低氧与肿瘤多药耐药

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1、低氧与肿瘤多药耐药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,梁后杰免疫学杂志2008HIF-1a与P-gp在结肠癌组织表达存在相关性两者相互作用共同参与结肠癌多药耐药的发生HIF-1a与P-gp在结肠癌组织中的表达及意义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