简介:TherearetwopossibleoutcomeswhenDNAdamageoccursinnormalmammaliancells:eitherinductionofcell-cyclecheckpointwhichinhibitstheprogressofthecellcyclesaswellasactivatesDNArepairpathways,oractivationofapoptosistoeliminatedamagedcells.Thep53tumour-suppressorgeneplaysakeyroleinselectingthesepathways.Inourpresentworks,thehumangastriccancercelllineAGSwastreatedwithtripchlorolide,apotentantitumorcompoundpurifiedfromaChineseherbTripterygiumWilfordiiHook.Singlecellgelelectrophoresis(Cometassay)showedthatthetreatmentoftripchlorolideresultedinDNAdamageinAGScells.ThedamagedAGScellswentthroughapoptosis,whichwastime-anddose-dependent.
简介:Recentstudiesindicatethatcell-cyclecheckpointsaretightlycorrelatedwiththeregulationofapoptosis,inwhichp53playsanimportantrole.OurpresentworksshowthattheexpressionofE6/E7oncogenesofhumanpapillomavirusinHeLacellsisinhibitedinthepresenceofanti-tumorreagenttripchlorolide(TC),whichresultsintheup-regulationofp53inHeLacells.Interestingly,underthesameTC-treatment,thecellsattheearlyS-phasearemoresusceptibletoapoptosisthanthoseatthemiddleS-phasealthoughp53proteinisstabilizedtothesamelevelinbothsituations.Significantdifferenceisexhibitedbetweenthetwospecifiedexpressionprofiles.Furtheranalysisdemonstratesthatanti-apoptoticgenesurvivinisup-regulatedbyp53intheTC-treatedmiddle-Scells,whereasitisdown-regulatedbyp53intheTC-treatedearly-Scells.Takentogether,thepresentstudyindicatesthatthedifferentialp53-regulatedexpressionofsurvivinatdifferentstagesofthecellcycleresultsindifferentcellularoutputsunderthesameapoptosis-inducer.
简介:Toevaluatetheeffectofadenovirus-mediatedp53gene(Adp53)onapoptosisandradiosensitivityofhumangastriccarcinomacelllines.Methods:Recombinantadenovirusexpressingwild-typep53lineswithdifferentp53geneticstatus.p53proteinexpressionwasdetectedbyimmunohistochemistryassayandwesternblotassay.Cellsurvivalwasassessedusingaclonogenicassay.TUNELassaywasusedindeterminationofapoptosis.FourhumangastriccarcinomacellsinfectedwithAdp53wereirradiatedwith4GyandcellcycledistributionandSub-G1peakwereassayedbyflowcytometry.Results:G2/Marrest,apoptosisandinhibitionoftumorcellproliferationwereinducedbyinfectionatAdp53at100MOIwhichcausedhightransferrateofwild-typep53andstrongexpressionofp53proteininfourhumangastriccarcinomacells.Theradio-enhancementratioofAdp53at4Gywere3.0forWcell,3.6forMcell,2.2forneocelland2.5for823cellinvitro.Conclusion:ThisstudydemonstratedthatAdp53transferincreasedcellularapoptosisandradiosensitivityofhumangastriccarcinomacelllinesinvitroindependentlyoncellularintrinsicp53statusthussupportingthecombinationofp53genetherapywithradiotherapyinclinicaltrials.
简介:Abstract:Thisstudyinvestigatedtherelationshipbetweenhumanpapillomavirus(HPV)genotypeandexpressionofp53andp21^WAH1.Expressionofp53andp21^WAH1in35casesofcondylomaacuminatumspecimensinfectedbyHPV6/llandHPV16/18werestudiedusingimmunohistochemicalstaining.Allspecimensofthecondylomaacuminatumcasewerepositiveforexpressionofp53andp21^WAH1.Theexpressionofp53incondylomaacuminatuminfectedbyHPV16/18wassignificantlylowerthanthatinspecimensinfectedbyHPV6/ll.However,expressionofp21wAHbetweenthetwogroupswasnotsignificantlydifferent.Expressionofp53incondylomaacuminatumislikelyrelatedtoHPVgenotype,expressionofp21^WAH1wasnotrelatedtoHPVgenotype.
简介:目的探讨p27^kipl、p53蛋白在胃癌中的表达关系和预后意义。方法用免疫组化法同步检测20例胃良性病变标本及80例胃癌组织中pZ7、p53的表达。结果80例胃癌中p27蛋白阳性率为41,25%(33/80),低于胃良性病变标本100%(20/20),p53阳性率在胃癌中为43.75%(35/80),而在胃良性病变标本中为0。胃癌p27阳性组的p53阳性率为66.67%,显著高于p27阴性组(P<0.05),p27与p53呈正相关,p27与预后弱相关,p53与预后密切相关。结论p27、p53相互作用,对胃癌发生发展起重要作用;p27表达愈强,p53表达愈弱,说明预后较好,反之则差,联合检测pZ7、p53可辅助胃癌诊断,估计预后,选择治疗方案。
简介:Objective:Toinvestigatethepost-transcriptionalregulationofp21WAF1/CIP1byp53.Methods:TheMDA-MB-468cellshaveendogenousmutantp53andtheMCF7cellslineshavewtp53.Recombinantp53expressionandp21WAF1/CIP1inductionweredetectedbyWesternblotanalysis.Northernblotanalysiswascarriedouttoexaminewhetherchangesinp21WAF1/CIP1proteinlevelsinMCF7cellstreatedwithAdCMVp53arereflectedatthemRNAlevel.FlowcytometricanalysisofMCF7cellsfollowingoverexpressionofrecombination.Results:Theratioofp53:p21WAF1/CIP1wasbelow1attheearlystagesofAdCMVp53infection,butincreasedto1.6byday3andto9.7byday5post-infection.Asexpected,p21WAF1/CIP1expressionwasnotdetectableinMDA-MB-468cellsdespitethepresenceofhighlevelsofmutantp53protein.TheG1/SratiosinuntreatedcontrolsandAdCMVβgalinfectedMCF7cellswere1.10and1.35,respectively.ByNorthernblotanalyzingthep21WAF1/CIP1:GAPDHratiosatdifferenttimepointsagainsttheratioattimepoint0,amaximum3-foldinductionofp21WAF1/CIP1mRNAexpressionrelativetountreatedcontrolwasobservedonday1post-infection.TheflowcytometricanalysisindicatedthatMCF7cellsinfectedwithAdCMVp53undergoG1arrestatbothtimepointsstudied,withG1/Sratiosrangingfrom5.54atday1to5.65atday7.TheG1/SratiosinuntreatedcontrolsandAdCMVβgalinfectedMCF7cellswere1.10and1.35,respectively.Conclusion:Thisstudydemonstratedthatp53couldregulatep21WAF1/CIP1geneexpressionatboththetranscriptionalandpost-transcriptionallevelsinMCF7cells.Thelattermechanismmaybeinvolvedinorberesponsiblefor,theinductionofcellcyclearrestbytranscription-defectivemutantsofp53.
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简介:目的:探讨肺鳞癌p53免疫组化图像定量分析中描述图像色彩的指标在不同分化程度、不同临床分期及老年与非老年间的区别.方法:采用S-P法进行肺癌p53免疫组化染色,应用计算机病理图像分析系统(MPIAS-500)进行图像分析.结果:20例中没有高分化者,中分化组和低分化组p53阳性各6例.p53染色的饱和度中分化组(4.95%)低于低分化组(10.95%),差异有非常显著性(t=4.208,P=0.002),说明低分化组阳性较强.临床分期没有Ⅰ期者,Ⅱ期与Ⅲ期p53阳性分别为5例和7例,分期之间未显示出显著性差异.老年与非老年p53阳性各6例,两组之间红、绿、蓝色值及灰度均以老年组较高(183.62、177.52、164.02、175.05),而非老年组较低(166.48、157.18、139.82、154.48),差异具有非常显著性(t=3.668,P=0.004;t'=5.570,P=0.001;t=4.305,P=0.002;t'=5.586,P=0.001),表明非老年组肺鳞癌细胞阳性强度高于老年组.结论:p53在肺癌的发生发展中具有重要作用;描述图像色彩的指标用于肺癌免疫组化图像定量分析可以弥补其他指标的不足.
简介:Theexpressionofp53Protein,c-erbB-2oncoprotein,Proliferatingcennuclearantigen(usA)werestudiedbythestreptavidinperotidaseconjugated(S-P)immunohistochemicalmethodandDNAcontentinsituwastested,inordertoexplorethesignificanceofP53,c-erbB-2,PCNAinPrimallUng...
简介:目的:探讨Dixon手术直肠下端切缘p53基因突变情况及其与肿瘤预后的关系。方法:分析1990年以来Dixon直肠癌根治手术病人后三年以内死亡和生存五年以上两组病的临床情况,采用免疫组化的方法,检测两组不同生存期病人的直肠癌下段切缘p53基因突变率,结果:两病例在肿瘤们于直肠的位置和病理的淋志移率有显著差异,在两组直肠下端病理均未见癌的情况下,三年组p53突变检测分析3/19阳性,而五年组为2/24阳性,无显著性差异。结论:病理检查肿瘤切缘为正常细胞的部位,确实存在分子水平的、肿瘤相关异常基因细胞,表现为散在性点状,巢状分布,这应非一种孤立的、偶然的表现。
简介:目的:为了解P53蛋白异常表达与非小细胞肺癌(NSCLC)预后的关系。方法:采用S-P免疫组织化学法.检测90例手术切除的NSCLC组织石蜡包埋标本。结果:53.3%(48/90)的标本显示P53蛋白向染色阳性.肺鳞癌和腺癌的阴性率分别为64.3%(36/56)和35%(12/34)。统计学分析显示P53蛋白染色结果与病人年龄、性别及肿瘤分期无显著关系,但与肿瘤组织类型显著相关。P53蛋白染色阳性和阴性组病人中位生存月数分别是24个月和55个月。Kaplan-Meir图显示二组病人术后生存概率有明显差异。逐步回归多因素分析显示P53蛋白染色阳性与病人术后生存时间呈显著负相关。结论:P53蛋白异常表达是非小细胞肺癌预后不良的独立判断指标。
简介:ObjectiveToinviestigatetheexpressionofgallbladdercanceranditsrelationshipwitheaneeration.MethodsImmunohistoehemistrytechniquesareusedtodetecttheexpressionofp53proteinin36easesofgallbladdercancerand23adenoma.Resultsp53proteinwerefoundedpositivein19cases(52.78%)ofgallbloddercancer,in5cases(21.74%)ofadenoma.ConclusionThereiscloserelationshipbetweentheoverexpressionandthecancemtionofgallbladder,p53genemutationandoverexpressionareintheearlystageofgallbladdercancer,andplayanimportantroleinthecancemtionofadenoma.
简介:目的探讨膀胱肿瘤中免疫逃避作用引起的细胞凋亡与P53的关系.方法采用免疫组织化学方法检测33例移行细胞癌,8例膀胱腺癌及11例膀胱炎组织石蜡切片中Fas-L与P53的表达.结果P53及Fas-L在膀胱炎及肿瘤中的表达具有显著性差异(P<0.05),在膀胱腺癌与移行细胞癌中P53、Fas-L的表达无显著性差异(P>0.05).G1、G2、G3级中P53表达具有显著性差异(P<0.05),Fas-L的表达无显著性差异(P=0.07).在膀胱肿瘤中,20例P53阳性患者中14例Fas-L阳性(70%),P53与Fas-L表达无显著性差异(p=0.238)及相关性(p=0.393).结论P53可能通过免疫逃避作用使肿瘤细胞凋亡下降,但不是唯一因素.