简介:Someantitumoractivitiesofcomponent(E),extractedfromtherootofFagopynumCymosum(Trev)Meisn(FCTM),haverecentlybeendiscoveredinvivoandinvitro.ThecomponentE(CE)’spatternofactionwithtumorcellularDNAatthemolecularpharmacologicallevelwasinvestigatedbymacromolecularsynthesisexperiment(MSE)andhumanDNAinteractionsystemestablishedinourlaboratory.Theexperimentsdemonstratedthat,invitro,theagentcouldmarkedlyinhibittheincorporationof3H-TdRintothecellularDNA,andtheIC50inP388leukemiacellandinSGC-7901cellwas17.86μg/mland110.4μg/ml,respectively.Theagent,atmg/mllevel,couldproduceanintercalationreversionpatternwithDNAwithinashorttime(2hours).Butwhentheintervalwasprolongedforover4hours,theactionchangedtointercalationirreversiblepattern.Accordingtotheseobservations,theauthorsinferthatCEinteractswithDNAintwoways-directlyandindirectly.Theindirectaction,especiallyinlowconcentr
简介:Objective:Chroniclymphocyticleukemia(CLL)andmantlecelllymphoma(MCL)cellsover-expressaguanineexchangefactor(GEF),Rasgrf-1.ThisGEFincreasesactiveRasasitcatalyzestheremovalofGDPfromRassothatGTPcanbindandactivateRas.ThisstudyaimstostudythemechanismofactionofRasgrf-1inB-cellmalignancies.Methods:N-terminustruncatedRasgrf-1variantshaveahigherGEFactivityascomparedtothefull-lengthtranscriptthereforeaMCLcelllinewithstableover-expressionoftruncatedRasgrf-1wasestablished.TheB-cellreceptor(BCR)andchemokinesignalingpathwayswerecomparedintheRasgrf-1over-expressingandacontroltransfectedcellline.Results:Cellsover-expressingtruncatedformofRasgrf-1haveahigherproliferativerateascomparedtocontroltransfectedcells.BCRwasactivatedbylowerconcentrationsofanti-IgMantibodyinRasgrf-1over-expressingcellsascomparedtocontrolcellsindicatingthatthesecellsaremoresensitivetoBCRsignaling.BCRsignalingalsophosphorylatesRasgrf-1thatfurtherincreasesitsGEFfunctionandamplifiesBCRsignaling.ThisactivationofRasgrf-1inover-expressingcellsresultedinahigherexpressionofphospho-ERK,AKT,BTKandPKC-alphaascomparedtocontrolcells.BesidesBCR,Rasgrf-1over-expressingcellswerealsomoresensitivetomicroenvironmentstimuliasdeterminedbyresistancetoapoptosis,chemotaxisandERKpathwayactivation.Conclusions:ThisGEFproteinsensitizesB-cellstoBCRandchemokinemediatedsignalingandalsoupregulatesanumberofothersignalingpathwayswhichpromotesgrowthandsurvivalofthesecells.
简介:目的研究E-cad在食管鳞状细胞癌中的表达及意义。方法免疫组化SABC法检测76例食管癌E-cad的表达。结果正常食管粘膜细胞膜E-cad表达呈阳性。在癌组织中,E-cad细胞膜表达减弱。E-cad减弱表达率为65.8%(50/76),E-cad表达与病理分化程度(P=0.02)、漫润深度(P=0.024)、静脉侵犯(P=0.04)、淋巴结转移(P=0.022)和临床分期(P=0.04)具有相关性;而与年龄、性别、病理类型无关(P>0.05)。在无淋巴结转移组E-cad表达降低占56.25%(27/48),有淋巴结转移组占82.14%(23/28),两者之间表达差异有显著性;有静脉侵犯组E-cad表达降低率为92.86%(13/14)和无静脉侵犯组为59.68%(37/62),两者之间差异有显著性。结论E-cad减弱表达与食管癌生物学行为有关,可能为食管癌预后差的因素之一。
简介:ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.
简介:Objective:ToinvestigatetheexpressionofE2FandBcl-2andtheclinicopathologicalsignificanceinhepatocellularcarcinoma.Methods:TheexpressionsofE2F-3andBcl-2in74patientswithhepaticcarcinoma,paracarcinomaand15patientswithlivercirrhosisweredetectedbyS-Pimmunohistochemicalstaining.Results:TheexpressionofE2Finhepaticcarcinomawassignificantlyhigherthanthatinparacarcinomaorlivercirrhosis(P<0.005),theexpressionofBcl-2inhepaticcarcinomawassignificantlyhigherthanthatinparacarcinoma(P<0.005),inwhichBcl-2expressionwaslowerthaninlivercirrhosis(P<0.05).TheexpressionofE2F-3wasrelatedwithhistologicalgrade,tumorsize,andtheexpressionofBcl-2wasrelatedwithhistologicalgrade,tumorsizeandtumornumber.TherewascorrelationbetweentheexpressionofE2F-3andBcl-2inhepaticcarcinoma.Conclusion:E2F-3andBcl-2expressionmayplayanimportantroleindevelopment,progressionandcellapoptosisoftumor.
简介:目的:探讨E-钙粘蛋白(E-cadherin,E-cad)的表达与胃癌的浸润、转移及预后的关系.方法:应用SP免疫组化方法检测76例胃癌E-cad的表达.结果:正常胃粘膜上皮中E-cad全部表达.Ⅰ期E-cad的异常表达率为19.6%,而Ⅱ、Ⅲ、Ⅳ期的异常表达率分别是57.2%、62.1%和69.3%,Ⅰ期和Ⅱ、Ⅲ、Ⅳ期间有非常显著性差异(P<0.01).伴有淋巴结转移者51例中异常表达为74.3%,而无淋巴结转移者40.2%,两者间有非常显著性差异(P<0.05).在进展期胃癌中按肿瘤生长方式分组,结节型E-cad异常表达率41.2%,而溃疡浸润型异常表达率67.3%,两者间有显著性差异(P<0.05);高中分化胃癌E-cad异常表达率32.0%,而低分化胃癌E-cad异常表达率69.6%,两者间有非常显著性差异(P<0.01).癌细胞浸润深度达粘膜、粘膜下层和肌层者E-cad异常表达率为30.1%、38.2%,而浸润至浆膜及浆膜外者异常率为67.3%,两者间有非常显著性差异(P<0.01).胃癌组织中E-cad的表达与癌组织分化、浸润和转移密切相关.结论:E-cad与肿瘤的发生、浸润、转移有关,可作为一种新的肿瘤标记物,对判断预后有一定价值.
简介:Objective:BethesdaSystemforReportingThyroidCytopathology(BSRTC)categoriesⅠ,Ⅲ,andⅤaccountforasignificantproportionoffineneedleaspirationcytology(FNAC)diagnoses.ThisstudyaimedtocomparethediagnosticefficacyofBRAFV600EmutationandtheThyroidImagingReportingandDataSystem(TIRADS)classificationindifferentiatingpapillarythyroidcancers(PTCs)frombenignlesionsamongBSRTCI,III,andVnodules.Methods:Atotalof472patientswith479noduleswereenrolledinthisprospectivestudy.Ultrasound,BRAFV600Emutationtesting,andFNACwereperformedineachnodule,followedbysurgeryorregularultrasoundexamination.Results:IntheBSRTCIcategory,BRAFV600Eshowedsimilarsensitivity,higherspecificity,andloweraccuracywhencomparedwithTIRADS.IntheBSRTCIII/Vcategory,thesensitivity,specificity,andaccuracyofBRAFV600EweresimilartothoseofTIRADS.IncomparisontoBRAFV600Ealone,thecombinationofthetwomethodssignificantlyimprovedsensitivity(BSRTCⅠ:93.6%vs.67.7%,P<0.01;BSRTCⅢ:93.8%vs.75.0%,P<0.01;BSRTCV:96.0%vs.85.3%,P<0.001).WhencomparedwithTIRADSalone,thecombinationimprovedsensitivityinBSRTCⅠnodules(93.6%vs.74.2%,P<0.05),increasedsensitivityanddecreasedaccuracyinBSRTCIIInodules(93.8%vs.75.0%,P<0.01,91.0%vs.93.6%,P<0.01),andimprovedbothsensitivityandaccuracyinBSRTCVnodules(96.0%vs.82.0%,P<0.001;94.2%vs.81.3%,P<0.001).Conclusions:BRAFV600EexhibitedhigherspecificityandloweraccuracycomparedwithTIRADSinBSRTCⅠnodules,whilethetwomethodsshowedsimilardiagnosticvalueinBSRTCⅢ/Ⅴnodules.ThecombinationofthetwomethodsdistinctlyimprovedsensitivityinthediagnosisofPTCsinBSRTCⅠ,Ⅲ,andⅤnodules.
简介:Chronicalcoholconsumptionisamajorriskfactorworldwideaffectingsignificantlybothmortalityandyearsoflifelost(YLL)(1).Ca.5%ofthewesternworldshowriskyalcoholconsumptionandinsomecountriessuchasChinaaregionalyearlyincreaseofalcoholconsumptionofover400%hasbeenobservedrecently(2,3).Theliveris
简介:DuckhepatitisBvims(DHBV)DNAwasdetectedindifferenttumorousnodulesofduckswithhepaticmulticentriccancerorintrahepaticmetastasisbySouthernblottechnique.Among7duckswithhepatocellularcarcinomaofmultipletumornodules,thehybridizationpatternofIntegratedDHBVDNAIndifferenttumorousnoduleswasidenticalin3casesanddifferentin2cases.OnecaseshowedasimilarhybridizationpatternintwotumorousnodulesandotheronewasnegativetorDHBVDNA.IntegratedDHBVDNAwasalsoidentifiedinametastaticlungcancerofduckswithhepatocellularcarcinoma.Thehybridizationpatternofmetastasisoflungswasasthesomeasthatinprimaryhepatocellularcarcinoma.ThesamediscretehybridizationbandsInthedifferenttumorousnodulesindicatethatthesenodulesmightarisefromonetransformedcell.ThedifferenthybridizationpatternsInvarioustumorousnodulesshowthatthesetumorousnodulesmightarisefromvarioustransformedcells.Theresultssuggestthatthehyb
简介:Objective:ToinvestigatetheeffectsofE7080andN5-(1-iminoethyl)-L-ornithinedihydrochloride(L-NIO)oncolorectalcanceraloneandincombination.Methods:HT29colorectalcancercelllinefromSapInstitutewasused.Real-timecellanalysis(xCELLigencesystem)wasperformedtodeterminetheeffectsofE7080andL-NIOoncolorectalcellproliferation.WhileapoptosiswasdeterminedwithAnnexinVstaining,andtheeffectofagentsonangiogenesiswasdeterminedwithchorioallantoicmembrane(CAM)model.Results:WefoundthatE7080hasastrongantiproliferativeeffectwithanhalfmaximuminhibitionofconcentration(IC50)valueof5.60×10–8mol/L.AlsoithasbeenobservedthatE7080showedantiangiogenicandapoptoticeffectsonHT29colorectalcancercells.AntiangiogenicscoresofE7080were1.2,1.0and0.6for100,10and1nmol/LE7080concentrations,respectively.Furthermore,apoptosishasbeendetectedin71%ofHT29colorectalcancercellsafteradministrationof100nmol/LE7080whichmayindicatestrongapoptoticeffect.MeanwhileadministrationofL-NIOalonedidnotshowanyeffect,butthecombinationofE7080withL-NIOincreasedtheantiproliferative,antiangiogenicandapoptoticeffectsofE7080.Conclusions:ResultsofthisstudyindicatethatE7080maybeagoodchoiceintreatmentofcolorectaltumors.FurthermoretheincreasedeffectsofE7080whencombinedwithL-NIOraisethepossibilitytousealowerdoseofE7080andthereforeavoid/minimizethesideeffectsobservedwithE7080.
简介:Objective:ToassesstheeffectofantiviraltherapyforhepatitisBvirus(HBV)-relatedhepatocellularcarcinoma(HCC)afterradicalhepatectomy.Methods:Atotalof478HBV-relatedHCCpatientstreatedbyradicalhepatectomywereretrospectivelycollected.Patientsinthetreatmentgroup(n=141)receivedpostoperativelamivudinetreatment(100mg/d),whereaspatientsinthecontrolgroup(n=337)didnot.Recurrence-freesurvival(RFS)rates,overallsurvival(OS)rates,treatmentsforrecurrentHCCandcauseofdeathwerecomparedbetweenthetwogroups.Propensityscorematching(PSM)analysiswasalsoconductedtoreduceconfoundingbiasbetweenthetwogroups.Results:The1-,3-,and5-yearRFSratesdidn’tsignificantlydifferbetweenthetwogroups(P=0.778);however,the1-,3-,and5-yearOSratesinthetreatmentgroupweresignificantlyhigherthanthoseinthecontrolgroup(P=0.002).Similarresultswereobservedinthematcheddata.SubgroupanalysisshowedthatantiviraltreatmentconferredasignificantsurvivalbenefitforBarcelonaClinicalLiverCancerstageA/Bpatients.FollowingHCCrecurrence,morepeopleinthetreatmentgroupwereabletochoosecurativetreatmentsthanthoseinthecontrolgroup(P=0.031).Forcauseofdeath,fewerpeopleinthetreatmentgroupdiedofliverfailurethanthoseinthecontrolgroup(P=0.041).Conclusion:PostoperativeantiviraltherapyincreaseschancesofreceivingcurativetreatmentsforrecurrentHCCandpreventsdeathbecauseofliverfailure,therebysignificantlyprolongingOS,especiallyinearly-orintermedian-stagetumors.
简介:许多人类疾病的发生和发展可归因于一些基因的异常表达,从而导致疾病的发生。其中一部分基因是在核因子kappaB(nuclearfactor-kappaB,NF—κB)调控下进行的。NF—κ是广泛存在于哺乳动物中的转录因子,是由Sen等于1986年首先在B细胞中发现的一种核蛋白。因它能与B细胞免疫球蛋白上的K轻链基因增强子κB序列(GGGACTITCC)特异结合而得名。实际上它能与多种细胞基因的启动子和增强子序列位点发生特异性结合,并促进转录和表达,参与众多与免疫和炎症反应有关的基因转录的调控。它的异常激活或完全抑制与多种疾病的发生有关。在控制细胞增殖、凋亡、肿瘤的发生、发展和耐药问题上均起着重要的作用。因此深入探讨NF—κB在体内病理状态下的活化机制以及其与细胞、基因之间的调节作用具有重要的意义。现就NF—κB的组成、结构、激活途径以及与肿瘤的关系作一综述。
简介:Objective:Cancercellradioresistanceisastumblingblockinradiationtherapy.TheactivityinthenuclearfactorkappaB(NFκB)pathwaycorrelateswithanti-apoptoticmechanismsandincreasedradioresistance.TheIKKcomplexplaysamajorroleinNFκBactivationuponnumeroussignals.Inthisstudy,weexaminedtheinteractionbetweenionizingradiation(IR)anddifferentmembersoftheIKK-NFκBpathway,aswellasupstreamactivators,RAF1,ERK,andAKT1.Methods:Theeffectof4GyofIRontheexpressionoftheRAF1-ERK-IKK-NFκBpathwaywasexaminedinA549andH1299lungcancercelllinesusingWesternblotanalysisandconfocalmicroscopy.WeexaminedchangesinradiationsensitivityusinggenesilencingorpharmacologicalinhibitorsofERKandIKKβ.Results:IKKα,IKKγ,andIκBαincreaseduponexposuretoIR,therebyaffectingnuclearlevelsofNFκB(phospho-p65).ERKinhibitionorsiRNA-mediateddown-regulationofRAF1suppressedthepost-irradiationsurvivaloftheexaminedlungcancercelllines.AsimilareffectwasdetectedonsurvivaluponsilencingIKKα/IKKγorinhibitingIKKβ.Conclusions:ExposureoflungcancercellstoIRresultsinNFκBactivationviaIKK.ThegeneticorpharmacologicalblockageoftheRAF1-ERK-IKK-NFκBpathwaysensitizescellstotherapeuticdosesofradiation.Therefore,theIKKpathwayisapromisingtargetfortherapeuticinterventionincombinationwithradiotherapy.