简介:目的探讨表生长因子受体家族EGFR、HER-2与HER-3蛋白在大肠良恶性肿瘤的相关性表达及临床意义。方法选取肠镜病理证实的大肠增生性息肉114例,大肠腺瘤121例,大肠腺癌120例。应用免疫组织化学方法,单克隆抗体既用型二步法技术,检测EEGFR、HER-2与HER-3蛋白的表达水平。结果EGFR、HER-2与HER-3蛋白表达在增生性息肉组的阳性表达率均较低,分别为35.1%、43.9%与17.5%;大肠腺瘤和大肠腺癌组的阳性表达率均较高,分别为81.8%、78.5%与39.7%和59.2%、76.7%与46.7%。各组间比较有显著差异(P<0.01),EGFR蛋白表达在管状腺瘤与管状绒毛状腺瘤中的阳性表达率显著增高(P<0.01);管状腺瘤与管状绒毛状腺瘤组中的HER-2蛋白表达的阳性率有显著差异(P<0.05),HER-3蛋白表达的阳性率较低,差异无显著性(P>0.05)。大肠癌的病理类型中EGFR、HER-2与HER-3蛋白的阳性表达呈显著相关性(P<0.01)。结论大肠不同性质的粘膜中EGFR家族蛋白的表达起着不同的作用,其表达形式具有不同的特点;大肠癌的发生发展中,三种蛋白在信号传导过程中有共同作用。
简介:背景:结直肠癌(CRC)是常见的消化系统恶性肿瘤,具有高度侵袭性和转移性,病死率高。人表皮生长因子受体2(HER2)在多种肿瘤中存在高表达,可抑制肿瘤细胞凋亡,是肿瘤预后不良的指标之一。目的:研究CRC组织中的HER2表达及其与肿瘤临床病理特征和预后的关系。方法:连续收集2010年2月─2011年2月北京航天总医院118例CRC患者,采用免疫组化染色检测癌组织HER2表达水平,分析其表达与肿瘤临床病理参数和患者预后的关系。结果:CRC组织中HER2表达阳性率为34.7%(41/118),其中高表达18例(15.3%),低表达23例(19.5%)。HER2表达与肿瘤浸润深度、淋巴结转移、TNM分期显著相关(P〈0.05)。HER2表达阴性、低表达、高表达患者随访期内死亡率依次增高,组间两两比较差异均有统计学意义(P〈0.05)。Cox比例风险模型分析显示HER2是CRC患者预后的独立影响因素(RR=2.134,95%CI:1.172~2.415,P=0.006)。结论:HER2高表达与CRC临床分期和患者预后有关,有望成为CRC预后评估的生物学标记物。
简介:AIMTodeterminetheroleofcorticotropinreleasingfactorreceptor(CRF2)inepithelialpermeabilityandenterocytecelldifferentiation.METHODSForthispurpose,weusedratSpragueDawleyandvariouscoloncarcinomacelllines(SW620,HCT8R,HT-29andCaco-2celllines).ExpressionofCRF2proteinwasanalyzedbyfluorescentimmunolabelinginnormalratcolonandthenbywesternblotindissociatedcolonicepithelialcellsandinthelysatesofcoloncarcinomacelllinesorduringtheearlydifferentiationofHT-29cells(tenfirstdays).ToassesstheimpactofCRF2signalingoncoloniccelldifferentiation,HT-29andCaco-2cellswereexposedtoUrocortin3recombinantproteins(Ucn3,100nmol/L).Insomeexperiments,cellswerepre-exposedtotheastressin2b(A2b)aCRF2antagonistinordertoinhibittheactionofUcn3.Intestinalcelldifferentiationwasfirstanalyzedbyfunctionalassays:thetrans-cellularpermeabilityandthepara-cellularpermeabilityweredeterminedbyDextran-FITCintakeandmeasureofthetransepithelialelectricalresistancerespectively.Morphologicalmodificationsassociatedtoepithelialdysfunctionwereanalyzedbyconfocalmicroscopyafterfluorescentlabelingofactin(phaloidin-TRITC)andintercellularadhesionproteinssuchasE-cadherin,p120ctn,occludinandZO-1.Theestablishmentofmatureadherensjunctions(AJ)wasmonitoredbyfollowingthedistributionofAJproteinsinlipidraftfractions,afterseparationofcelllysatesonsucrosegradients.Finally,themRNAandtheproteinexpressionlevelsofcharacteristicmarkersofintestinalepithelialcell(IEC)differentiationsuchasthetranscriptionalfactorkrüppel-likefactor4(KLF4)orthedipeptidylpeptidaseIV(DPPIV)wereperformedbyRT-PCRandwesternblotrespectively.ThespecificactivitiesofDPPIVandalkalinephosphatase(AP)enzymesweredeterminedbyacolorimetricmethod.RESULTSCRF2proteinispreferentiallyexpressedinundifferentiatedepithelialcellsfromthecryptsofcolonandinhumancoloncarcinoma
简介:Medicaltherapyfortype2diabetesmellitusisineffectiveinthelongtermduetotheprogressivenatureofthedisease,whichrequiresincreasingmedicationdosesandpolypharmacy.Conversely,bariatricsurgeryhasemergedasacost-effectivestrategyforobesediabeticindividuals;ithaslowcomplicationratesandresultsindurableweightloss,glycemiccontrolandimprovementsinthequalityoflife,obesity-relatedco-morbidityandoverallsurvival.Thefindingthatglucosehomeostasiscanbeachievedwithaweightloss-independentmechanismimmediatelyafterbariatricsurgery,especiallygastricbypass,hasledtotheparadigmofmetabolicsurgery.However,theprimaryfocusofmetabolicsurgeryisthealterationofthephysio-anatomyofthegastrointestinaltracttoachieveglycemiccontrol,metaboliccontrolandcardio-metabolicriskreduction.Todate,metabolicsurgeryisstillnotwelldefined,asitisusedmostfrequentlyforlessobesepatientswithpoorlycontrolleddiabetes.Themechanismofglycemiccontrolisstillincompletelyunderstood.Publishedresearchfindingsonmetabolicsurgeryarepromising,butmanyaspectsstillneedtobedefined.Thispaperexaminestheproposedmechanismofdiabetesremission,theefficacyofdifferenttypesofmetabolicprocedures,thedurabilityofglucosecontrol,andtherisksandcomplicationsassociatedwiththisprocedure.Weproposeatailoredapproachfortheselectionoftheidealmetabolicprocedurefordifferentgroupsofpatients,consideringtheindicationsandprognosticfactorsfordiabetesremission.
简介:目的探讨微小RNA-363(miR-363)靶向调控E2F转录因子3(E2F3)的表达对HepG2细胞增殖和凋亡的影响。方法体外培养HepG2细胞,采用Lipofectamine法将miR-363抑制剂或其阴性对照转染到HepG2细胞,继续培养48h,收获细胞,采用四噻唑蓝(MTT)法测定细胞增殖率,使用流式细胞术法检测细胞凋亡率,采用实时荧光RT-PCR法检测HepG2细胞miR-363mRNA水平,采用WesternBlot法检测HepG2细胞E2F3、BAX和Caspase-3蛋白表达水平。结果对照组HepG2细胞增殖率为(96.4±9.7)%,显著高于抑制剂处理组【(72.3±6.5)%,P<0.05】,凋亡率为(8.2±1.4)%,显著低于抑制剂处理组【(9.7±0.8)%,P<0.05】;对照组HepG2细胞miR-363mRNA相对水平为(1.0±0.1),显著高于抑制剂处理组【(0.6±0.2),P<0.05】,E2F3蛋白表达量为(1.0±0.1),显著高于抑制剂处理组【(0.6±0.1),P<0.05】,而对照组HepG2细胞Bax和Caspase-3蛋白表达量分别为(0.4±0.0)和(0.5±0.1),均显著低于抑制剂处理组【(0.6±0.1)和(0.7±0.0),P均<0.05】。结论miR-363可靶向调控E2F3的表达,抑制HepG2细胞增殖,诱导其凋亡。本研究结果为肝癌靶向治疗提供了一定的理论依据。
简介:瞄准:Disabled-2(DAB2)是在卵巢的癌症识别否定地影响生长因素和块地岬活动的致有丝分裂信号转导变异的候选人tumor-suppressor基因。在最近的研究,我们用cDNA在ESCC观察了DAB2抄本的下面规定微数组。在现在的学习,我们试图在食道的肿瘤发生决定DAB2蛋白质的损失的临床的意义,假设那个DAB2倡导者调停hypermethylation的基因silencing可以说明蛋白质的损失。方法:DAB2表示被免疫组织化学在50主要食道的有鳞的房间分析癌(ESCC),30不同增生,15发育异常和10非恶意的食道的纸巾。决定倡导者hypermethylation是否在ESCC贡献DAB2表示的损失,DAB2倡导者的甲基化地位用methylation特定的PCR在DAB2免疫否定的肿瘤被分析。结果:DAB2蛋白质的损失在5/30(17%)被观察增生,10/15(67%)发育异常和34/50(68%)ESCC。DAB2蛋白质的重要损失从食道的正常粘膜被观察到增生,发育异常和侵略癌症(P(趋势)<0.001)。DAB2的倡导者hypermethylation在10中的2个被观察(20%)DAB2免疫否定的ESCC。结论:DAB2蛋白质表示的损失发生在食道的癌症的开发的早pre肿瘤的阶段并且在致瘤的小径下面被支撑。在ESCC的很少发生的DAB2倡导者甲基化建议渐成说基因silencing仅仅是在ESCC引起DAB2表示的损失的机制之一。
简介:肝脏的外分泌功能具有非常重要的作用,除了参与消化吸收以外,人体内大量化合物的代谢都需肝脏的处理并由胆汁排泄,这个外分泌过程就需要肝胆转运系统的参与,肝脏的转运系统中包含着许多的载体蛋白,这些载体蛋白与肝炎,肝内胆汁郁积,肿瘤化疗药物的耐受以及多种肝脏遗传性疾病有着密切的关系.本文所要综述的多药耐药相关蛋白2(themuhidrugresistanceprotein2,MRP2)就是这类载体中的一个.目前关于MRP2的研究主要集中在MRP2介导的肿瘤耐药以及MRP2缺乏所导致的高胆红素血症这两个方面.本文从MRP2的结构功能、与肿瘤化疗耐药之间的关系,MRP2缺乏与高胆红素血症之间的关系以及MRP2表达障碍时MRP3对其代偿作用等方面,对MRP2的研究进展作一简单介绍.
简介:瞄准:检验矩阵metalloproteinase-2(MMP-2)在胃的癌症纸巾并且到的表示与淋巴节点评估它的关系微转移。方法:作者从30学习了850淋巴结resected与淋巴腺切除术经历了胃切除术用的有胃的癌的病人颠倒抄写聚合酶链反应(RT-PCR)试金除了他染色。肿瘤纸巾的MMP-2表示被免疫检测组织化学的技术(EliVision加)。结果:MMP-2表示在21是积极的(70%)在9的盒子和negative(30%)盒子。没有重要关联在象年龄,性,肿瘤地点,肿瘤直径,Lauren分类和淋巴的侵略那样的MMP-2表示和另外的变量之间被发现。相反,MMP-2表示与肿瘤渗入的深度显著地相关(P=0.022),淋巴节点转移(P=0.030)并且肿瘤区别(P=0.043)。淋巴节点微转移在77被检测(12.5%)14的淋巴节点(46.7%)胃的癌病人。MMP-2表示在12是积极的(85.7%)有淋巴节点的14个病人微转移,并且在9(56.3%)没有淋巴节点的16个病人微转移(P=0.118)。结论:我们的结果证明那MMP-2表情与肿瘤侵略,肿瘤区别和淋巴节点转移有重要关联。MMP-2表示可以是一个重要生物特征和胃的癌的重要预示的参数。我们也断定MMP-2可以参予淋巴节点的发展胃的癌的微转移。进一步的调查被需要得出一个结论。
简介:AIM:ToinvestigatetheeffectofhepatitisBvirus(HBV)XgeneonapoptosisandexpressionsofapoptosisfactorsinXgene-transfectedHepG2cells.METHODS:TheHBVXgeneeukaryonexpressionvectorpcDNVA3-XwastransientlytransfectedintoHepG2cellsbylipid-mediatransfection.UntransfectedHepG2andHepG2transfectedwithpcDNA3wereusedascontrols.ExpressionofHBxinHepG2wasidentifiedbyPT-PCR.MTTandTUNELwereemployedtomeasureproliferationandapoptosisofcellsin.threegroups.Semi-quantifiedRT-PCRwasusedtoevaluatetheexpressionlevelsofFas/FasL,Bax/Bcl-xL,andc-mycineachgroup.RESULTS:HBVXgenewastransfectedintoHepG2cellssuccessfully.RT-PCRshowedthatHBxwasonlyexpressedinHepG2/pcDNA3-Xcells,butnotexpressedinHepG2andHepG2/pcDNA3cells.AnalyzedbyMTT,cellproliferationcapacitywasobviouslylowerinHepG2/pcDNA3-Xcells(0.08910±0.003164)thaninHepG2(0.14410±0.004927)andHepG2/pcDNA3cells(0.12150±0.007159)(P<0.05andP<0.01).AnalyzedbyTUNEL,cellapoptosiswasmuchmoreinHepG2/pcDNA3-Xcells(980/2000)thanHepG2(420/2000),HepG2/pcDNA3cells(520/2000)(P<0.05andP<0.01).Evaluatedbysemi-quantifiedRT-PCR,theexpressionlevelofFas/FasLwassignificantlyhigherinHepG2cellstransfectedwithHBxthaninHepG2andHepG2/pcDNA3cells(P<0.05andP<0.01).Bax/Bcl-xLexpressionlevelwasalsoelevatedinHepG2/pcDNA3-Xcells(P<0.05andP<0.01).Expressionofc-mycwasmarkedlyhigherinHepG2/pcDNA3-XcellsthaninHepG2andHepG2/pcDNA3cells(P<0.05andP<0.01).CONCLUSION:HBVXgenecanimpaircellproliferationcapacity,improvecellapoptosis,andupregulateexpressionofapoptosisfactors.TheinterventionofHBVXgeneontheexpressionofapoptosisfactorsmaybeapossiblemechanismresponsibleforthechangeincellapoptosisandproliferation.
简介:AIM:Toinvestigatetheefficacyofneoadjuvantchemoradiotherapy(NACRT)forresectabilityoflocallyadvancedgastriccancer(LAGC).METHODS:BetweenNovember2007andJanuary2014,29patientswithLAGC(clinicallyT3withdistalesophagusinvasion/T4orbulkyregionalnodemetastasis)thatweretreatedwithNACRTfollowedbyD2gastrectomywereincludedinthisstudy.ResectabilitywasevaluatedwithradiologicandendoscopicexamsbeforeandafterNACRT.Usingthreedimensionalconformalradiotherapy,patientsreceived45Gy,withadailydoseof1.8Gy.Theentiretumorextentandtheregionalmetastaticlymphnodeswereincludedinthegrosstumorvolume.PatientspresentingwitharesectabletumorafterNACRTreceivedatotalorsubtotalgastrectomywithD2dissection.ThepathologictumorresponsewasevaluatedusingJapaneseGastricCancerAssociationhistologicevaluationcriteria.PostoperativemorbiditywasevaluatedusingtheNationalCancerInstitute-CommonTerminologyCriteriaforAdverseEventsversion4.0.Overallsurvival(OS)andprogression-freesurvival(PFS)rateswereestimatedusingaKaplan-Meieranalysisandcomparedusingthelog-ranktest.RESULTS:Allpatientswereassessedasunresectablecases.Twenty-fourpatients(24/29;82.8%)showedLAGConpositronemissiontomography-computedtomography(CT)andcontrast-enhancedCT,whereasfourpatients(4/29;13.8%)withvagueinvasionorabutmenttoanadjacentorganunderwentdiagnosticlaparoscopy.Onepatient(1/29;3.4%),initiallyassessedasaresectablecase,underwentan'openandclosure'afterthetumorwasfoundtobeunresectable.Abutmenttoanadjacentorgan(34.5%)wasthemostcommonreasonforNACRT.TheclinicalresponserateonemonthafterNACRTwas44.8%.AfterNACRT,69%(20/29)ofpatientshadaresectabletumor.Ofthe20patientswitharesectabletumor,18patients(62.1%)underwentaD2gastrectomy.TheR0resectionratewas94.4%andtwopatients(2/18;11.1%)showedacompleteresponse.Themedianfollow-updurationwas13.5mo.Theone-yearOSandPFS
简介:AIM:Toinvestigateifanimmuneimbalancemayaccountforthedevelopmentandprogressionofchronicradiationenteritis.WeanalyzedtheTh1/Th2immuneresponseprofileearlyand6moafterfractionatedcolorectalirradiation.METHODS:Aratmodeloffractionatedcolorectalγ-irradiation(4-Gyfractions,3fractionsperweek)wasdesignedtoinvestigatetheeffectsofcumulativedoseoninflammatorymediators(cytokinesandchemo-kines)andimmuneresponse(Th1/Th2profileandim-munosuppressivemediatorIL-10)duringacute(early)responseand6moaftertheendoffractionatedirradia-tion(chronicresponse).Analyseswereperformed1dafterthecumulativedosesof16Gyand36Gyand1d,3d,and26wkafterthecumulativedoseof52Gy.RESULTS:Withoutcausinghistologicaldamage,fractionatedradiationinducedelevatedexpressionofIL-1β,TNFα,MCP-1,andiNOSindistalcolonicmucosaduringtheearlypost-irradiationphase.Atthattime,aTh2profilewasconfirmedbyexpressionofboththeTh2-specifictranscriptionfactorGATA-3andthechemokinereceptorCCR4andbysuppressionoftheTh1cytokineIFNγ/IP-10throughouttheirradiationprotocol.After6mo,despitethe2-foldreductionofiNOSandMCP-1levels,theTh2profilepersisted,asshownbya50%reductionintheexpressionoftheTh1transcriptionfactorT-bet,thechemokinereceptorCCXCR3,andtheIFNγ/STAT1pathway.Atthesametime-point,theimmuno-suppressiveIL-10/STAT3pathway,knowntoregulatetheTh1/Th2balance,wasexpressed,inirradiatedrats,atapproximatelyhalfitslevelascomparedtocontrols.ThissuppressionwasassociatedwithanoverexpressionofSOCS3,whichinhibitsthefeedbackoftheTh1polarizationandregulatesIL-10production.CONCLUSION:ColorectalirradiationinducesTh2polarization,defectiveIL-10/STAT3pathwayactivationandSOCS3overexpression.Thesechanges,inturn,maintainaimmunologicalimbalancethatpersistsinthelongterm.