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持续暴露于抗癌药物会使人类诱导多能干细胞衍生的心肌细胞暴露出其心脏毒性作用。

Continued exposure of anti-cancer drugs to human iPS cell-derived cardiomyocytes can unmask their cardiotoxic effects.

机构信息

Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

出版信息

J Pharmacol Sci. 2019 Aug;140(4):345-349. doi: 10.1016/j.jphs.2019.08.005. Epub 2019 Aug 27.

DOI:10.1016/j.jphs.2019.08.005
PMID:31521491
Abstract

Although the cardiotoxicity of anti-cancer drugs is an important issue, the underlying mechanisms remain unknown. To develop a sensitive assay system for cardiotoxicity, we examined effects of anti-cancer drugs on contractile functions of human iPS cell-derived cardiomyocytes by using non-invasive motion field imaging analysis with extended drug exposure time. We succeeded in continuously measuring stable contractile function. The continued exposure revealed that the difference in cardiotoxicity between cardiotoxic doxorubicin and less toxic erlotinib was more evident after 8 days of treatment than with 3 days of treatment, suggesting that continued exposure improved the predictive power for cardiotoxicity of anti-cancer drugs.

摘要

尽管抗癌药物的心脏毒性是一个重要问题,但其中的潜在机制尚不清楚。为了开发一种用于心脏毒性的敏感检测系统,我们通过使用具有延长药物暴露时间的非侵入性运动场成像分析,研究了抗癌药物对人诱导多能干细胞源性心肌细胞收缩功能的影响。我们成功地实现了稳定收缩功能的连续测量。持续暴露表明,在 8 天的治疗后,与 3 天的治疗相比,心脏毒性的多柔比星和毒性较小的厄洛替尼之间的心脏毒性差异更为明显,这表明持续暴露提高了抗癌药物心脏毒性的预测能力。

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