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[紫杉烷诱导的周围神经病变的生物标志物鉴定及新疗法]

[Identification of biomarkers and new therapies for taxane-induced peripheral neuropathy].

作者信息

Koyanagi Madoka, Imai Satoshi, Nakagawa Takayuki, Matsubara Kazuo

机构信息

Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital.

出版信息

Nihon Yakurigaku Zasshi. 2019;154(5):241-244. doi: 10.1254/fpj.154.241.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. We have previously demonstrated that paclitaxel preferentially impair myelin-forming Schwann cells, and consequently induce dedifferentiation and demyelination of Schwann cells. Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.

摘要

化疗引起的周围神经病变(CIPN)是紫杉烷类药物常引发的一种副作用。由于CIPN发病机制的根本原因仍有待充分阐明,所以不存在像生物标志物那样用于客观诊断的指标。此外,CIPN的治疗选择仍不尽人意。我们之前已经证明,紫杉醇优先损害形成髓鞘的施万细胞,进而诱导施万细胞去分化和脱髓鞘。最近,在一个紫杉醇诱导的CIPN模型小鼠中,我们发现一种炎症因子从小鼠坐骨神经中去分化的施万细胞释放到血液中,这与机械性超敏反应的发生高度相关。另一方面,考虑到我们之前的研究结果,似乎一些能在脱髓鞘病变部位提供新形成的成熟施万细胞的药物,可能是治疗紫杉烷类药物引起的周围神经病变的一种新的有效疗法。在这篇综述中,我们将基于这一概念介绍我们关于紫杉烷相关CIPN新治疗候选药物以及用于检测CIPN发生和进展的血浆生物标志物的研究结果。

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