低氧与肿瘤多药耐药.ppt

低氧与肿瘤多药耐药 Hypoxia and Multidrug Resistance Professor Chen bao-an Dept. of Hematology Affiliated Zhongda Hospital Southeast University * Content Research background Research progression Clinical application Job from our own Lab * Part I Research Background * Reason of Death Multidrug Resistance (MDR) Transfer Complication Tumor relapse Others 90% * Mechanism of Multidrug Resistance * Michael M. et al; nature reviews 2002,2:48-57 * Cellular Factors of Cause MDR Michael M. et al; nature reviews 2002,2:48-57 * Focus on How to raise accumulation of chemotherapy drug in cell ? How to decrease the toxicity function of chemotherapy drug? * Research Field Structure Genetic alterations Epigenetic changes Function Immune Factor: antibody、immune cell、cell factor Gene Technology: RNAi、AOD、Ribozyme Hypoxia (hypoxia induce factor-1,HIF-1) * HIF-1a Structure * Hypoxia and HIF-1a Brian Keith; et al; Cell 129, 2007,May(4):465-476 * HiF-1a and Apoptosis * Conclusion of Part I Hypoxia play roles in MDR failure Target HIF-1 gene therapy should be available for MDR patient * Part Ⅱ Research Progression of both HIF-1 and MDR * 丁震宇,梁后杰 免疫学杂志 2008 HIF-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 * Min Liu, et al, JBC,2007 online PO2-dependent differential regulation of multi-drug resistance 1 gene expression by the c-Jun NH2-terminal Kinase Pathway The JNK pathway plays PO2-dependent