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药物介导的毒性:通过细胞分析方法在试管中阐明“不良”情况?

Drug-mediated toxicity: illuminating the 'bad' in the test tube by means of cellular assays?

机构信息

German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, Department of Product Safety, 10589 Berlin, Germany.

出版信息

Trends Pharmacol Sci. 2012 Jul;33(7):353-64. doi: 10.1016/j.tips.2012.03.015. Epub 2012 May 1.

Abstract

Health problems are rising worldwide, be it as a consequence of lifestyle and longevity in increasingly affluent societies or due to a sharp rise in bacterial antibiotic resistance. The pharmaceutical industry is caught between high rates of attrition and the rather slow pace of a historically large regulatory system for pharmacological safety. Meanwhile, the past decade has seen a tremendous evolution of the biological toolbox, most notably of cellular assays, stem-cell differentiation and organ-mimicking systems. These systems were readily adapted for lead-compound identification. However, their use as toxicological test systems is lagging behind, not least because of a lack of regulatory acceptance. This review tries to elucidate the scale of the problem and discusses the applicability of the assays currently available, with particular regard to the use of stem cells.

摘要

全球健康问题不断增多,其成因包括日益富裕的社会中生活方式和寿命的变化,以及细菌抗生素耐药性的急剧上升。制药行业一方面面临高淘汰率,另一方面又受制于历史悠久、规模庞大的药理学安全监管体系,进展缓慢。与此同时,过去十年间生物学工具包经历了巨大的发展,尤其是细胞分析、干细胞分化和类器官系统。这些系统很容易被用于鉴定先导化合物。然而,它们作为毒理学测试系统的应用却滞后不前,这主要是因为缺乏监管部门的认可。本文试图阐明这一问题的严重程度,并讨论目前可用的检测方法的适用性,特别是干细胞的应用。

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