简介:神经胶质瘤是中枢神经系统(CNS)最常见的一类肿瘤,占了颅内原发肿瘤的35%-60%。2007年世界卫生组织(WH0)中枢神经系统肿瘤分类中将胶质瘤分为Ⅰ-Ⅳ级,其中Ⅲ、Ⅳ级为恶性胶质瘤,大约占所有胶质瘤的77.5%。目前对神经胶质瘤的临床治疗采取以手术治疗为主,结合放疗、化疗等疗法的综合治疗.虽然能延长患者生存时间,但存在高复发率、高致残率、高病死率等问题,总体预后仍然较差。自20世纪70年代以来.维生素C(VC)抗肿瘤作用的研究日益进展,国外的医疗工作者已将其作为肿瘤治疗的补充和替代疗法之一.并报道了静脉注射维生素C治疗神经胶质瘤、卵巢癌、肾细胞癌、乳腺癌、大肠癌、非霍奇金淋巴瘤、前列腺癌、膀胱癌等肿瘤的临床病例,认为其能改善患者的临床症状、提高生存质量、延长生存期。本文就维生素C对神经胶质瘤的治疗作用做一综述。
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: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:DuckhepatitisBvims(DHBV)DNAwasdetectedindifferenttumorousnodulesofduckswithhepaticmulticentriccancerorintrahepaticmetastasisbySouthernblottechnique.Among7duckswithhepatocellularcarcinomaofmultipletumornodules,thehybridizationpatternofIntegratedDHBVDNAIndifferenttumorousnoduleswasidenticalin3casesanddifferentin2cases.OnecaseshowedasimilarhybridizationpatternintwotumorousnodulesandotheronewasnegativetorDHBVDNA.IntegratedDHBVDNAwasalsoidentifiedinametastaticlungcancerofduckswithhepatocellularcarcinoma.Thehybridizationpatternofmetastasisoflungswasasthesomeasthatinprimaryhepatocellularcarcinoma.ThesamediscretehybridizationbandsInthedifferenttumorousnodulesindicatethatthesenodulesmightarisefromonetransformedcell.ThedifferenthybridizationpatternsInvarioustumorousnodulesshowthatthesetumorousnodulesmightarisefromvarioustransformedcells.Theresultssuggestthatthehyb
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.
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:Toinvestigatephospho-(-cateninexpressioninnon-smallcelllungcancer(NSCLC)andtostudytherelationshipbetweenphospho-(-cateninexpressionandsomeclinicalpathologicalfactors.Methods:Theexpressionofphospho-(-cateninin67primaryNSCLCcasesdetectedimmunohistochemically.Results:phospho-(-cateninwasnotexpressedinnormalbronchialmucouscellandshowedcytoplasmicandnuclearexpressioninNSCLCcell.Totalpositiveexpressionratereached62.7%,andpositiveexpressionrateofnucleuswas38.8%.Thepositiveexpressionrate(87.5%)andnuclearexpressionrateofadenocarcinoma(62.5%)wereapparentlyhigherthanthoseofsquamouscellcancer(40.0%and17.1%)(P<0.01).Expressionofphospho-(-cateninhadnorelationshiptodifferentiationdegreeandlymphaticmetastasis.Thepostoperativesurvivaltimeisnotrelatedtophospho-(-cateninexpression.(Log-ranktest,P=0.9198;P=0.6274).COXmodelanalysisshowedthattumorstageanddifferentiationareindependentriskfactorstoprognosis(P=0.001;P=0.020).Conclusion:NSCLCcellsshowpositiveexpressionofphospho-(-catenin,phospho-(-cateninnuclearexpressionisrelevanttohistologicaltypes.Thereisnodifferenceinpostoperativesurvivaltimebetweenpatientswithphospho-(-cateninpositiveexpressionandpatientswithnegativeexpression,expressionofphospho-(-cateninisnotindependentriskfactortoprognosis.
简介:Objective:Toassesstheclinicalfeatures,survivalandprognosticfactorsofprimarytesticulardiffuselargeB-celllymphoma(DLBCL).Methods:Aretrospectivestudyof37patientswithprimarytesticularDLBCLwascarriedoutfromNovember2003toMay2012.Theirclinicalfeatures,survivalandprognosticfactorswereanalyzed.Results:Duringamedianfollow-upperiodof39.8months(5.4-93.0months),themedianprogression-freesurvival(PFS)was26.2months(95%CI:0-65months)andthe3-yearoverallsurvival(OS)ratewas78.4%.Withinthewholecohort,thefactorssignificantlyassociatedwithasuperiorPFSwerelimitedstage(stageI/II),lactatedehydrogenase(LDH)≤245U/L,internationalprognosticindex(IPI)≤1,primarytumordiameter<7.5cm,andpatientswhohadcompleteresponse(CR)andreceiveddoxorubicin-containedchemotherapy(P<0.05).Therewasatrendtowardsuperioroutcomeforpatientswhoreceivedcombinedtherapy(surgery/chemotherapy/radiotherapy)(P=0.055).PatientswhohadCR,primarytumordiameter<7.5cmandIPIscore≤1weresignificantlyassociatedwithlongerPFSatmultivariateanalysis.Conclusions:PrimarytesticularDLBCLhadpoorersurvival.CR,primarytumordiameterandIPIwereindependentprognosticfactors.Thecombinedtherapyoforchectomy,doxorubicin-containedchemotherapyandcontralateraltesticularradiotherapy(RT)seemedtoimprovesurvival.