溶瘤腺病毒表達穿膜肽修飾的SOCS3的抗癌研究.pdf

1、東北農(nóng)業(yè)大學(xué)碩士學(xué)位論文溶瘤腺病毒表達穿膜肽修飾的SOCS3的抗癌研究姓名：崔強申請學(xué)位級別：碩士專業(yè)：預(yù)防獸醫(yī)學(xué)指導(dǎo)教師：魏萍20070620STUDIES0NCANCERTHERAPYBYONCOLYTICADENOVIRUSEXPRESSINGCPP—FUSEDSOCS3AbstractNowadays，cancerisbecomingOlleofthemostthreateningdiseasesforthehumanhealt

2、hMethodsforcancertherapy、^∞∞developedbymanyscientistsManytraditionallytherapeutictechniqueswerelimitedformalignanttulnorssuchassurgery、actinotheraphy、chemotherapyeta1Consideredthesenhstaclesitisveryimportanttooptimizecan

3、certherapyGenetherapywasakindofnewscientificfieldsfordiseasetherapyrecentlySince1980s，genetherapyhadbeenraised，andsonicofthesemethodswereputintoclinicalphasesofwhich63％WaSappliedforcancerButcancergenetherapyremainedtobeo

4、ptimized，speciallyinthechoiceofthegeneandvectorsTheveotorsusedwidelywereincludedIenlivirus，bacilliformvirusedencassociatcdvirusandreplicationdefectiveadenovirus，butmostofthe∞wereshortoftumorselectivityRecentlyminorselect

5、ivereplicationadenovirus(oncolyticvirus)becametobefocusedBecausethattlleycouldselectivelyreplicatedintumorcellsandIdIlthematthesametimetheyhadlittletoxicity、vj廿lnormalcellsSoadenoviralvectorswerepmmismgtobedevelopedforba

6、nkergenetherapySOCS3couldnegativelyregt慨JAK／STATpathwaytokeepphysiologicalfonetiolLIthasbe朗revealedthatSOCS3isfrequentlysilencedinsometumorcellsduetohypennethylationatCpOislandofitsfunctionalpromoterThus，itssilenceintiss

7、uesmayresultinuoregulatedSTAT3phosphorylationS1=l^1Ialeactivatedinresponsetoeytokinesandgrowthfactorsandarcrecruitedtospecific1％mptorphosphotyrosinesatwhichtheyarephosphorylatedbyJAKkinasesAfteractivationSTATsdimerizeand

8、translocatetothenucleuswhereit咖activetargetgenetranslationincludingapoptosisassociatedandcellcycleregulatorygenes。suchasCyelinDl，Bcl2BclxLetaltopromoteoneogenesisThesefindingssuggestthatrestorationofSOCS3inUmlorcellsmayi

9、nhibitSTAT3aetivityandControllpJulorcellgrowthviagenetransferapproachinthisstudyWehaveexploredwhetherrestorationofSOCS3byoncolyticadenoviralvectorPEN305couldinhibittheconstitutiveactivationofJAK／STATpalllwayandsuppresstu

10、morgrowthOurdatashowedthatSOCS3wasdownexpressedinalltumorcelllinesIncorporationofSOCS3orSOCS3fusedwithcellpenetratingpeptidas(eppSOCS3)didnotselectivelyalteradenoviralreplicationintumorcellsInfectionofcellswithAdeN305SOC