紫杉醇会改变黑色素生成,导致妇科癌症患者皮肤出现色素沉着。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-07-23 DOI:10.1111/fcp.12943
Paula Montero, Celia Sanz, Jose Alejandro Pérez-Fidalgo, Martín Pérez-Leal, Javier Milara, Julio Cortijo
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引用次数: 0

摘要

背景:紫杉醇(PTX)是一种稳定微管的抗肿瘤药物,已被证明会损害皮肤等健康组织。色素沉着是 PTX 引起的不良反应之一,但文献资料有限,PTX 引起色素改变的机制尚不清楚:本研究旨在描述 PTX 引起的色素改变,并确定 PTX 对黑色素细胞的影响:方法:使用特定探针测定黑色素指数和色素沉着水平,测量20名接受PTX治疗的妇科癌症患者的皮肤色素改变。用紫杉醇培养黑色素细胞,分析黑色素生成标记基因的表达、黑色素含量和转录因子的激活情况:结果:紫杉醇可诱导皮肤色素的改变,但无明显的临床表现。接受紫杉醇治疗的妇科癌症患者的黑色素指数和色素沉着水平均有所增加。在体外,PTX暴露于黑色素细胞会增加黑色素生成标记物的表达、黑色素含量,并诱导ERK和MITF的活化:结果表明,PTX会改变患者的色素沉着,但临床上并无明显表现,这些改变可能是由于PTX能够通过MITF激活途径刺激黑色素细胞的黑色素生成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Paclitaxel alters melanogenesis and causes pigmentation in the skin of gynecological cancer patients

Background

Paclitaxel (PTX) is a microtubule-stabilizing antineoplastic that has been shown to damage healthy tissues like the skin. Hyperpigmentation can be found among the adverse effects caused by PTX, but the literature is limited and the mechanisms driving PTX-induced pigmentary alterations are unknown.

Objectives

This study aimed to describe the pigmentary alterations caused by PTX and to determine the effects of PTX on melanocytes.

Methods

Pigmentary skin alterations were measured in 20 gynecological cancer patients under PTX treatment by using specific probes, which determine the melanin index and the pigmentation level. Melanocytes were incubated with paclitaxel to analyze melanogenesis markers gene expression, melanin content, and transcription factors activation.

Results

Paclitaxel induced alterations in the skin pigmentation with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had an increase in the melanin index and pigmentation levels. In vitro, PTX exposure to melanocytes increased the expression of melanogenesis markers, melanin content, and induced activation of ERK and MITF.

Conclusions

The results suggest that PTX alters pigmentation in patients with no clinically visible manifestations, and these alterations might be driven by its capacity to stimulate melanogenesis on melanocytes through the MITF activation pathway.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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