interacts_with DB00714?
No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD . Results from pharmacogenetic investigations of methylphenidate ( DB00422 ) response in patients with ADHD are still inconsistent , especially among adults . This study investigates the role of genetic variants ( P31645 , P28222 , Q8IWU9 , P09172 , P21917 , P21964 , and P60880 ) in the response to DB00422 in a sample of 164 adults . Genes were chosen owing to previous evidence for an influence in ADHD susceptibility . No significant differences in allele or genotype frequencies between DB00422 responders and nonresponders were detected . In conclusion , our findings do not support an effect of these genes in the pharmacogenetics of DB00422 among adults with ADHD . Rosiglitazone regulates P05231 -stimulated lipolysis in porcine adipocytes . Interleukin ( IL ) -6 , a proinflammatory cytokine , stimulates adipocyte lipolysis and induces insulin resistance in obese and diabetic subjects . However , the effects of the anti-diabetic drug rosiglitazone on P05231 -stimulated lipolysis and the underlying molecular mechanism are largely unknown . In this study , we demonstrated that rosiglitazone suppressed P05231 -stimulated lipolysis in differentiated porcine adipocytes by inactivation of extracellular signal-related kinase ( P29323 ) . Meanwhile , rosiglitazone enhanced the lipolysis response of adipocytes to isoprenaline . In addition , rosiglitazone significantly reversed P05231 -induced down-regulation of several genes such as perilipin A , peroxisome proliferators activated receptor gamma ( Q07869 & gamma ; ) , and fatty acid synthetase , as well as the up-regulation of P05231 mRNA . However , mRNA expression of Q07869 & gamma ; coactivator-1 alpha ( DB01053 -1 & alpha ; ) was enhanced by rosiglitazone in P05231 -stimulated adipocytes . These results indicate that rosiglitazone suppresses P05231 -stimulated lipolysis in porcine adipocytes through multiple molecular mechanisms . Genetics of Alzheimer 's disease . A rapidly evolving field . Genetic factors have a variable impact on Alzheimer 's Disease ( AD ) , ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD , where a polygenic component is present . Most genes conferring susceptibility to AD are related to amyloid-beta deposition ( P05067 ; P49768 ; PS2 ; P02649 ; P01034 ; ubiquilin-1 ) , oxidative stress ( NOS2 ; NOS3 ) and inflammatory response ( P01583 ; P01584 ; P05231 ; P01375 ) . Genome-wide analyses , transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability . Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes ( P21964 ) , transporters ( 5-HTTLPR ) and receptors ( P21728 ; P35462 ) . Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia , while it is generally not recommended as a predictive testing for AD in asymptomatic individuals . Drugs currently in use to treat AD are effective in only 20 % of patients ; their therapeutic effect is predominantly under genetic control ( O43174 gene ; P02649 ) . Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression , schizophrenia and ADHD . The study of gene-environment interactions in AD , that are still poorly understood , is essential to predict disease-risk in asymptomatic individuals . Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs . Catalog of 178 variations in the Japanese population among eight human genes encoding G protein-coupled receptors ( GPCRs ) . We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms ( SNPs ) in eight genes encoding G protein-coupled receptors ( GPCRs ) by directly sequencing the entire relevant genomic regions except for repetitive-sequence elements . This approach identified 147 SNPs and 31 insertion/deletion polymorphisms among the eight GPCR genes . On average , we identified one SNP in every 584 nucleotides . Of the 147 SNPs , 69 were identified in P30556 , 12 in P50052 , nine in P35414 , 20 in P37288 , nine in P30518 , 16 in P21728 , six in P08514 , and six in P43119 . Twenty-one SNPs were located in 5' flanking regions , 76 in introns , 32 in exons , and 18 in 3' flanking regions . These variants should contribute to investigations of possible correlations between genotypes and phenotypes as regards susceptibility to disease or responsiveness to drug therapy . Xaliproden ( SR57746A ) induces P08908 receptor-mediated Q96HU1 kinase activation in PC12 cells . Neurotrophic growth factors are involved in cell survival . However , natural growth factors have a very limited therapeutic use because of their short half-life . In the present study , we investigated the mechanism of action of a non-peptidic neurotrophic drug , Xaliproden , a potential molecule for the treatment of motoneuron diseases , since the transduction pathways of this synthetic P08908 agonist are very poorly understood . Xaliproden does not activate the Trk receptor but causes a rapid increase in the activities of the P27361 and P28482 isoforms of Q96HU1 kinase , which then rapidly decrease to the basal level . We demonstrate that isoforms of the P29353 adapter protein are phosphorylated independently of each other and are probably not the source of the Xaliproden-induced Q96HU1 kinases activation . The inhibitor of Ras farnesylation , FPT-1 , and the protein kinase C inhibitors , GF 109203X and chelerythrine , inhibited the Xaliproden-induced Q96HU1 kinase activation , suggesting p21Ras and PKC involvement . Moreover , the observations that the P08908 antagonist , pindobind , and pertussis toxin abolished the Xaliproden-induced P29323 stimulation suggested that Xaliproden activates the Q96HU1 kinase pathways by stimulating the G protein-coupled receptor , P08908 . These results demonstrate clearly that the non-peptidic compound , Xaliproden , exerts its neurotrophic effects through a mechanism of action differing from that of neurotrophins . These findings suggest that this compound does not involve MAPK activation by TrkA receptor stimulation but acts by Q96HU1 kinase pathway by a pertussis toxin-sensitive mechanism involving P08908 receptors , P38936 Ras and MEK-1 and by PKC and Akt pathways . Association testing of panic disorder candidate genes using Q13308 challenge in healthy volunteers . Despite continuing efforts to determine genetic vulnerability to panic disorder ( PD ) , the studies of candidate genes in this disorder have produced inconsistent or negative , results . Laboratory panic induction may have a potential in testing genetic substrate of PD . In this study we aimed to explore the effects of several genetic polymorphisms previously implicated in PD on the susceptibility to cholecystokinin-tetrapeptide ( Q13308 ) challenge in healthy subjects . The study sample consisted of 110 healthy volunteers ( 47 males and 63 females , mean age 22.2 +/- 5.2 ) who participated in Q13308 challenge test . Nine gene-candidates , including 5-HTTLPR , P21397 VNTR , Q8IWU9 rs1386494 , 5- P08908 -1019C-G , 5- P28223 102T-C , CCKR1 246G-A , CCKR2 -215C-A , P21728 -94G-A and P21964 Val158Met , were selected for genotyping based on previous positive findings from genetic association studies in PD . After Q13308 challenge , 39 ( 35.5 % ) subjects experienced a panic attack , while 71 subjects were defined as non-panickers . We detected significant differences for both genotypic and allelic frequencies of 1386494A/G polymorphism in Q8IWU9 gene between panic and non-panic groups with the frequencies of G/G genotype and G allele significantly higher in panickers . None of the other candidate loci were significantly associated with Q13308 -induced panic attacks in healthy subjects . In line with our previous association study in patients with PD , we detected a possible association between Q8IWU9 rs1386494 polymorphism and susceptibility to panic attacks . Other polymorphisms previously associated with PD were unrelated to Q13308 -induced panic attacks , probably due to the differences between complex nature of PD and laboratory panic model . Association of platelet P08514 and P05106 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects . DB08816 ( Q8NDX1 ) is the first reversible Q9H244 receptor antagonist that exhibits rapid antiplatelet effect by indirect inhibition of the P08514 /IIIa complex . Polymorphisms in genes coding P08514 /IIIa , namely P08514 and P05106 , are associated with aspirin resistance and risk for thrombotic diseases . We assessed whether P08514 and P05106 polymorphisms can influence the ex vivo antiplatelet activity of ticagrelor in Chinese population . A total of 196 healthy Chinese male individuals were recruited . ADP-induced platelet aggregation was determined using optical aggregometry at baseline and after incubation of the platelet-rich plasma with 15 and 50 μM ticagrelor , respectively . Single nucleotide polymorphisms in P08514 ( rs5911 G > T ) and P05106 ( rs4642 A > G and rs4634 G > A ) were genotyped by sequencing . Q8NDX1 at both concentrations of 15 and 50 μM decreased ADP-induced platelet aggregation significantly ( P < 0.05 , respectively ) . As compared to P08514 rs5911 GG homozygotes , individuals with the rs5911 TG genotype showed significantly increased inhibition of platelet aggregation ( IPA ) by both 15 and 50 μM ticagrelor incubation ( P < 0.05 , respectively ) . Neither rs4642 nor rs4634 polymorphism affected ticagrelor-induced IPA . We suggest that the P08514 rs5911 GG genotype is associated with decreased ex vivo antiplatelet activity of ticagrelor in healthy Chinese male subjects . DB02546 and bortezomib synergistically cause ubiquitinated protein accumulation in prostate cancer cells . PURPOSE : Protein ubiquitination is a novel strategy used to treat malignancies . We investigated whether the histone deacetylase inhibitor vorinostat ( Cayman Chemical , Ann Arbor , Michigan ) and the proteasome inhibitor bortezomib ( LC Laboratories , Woburn , Massachusetts ) would synergistically cause the accumulation of ubiquitinated proteins in prostate cancer cells . MATERIALS AND METHODS : LNCaP , PC-3 and DU 145 cells ( ATCC™ ) were treated with vorinostat and/or bortezomib . Cell viability and induction of apoptosis were assessed . In vivo efficacy was evaluated in a murine subcutaneous tumor model using PC-3 cells . The influence of androgen receptor expression on bortezomib efficacy was examined using RNA interference . Changes in the expression of ubiquitinated proteins , cell cycle associated proteins and acetylated histone were evaluated . RESULTS : P10275 expression seemed to decrease bortezomib activity . PC-3 and DU 145 cells were more susceptible to bortezomib than LNCaP cells and the silencing of androgen receptor expression in LNCaP cells enhanced bortezomib activity . DB02546 and bortezomib synergistically induced apoptosis , inhibited prostate cancer cell growth and suppressed tumor growth in a murine xenograft model . The combination decreased cyclin D1 and cyclin-dependent kinase 4 expression , and increased P38936 expression . The combination synergistically caused the accumulation of ubiquitinated proteins and histone acetylation . This histone acetylation was a consequence of the accumulation of ubiquitinated proteins . CONCLUSIONS : DB02546 and bortezomib inhibit the growth of prostate cancer cells synergistically by causing ubiquitinated proteins to accumulate in cells . The current study provides a framework for testing the combination in patients with advanced prostate cancer . Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine P13500 in the central nervous system . Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation . This involves cellular migration across various structures associated with the blood-brain barrier : the vascular endothelium , the glia limitans , and the perivascular space between them . Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic ( Tg ) mice that overexpress P13500 under control of a CNS-specific promoter . The Tg mice show no clinical symptoms , even though leukocytes have crossed the endothelial basement membrane . Pertussis toxin ( PTx ) given i.p. induced encephalopathy and weight loss in Tg mice . We used flow cytometry , ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging , and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma , identifying this as the critical step in inducing clinical symptoms . Metalloproteinase ( MPs ) enzymes are implicated in leukocyte infiltration in neuroinflammation . Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1 , matrix metalloproteinase ( MMP ) -10 , and -12 mRNA in the brain . PTx further induced expression of tissue inhibitor of metalloproteinase-1 , metalloproteinase disintegrins-12 , P22894 , and -10 in brains of Tg mice . Levels of the microglial-associated MP P51511 were not affected in control or PTx-treated Tg mice . PTx also up-regulated expression of proinflammatory cytokines IL-1beta and P01375 mRNA in Tg CNS . Weight loss and parenchymal infiltration , but not perivascular accumulation , were significantly inhibited by the broad-spectrum MP inhibitor BB-94/ DB03880 . Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation , such as multiple sclerosis . P06401 level as a predictor of response to megestrol acetate in advanced breast cancer : a retrospective study . DB00351 ( 160 mg/day ) produced a response rate of 44 % in a retrospective series of 39 evaluable patients with advanced breast cancer . The estrogen-receptor ( ER ) level was greater than 10 fmols/mg of protein in 28 patients , and the progesterone-receptor ( PR ) level was greater than 10 fmols/mg of protein in 26 patients . ER and PR levels , age , and disease-free interval were analyzed for their relationship to response . The PR was the single best predictor of response to megestrol acetate ; the addition of ER added 2 % to the predictive accuracy rate of PR alone . Post-synaptic P08908 receptor involvement in yawning and penile erections induced by apomorphine , physostigmine and mCPP in rats . DB00714 and mCPP induced yawning associated with penile erections in rats , whereas physostigmine induced only yawns . DB00714 -induced yawning and penile erections were antagonized by low doses of raclopride , whereas physostigmine-induced yawning and mCPP-induced effects were only partly inhibited at high doses of raclopride . DB00747 as well as clozapine antagonized yawning and penile erections induced by apomorphine , mCPP and physostigmine . Similarly , the P08908 agonists 8-OH-DPAT and S 14506 inhibited yawning and penile erections induced by apomorphine , mCPP and physostigmine , and at similar doses induced lower lip retraction and hyperreactivity to handling . The beta/ P08908 antagonist tertatolol reversed the inhibitory effects of 8-OH-DPAT and S 14506 on drug-induced yawning and penile erections and increased apomorphine- and physostigmine-induced yawn frequency but not penile erection frequency . Like tertatolol , propranolol increased apomorphine- and physostigmine-induced yawn frequency , whereas ICI 118551 increased only physostigmine-induced yawning . 8-OH-DPAT- and S 14506-induced lower lip retraction and hyperreactivity to handling were also significantly antagonized by tertatolol . Finally , p-chlorophenylalanine pretreatment produced about 95 % depletion in 5-HT in hypothalamus , hippocampus , striatum and frontal cortex and modified neither the responses of the inducing drugs nor the inhibitory effects of 8-OH-DPAT and S 14506 on drug-induced yawning and penile erections. ( ABSTRACT TRUNCATED AT 250 WORDS ) DB00714 -induced aggressiveness and [3H]citalopram binding after antidepressant treatment in rats . The effects of acute and repeated administration of antidepressive drugs on apomorphine-induced aggressive behavior and [3H]citalopram binding were studied . In acute behavioral experiments with apomorphine pretreated ( 1.0 mg/kg , once daily ) animals , desipramine ( 10 mg/kg ) and clomipramine ( 10 mg/kg ) enhanced , buspirone ( 2.5 and 5.0 mg/kg ) completely blocked , but fluoxetine , amitriptyline , imipramine ( 10 mg/kg ) , and citalopram ( 10 and 20 mg/kg ) had no effect on the intensity of aggressive behavior . Repeated concomitant apomorphine ( 1.0 mg/kg ) and citalopram ( 10 mg/kg ) administration reduced the affinity ( Kd ) of the 5-HT transporter binding sites in three brain regions . This finding was confirmed by an additional experiment as the effect of citalopram treatment . Repeated apomorphine ( 1.0 mg/kg ) or apomorphine ( 1.0 mg/kg ) plus desipramine ( 10 mg/kg ) treatment had no unidirectional effect on Kd , the maximal number of apparent binding sties ( Bmax ) was unchanged in all experiments . Our study indicates that the 5-HT reuptake blockade has no major influence on the apomorphine-induced aggressive behavior , but the P08908 receptor subtype may be involved in the mediation of the aggressive behavior in this paradigm . Allele frequencies of single nucleotide polymorphisms ( SNPs ) in 40 candidate genes for gene-environment studies on cancer : data from population-based Japanese random samples . Knowledge of genetic polymorphisms in gene-environment studies may contribute to more accurate identification of avoidable risks and to developing tailor-made preventative measures . The aim of this study was to describe the allele frequencies of single nucleotide polymorphisms ( SNPs ) of select genes , which may be included in future gene-environment studies on cancer in Japan . SNP typing was performed on middle-aged Japanese men randomly selected from the general population in five areas of Japan . We genotyped and calculated allele frequencies of 153 SNPs located on 40 genes : P04798 , Q16678 , P11712 , P33261 , P05181 , P05093 , P11511 , P35869 , P03372 , Q92731 , ERRRG , P06401 , P07099 , P34913 , P37059 , P37058 , P28161 , P21266 , GSTT2 , P09211 , NAT1 , NAT2 , P21964 , P07327 , P00325 , P00326 , P05091 , P35228 , NOS3 , P01583 , P01584 , O15527 , P36639 [ P36639 ] , P14416 , P35462 , P21917 , P31645 , P04150 [ GCCR ] , P42898 , and P15559 . In the present study , the Japanese allele frequencies were verified by using nationwide population samples . Sex steroid receptors , secondary bile acids and colorectal cancer . A possible mechanism of interaction . AIM : The aim of the work was to study in colon-rectum cancer mucosae the binding charateristics , as sex steroid receptors . METHODS : Specific androgen ( AR ) , estrogen ( ER ) and progesterone ( PgR ) receptors were measured in the tissue samples of 35 patients ( 15 males , 20 females ) undergoing colectomy or coloproctectomy for adenocarcinoma . The characteristics of androgen receptor ( AR , DB02901 -R : dihydrotestosterone receptor ) were also investigated using competitive activity of cyproterone acetate , cortisol , aldosterone and steroid-like substances such as deoxycholic and lithocholic acid , present in the milieu of the considered organ . Binding assays and competition tests were conducted using a charcoal dextran method . RESULTS : When present ( 50 % ) , ER and PgR receptors showed very low levels and no difference was noted between cancerous and the surrounding healthy mucosa . AR were found in all samples from both neoplastic and non neoplastic surrounding mucosa , with no significant difference . P10275 however exhibited an altered binding activity in cancer specimens . DB04839 did not displace DB02901 from AR while significant displacing activity was elicited by DB02901 , testosterone , as well as by lithocholic acid , but not by deoxycholic acid . CONCLUSION : In cancerous large bowel mucosa , androgen receptors show altered binding characteristics . The selective binding of lithocholic acid to AR supports the hypothesis that diet-related endoluminal substances may play a role in cancer development model where molecular alterations such as DNA damage or mutation is the 1st event . Influence of P14416 and Q8NFD2 genotypes on apomorphine-induced growth hormone ( GH ) response in alcohol-dependent patients . BACKGROUND : D(2) receptor function can be assessed by growth hormone ( GH ) response to apomorphine . Several association studies between dopamine receptor polymorphisms and results of the apomorphine challenge test with normal and alcohol-dependent subjects yielded inconsistent results . In this pilot study , we tested polymorphisms from the P14416 region for GH response to apomorphine challenge in more detail . METHODS : DB00714 challenge tests measuring GH responses on 5 time points were performed on day 1 of alcohol detoxification in 43 patients with alcohol dependence ; patients were genotyped for 11 polymorphisms including P14416 , Q8NFD2 , P13591 and Q9H892 . RESULTS : Associations ( p < 0.05 ) were found for Q8NFD2 ( rs11604671 , rs1800497 ) and P14416 ( rs6276 , rs1076560 ) , which are located on adjacent chromosomal positions . Consistent with PET studies suggesting a reduced D(2) receptor availability in patients carrying the Q8NFD2 rs1800497 T polymorphism ( formerly known as P14416 TaqI A1 ) we found a reduced GH response to apomorphine in those subjects . CONCLUSION : This has been the first study showing significant associations between apomorphine-induced GH response and SNPs in P14416 and Q8NFD2 in alcohol-dependent patients . In this respect , our preliminary results are in line with other reports which suggested that P14416 and Q8NFD2 polymorphisms influence D(2) receptor availability and signal transduction in the dopaminergic pathways . Small sample size in our study limits the generalizability of our results . PPARgamma activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via SOD-mediated down-regulation of superoxide . Native LDL would be a mitogenic and chemotactic stimulus of VSMC proliferation and differentiation in the atherosclerotic lesion where endothelial disruption occurred . In previous studies , our group investigated the molecular mechanisms by which LDL induces P10145 production and by which PPARalpha activation abolishes LDL effects in human aortic SMCs ( hAoSMCs ) . Herein is the first report of PPARgamma activation by troglitazone ( TG ) exerting its inhibitory effects on LDL-induced cell proliferation via generation not of H(2)O(2) , but of O2(.-) , and the subsequent activation of Erk1/2 in hAoSMCs . Moreover , in this study TG abolished the LDL-accelerated G(1)-S progression to control levels via down-regulation of active cyclinD1/ P11802 and cyclinE/ P24941 complexes and up-regulation of P38936 (Cip1) expression . TG exerted its anti-proliferative effects through the up-regulation of basal superoxide dismutase ( SOD ) expression . This data suggests that the regulation of O2(.-) is located at the crossroads between LDL signaling and cell proliferation . The P38936 codon 31*C- and P14416 codon 313*T-related genotypes/alleles , but not P18887 codon 399 , hOGG1 codon 326 , and P21728 -48 polymorphisms , are correlated with the presence of leiomyoma . OBJECTIVE : To investigate whether the gene polymorphisms for P38936 , X-ray repair cross-complementing group 1 ( P18887 ) , human 8-oxoguanine glycosylase 1 ( hOGG1 ) , and dopamine D1 and D2 receptors ( P21728 , -2 ) are associated with leiomyoma susceptibility . DESIGN : Prospective study . SETTING : Departments of gynecology and genetics in a medical center . PATIENT(S) : Women were divided into two groups : leiomyoma ( n = 120 ) and nonleiomyoma ( n = 112 ) . INTERVENTION(S) : The P38936 codon 31 , P18887 codon 399 , hOGG1 codon 326 , P21728 -48 , and P14416 codon 313 polymorphisms were genotyped by polymerase chain reaction with restriction enzyme digestions ( Blp I , MspI , Fnu4HI , Dde I , and NcoI , respectively ) . MAIN OUTCOME MEASURE(S) : Genotypes and allelic frequencies . RESULT(S) : The P38936 codon 31(*)C- and P14416 codon 313(*)T-related genotypes/alleles were associated with the presence of leiomyomas . The proportions of P38936 (*)CC/CA/AA and P14416 (*)CC/CT/TT in both groups were 27.5/68.3/4.2 % and 12.5/51.7/35.8 % ( leiomyoma ) ; and 14.3/51.8/33.9 % and 33.9/40.2/25.9 % ( nonleiomyoma ) . P18887 , hOGG1 , and P21728 were not correlated with the presence of leiomyomas . P18887 (*)GG/GA/AA , hOGG1(*)TT/TA/AA , and P21728 (*)GG/GA/AA were 54.2/37.5/8.3 % , 36.7/44.2/19.1 % , and 3.3/25.8/70.8 % ( leiomyoma ) ; and 48.2/47.3/4.5 % , 43.6/41/15.4 % , and 3.6/25/71.4 % ( nonleiomyoma ) . CONCLUSION(S) : The P38936 codon 31(*)C- and P14416 codon 313(*)T-related genotypes/alleles were associated with the presence of leiomyoma . P18887 , hOGG1 , and P21728 were not correlated with leiomyoma development . Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma . Hepatoblastoma is an embryonal tumour of the liver , which often contains tissue components with multidirectional differentiation . The occurrence of cell surface antigens in this tumour has not been studied systematically , and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen ( P08473 ) and cell adhesion molecules ( CAMs ) in their different tissue components . Epithelial tumour cells of fetal differentiation contained P12830 . This protein did not occur in tumour areas with embryonal or mesenchymal differentiation . In contrast , immature embryonal and anaplastic cells expressed P08473 and the hyaluronate receptor ( HCAM , P16070 ) . Both fetal and embryonal areas stained irregularly positive for P05362 , which , in contrast , was not present on anaplastic cells . Immature fibrous tissue did not contain any of these molecules except for P05362 . However , some cells adjacent to , or enclosed in , osteoid were positive for HCAM and P13591 . Like small undifferentiated hepatoblastoma cells , primitive mesenchymal spindle-shaped cells also expressed P08473 , HCAM , and the polysialylated embryonic form of P13591 strongly . This last is not present on other epithelial or mesenchymal tumour cells . Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and P08473 . Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases . Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells . The higher frequency of lung adenocarcinoma in women smokers than in men smokers suggests a role for gender-dependent factors in the etiology of lung cancer . We evaluated estrogen receptor ( ER ) alpha and beta expression and activity in human lung adenocarcinoma cell lines and normal lung fibroblasts . Q8N1N2 -length ERalpha and ERbeta proteins were expressed in all cell lines with higher ERbeta than ERalpha . Although estradiol ( E(2) ) binding was similar , E(2) stimulated proliferation only in cells from females , and this response was inhibited by anti-estrogens 4-hydroxytamoxifen ( DB04468 ) and DB00947 . In contrast , E(2) did not stimulate replication of lung adenocarcinoma cells from males and DB04468 or ICI did not block cell proliferation . Similarly , transcription of an estrogen response element-driven reporter gene was stimulated by E(2) in lung adenocarcinoma cells from females , but not males . P06401 ( PR ) expression was increased by E(2) in two out of five adenocarcinoma cell lines from females , but none from males . E(2) decreased P12830 protein expression in some of the cell lines from females , as it did in MCF-7 breast cancer cells , but not in the cell lines from males . Thus , ERalpha and ERbeta expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells . On the other hand , coactivator Q15648 expression was higher in lung adenocarcinoma cells from females versus males and higher in adenocarcinoma cells than in normal human bronchial epithelial cells . Q15648 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males . Comparison of effects of a range of 5-HT receptor modulators on consumption and preference for a sweetened ethanol solution in rats . This study assessed the effects of a range of serotonergic agents on preference for a slightly sweetened ethanol solution ( 10 % ethanol , 3 % glucose ) in rats . A two-bottle , free-choice paradigm was used following induction of ethanol consumption . The model used provides a robust and reliable level of ethanol self-administration in normal laboratory rats . DB00898 consumption was significantly and selectively reduced by the 5-hydroxytryptamine-1A ( P08908 ) full agonist 8-OH-DPAT ( 0.3-1.0 mg/kg ) and the 5- Q9H205 antagonist granisetron ( 0.1-1.0 mg/kg ) . Non-specific reductions in fluid consumption were induced by the P28222 agonist RU 24969 ( 0.1-1.0mg/kg ) and the 5-HT2 antagonist ritanserin ( 1.0-6.0 mg/kg ) . These studies thus confirm the potential for decreasing ethanol consumption and ethanol preference of P08908 agonists and 5- Q9H205 antagonists , but failed to find any selective effects for agents acting at P28222 or 5-HT2 receptors . Is phentermine an inhibitor of monoamine oxidase ? A critical appraisal . DB00191 produces a spectrum of concentration-dependent biochemical effects . It interacts with NE transporters at 0.1 microM , DA transporters at about 1 microM , 5-HT transporters at 15 microM and P21397 at about 100 microM . When administered at typical anorectic doses , phentermine primarily interacts with DA and NE transporters and does not produce biochemical or neurochemical effects which would occur if it were inhibiting P21397 . Some other explanation other than MAO inhibition must be sought to explain how oral phentermine increases platelet 5-HT , since platelet P27338 does not metabolize platelet 5-HT , and since amphetamine-type drugs are even weaker inhibitors of P27338 than P21397 . Clinical studies in humans have shown that amphetamine , which is a more potent inhibitor of P21397 than phentermine , does not inhibit P21397 at therapeutic doses . Neither phentermine alone , fluoxetine alone or their combined use have been associated with cardiac valvulopathy , and clinical experience has shown their combined use to be free of significant adverse effects . Viewed collectively , there appears to be no data to support the hypothesis that phentermine inhibits MAO at typical therapeutic doses . Determination of fenofibric acid concentrations by HPLC after anion exchange solid-phase extraction from human serum . Triglycerides are increasingly being recognized as a risk factor for cardiovascular disease . Research efforts to identify sources of variability in triglyceride-lowering response to the lipid-lowering drug fenofibrate require quantification of the active acidic form of this Q07869 agonist . Anion-exchange solid-phase extraction , in combination with reverse-phase high-performance liquid chromatography ( HPLC ) , rapidly and accurately determines steady-state fenofibric acid serum concentrations . Chromatographic separation under isocratic conditions , with use of ultraviolet detection at 285 nm , provides clean baseline and sharp peaks for clofibric acid , 1-napthyl acetic acid ( internal standards ) , and fenofibric acid . Commonly prescribed and over-the-counter nonsteroidal anti-inflammatory drugs ( NSAIDs ) were screened for assay interference , and the assay was employed to quantify fenofibric acid in more than 800 human subject specimens . DB01039 analysis was found to be linear over the range of 0.5 to 40 mg/L and was validated with either internal standard . Accuracies ranged from 98.65 % to 102.4 % , whereas the within- and between-day precisions ranged from 1.0 % to 2.2 % and 2.0 % to 6.2 % , respectively . NSAIDs had minimal interference with the assay , which succeeded in quantifying fenofibric acid in more than 843 of 846 serum samples from human subjects , many taking a variety of coadministered medications . Anion-exchange solid-phase extraction in combination with reverse-phase HPLC accurately determines steady-state fenofibric acid serum concentrations in humans without interference from NSAIDs or commonly administered medications . This method is suitable for quantification of fenofibric acid for clinical pharmacokinetic studies in patients with dyslipidemia . D2-dopamine receptor and alpha2-adrenoreceptor-mediated analgesic response of quercetin . DB04216 , a bioflavonoid ( 100-300 mg/kg ) produced dose dependent increase in tail-flick latency , the analgesic effect being sensitive to reversal by naloxone ( 1 mg/kg ) . Prior treatment with haloperidol ( 1 mg/kg ) , D1/D2 receptor antagonist haloperidol , sulpiride ( 50 mg/kg ) , a selective D2 receptor antagonist , yohimbine ( 5 mg/kg ) , a alpha2-adrenoreceptor antagonist but not by P35240 23390 a , selective D1 receptor antagonist blocked this response . DB00714 ( 1 mg/kg ) a mixed D1/D2 dopamine receptor agonist , and quinpirole ( 0.5 mg/kg ) , a selective D2 receptor agonist also produced antinociception , that was reversed by haloperidol ( 1 mg/kg ) , sulpiride ( 50 mg/kg ) , but not by yohimbine ( 5 mg/kg ) . The antinociceptive action of quercetin ( 200 mg/kg ) was potentiated by D2 agonist quinpirole ( 0.2 mg/kg ) . P21728 agonist SKF38393 ( 10 and 15 mg/kg ) failed to alter the antinociceptive effect of quercetin ( 200 mg/kg ) . DB04216 ( 200 mg/kg ) reversed reserpine ( 2 mg/kg-4 hr ) induced hyperalgesia , which was reversed by sulpiride but not by yohimbine . Thus , a role of dopamine D2 and alpha2-adrenoreceptors is postulated in the antinociceptive action of quercetin . Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese . DB00682 is a commonly used anticoagulant , whose dose needs to be determined for each individual patient owing to large inter-individual variability in its therapeutic dose . Although several clinical and genetic variables influencing warfarin dose have been identified , uncovering additional factors are critically important for safer use of warfarin . Through a genome-wide association study , we identified single-nucleotide polymorphism ( SNP ) rs2108622 [ cytochrome P450 , family 4 , subfamily F , polypeptide 2 ( P78329 ) ] as a genetic determinant of warfarin responsiveness for Japanese . Stratifying subjects who have been pre-classified according to the genotypes of SNP rs10509680 [ cytochrome P450 , family 2 , subfamily C , polypeptide 9 ( P11712 ) ] and SNP rs9923231 [ vitamin K epoxide reductase complex subunit 1 ( Q9BQB6 ) ] , based on their genotypes of rs2108622 allowed identification of subjects who require higher dose of warfarin . Incorporating genotypes of rs2108622 into a warfarin dosing algorithm that considers age , body surface area , status of amiodarone co-administration and genotypes of SNPs in the P11712 and Q9BQB6 genes improved the model 's predictability to 43.4 % . In this study , the association of P78329 with warfarin dose of the Japanese has been established for the first time . Besides , a warfarin dosing algorithm that incorporates genotypes of rs2108622 and amiodarone co-administration status was suggested for the Japanese . Our study also implied that common SNPs other than those in the P11712 , Q9BQB6 and P78329 genes that show strong effect on the therapeutic warfarin dose might not exist . The potential role of PD0332991 ( DB09073 ) in the treatment of multiple myeloma . INTRODUCTION : Multiple myeloma ( MM ) remains an incurable malignancy indicating a need for continued investigation of novel therapies . Recent studies have highlighted the role of cyclin-dependent kinases ( CDK ) in the pathogenesis of MM . PD0332991 ( DB09073 ) is an orally bioavailable , highly selective inhibitor of the P11802 /6-cyclin complex and downstream retinoblastoma protein ( Rb ) activation pathway that induces cell cycle arrest in the P55008 phase . AREAS COVERED : In this review , the authors summarize the role of the P11802 /6 signaling pathway in MM . They also summarize the development of PD0332991 as a specific inhibitor of P11802 /6 , and the reported preclinical and clinical data supporting the potential role of PD0332991 in MM . EXPERT OPINION : While PD0332991 is essentially cytostatic , inducing prolonged P55008 arrest , it enhances the cytotoxic effect of other agents effective in MM , including bortezomib and lenalidomide , as confirmed in early phase clinical trials . However , with a plethora of other drugs of different classes being tested in MM , further development of PD0332991 will depend on defining the most efficacious combination with least toxicity . An unexplored opportunity remains the potential protective effect of PD0332991 against lytic bone lesions of MM . The next few years are likely to better define the place of PD0332991 in the treatment of MM .