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可以说,陈竺夫妇之所以能够在院士的神圣殿堂比翼双飞,很大程度受惠于砒霜和雄黄,分析他们取得如此成就的原因可能是:
(1)机遇垂青有准备的头脑:在改革开放之初,他们双双考上了血液学家王振义教授的研究生,而导师在此期间正好根据国际上采用诱导分化治疗白血病的设想,阴差阳错地利用上海的药厂只能合成出全反式维甲酸进行试验(原计划采用13顺式维甲酸),1985年首次用于急性早幼粒细胞白血病的治疗,获得满意结果,开创了将白血病细胞“改造”成接近“正常”细胞的先例(国外学者后来证明,13顺式维甲酸对白血病的疗效不佳)。
(2)国际视野让他们具备更高素养:陈竺曾回忆说,“1987年,我的导师王振义先生带领上海血液学研究所突破白血病分化治疗的方法,但在向国际一著名血液学期刊投稿时,论文被两次拒绝。第一次说结果令人怀疑,学术上有问题,第二次说英文写作有问题。当时,一位著名的美国血液学教授正在上海访问,他看了研究结果后觉得很不公正,于是按美国人的英文标准将论文重写了一遍,并要求该期刊务必接受,这样论文才得以发表。论文发表后即引起轰动,被誉为白血病治疗的‘中国革命’。”显然,王振义教授后来成为院士也与该论文的发表密切相关。而且,如前所述张亭栋和黄世林的成名也与陈竺夫妇的的工作和推荐有关。
(3)淘宝精神:我让学生搜索了陈竺夫妇发表的关于白血病的英文文献(附图),其中相当多的文献涉及中医药研究,所以陈竺院士自称为“中医迷”。记得当年他们对张亭栋的研究也是将信将疑,但当他们正式合作以后就发现,中药里面确实存在宝藏,于是一发而不可收。陈竺夫妇的贡献,是把三氧化二砷治疗急性早幼粒性白血病的效果推广介绍到国际上,并找到了三氧化二砷的治疗靶点,使三氧化二砷治疗白血病的研究国际化(其主要临床研究见表1。如今,研究证明三氧化二砷可通过诱导细胞分化和凋亡、降解PML—RARo、清除LIC、抑制肿瘤细胞增殖和抑制血管生成等多条途径发挥抗肿瘤作用,其中三氧化二砷和维甲酸分别作用于PML—RAR0的PML部分和RAR仅部分,协同降解PML—RARa而无交叉耐药,被认为是治疗APL最重要的分子机制,也是临床以ATRA+As2O3联合治疗APL的重要理论依据,树立了肿瘤靶向治疗的成功典范)。
附:陈竺夫妇发表的有关“白血病”研究文章(英文)
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74. Wang QR,Shi JY,Shi L,Chen SJ. Mutational detection of full-length mixed lineage leukemia gene in patients with de novo AML-M4 and M5. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012 Feb;20(1):12-7
75. Wang L,Shi WY,Yang F,Tang W,Gapihan G,Varna M,Shen ZX,Chen SJ,Leboeuf C, Janin A,Zhao WL. Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells. Haematologica. 2011 Jun;96(6):927-31.
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77. Chen SJ. Mutation associations in RA-defiant APL. Blood. 2012 Sep 6;120(10):1969-70.
78. Dong S,Chen SJ,Tweardy DJ. Cross-talk between retinoic acid and STAT3 signaling pathways in acute promyelocytic leukemia. Leuk Lymphoma. 2003 Dec;44(12):2023-9. Review.
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