简介:AIMToinvestigatetherolesandinteractionsofmutThomolog(MTH)-1andhypoxia-induciblefactor(HIF)-1αinhumancolorectalcancer(CRC).METHODS:TheexpressionanddistributionofHIF-1αandMTH-1proteinsweredetectedinhumanCRCtissuesbyimmunohistochemistryandquantitativerealtimepolymerasechainreaction(qRT-PCR).SW480andHT-29cellswereexposedtonormoxiaorhypoxia.ProteinandmRNAlevelsofHIF-1αandMTH-1wereanalyzedbywesternblottingandqRT-PCR,respectively.InordertodeterminetheeffectofHIF-1αontheexpressionofMTH-1andtheamountof8-oxodeoxyguanosinetriphosphate(dGTP)inSW480andHT-29cells,HIF-1αwassilencedwithsmallinterferingRNA(siRNA).GrowthstudieswereconductedoncellswithHIF-1αinhibitionusingaxenografttumormodel.Finally,MTH-1proteinwasdetectedbywesternblottinginvivo.RESULTS:HighMTH-1mRNAexpressionwasdetectedin64.2%ofcases(54/84),andthiswassignificantlycorrelatedwithtumorstage(P=0.023)andsize(P=0.043).HIF-1αproteinexpressionwascorrelatedsignificantlywithMTH-1expression(R=0.640;P〈0.01)inhumanCRCtissues.HypoxicstressinducedmRNAandproteinexpressionofMTH-1inSW480andHT-29cells.InhibitionofHIF-1αbysiRNAdecreasedtheexpressionofMTH-1andledtotheaccumulationof8-oxo-dGTPinSW480andHT-29cells.Intheinvivoxenografttumormodel,expressionofMTH-1wasdecreasedintheHIF-1αsiRNAgroup,andthetumorvolumewasmuchsmallerthanthatinthemocksiRNAgroup.CONCLUSION:MTH-1expressioninCRCcellswasupregulatedviaHIF-1αinresponsetohypoxicstress,emphasizingthecrucialroleofHIF-1α-inducedMTH-1intumorgrowth.
简介:程序性死亡分子-1(PD-1)是T淋巴细胞膜表面表达的负向协同刺激分子,与其主要配体(PD-L1)形成通路后,可以减弱T淋巴细胞的免疫反应,甚至导致T淋巴细胞功能衰竭。PD-1/PD-L1信号通路在乙型肝炎病毒感染后的效应T细胞免疫耐受中具有重要作用,阻断该途径可能是抗病毒治疗的方向之一,具有良好的应用前景。
简介:AIM:Toanalyzethemismatchrepair(MMR)statusandtheARID1Aexpressionaswellastheirclinicopathologicalsignificanceingastricadenocarcinomas.METHODS:WeexaminedtheexpressionsofMMRproteinsandARID1Abyimmunohistochemistryinconsecutive489primarygastricadenocarcinomas.Theresultswerefurthercorrelatedwithclinicopathologicalvariables.RESULTS:ThelossofanyMMRproteinexpression,indicativeofMMRdeficiency,wasobservedin38cases(7.8%)andwassignificantlyassociatedwithanolderage(68.6±9.2vs60.4±11.7,P<0.001),afemalesex(55.3%vs31.3%,P=0.004),anantrallocation(44.7%vs25.7%,P=0.021),andadifferentiatedhistology(57.9%vs39.7%,P=0.023).AbnormalARID1Aexpression,includingreducedorlossofARID1Aexpression,wasobservedin109cases(22.3%)andwassignificantlycorrelatedwithlymphaticinvasion(80.7%vs69.5%,P=0.022)andlymphnodemetastasis(83.5%vs73.7%,P=0.042).ThetumorswithabnormalARID1AexpressionmorefrequentlyindicatedMMRdeficiency(47.4%vs20.2%,P<0.001).AmultivariateanalysisidentifiedabnormalARID1Aexpressionasanindependentpoorprognosticfactor(HR=1.36,95%CI:1.01-1.84;P=0.040).CONCLUSION:OurobservationssuggestthattheAIRD1Ainactivationisassociatedwithlymphaticinvasion,lymphnodemetastasis,poorprognosis,andMMRdeficiencyingastricadenocarcinomas.
简介:背景:研究表明神经肽S受体1(NPSR1)基因多态性与欧洲人群炎症性肠病(IBD)的遗传易感性相关,但尚无研究探讨两者在中国人群中的相关性。目的:探讨中国汉族人群中NPSR1基因多态性与IBD的关系。方法:收集武汉大学中南医院457例确诊IBD患者[溃疡性结肠炎(UC)组355例,克罗恩病(CD)组102例]和500名健康对照者,以PCR和测序技术分析NPSR1基因rs323922(C→G突变)、rs740347(G→C突变)位点多态性。结果:UC组与对照组间、CD组与对照组间rs323922、rs740347位点的基因型频率和等位基因频率差异均无统计学意义(P〉0.05)。基因型与IBD临床表型的相关性分析显示:①rs323922位点突变型CG基因型与男性CD(OR:0.441,95%CI:0.230~0.844)和结肠型CD(OR:0.425,95%CI:0.199~0.911)相关,为保护因素。②rs740347位点突变型CC基因型与CD早期发病(〈16岁)相关(OR:15.019,95%CI:2.634~86.470),突变型C等位基因与结肠型CD相关(OR:2.142,95%CI:1.709~4.294),两者均为危险因素。结论:NPSR1基因rs323922、rs740347位点多态性与中国汉族人群的IBD遗传易感性无关,但与IBD的某些临床表型有关。