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药物蛋白质组学方法在药物作用模式、毒性及耐药性研究中的应用:在糖尿病和癌症中的应用

Pharmacoproteomic approach to the study of drug mode of action, toxicity, and resistance: applications in diabetes and cancer.

作者信息

Chapal Nicolas, Molina Laurence, Molina Franck, Laplanche Marion, Pau Bernard, Petit Pierre

机构信息

INNODIA S.A.S., 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.

出版信息

Fundam Clin Pharmacol. 2004 Aug;18(4):413-22. doi: 10.1111/j.1472-8206.2004.00258.x.

Abstract

Proteomics is a powerful technique for investigating protein expression profiles in biological systems and their modifications in response to stimuli or to particular physiological or pathophysiological conditions. It is therefore a technique of choice for the study of drug mode of action, side-effects, toxicity and resistance. It is also a valuable approach for the discovery of new drug targets. All these proteomic applications to pharmacological issues may be called pharmacoproteomics. The pharmacoproteomic approach could be particularly useful for the identification of molecular alterations implicated in type 2 diabetes and for further characterization of existing or new drugs. In oncology, proteomics is widely used for the identification of tumour-specific protein markers, and pharmacoproteomics is used for the evaluation of chemotherapy, particularly for the characterization of drug-resistance mechanisms. The large amount of data generated by pharmacoproteomic screening requires the use of bioinformatic tools to insure a pertinent interpretation. Herein, we review the applications of pharmacoproteomics to the study of type 2 diabetes and to chemoresistance in different types of cancer and the current state of this technology in these pathologies. We also suggest a number of bioinformatic solutions for proteomic data management.

摘要

蛋白质组学是一种强大的技术,可用于研究生物系统中的蛋白质表达谱及其在响应刺激或特定生理或病理生理条件时的修饰。因此,它是研究药物作用模式、副作用、毒性和耐药性的首选技术。它也是发现新药靶点的宝贵方法。所有这些蛋白质组学在药理学问题上的应用都可称为药物蛋白质组学。药物蛋白质组学方法对于鉴定与2型糖尿病相关的分子改变以及进一步表征现有或新药可能特别有用。在肿瘤学中,蛋白质组学广泛用于鉴定肿瘤特异性蛋白质标志物,而药物蛋白质组学则用于评估化疗,特别是用于表征耐药机制。药物蛋白质组学筛选产生的大量数据需要使用生物信息学工具来确保进行相关解释。在此,我们综述了药物蛋白质组学在2型糖尿病研究和不同类型癌症的化疗耐药性研究中的应用,以及该技术在这些疾病中的现状。我们还提出了一些用于蛋白质组学数据管理的生物信息学解决方案。

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