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奥沙利铂所致神经病变:遗传和表观遗传特征,以更好地理解如何改善这种副作用。

Oxaliplatin-Induced Neuropathy: Genetic and Epigenetic Profile to Better Understand How to Ameliorate This Side Effect.

作者信息

Branca Jacopo Junio Valerio, Carrino Donatello, Gulisano Massimo, Ghelardini Carla, Di Cesare Mannelli Lorenzo, Pacini Alessandra

机构信息

Histology and Anatomy Section, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Firenze, Firenze, Italy.

出版信息

Front Mol Biosci. 2021 May 7;8:643824. doi: 10.3389/fmolb.2021.643824. eCollection 2021.

Abstract

In the most recent decades, oxaliplatin has been used as a chemotherapeutic agent for colorectal cancer and other malignancies as well. Oxaliplatin interferes with tumor growth predominantly exerting its action in DNA synthesis inhibition by the formation of DNA-platinum adducts that, in turn, leads to cancer cell death. On the other hand, unfortunately, this interaction leads to a plethora of systemic side effects, including those affecting the peripheral and central nervous system. Oxaliplatin therapy has been associated with acute and chronic neuropathic pain that induces physicians to reduce the dose of medication or discontinue treatment. Recently, the capability of oxaliplatin to alter the genetic and epigenetic profiles of the nervous cells has been documented, and the understanding of gene expression and transcriptional changes may help to find new putative treatments for neuropathy. The present article is aimed to review the effects of oxaliplatin on genetic and epigenetic mechanisms to better understand how to ameliorate neuropathic pain in order to enhance the anti-cancer potential and improve patients' quality of life.

摘要

在最近几十年里,奥沙利铂一直被用作治疗结直肠癌及其他恶性肿瘤的化疗药物。奥沙利铂主要通过形成DNA-铂加合物来干扰肿瘤生长,进而抑制DNA合成,最终导致癌细胞死亡。然而,不幸的是,这种相互作用会引发大量全身性副作用,包括影响外周和中枢神经系统的副作用。奥沙利铂治疗与急慢性神经性疼痛相关,这促使医生减少药物剂量或停止治疗。最近,已有文献证明奥沙利铂能够改变神经细胞的基因和表观遗传特征,而对基因表达和转录变化的理解可能有助于找到治疗神经病变的新的潜在方法。本文旨在综述奥沙利铂对基因和表观遗传机制的影响,以便更好地理解如何改善神经性疼痛,从而增强抗癌潜力并提高患者的生活质量。

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