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1、低氧與腫瘤多藥耐藥HypoxiaandMultidrugResistanceProfessorChenbao-anDept.ofHematologyAffiliatedZhongdaHospitalSoutheastUniversityContentResearchbackgroundResearchprogressionClinicalapplicationJobfromourownLabPartIResearchBackgroundReasonofDeathMultidrugResistance(MDR)TransferComplicationTumorrelapseOthers90%Me
2、chanismofMultidrugResistanceMichaelM.etal;naturereviews2002,2:48-57CellularFactorsofCauseMDRMichaelM.etal;naturereviews2002,2:48-57FocusonHowtoraiseaccumulationofchemotherapydrugincell?Howtodecreasethetoxicityfunctionofchemotherapydrug?ResearchFieldStructureGeneticalterationsEpigeneticchangesFunctio
3、nImmuneFactor:antibody、immunecell、cellfactorGeneTechnology:RNAi、AOD、RibozymeHypoxia(hypoxiainducefactor-1,HIF-1)HIF-1aStructureHypoxiaandHIF-1aBrianKeith;etal;Cell129,2007,May(4):465-476HiF-1aandApoptosisConclusionofPartIHypoxiaplayrolesinMDRfailureTargetHIF-1genetherapyshouldbeavailableforMDRpatien
4、tPartⅡResearchProgressionofbothHIF-1andMDR丁震宇,梁后杰免疫學(xué)雜志2008HIF-1a與P-gp在結(jié)腸癌組織表達(dá)存在相關(guān)性兩者相互作用共同參與結(jié)腸癌多藥耐藥的發(fā)生HIF-1a與P-gp在結(jié)腸癌組織中的表達(dá)及意義MinLiu,etal,JBC,2007onlinePO2-dependentdifferentialregulationofmulti-drugresistance1geneexpressionbythec-JunNH2-terminalKinasePathwayTheJNKpathwayplaysPO2-dependentdifferentr
5、olesinregulatingMDR1expressiondown-regulationofMDR1expressioninnormoxia.up-regulationofMDR1expressioninhypoxia.JNKdown-regulatesMDR1expressioninnormoxiaandup-regulatesMDR1expressioninhypoxiaResearchResultsXianrang,etalCancerChemotherPharmacol,2006onlineHypoxia-inducedresistancetocisplatinanddoxorubi
6、cininnon-smallcelllungcancerisinhibitedbysilencingofHIF-1geneHypoxia-inducedchemoresistancetocisplatinanddoxorubicinisthroughtheHIF-1apathway.CombiningdeliveryofHIF-1RNAilentiviralvectorwithcisplatin-relatedchemotherapyregimensmayenablemorestrategyforNSCLCtherapy.EffectofO2concentrationonsurvivalofH
7、IF-1genesilencingNSCLCcellstochemotherapydrugPartⅢClinicalapplicationRoyVergis,LancetOncol.2008onlineIntrinsicmarkersofhypoxiaandangiogenesisinrelationtotheoutcomeofradicaltreatmentofprostatecancer.In
