低氧与肿瘤多药耐药.ppt
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1、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) Trans
2、fer 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 functio
3、n 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):46
4、5-476,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 ,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,
5、 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 expressio
6、n in hypoxia.,JNK down-regulates MDR1 expression in normoxia and up-regulates MDR1 expression in hypoxia,Research Results,Xianrang, et al Cancer Chemother Pharmacol,2006 online,Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1 ge
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- 低氧 肿瘤 耐药
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