hypothesis that chronic medullary hypoxia secondary to hemoglobinopathy may be involved in the pathogenesis of RMC is suggested by strong vascular endothelial growth factor and hypoxia inducible factor expression and positivity for P04637 . Expression of vitamin D3 receptor and retinoid receptors in human breast cancer : identification of potential heterodimeric receptors . DB00169 ( VD ) and all-trans-retinoic acid ( DB00755 ) have been postulated as a novel treatment option for breast carcinoma . Since the combined effects of retinoids and VD derivatives are attributed to heterodimeric interactions between members of the nuclear receptor family , the expression patterns of the heterodimers formed by vitamin D3 receptor ( P11473 ) and the retinoid receptors RARs ( P10276 , P10826 and P13631 ) and RXRs ( RXR-alpha , RXR-beta and RXR-gamma ) have been studied by immunohistochemistry in benign and malignant breast tissues . Present results revealed that immunoexpressions to all receptor types studied were higher in both in situ and infiltrative carcinomas than in benign breast diseases . In a variable number of cases of infiltrative carcinoma , immunostaining appeared in the nucleus , whereas in the other two disorders immunostaining was only cytoplasmic . The correlation established between P11473 and the different isoforms of retinoid receptors revealed that P11473 seems to select mainly P10276 to form heterodimers and to exert their properties as transcription factor . The results of this study suggest that this heterodimer plays a critical role in cancer malignancy , and its presence indicates those patient groups presenting a better response to adjuvant therapies based on the combination of vitamin D and DB00755 . DB06212 , a selective oral vasopressin V2 receptor antagonist , ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats . BACKGROUND : Proteinuria caused by glomerular disease is characterized by podocyte injury . P30518 antagonists are effective in reducing albuminuria , although their actions on glomerular podocytes have not been explored . The objective of this study was to evaluate the effects of tolvaptan , a selective oral V2 receptor antagonist , on podocytes in a puromycin aminonucleoside ( PAN ) -induced nephrosis rat model . METHODS : Rats were allocated to a control , PAN nephrosis , or tolvaptan-treated PAN nephrosis group ( n = 9 per group ) . Urinary protein excretion and serum levels of total protein , albumin , creatinine , and total cholesterol were measured on day 10 . The influence of tolvaptan on podocytes was examined in renal tissues by immunofluorescence and electron microscopy . RESULTS : PAN induced massive proteinuria and serum creatinine elevation on day 10 , both of which were significantly ameliorated by tolvaptan . Immunofluorescence studies of the podocyte-associated proteins nephrin and podocin revealed granular staining patterns in PAN nephrosis rats . In tolvaptan-treated rats , nephrin and podocin expressions retained their normal linear pattern . Electron microscopy showed foot process effacement was ameliorated in tolvaptan-treated rats . CONCLUSIONS : DB06212 is protective against podocyte damage and proteinuria in PAN nephrosis . This study indicates that tolvaptan exerts a renoprotective effect by affecting podocyte morphology and probably function in PAN nephrosis . DB06212 is a promising pharmacological tool in the treatment of renal edema . Exome-level comparison of primary well-differentiated neuroendocrine tumors and their cell lines . Neuroendocrine cancer cell lines are used to investigate therapeutic targets in neuroendocrine tumors ( NET ) and have been instrumental in the design of clinical trials targeting the PI3K/AKT/ P42345 pathways , P15692 inhibitors , and somatostatin analogues . It remains unknown , however , whether the genomic makeup of NET cell lines reflect that of primary NET since comprehensive unbiased genome sequencing has not been performed on the cell lines . Four bronchopulmonary NET ( BP-NET ) -NCI-H720 , NCI-H727 , NCI-H835 , and UMC11-and two pancreatic neuroendocrine tumors ( panNET ) -BON-1 and QGP1-were cultured . DNA was isolated , and exome sequencing was done . GATK and EXCAVATOR were used for bioinformatic analysis . We detected a total of 1,764 nonsynonymous single nucleotide variants at a rate of 8 per Mb in BP-NET and 4.3 per Mb in panNET cell lines , including 52 mutated COSMIC cancer genes in these cell lines , such as P04637 , P38398 , P06400 , P49815 , P46531 , Q09472 , GNAS , P35968 , Q15831 , and P25054 but not P46100 , Q9UER7 , nor O00255 . Our data suggest that mutation rate , the pattern of copy number variations , and the mutational spectra in the BP-NET cell lines are more similar to the changes observed in small cell lung cancer than those found in primary BP-NET . Likewise , mutation rate and pattern including the absence of mutations in P46100 / Q9UER7 , O00255 , and P25490 in the panNET cell lines BON1 and QGP1 suggest that these cell lines do not have the genetic signatures of a primary panNET . These results suggest that results from experiments with BP-NET and panNET cell lines need to be interpreted with caution . Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes . OBJECTIVE : Type 2 diabetes is a common complex disorder with environmental and genetic components . We used a candidate gene-based approach to identify single nucleotide polymorphism ( SNP ) variants in 222 candidate genes that influence susceptibility to type 2 diabetes . RESEARCH DESIGN AND METHODS : In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant , we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs , providing 99.9 % coverage of common HapMap variants in the 222 candidate genes . Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant , also from Finland . RESULTS : Using SNP- and gene-based analysis methods , we replicated previously reported SNP-type 2 diabetes associations in P37231 , Q14654 , and P11168 ; identified significant SNPs in genes with previously reported associations ( P22413 [ rs2021966 , P = 0.00026 ] and NRF1 [ rs1882095 , P = 0.00096 ] ) ; and implicated novel genes , including Q13905 ( rs4740283 , P = 0.00013 ) and P04637 ( rs1042522 , Arg72Pro , P = 0.00086 ) , in type 2 diabetes susceptibility . CONCLUSIONS : Our study provides an effective gene-based approach to association study design and analysis . One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis . Analysis of additional samples will be necessary to determine their effect on susceptibility . Characterization of the genomic architecture and mutational spectrum of a small cell prostate carcinoma . We present the use of a series of laboratory , analytical and interpretation methods to investigate personalized cancer care for a case of small cell prostate carcinoma ( SCPC ) , a rare and aggressive tumor with poor prognosis , for which the underlying genomic architecture and mutational spectrum has not been well characterized . We performed both SNP genotyping and exome sequencing of a Virchow node metastasis from a patient with SCPC . A variety of methods were used to analyze and interpret the tumor genome for copy number variation , loss of heterozygosity ( LOH ) , somatic mosaicism and mutations in genes from known cancer pathways . The combination of genotyping and exome sequencing approaches provided more information than either technique alone . The results showed widespread evidence of copy number changes involving most chromosomes including the possible loss of both alleles of P46527 ( p27/Kip1 ) . LOH was observed for the regions encompassing the tumor suppressors P04637 , P06400 , and O14646 . Predicted damaging somatic mutations were observed in the retained P04637 and P06400 alleles . Mutations in other genes that may be functionally relevant were noted , especially the recently reported high confidence cancer drivers P55317 and Q8IX12 . The disruption of multiple cancer drivers underscores why SCPC may be such a difficult cancer to manage . Prasugrel : a new antiplatelet drug for the prevention and treatment of cardiovascular disease . Prasugrel , trade name DB06209 , is an investigational new antiplatelet drug currently under review for clinical use by the Food and Drug Administration . It is a thienopyridine analog with a structure similar to that of clopidogrel and ticlopidine . Thienopyridine derivatives inhibit platelet aggregation induced by adenosine diphosphate by irreversibly inhibiting the binding of adenosine diphosphate to the purinergic Q9H244 receptor on the platelet surface . Prasugrel has been shown to be a potent antiplatelet agent with a faster , more consistent , and greater inhibition of platelet aggregation compared with clopidogrel . It is debatable , however , how effectively these pharmacologic benefits will translate to clinical benefits . The results of the large TRITON-TIMI 38 trial , which compared prasugrel and clopidogrel in patients with acute coronary syndrome who were scheduled to receive coronary stents , demonstrated a significant reduction in ischemic events , including stent thrombosis , with prasugrel , but with an increased risk of major bleeding . The exact role of prasugrel in the management of ischemic heart disease is still being defined , but the risk:benefit ratio will likely play a major role in directing the best place for therapy with this new agent . Synthesis , biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors . The synthesis and biochemical evaluation of new hybrids of tacrine ( DB00382 ) and 4-fluorobenzoic acid ( 4-FBA ) possessing activity towards acetylcholinesterase ( P22303 ) and butyrylcholinesterase ( BuChE ) inhibition are presented . The compounds of interest were obtained from the reaction of activated 4-FBA and diamino derivatives of 1,2,3,4-tetrahydroacridine . The compounds P13671 -2KW/HCl , P13671 -4KW/HCl and P13671 -3KW/HCl have four-fold higher antiacetylcholinesterase activity than DB00382 . All of the acquired compounds present higher selectivity towards P22303 than DB00382 and lower selectivity towards BuChE . In addition , a rapid , selective and stability-indicating HPLC method was developed and validated for the determination of P13671 -2KW/HCl , P13671 -3KW/HCl and P13671 -4KW/HCl . DB00382 and 4-FBA were found to be the main impurities . Chromatographic separation was achieved isocratically on a Waters Symmetry C18 150 × 3.9 mm , 4 μm column with a mobile phase of acetonitrile/buffer ( 17 mM sodium dodecyl sulphate and 8.3 mM sodium dihydrogen phosphate , 50:50 v/v ) ( overall pH 4 ) . A 1.5 ml/min flow rate and a 247 nm wavelength were chosen for this method . P13671 -2KW/HCl , P13671 -3KW/HCl and P13671 -4KW/HCl were subjected to acidic and basic hydrolysis , chemical oxidation , thermal exposition at 60 °C and intense UV light . The limits of detection ( LOD ) and quantification ( LOQ ) were less than 2 μg/ml and 6 μg/ml for P13671 -2KW/HCl , P13671 -3KW/HCl and P13671 -4KW/HCl , 0.04 μg/ml and 0.12 μg/ml for DB00382 , 0.42 μg/ml and 1.41 μg/ml for 4-FBA , respectively . Effect of dietary NaCl on tyrosine hydroxylase in the superior cervical ganglia of Dahl rats . To investigate the involvement of peripheral catecholamines in the development of Dahl-Iwai salt-sensitive ( Q8IX12 /Eis ) hypertension , we performed immunohistochemical staining of tyrosine hydroxylase ( TH ) in the superior cervical ganglia ( SCG ) of Q8IX12 /Eis rats and Dahl-Iwai salt-resistant ( P30518 /Eis ) rats , and in situ hybridization histochemistry for demonstration of TH mRNA localization in the SCG of these rats . Q8IX12 /Eis and P30518 /Eis rats were fed on a high ( 8 % ) salt diet or on a low ( 0.3 % ) salt diet for 4 weeks . Nerve cells in the SCG of Q8IX12 /Eis high salt rats exhibited more intense TH-immunoreactivity ( P < 0.01 ) and hybridization signals ( P < 0.01 ) than those of the other experimental groups . These findings suggest that activation of peripheral sympathetic nerves may account for hypertension in Q8IX12 /Eis rats on a high salt diet . P78423 activates a signal transduction pathway similar to Q9H244 and is associated with impaired clopidogrel responsiveness . OBJECTIVE : P78423 ( P78423 ) activates a G(αi) protein-coupled signaling pathway similar to the one activated by ADP via P2Y(12) , which is the drug target of clopidogrel . P78423 levels are increased under several disease conditions associated with impaired clopidogrel responsiveness . METHODS AND RESULTS : Blood samples were obtained from healthy volunteers and from 40 patients under chronic clopidogrel treatment . P78423 reduced prostaglandin E1-induced vasodilator-stimulated phosphoprotein phosphorylation by ≈ 25 % ( P < 0.01 ) at least partially mimicking the effect of ADP via P2Y(12) . In vitro , P78423 increased platelet reactivity index in clopidogrel-treated patients indicating potential activation of downstream targets of P2Y(12) . When stratifying patients by their P78423 levels , patients within the highest quartile of P78423 ( 2042 ± 25 pg/mL ) had the weakest response to clopidogrel ( platelet reactivity index , 68 ± 4 % ) , and patients within the lowest quartile ( 479 ± 50 pg/mL ) had the strongest response ( platelet reactivity index , 48 ± 7 % ; P=0.0106 ) . P78423 by itself induced phosphoinositide 3-kinase activation leading to Akt phosphorylation at DB00133 (473) ( P < 0.01 versus basal ) . CONCLUSIONS : In addition to desensitizing platelets to prostaglandin E1 via G(αi) , P78423 induces phosphoinositide 3-kinase-dependent Akt phosphorylation via a G(βγ) protein similar to ADP signaling through P2Y(12) . P78423 increased the platelet ADP response in clopidogrel-treated patients . Once released from an atherosclerotic lesion , this mechanism could contribute locally to impaired clopidogrel responsiveness at the vulnerable plaque . [ Clinical and cytogenetic analyses of 45 adult patients with acute lymphoblastic leukemia ] . OBJECTIVE : To analyze the correlation between clinical features and cytogenetic finding of 45 adult patients with acute lymphoblastic leukemia ( ALL ) , and to assess the value of chromosomal examination for the diagnosis and prognosis . METHODS : Fluorescence in situ hybridization ( Q5TCZ1 ) was utilized for detecting the P11274 / P00519 fusion gene and P04637 gene . Median survival time ( MST ) of patients was compared using Log-rank test . RESULTS : Respectively , the MST of patients with white blood cell count ( WBC ) ≤30 × 10(9)/L , normal karyotype , or without a Philadelphia chromosome were significantly greater than those with WBC > 30 × 10(9)/L , abnormal karyotype or Philadelphia chromosome ( P < 0.05 ) . CONCLUSION : WBC , karyotype abnormalities and presence of Philadelphia chromosome are independent factors for the prognosis of ALL in adult patients . P10997 -driven metabolic reprogramming induces regression of p53-deficient tumours in vivo . P04637 is commonly altered in human cancer , and Tp53 reactivation suppresses tumours in vivo in mice ( P04637 and Tp53 are also known as p53 ) . This strategy has proven difficult to implement therapeutically , and here we examine an alternative strategy by manipulating the p53 family members , Tp63 and Tp73 ( also known as p63 and p73 , respectively ) . The acidic transactivation-domain-bearing ( TA ) isoforms of p63 and p73 structurally and functionally resemble p53 , whereas the ΔN isoforms ( lacking the acidic transactivation domain ) of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53 , TAp63 and TAp73 to inhibit their tumour-suppressive functions . The p53 family interacts extensively in cellular processes that promote tumour suppression , such as apoptosis and autophagy , thus a clear understanding of this interplay in cancer is needed to treat tumours with alterations in the p53 pathway . Here we show that deletion of the ΔN isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregulation of P10997 , the gene that encodes amylin , a 37-amino-acid peptide co-secreted with insulin by the β cells of the pancreas . We found that P10997 is causally involved in this tumour regression and that amylin functions through the calcitonin receptor ( CalcR ) and receptor activity modifying protein 3 ( O60896 ) to inhibit glycolysis and induce reactive oxygen species and apoptosis . DB01278 , a synthetic analogue of amylin that is currently used to treat type 1 and type 2 diabetes , caused rapid tumour regression in p53-deficient thymic lymphomas , representing a novel strategy to target p53-deficient cancers . DB06779 , a low-molecular-weight heparin , promotes angiogenesis mediated by heparin-binding P15692 in vivo . Tumors are angiogenesis dependent and vascular endothelial growth factor-A ( P15692 ) , a heparin-binding protein , is a key angiogenic factor . As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin ( LMWH ) are common in cancer patients , we investigated whether angiogenesis in vivo mediated by P15692 is modulated by metronomic-type treatment with : ( i ) the LMWH dalteparin ; ( ii ) low-dosage cytostatic epirubicin ; or ( iii ) a combination of these two drugs . Using the quantitative rat mesentery angiogenesis assay , in which angiogenesis was induced by intraperitoneal injection of very low doses of P15692 , dalteparin sodium ( Fragmin(®) ) and epirubicin ( Farmorubicin(®) ) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days . DB06779 was administered at 27 , 80 , or 240 IU/kg/day , i.e. , doses that reflect the clinical usage of this drug , while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day . While dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner , epirubicin did not significantly affect angiogenesis . However , concurrent treatment with dalteparin and epirubicin significantly inhibited angiogenesis . The effect of dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo . The fact that co-treatment with dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect . [ Peptide fragments of chemokine domain of fractalkine : effect on human monocyte migration ] . Leukocyte chemotaxis to the area of tissue damage is mediated by chemokines . According to the primary structure , chemokines are divided into four families , fractalkine ( P78423 ) is the only one member of CX3C family and the only membrane-bound chemokine . P78423 molecule includes the extracellular N-terminal chemokine domain , mucin-like rod , the transmembrane and the intracellular domains . In membrane-bound state fractalkine has the properties of an adhesion molecule . Chemokine domain of fractalkine ( P05231 ) is released from cell membrane by proteolysis , and this soluble form acts as a chemoattractant for leukocytes expressing fractalkine receptor P49238 . P78423 is involved in development of a number of pathological processes caused by inflammation , and therefore a search for fractalkine inhibitors is very important . For this purpose we identified several antigenic determinants -- the fragments of P05231 , and the following peptides were synthesized -- P41-52 H- DB00149 - DB00142 - DB00156 - DB00125 -Gln- DB00117 - DB00125 - DB00149 - DB00120 - DB00151 -Ala- DB00128 -NH2 , P04637 -60 H-Pro-Lys- DB00142 -Gln- DB00150 - DB00161 -Lys- DB00128 -NH2 and O14879 -71 H- DB00128 -Ala- DB00134 -Gln- DB00117 - DB00149 - DB00128 - DB00125 -Gln-Ala-Ala-Ala-NH2 . The peptide effects on adhesion and migration of human peripheral blood monocytes expressing fractalkine receptors were investigated . In the presence of P05231 and P41-52 we observed the increased adhesion and migration of monocytes compared with spontaneous values . Peptides P04637 -60 and O14879 -71 significantly inhibited monocyte adhesion and migration stimulated by P05231 . Since the chemotactic activity of chemokines was shown to be dependent on their binding to glycosaminoglycans of the cell surface and extracellular matrix , the effect ofpeptides on the interaction of P05231 with heparin was analyzed by ELISA . Peptide P41-52 competed with P05231 for heparin binding , while peptides P04637 -60 and O14879 -71 had no significant activity .