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 Mechanism of Multidrug Resistance Michael M. et al; nature reviews 2002,2:48-57 Cellular Factors of Cause MDR 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 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 different roles in regulating MDR1 expression down-regulation of MDR1 expression in normoxia. up-regulation of MDR1 expression in hypoxia. Research Results Xianrang, et al Cancer C