攜帶Apoptin雙調控溶瘤腺病毒治療肝癌的研究.pdf

1、浙江理工大學碩士學位論文攜帶Apoptin雙調控溶瘤腺病毒治療肝癌的研究姓名：錢靜申請學位級別：碩士專業(yè)：生物化學與分子生物學指導教師：劉新垣20100317浙江理丁大學碩士學位論文Studyondouble—regulatedoncolyticadenovirusarmedwithApoptinforHepatocenuIarcarcinomaAbstractCurrentlymalignanttumorshavebecomethef

2、irstleadinglethiferousdiseaseAlthoughthemorbidityandmortalityoftumorpatientshaveincreaseddramaticallyeachyearthesurvivalratesofthemajorityofcancerpatientshavenotbeenimprovedTraditionaltherapiessuchassurgeryradiotherapyan

3、dchemotherapywerefoundverylimitedantitumoreffectandtumorrecurrentratesandmortalityratesremainvery11igh，whichindicatethatthedevelopmentoftraditionaltherapieshavebeentrappedTherefore，itisurgenttodevelopmoreeffectiveandsecu

4、retherapeuticprogramstobreaktheawkwardsituationthatcancerCannotbecuredAsgenetherapyandvirotherapyforcancertreatmenthavewelldevelopedinthesedays，thebiologicaltherapysuchastheconditionallyreplicatingadenoviruses(oncolytica

5、denoviruses)hasbecomeahotresearchProfLiuthencombinestheadvantagesofgenetherapyandvirotherapyandproposesanovelstrategyforcancertreatmentnamed“TargetingGeneVirotherapyofCancer’Thestrategyistoincorporateoneormoretherapeutic

6、genesintooncolyticviralvectorwhichhasbroughtnewlightandhopeforcancertreatmentSincetheE1AandE1Bplaycriticalrolesinregulatingadenoviralreplication，modificationswereusuallylocatedinE1regionofadenoviralDNAWeCantargetdiverses

7、ignalpathwaysbydeletingE1B55kDaorE1A一24bp，thusadenoviruscanreplicateonlyintumorcellsWeCanalsousethecancerortissuespecificpromoterstoreplacetheE1AorE1Bwild—typepromotersApoptinaproteinseparatedfromavianviruses，isunabletoi

8、nduceapoptosisinnon—transformednormalhumancellsWeintroducedapoptingeneintoadouble—regulatedoncolyticadenovirusAd’eAFP—E1AE1B(A55)andconstructedAd‘eAFP—E1A—E1B(A55)一ApoptinOurresultsshowedthatAd。eAFP—E1AE1B(Lx55)一Apoptinh