简介:Glioblastoma(GBM)isoneofthemostlethalhumancancers.GenomicanalysesdefinethemoleculararchitectureofGBMandhighlightacentralfunctionformechanistictargetofrapamycin(mTOR)signaling.mTORkinaseexistsintwomultiproteincomplexes,namely,mTORC1andmTORC2.Thesecomplexesdifferintermsoffunction,regulationandrapamycinsensitivity.mTORC1iswellestablishedasacancerdrugtarget,whereasthefunctionsofmTORC2incancer,includingGBM,remainspoorlyunderstood.ThisstudyreviewstherecentfindingsthatdemonstrateacentralfunctionofmTORC2inregulatingtumorgrowth,metabolicreprogramming,andtargetedtherapyresistanceinGBM,whichmakesmTORC2asacriticalGBMdrugtarget.
简介:Objective:Toinvestigatetheeffectofbreast-conservationtherapyinearlystagebreastcancer.Methods:Atotalof234earlystagebreastcarcinomapatientsreceivedbreastconservingtreatmentinourhospital.Aftertheoperation,theyunderwentadjuvantchemotherapyandradiotherapy.Allofthesepatientsdesiredtopreservetheirbreasts.Results:Aftermedianfollow-upof29.46months(rangefrom3to100months),3caseshadlocalrelapseand8caseshaddistantmetastasis.Theoverallsurvivalrateof5yearwas96.7%,andthediseasefreesurvivalrateof5yearwas87.85%.Conclusion:Forearlystagebreastcarcinomapatients,classicquadrantectomy,axillarydissectionandpost-operativeadjuvantchemotherapyandradiotherapyleadtoexcellentlocalcontrolandgoodsurvival.
简介:目的总结门静脉压力(FPP)≥35cmH2O肝癌病人的外科治疗经验。方法回顾性分析1998年1月至2004年10月外科手术的11例FPP≥35cmH2O肝癌病人的手术资料、术后近期并发症及随访情况。结果全部病例手术均获得成功,无术中死亡。围手术期死亡率18.2%,术后并发症发生率100%,其中因上消化道大出血及肝功能衰竭死亡各2例(36.4%)。术后3mo、6mo及1年、2年、3年生存率分别为63.4%、36.4%、18.2%、18.2%、0%。结论FPP≥35cmH2O肝癌病人的手术切除有较高的并发症和死亡率,因此作者建议应将FPP≥35cmH2O肝癌视为肝部分切除的相对禁忌症。
简介:Theexpressionofp53Protein,c-erbB-2oncoprotein,Proliferatingcennuclearantigen(usA)werestudiedbythestreptavidinperotidaseconjugated(S-P)immunohistochemicalmethodandDNAcontentinsituwastested,inordertoexplorethesignificanceofP53,c-erbB-2,PCNAinPrimallUng...
简介:Objective:TodeterminewhetherInterferon-alpha-2b(IFN-α2b)canmodulatetheautophagicresponseinhepatocellularcarcinomacells.Methods:HepatocellularcarcinomacellsweretreatedwithIFN-α2b.Autophagywasassessedbyacridineorangestaining,GFP-LC3dottedassay,transmissionelectronmicroscopyandimmunoblotting.Results:AcridineorangestainingshowedthatIFN-α2btriggeredtheaccumulationofacidicvesicularandautolysosomesinHepG2cells.TheacridineorangeHepG2cellratioswere(4.3±1.0)%,(6.9±1.4)%,and(13.1±2.3)%,respectively,aftertreatmentwith100,1,000,and10,000IU/mLIFN-α2bfor48h.AmarkedlypunctatepatternwasobservedinHepG2cellstreatedwith10,000IU/mLIFN-α2bfor48h,butonlydiffuseandweaklyfluorescentGFP-LC3punctawasobservedincontrolcells.HepG2cellstreatedwith10,000IU/mLIFN-α2bfor48hdevelopedautophagosome-likecharacteristics,includingsingle-ordouble-membranevacuolescontainingintactanddegradedcellulardebris.TheBeclin1andLC3-IIproteinexpressionwasup-regulatedbyIFN-α2btreatment.Conclusion:Autophagycanbeinducedinadose-dependentmannerbytreatmentwithIFN-α2binHepG2cells,andtheBeclin1signalingpathwaywasstimulatedbyIFN-α2b.
简介:Objective:TheexpressionofB-celllymphoma2(Bcl-2)seemstobeinfluencedbytheendocrineenvironment.NumerousreportsdemonstratethediverseexpressionofBcl-2familymembersundersexsteroidregulation.Withtheexceptionofestrogen-relatedtumors,androgen-relatedtumorshaveshowntheircharacteristicsinBcl-2expression.Inthisstudy,thestatusofBcl-2expressioninmalehepatocellularcarcinoma(HCC)patientswasexaminedtoverifythehighincidenceofHCCinmales.Methods:TumortissuemicroarraywasusedtoexamineBcl-2expressionlevelsin374HCCcasesincluding306malesand68females.Kaplan-Meiermethod,log-ranktest,andCoxproportionalhazardsmodelwereappliedtoinvestigatethepredictivevalueofBcl-2inHCCpatients.Results:ImmunohistochemistryanalysisshowedthatmalepatientswithhigherBcl-2levelshadsignificantlylongermediansurvivaltimeandrecurrencetimethanthosewithlowerlevels.However,nosignificantdifferencesinoutcomeswerefoundbetweendifferentBcl-2levelsinfemalepatients.Whenthemalepatientswerestratifiedintoseveralagepoints,thelevelofBcl-2expressionshowedpoorerpredictiveefficiencyinthe45–49and55–60agegroupsinandropause-agepatientscomparedwithotheragegroups.Bcl-2wasanindependentprognosticfactorforbothoverallsurvival(P<0.0001)andrecurrencetime(P=0.0001)inmalepatients.Afterexcludingmalepatientsinthe45–60agegroup,thepredictiveefficiencywasenhanced(n=147,OS,P=0.0002,TTR,P<0.0001).Conclusions:Bcl-2expressionisanindependentpredictorofsurvivalandrecurrenceinmaleHCC.Bcl-2levelsmayalsoberegulatedbyandrogensorandrogenreceptorsinmaleHCCpatients.Bcl-2levelschangeandexhibitpoorpredictiveefficiencywhenandrogenlevelsvarydramatically(andropauseage).
简介:目的:体外观察黄芪对人喉癌细胞系Hep-2的抑制增殖和转移能力的作用并探讨其作用机制。方法:用20、100、200μg/ml的黄芪作用于Hep-2细胞24h,MTT法检测细胞增殖,流式细胞仪检测细胞周期分布和细胞凋亡率,侵袭实验观察药物对Hep-2细胞侵袭转移能力影响,AO/EB染色观察细胞凋亡,Westernblot检测Bcl-2和Bax蛋白的表达。结果:MTT结果显示黄芪对Hep-2细胞的增殖抑制作用具有明显的剂量依赖性;流式细胞仪检测发现随着黄芪浓度增高,细胞凋亡率逐渐升高,统计学分析,各实验组之间及其与对照组之间的差异均有统计学意义(P〈0.05);AO/EB染色后可见典型细胞凋亡的形态变化;Hep-2细胞体外侵袭能力明显受抑制,存在剂量依赖性;Westernblot检测显示黄芪可剂量依赖性地抑制Bcl-2蛋白表达。结论:黄芪可通过抑制Bcl-2蛋白表达,上调Bax表达,引起喉癌细胞增殖抑制和凋亡,发挥抗癌作用。
简介:目的:研究microRNA203(miR-203)对胃癌EIF5A2表达的影响,为进一步阐明miR-203与胃癌的关系提供理论基础。方法:分别应用免疫荧光化学和免疫组织化学检测胃癌细胞和组织中EIF5A2的表达;脂质体miR-203转染干预胃癌细胞后,RealtimePCR和Westernblot检测细胞中EIF5A2mRNA和蛋白的表达情况。结果:胃癌细胞株SGC7901胞浆中大量表达EIF5A2蛋白,而细胞核中表达较少;胃癌组织中EIF5A2的表达量明显升高;EIF5A2的表达在脂质体miR-203转染干预胃癌细胞后明显受到抑制。结论:胃癌细胞和组织中存在EIF5A2的表达,且miR-203显著抑制了EIF5A2的表达。
简介:目的探讨Gab2基因在胃癌中的表达及对胃癌细胞增殖、凋亡、迁移及对AKT、P-AKT、Bax、Bcl-2表达的影响。方法采用RT-PCR及WesternBlot检测胃癌组织和癌旁组织中Gab2的表达。培养人胃癌细胞株SGC-7901,分别用Gab2小干扰RNA(Gab2-siRNA)和阴性对照(siRNA-NC)转染细胞,以空脂质体转染的细胞作为对照组,各组细胞培养48h。应用WestemBlot检测细胞中Gab2、AKT、p-AKT、Bax、Bcl-2蛋白表达的变化,CCK.8检测细胞增殖情况,流式细胞仪检测细胞凋亡,Transwell小室检测细胞迁移能力。结果胃癌组织中Gab2的mRNA及蛋白表达水平均明显高于癌旁组织(P〈0.01);Gab2.siRNA组Gab2蛋白表达水平明显低于对照组(P〈0.01);siRNA.NC组细胞的存活率、凋亡率、迁移数及AKT、P.AKT、Bax、Bcl.2蛋白表达与对照组比较,差异均无统计学意义(P〉O.05);Gab2.siRNA组细胞的AKT蛋白表达与对照组比较,差异无统计学意义(P〉O.05),细胞的存活率、迁移数及P.AKT、Bcl.2蛋白表达明显低于对照组(P〈0.01),细胞凋亡率及Bax蛋白表达明显高于对照组(P〈0.01)。结论Gab2在胃癌组织高表达,沉默Gab2的表达能显著抑制人胃癌细胞株SGC-7901的增殖和迁移,并通过调节Bax、Bcl-2蛋白表达促进细胞凋亡,其可能的机制与AKT信号通路的调控有关。
简介:Objective:Toinvestigatetheeffectoftwoantisenseoligonucleotidesoncellsurviving,bcl-2expressionandapoptosisofleukemiacells.Methods:Theexperimentalassayswereperformedwithcellculture,immunochemistryandflowcytometry.Results:Thetwoantisenseoligodeoxynucleotides,combinedwithVp16orAra-corDNR,wereabletodeclinethesurvivalrateofmyeleukemiccells,downregulatebcl-2geneexpressionandinduceapoptosisofleukemiccellssignificantly,ascomparedwithVp16orAra-corDNRalone.Conclusion:Itispossibleforthetwonewbcl-2antisensestobedevelopedintoclinicaltrialsforleukemiaandtumorwithbcl-2geneoverexpression.
简介:Objective:TostudythedifferencesandsimilaritiesoftheantisensedrugswithdifferentstructuresonthebiologicalfunctionsofK562cells.Methods:Cytotoxiceffectsweremeasuredbyuseofacellviabilityassay.FlowcytometricanalysisandagarosegelelectrophoresisofDNAfragmentationwerealsoperformed.Theexpressionlevelofproteinwasassayedbyimmunofluorescenceusingfluoresceisothiocyanatelabel.Results:PNAtargetingthecodingregionoftheBcl-2messengerRNAcouldeffectivelyinhibitK562cellviability,down-regulatethesynthesisoftheBcl-2proteinandincreasecellapoptosis.By72haftertheBcl-2antisensePNAtreatment,K562cellsshowedmorereductioninthelevelofBcl-2proteincomparedwithcellstreatedwiththeantisenseODN.Aftertreatmentwith10μmol/LofBcl-2antisensePNAorantisenseODNfor72h,apoptoticratesofK562cellswere13.15±1.13and11.72±1.12,respectively.Furthermore,therewassignificantdifferenceinthepercentageofapoptoticcellsbetweenantisensePNAgroupandantisenseODNgroup.Conclusion:TheresultssuggestthatantisensePNAtargetingthecodingregionofBcl-2mRNAhasbetterantisenseeffectsthantheantisenseoligonucleotidesoninducingapoptosisofK562cells.
简介:目的比较线粒体融合蛋白-2(Mfn2)在乳腺癌、甲状腺癌和大肠癌组织及相应正常组织中的表达差异,探讨Mfn2与肿瘤发生的关系.方法选取经病理检查确诊的乳腺癌、甲状腺癌和大肠癌标本各20例,另取相应癌旁正常组织作为对照,采用免疫组织化学染色SABC法对Mfn2在不同组织中的表达水平进行测定和对比分析.结果免疫组化染色显示,在乳腺癌、甲状腺癌、大肠癌组织中表达水平均明显低于相应正常组织(P〈0.01).结论Mfn2在乳腺癌、甲状腺癌和大肠癌组织中表达低于正常组织,Mfn2与这3种恶性肿瘤的发生、发展密切相关,可作为预测三种恶性肿瘤转移及其预后的参考指标.
简介:Minimalresidualdisease(MRD)playsacausativeroleintumorrecurrenceandestablishmentofeffectiveandsensitiveassessmentofMRDcouldbeveryusefulforstagingandevaluationoftreatmentofdisease.Inthisstudy,weassessedtheusefulnessofhcf-2/JHPCRanalysisonoccultlymphoma...
简介:目的分析绝经前雌激素受体(ER)阳性、人类表皮生长因子受体2(HER2)阴性乳腺癌患者复发转移特征。方法回顾性分析154例ER阳性HER2阴性绝经前复发转移性乳腺癌患者的临床资料,对患者临床及复发转移特征进行总结分析。结果154例绝经前ER阳性HER2阴性乳腺癌患者,中位发病年龄45岁(26~53岁),中位无病生存时间(DFS)52.4个月(6.1~329.1个月),复发转移多发生在术后2~5年(49.4%,76/154);非内脏转移较内脏转移多发(55.8%vs44.2%);骨转移最多(52.6%,81/154),内脏转移以肺多见(26.6%,41/154);多因素分析显示,淋巴结转移状态是DFS的主要影响因素(P﹤0.05)。结论绝经前ER阳性HER2阴性乳腺癌患者复发转移多发生在术后2~5年,主要为非内脏转移,骨转移最多;淋巴结转移状态是影响DFS的重要因素。
简介:背景与目的:ABCG2是ATP转运蛋白(ATPbindingcassette,ABC)家族中G2成员,具有编码乳腺癌耐药蛋白(breastcancerresistanceprotein,BCRP)功能,在肿瘤研究中又可作为SP细胞标志蛋白来筛选肿瘤干细胞,本研究旨在逆转其耐药作用。方法:尼卡地平(NCDP)、尼莫司汀(AGNU)分别和联合作用于人脑多形性胶质母细胞瘤(GBM)体外细胞系和裸小鼠脑移植瘤。体外实验:用MTr比色法检测药物作用后GBM细胞存活率,流式细胞仪检测细胞凋亡率;体内实验:观察荷瘤裸小鼠的生存期及移植瘤病理。结果:体外实验中,AC-NU+NCDP组对肿瘤抑制和促进凋亡作用都显著高于ACNU组(P〈0.01)。体内实验中,ACNU+NCDP组的生存期比ACNU组明显延长(P〈O.01)。结论:随着胶质瘤恶性程度增高而表达率增加的ABCG2耐药基因功能因被NCDP抑制后增强了ACNU对胶质瘤细胞的杀伤、促进凋亡和延长荷瘤鼠生存期的作用。
简介:Objective:Toinvestigatetheimpactofbeta-elemeneinjectiononthegrowthandalpha-tubuleofhumanhepatocarcinomaHepG2cells.Methods:CellproliferationwasassessedbyMTTassay.Cellcycledistributionwasdetectedbyflowcytometry(FCM).ThemRNAexpressionofalpha-tubulinwasmeasuredbyRT-PCR.Westernblotanalysiswasusedtodetermineproteinexpressionofalpha-tubulinandthepolymerizationoftubulin.Results:Beta-elemeneinjectioninhibitedHepG2cellsproliferationinadose-andtime-dependentmanner;FCManalysisindicatedbeta-elemeneinjectioninducedcellcyclearrestedatSphase.RT-PCRandwesternblotanalysisshowedthatbeta-elemeneinjectiondown-regulatedalpha-tublinatbothmRNAandproteinlevels,presentingadose-dependentmanner.Moreover,beta-elemeneinjectionreducedthepolymerizationofmicrotubulesinadose-dependentmanner.Conclusions:Beta-elemeneinjectioncaninhibittheproliferationofhepatomaHepG2cellsandinducecellapoptosis,themechanismmightbepartlyrelatedtothedown-regulationofalpha-tubulinandinhibitionofmicrotubularpolymerization.