在化疗诱导的外周神经病变患者中,在帕克利塔克塞尔治疗后皮肤细胞外基质分解
Nathan P Staff1, Sybil C Hrstka1, Surendra Dasari1
1Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Cancers
|August 26, 2023
概括
帕克利塔塞尔化疗会引起外围神经病变,但皮肤神经纤维密度不会改变. 皮肤重塑和MMP-13上调是化疗诱导的周围神经病变 (CIPN) 的关键因素.
科学领域:
- 在瘤学瘤学.
- 神经学 神经学
- 皮肤病学 皮肤病学
背景情况:
- 帕克利塔塞尔化学疗法可能会导致外围神经病变,这是影响癌症患者生活质量的重大副作用.
- 化疗诱导的周围神经病变 (CIPN) 是常见的,限制剂量的毒性帕克利塔塞尔治疗.
- 以前的研究表明,皮肤变化在CIPN中起着作用,对斑马鱼和动物进行了研究.
研究的目的:
- 调查帕克利塔塞尔治疗对患有CIPN.乳腺癌的乳腺癌患者皮肤的影响.
- 要将患者报告的CIPN症状与客观的皮肤变化相关联,包括神经纤维密度和分子变化.
- 探索CIPN.皮肤变化背后的分子机制.
主要方法:
- 进行了神经学检查和生活质量调查问卷,以评估CIPN症状.
- 皮肤穿孔活检用于皮肤内神经纤维 (IENF) 密度评估.
- 用RNA测序,MMP-13免疫染色和传输电子显微镜来分析分子和超结构性皮肤变化.
主要成果:
- 尽管报告了症状,但在CIPN和没有CIPN的患者之间没有观察到IENF密度的显著差异.
- 在CIPN患者的皮肤中检测到显著上调的矩阵金属蛋白酶13 (MMP-13).
- 在与细胞外矩阵,微管,细胞循环和神经系统调节相关的途径中注意到了差异性基因表达. 超结构分析显示了原和底层膜的变化.
结论:
- 在没有减少IENF密度的情况下,CIPN可以表现出来,这表明了替代机制.
- 皮肤重塑,通过改变细胞外基质和底层膜结构来表明,在帕克利塔塞尔诱导的外周神经病变中起着至关重要的作用.
- 皮肤中MMP-13的升级是与CIPN相关的关键分子事件.
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