肿瘤的多因素多步骤发病过程-2015.ppt

All-trans-retinol All-trans-retinoic acid OH COOH 13-cis-Retinoic acid COOH COOH OH CH2OH 9-cis-Retinoic acid 14-Hydroxy-4, 14-retro-retinol (Adapted from Warrell et al, N Eng J Med, 1993) Differentiation agents proposed as cancer therapy APL : a unique subtype 1957 1977 1973 In vitro differentiation Induction in AML cells 1978 1988 Differentiation Therapy successful Blood, 1997; 89 : 376-387 分子诊断 发病机制 治疗手段 As2O3 ATRA Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhao L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72. Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3 ) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1;88(3):1052-61. Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM, Liu MM, He KL, Niu C, Ma J, Zhang P, Zhang TD, Paul P, Naoe T, Kitamura K, Miller W, Waxman S, Wang ZY, de The H, Chen SJ, Chen Z.Use of arsenic trioxide (As2O3 ) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 1997 May 1;89(9):3345-53. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY. Use of arsenic trioxide (As2O3 ) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997 May 1;89(9):3354-60. Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de Thé H, Chen SJ, Chen Z.