简介:Objective:Inthisstudy,weexaminetheeffectsofrecombinantadenovirus-p53(rAd-p53)onthepancreaticcarcinomacelllineSW1990.Specifically,wedetermineifexpressionofrAd-p53sensitizesthesecellstoradiation.Methods:FollowingtransfectionofSW1990cellswithrAd-p53,wemeasuredexpressionofP53,P21andBaxbyimmunocytochemistry.Bothtransfectedandcontrolcelllineswereirradiatedwitharangeofdoses,andthesurvivalfractions(SF)werecalculated.Dosesurvivalcurveswereconstructedandmodeledforcomparison.Results:TransfectionofSW1990cellswithrAd-p53resultedinincreasedexpressionofP53,P21andBaxinatime-dependentmanner.At96haftertransfection,89.92%ofcellsexpressedP53,56.8%expressedP21,and76.50%expressedBax.TheSFfollowingradiationwaslowerintherAd-p53transfectedcellscomparedtothecontrolcells,suggestingthatrAd-p53sensitizesSW1990cellstoradiation(D0fortheexperimentalandcontrolgroupswas2.199and2.462,respectively).Conclusions:UseoftheadenoviralvectorisaneffectivemeansoftransfectingSW1990cellswithwild-typeP53,andthissensitizesthecelllinetoirradiation.ThisworksuggeststhatcombiningrAd-p53withradiationtherapyinpancreaticcancermaybetherapeuticallybeneficial.
简介:Objective:Toassessthesafetyandclinicalantiangiogeniceffectofrecombinantadenovirus-p53(rAd-p53)combinedwithhyperthermiaplusornotplusradiotherapyinadvancedcancer.Methods:ExpressionofVascularepithelialgrowthfactor(VEGF)afterintratumoralinjectionofrAd-p53wasassayedbyimmunohistochemistry(IHC)imaging.Forty-fourpatientswithadvancedcancerwereenrolledintothisclinicalstudy.ThepatientswereintratumorallyinjectedwithrAd-p53(Gendicine)atadoseof1×1012vponceaweek,withatotalof4-54(mean7.7)times.Totalof4-29(mean8.5)timesofhyperthermiawasgiventothepatients.Amongthe44patients,30patientswereconcurrentlyaddedwithradiotherapyofatotaldose30-76Gy/15-38f/3-8w(mean58Gy).Results:BeforeandafterintratumoralinjectionofrAd-p53,theVEGFIHCpositivecellscoreswere2.80and1.50,respectively(P=0.031).ThetreatmentofrAd-p53combinedwithhyperthermiaplusornotplusradiotherapyinadvancedcancerachievedCRrateof13.60%(6/44),andPRrateof29.6%(13/44),andthustheeffectiveratewas43.2%.Inadditionto6patientswithCR,19patients(19/38,50.0%)hadlowdensityarea(LDA)ofmorethan50%areaonCTimagewithintumorindicatingtumortissuenecrosis.Conclusions:OurdataindicatethatrAd-p53inhibitsVEGFexpressionandangiogenesis,andpromotestumornecrosisandshrinkageinducedbyhyperthermiaplusornotplusradiotherapyinadvancedcancer.
简介:p90核糖体S6蛋白激酶(rihosomalS6kinase,RSK)为Ras信号转导通路下游途径的重要调控因子,对Ras通路起调控作用。近年发现RSK家族与恶性肿瘤发生、发展密切相关。本文就RSK家族与恶性肿瘤的关系作简要综述。
简介:Theacquisitionofsecondarychromosomalaberrationsinchronicmyeloidleukemia(CML)patientswithPhiladelphiachromosome-positive(Ph+)karyotypesignifiesclonalevolutionassociatedwiththeprogressionofthediseasetoitsacceleratedorblasticphase.Therefore,theseaberrationshaveclinicalandbiologicalsignificance.T(3;12)(q26;p13),whichisarecurrentchromosomalaberrationobservedinmyeloidmalignancies,istypicallyassociatedwithdysplasiaofmegakaryocytes,multilineageinvolvement,shortdurationofanyblasticphase,andextremelypoorprognosis.Wehaveidentifiedarecurrentreciprocaltranslocationbetweenchromosomes3and12withdifferentbreakpointatbands3q21inthemalignantcellsfroma28-year-oldman.ThepatientwasinitiallydiagnosedashavingPh+CMLinthechronicphase.Thet(3;12)(q21;p13)translocationoccurred4yearsafterthepatientwasfirstdiagnosedwithCMLwhileundergoingtyrosinekinaseinhibitortherapy.Weconfirmedthet(3;12)(q21;p13)translocationviafluorescenceinsituhybridizationassaybyusingwhole-chromosomepaintprobesforchromosomes3and12.Ourfindingsdemonstratethat,similartootherrecurrenttranslocationsinvolving3q26suchast(3;3)andt(3;21),thet(3;12)(q21;p13)translocationisimplicatednotonlyinmyelodysplasticsyndromeandacutemyeloidleukemiabutalsointheprogressionofCML.Thesefindingsextendthediseasespectrumofthiscytogeneticaberration.
简介:Objectiveandbackground:Althoughp21rashasbeenreportedtobeupregulatedinhepatocellularcarcinomacomplicatingchronichepatitisCtypeI,p21rashasadifferentroleinadvancedstages,asithasbeenfoundtobedownregulated.Thegoalofthisstudywastoinvestigatethestatusofp21rasinearly-stage/low-gradeandlate-stage/high-gradehepatocellularcarcinomaanditspossiblelinktoapoptosis.Materialandmethods:Thirty-fivecaseseachofchronicHCVhepatitistype4(groupI)andcirrhosiswithhepatocellularcarcinoma(HCC)complicatingchronicHCVhepatitis(groupsIIandIII)wereimmunohistochemicallyevaluatedusingap21raspolyclonalantibody.Theapoptoticindexwasdeterminedinhistologicsectionsusingtheterminaldeoxynucleotidyltransferase-mediatedd-UTPbiotinnickendlabeling(TUNEL)assay.Results:Significantdifferences(P=0.001)weredetectedinp21rasproteinexpressionbetweenthethreegroups.Anear2-foldincreaseinp21rasstainingwasobservedinthecirrhoticcasescomparedtothehepatitiscases,andp21rasexpressionwasdecreasedintheHCCgroup.p21rasexpressioncorrelatedwithstage(r=0.64,P=0.001)andgrade(r=-0.65,P=0.001)intheHCCgroupandgradeintheHCVgroup(r=0.44,P=0.008).Bothp21rasexpressionandTUNEL-LIweresignificantlylowerinlargeHCCscomparedtosmallHCCs(P=0.01each).TheTUNELvalueswerenegativelycorrelatedwithstageintheHCCgroup(r=-0.85,P=0.001).TheTUNELvalueswerealsonegativelycorrelatedwithgradeinboththeHCVandHCCgroups(r=0.89,P=0.001andr=-0.53,P=0.001,respectively).Thep21rasscoresweresignificantlycorrelatedwiththeTUNEL-LIvaluesintheHCCgroup(r=0.63,P=0.001)andHCVgroup(r=0.88,P=0.001).Conclusions:p21rasactsasaninitiatorinHCCcomplicatingtype4chronicHCVandisdownregulatedwithHCCprogression,whichmostlikelypromotestumorcellsurvivalbecauseitfacilitatesthedownregulationofapoptosiswithtumorprogression.
简介:背景与目的:近年来的一系列实验证实,骨形成发生蛋白4(bonemorphogeneticproteins4,BMP41在体内外可以抑制肿瘤的生长,但其机制还不清楚。本研究旨在探讨BMP4在胶质母细胞瘤多药耐药中的作用及机制。方法:检测人脑胶质母细胞瘤和正常脑组织标本中BMPd的表达量:构建多药耐药细胞株并进行鉴定.检测在多药耐药细胞株和正常胶质母细胞瘤细胞株内BMP4的表达量:通过在多药耐药细胞株中高表达BMP4.检测BMP4逆转多药耐药的可能性:通过检测高表达BMP4后耐药相关基因的表达变化.初步筛选出BMPd调节胶质母细胞瘤多药耐药的可能机制。结果:在胶质母细胞瘤内,BMP4表达量降低:多药耐药细胞株构建成功.且与对照组相比,多药耐药细胞株的BMP4表达量明显降低,高表达BMP4可以逆转多药耐药:高表达BMP4后,多药耐药相关的基因中,BCL-2和GDNF表达量明显降低。结论:BMP4可以逆转胶质母细胞瘤多药耐药.其可能机制是通过调节BCL-2和GDNF的表达.