減毒沙門菌靶向介導(dǎo)TIP30和干擾素-γ基因抗頭頸癌的實驗研究.pdf

1、第二軍醫(yī)大學博士學位論文減毒沙門菌靶向介導(dǎo)TIP30和干擾素γ基因抗頭頸癌的實驗研究姓名：江中明申請學位級別：博士專業(yè)：口腔頜面外科學指導(dǎo)教師：呂春堂20040401AnexperimentalresearchonattenuatedSalmonellamediatedtargetedTIP30andinterferon3geneanticarcinomaofheadandneckAbstractobjective：Toevaluate

2、thefeasibilityofattenuatedSalmonellatyphimuriumasgenetargetedvectorandtoobservetheconstructedattenuatedSalmonellatyphimuriumhaboringaneukaryoticexpressionplasmidencodingTIP30，aneukaryoticexpressionplasmidencodingIFNYanda

3、neukaryoticCOexpressionplasmidencodingTip30andhumanIFN／genetherapyonthetransplanttumorinBALB，cmicewithcarcinomaofheadandneckMethod：1RecombinantexpressionplasmidspCITip30petIFNandrecombinantCOexpressionplasmidpClTip30／IFN

4、wereconstructed，andthethreerecombinantplasmidswereidentified，threerecombinantexpressionplasmidspCITip30，pCl—IFNandpClTip30／IFNweretransformedint0anattenuatedAroA。autotrophicmutant0fSalmonellat)phimuriumSL7207，developedth

5、reerecombinantattenuatedSalmonellatyphimuriumsSL7207／pCITip30、SL7207／pCIIFNandSL7207／pCITip30／IFN，theresultantbacteriawereidentifiedrespectively2TheACC一2ACCMandTCA一8113tumormodelsinnudemicewereaccepteddifferenttherapyofP

6、BS，SL7207，SL7207／pCI—IFN，SL7207／pCI—Tip30andSL7207／pCITip30／IFNbyoraladministrationrespectivelyandthetherapyeffectsWereobservedResult：1ThreeeukaryoticexpressionplasmidspCITip30，pCIIFNandpCI—Tip30／IFNweresuccessfullyconst

7、ructedandwerepassedtheidentification，theattenuatedSalmonella砂phimuriumcouldeffectivetransfergeneandexpressthetargetedgene2SL7207，SL7207／pCIIFN，SL7207／pCITip30andSL7207／pCITip30／IFNhadevidentinhibitoreffectonthetumorgrowt

8、handmetastasis，SL7207／pCITip30／IFNhadthebesttherapyresultsConclusion：1TheattenuatedSalmonellatyphimuriumcouldbeusedastheexteriorgenevector2TherecombinantattenuatedSalmonellatyphimuriumhaboringplasmidpCITip30plasmidpCIIFN

9、andCO—expressingplasmidpCITip30／IFNhadevidenttherapyresultstothenudemousewithcarcinomaofheadandneck；theunitegenestherapyresultshadbetterthanthesimpergene，ithadsynergisticactionKeywords：AttenuatedSalmonellaophimurium；TIP3