کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8553431 | 1562587 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modeling trastuzumab-related cardiotoxicity in vitro using human stem cell-derived cardiomyocytes
ترجمه فارسی عنوان
مدلسازی سمیت کراتوتیک مرتبط با تروستوزومب در آزمایشگاهی با استفاده از کاردیومیوسیت های مشتق شده از سلول های بنیادی انسان
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Trastuzumab (Herceptin®), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed. We observed no cardioprotective effects of ErbB2/4 signaling without cellular stress (doxorubicin exposure in this study). In addition to neuregulin-1 (NRG-1), we show that heparin-binding epidermal growth factor-like growth factor (HB-EGF) also provides cardioprotective effects for iPS-CMs. Finally, we demonstrate a simple, high-throughput co-culture platform utilizing iPS-CMs and endothelial cells that is capable of detecting trastuzumab-related cardiotoxicity. We conclude that iPS-CMs can recapitulate trastuzumab-related cardiotoxicity, and may be used to elucidate additional modes of toxicity of trastuzumab and related compounds.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 285, 15 March 2018, Pages 74-80
Journal: Toxicology Letters - Volume 285, 15 March 2018, Pages 74-80
نویسندگان
Yosuke K. Kurokawa, Michael R. Shang, Rose T. Yin, Steven C. George,