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[癌细胞的恶性进展与耐药性:一种类似于单细胞生物在环境攻击诱导下的SOS系统的可诱导生存程序]

[Malignant progression and resistance of cancer cells: an inducible survival program similar to the SOS system of unicellular organisms induced by environmental assaults].

作者信息

Israël L

机构信息

l'Université Paris XIII, Paris.

出版信息

Bull Acad Natl Med. 1998;182(1):49-57.

PMID:9622931
Abstract

The hypothesis discussed in this paper states that defence and survival strategies of cancer cells against therapeutic approaches are similar in their mechanisms and homologous in several genes to the SOS program known in bacteria and induced by several assaults. The almost ineluctable malignant progression and its acceleration in response to various therapies should then be considered as an inducible system inherited from prokaryotes and repressed in multicellular organisms through the anti-oncogene system. The later, weakened in case of some inherited mutations yields even in sporadic cases to repeated assaults and to the decrease with time of internal defences, including antioxidant mechanisms. This theory which presents in a new perspective the biological status of cancer in the frame of Darwinian evolution and hence the strategies able to control its progression, leads itself to some predictions and testable assertions: absence of any anti-oncogene homologues in unicellular organisms, built-in weaknesses in anti-oncogenes, existence of a common repressor and a common derepressor mechanism for several distinct genes involved in cancer and in response to an environmental assault, and finally a possible transfer of drug resistance genes in malignant cells as it is the case for bacteria submitted to stress conditions.

摘要

本文所讨论的假说指出,癌细胞针对治疗方法的防御和生存策略在机制上相似,且在若干基因上与细菌中已知的SOS程序同源,该程序由多种攻击诱导产生。那么,几乎不可避免的恶性进展及其对各种疗法的加速反应应被视为一种从原核生物遗传而来的可诱导系统,在多细胞生物中通过抗癌基因系统受到抑制。在某些遗传性突变的情况下,后者功能减弱,即使在散发性病例中,面对反复的攻击以及随着时间推移包括抗氧化机制在内的内部防御能力下降时,也会出现这种情况。该理论从新的视角呈现了癌症在达尔文进化框架下的生物学状态,进而呈现了能够控制其进展的策略,这一理论本身引发了一些预测和可检验的论断:单细胞生物中不存在任何抗癌基因同源物,抗癌基因存在内在弱点,参与癌症以及对环境攻击作出反应的若干不同基因存在共同的阻遏物和共同的去阻遏机制,最后,恶性细胞中可能存在耐药基因转移,就如同处于应激条件下的细菌那样。

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