腺病毒介導(dǎo)的HSV-tk基因聯(lián)合GCV治療人膀胱癌SCaBER的實(shí)驗(yàn)研究.pdf

1、蘇州大學(xué)碩士學(xué)位論文腺病毒介導(dǎo)的HSVtk基因聯(lián)合GCV治療人膀胱癌SCaBER的實(shí)驗(yàn)研究姓名：鄭志濤申請學(xué)位級(jí)別：碩士專業(yè)：泌尿外科指導(dǎo)教師：溫端改侯建全20030501腺病毒介導(dǎo)的HSVtk基因聯(lián)合GCV治療人膀胱癌SCaBER的實(shí)驗(yàn)研究英文摘要AbstractBaekground：Recenttrialsofsuicidegenetherapyforbladdercancerhaveshownthatthesethreatment

2、swerewelltoleratedwithsignificanteffectsandminimalsideeffectsButpatientswithhighgradebladdercancerfrequentlyexperiencerecurrenceandprogressandthereisminimalthreatmentsuccesswitllsurgerychemotherapyorradiotherapyinmetasta

3、sisbladdercancerInthisstudyweevaluatedthefeasibilityandefficacyofsuicidegenetherapyusingadnovirusmediatedherpessimplexvirusthymidinekinasegenecombinedwithganciclovirasapotentialtherapeuticapproachinmurinesubcutaneousblad

4、dercancermodelsMethods：AreplicationdeflectiveadenovirusvectorcontainingtoxicHSV—tkgeneundertheWanscriptionalcontrolofCMVpromoterwasusedSubcutaneousbladdercancerwasestablishedwith1106humanbladdercancercellsinBALB／cnudemic

5、eIntratumoralinjectionofAdCMVtk(5108plaqueformingunitsPFU)incombinationwithGCV(40mgⅨgbodyweight／dayipbidx10days)wasadministeredinvivofortledeterminationoftreatmentefficacyWealsodeterminatedtumormicrovesseldensity(MVD)，pr

6、oliferatingcellnuclearantigen(PCNA)expressionandCDSTcellinfiltrationbyimmunohistochemicalmethodsResults：InvivoexperimentsdemonstratedgreaterinhibitioninSCaBERRimorgrowthfortheanimalstreatedwithAdCMVtk／GCVtherapyfP001)Cen

7、traltumornecrosisandapoptosiswererevealedbyhistomorphologyandFCMcomparedwithothercontrolanimals(AdCMVt14PBS，PBS／GCVPBSalone)ThemicrovesseldensityandPCNAweresignificandydecreasedcomparedwithothercontrolanimalsrevealedbyim

8、munohistochemicalmethods(P001)TheCD$TcellinfiltrationWaSalsofoundinAdCMVtktreatmenttUlTIOrTheexpressionofHSVn(butnottheadenoviralE1geneWSSdeterminedbyPCRDerectintratumoralinjectionwithAdCMVtkfollowedbyGCValsoresultedinsi