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[个体对电离辐射的反应:选择何种预测性检测方法?]

[Individual response to ionising radiation: What predictive assay(s) to choose?].

作者信息

Granzotto Adeline, Joubert Aurélie, Viau Muriel, Devic Clément, Maalouf Mira, Thomas Charles, Vogin Guillaume, Malek Karim, Colin Catherine, Balosso Jacques, Foray Nicolas

机构信息

Inserm, U, groupe de radiobiologie, institut des neurosciences, chemin Fortuné-Ferrini, Grenoble, France.

出版信息

C R Biol. 2011 Feb;334(2):140-57. doi: 10.1016/j.crvi.2010.12.018.

Abstract

Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) [1]. To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomic technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensoring and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavoured to analyse the contributions of these major approaches to predict human radiosensitivity.

摘要

个体对电离辐射的反应是实施有效的肿瘤放射治疗以及避免对正常组织产生任何不良反应所需的重要信息。1981年,费蒂尔(Fertil)和马拉伊斯(Malaise)证明,体内测定的照射后局部肿瘤控制与体外评估的克隆源性细胞存活相关。此外,这些作者还提醒了特定于每个个体器官的内在放射敏感性概念的相关性(费蒂尔和马拉伊斯,1981年)[1]。迄今为止,由于克隆形成试验耗时过长且无法提供任何其他分子信息,众多研究团队试图确定内在放射敏感性的分子基础,以便提出可靠且更快的预测试验。为此,已开发出多种方法。值得注意的是,基因组学和蛋白质组学技术的最新变革提供了大量数据,但其与放射敏感性的联系仍有待阐明。另一方面,对一些可能参与辐射反应的候选基因进行系统筛选,凸显了DNA损伤传感和信号传导的分子和细胞机制的复杂性,并表明异常的辐射反应不一定是由于单一蛋白质的损伤所致。最后,更适度的方法,即专注于DNA修复的某些特定功能,似乎为预测放疗引起的过度急性反应提供了更可靠的线索。在本综述中,我们力图分析这些主要方法对预测人类放射敏感性的贡献。

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