Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice.
Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice.
复制标题
DOI：
10.1371/journal.pone.0079543
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wu WJ
中科院分区：
文献类型：
--
作者：
ElZarrad MK;Mukhopadhyay P;Mohan N;Hao E;Dokmanovic M;Hirsch DS;Shen Y;Pacher P;Wu WJ
曲妥珠单抗（一种针对人表皮生长因子受体 2 (HER2) 细胞外结构域的人源化单克隆抗体）的治疗非常成功地改善了 HER2 阳性乳腺癌女性的预后。然而，曲妥珠单抗治疗最近与潜在的不可逆转的严重心脏毒性有关，其机制在很大程度上难以捉摸。这项研究报告称，曲妥珠单抗显着改变了 DNA 修复、心脏和线粒体功能所必需的心肌基因的表达，这与小鼠左心室功能受损以及电子显微镜显示的心肌细胞显着超微结构改变有关。此外，曲妥珠单抗治疗还促进小鼠心肌氧化应激和细胞凋亡，并提高心肌肌钙蛋白-I (cTnI) 和心肌肌球蛋白轻链-1 (cMLC1) 的血清水平。接受曲妥珠单抗治疗的小鼠中 cMLC1 血清水平升高，凸显了 cMLC1 可能成为曲妥珠单抗诱导的心脏毒性的有用生物标志物的潜力。
Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity.
登录
查看更多内容
DOI：
10.1073/pnas.122249299
发表时间：
2002-06-25
影响因子：
11.1
作者：
Özcelik, C;Erdmann, B;Garratt, AN
通讯作者：
Garratt, AN
影响因子：
6
作者：
Okamoto, Y;Chaves, A;Hai, T
通讯作者：
Hai, T
影响因子：
4.6
作者：
Huang, CQ;Sheikh, F;Chen, J
通讯作者：
Chen, J
影响因子：
45.3
作者：
Cardinale, Daniela;Colombo, Alessandro;Cipolla, Carlo M.
通讯作者：
Cipolla, Carlo M.
影响因子：
3.7
作者：
DeCara, Jeanne M.
通讯作者：
DeCara, Jeanne M.