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神经毒性测试:化疗引起的周围神经毒性的经验教训

neurotoxicity testing: lessons from chemotherapy-induced peripheral neurotoxicity.

作者信息

Tarasiuk Olga, Invernizzi Chiara, Alberti Paola

机构信息

Experimental Neurology Unit, School of Medicine and Surgery, Monza, Italy.

NeuroMI (Milan Center for Neuroscience), Milan, Italy.

出版信息

Expert Opin Drug Metab Toxicol. 2024 Nov-Dec;20(11-12):1037-1052. doi: 10.1080/17425255.2024.2401584. Epub 2024 Sep 10.

Abstract

INTRODUCTION

Chemotherapy induced peripheral neurotoxicity (CIPN) is a long-lasting, or even permanent, late toxicity caused by largely used anticancer drugs. CIPN affects a growing population of cancer survivors and diminishes their quality of life since there is no curative/preventive treatment. Among several reasons for this unmet clinical need, there is an incomplete knowledge on mechanisms leading to CIPN. Therefore, bench side research is still greatly needed: studies are pivotal to both evaluate neurotoxicity mechanisms and potential neuroprotection strategies.

AREAS COVERED

Advantages and disadvantages of approaches are addressed with respect to their applicability to the CIPN field. Different cell cultures and techniques to assess neurotoxicity/neuroprotection are described. PubMed search-string: (chemotherapy-induced) AND (((neuropathy) OR neurotoxicity) OR neuropathic pain) AND (in vitro) AND (((((model) OR SH-SY5Y) OR PC12) OR iPSC) OR DRG neurons); (chemotherapy-induced) AND (((neuropathy) OR neurotoxicity) OR neuropathic pain) AND (model) AND (((neurite elongation) OR cell viability) OR morphology). No articles published before 1990 were selected.

EXPERT OPINION

CIPN is an ideal experimental setting to test axonal damage and, in general, peripheral nervous system mechanisms of disease and neuroprotection. Therefore, starting from robust preclinical data in this field, potentially, relevant biological rationale can be transferred to other human spontaneous diseases of the peripheral nervous system.

摘要

引言

化疗引起的周围神经毒性(CIPN)是由大量使用的抗癌药物引起的一种持久甚至永久性的晚期毒性。由于没有治愈性/预防性治疗方法,CIPN影响着越来越多的癌症幸存者,并降低了他们的生活质量。在导致这一未满足临床需求的几个原因中,对导致CIPN的机制了解不完整。因此,仍然非常需要基础研究:这些研究对于评估神经毒性机制和潜在的神经保护策略都至关重要。

涵盖领域

针对其在CIPN领域的适用性,讨论了各种方法的优缺点。描述了用于评估神经毒性/神经保护的不同细胞培养和技术。PubMed搜索词:(化疗诱导的)AND(((神经病变)或神经毒性)或神经性疼痛)AND(体外)AND((((模型)或SH-SY5Y)或PC12)或诱导多能干细胞)或背根神经节神经元);(化疗诱导的)AND(((神经病变)或神经毒性)或神经性疼痛)AND(模型)AND(((神经突伸长)或细胞活力)或形态)。未选择1990年以前发表的文章。

专家观点

CIPN是测试轴突损伤以及一般周围神经系统疾病和神经保护机制的理想实验环境。因此,从该领域可靠的临床前数据出发,潜在的相关生物学原理可以应用于其他人类周围神经系统的自发性疾病。

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