کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8553935 | 1562695 | 2018 | 47 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vitro assessment of chemotherapy-induced neuronal toxicity
ترجمه فارسی عنوان
بررسی درون سلولی سمیت عصبی ناشی از شیمیدرمانی
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کلمات کلیدی
DRGIPSCCIPNMOAApoptosis - خزان یاختهایCNS - دستگاه عصبی مرکزیinduced-pluripotent stem cell - سلول های بنیادی القا شده و پلورپوفتونNeurotoxicity - سمیت عصبیcentral nervous system - سیستم عصبی مرکزیchemotherapy-induced peripheral neuropathy - شیمی درمانی نوروپاتی محیطیIn vitro models - مدل های in vitroMechanism of action - مکانیسم عملNeuropathy - نوروپاتیperipheral neuropathy - پلینوریتdorsal root ganglia - گانگلیس ریشه پشتی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Neurotoxicity is a major concern during drug development, and together with liver and cardio-toxicity, it is one of the main causes of clinical drug attrition. Current pre-clinical models may not sufficiently identify and predict the risk for central or peripheral nervous system toxicity. One such example is clinically dose-limiting neuropathic effects after the administration of chemotherapeutic agents. Thus, the need to establish novel in vitro tools to evaluate the risk of neurotoxicities, such as neuropathy, remains unmet in drug discovery. Though in vitro studies have been conducted using primary and immortalized cell lines, some limitations include the utility for higher throughput methodologies, method reproducibility, and species extrapolation. As a novel alternative, human induced-pluripotent stem cell (iPSC)-derived neurons appear promising for testing new drug candidates. These iPSC-derived neurons are readily available and can be manipulated as required. Here, we describe a novel approach to assess neurotoxicity caused by different classes of chemotherapeutics using kinetic monitoring of neurite dynamic changes and apoptosis in human iPSC-neurons. These studies show promising changes in neurite dynamics in response to clinical inducers of neuropathy, as well as the ability to rank-order and gather mechanistic insight into class-specific compound induced neurotoxicity. This platform can be utilized in early drug development, as part of a weight of evidence approach, to screen drug candidates, and potentially reduce clinical attrition due to neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 50, August 2018, Pages 109-123
Journal: Toxicology in Vitro - Volume 50, August 2018, Pages 109-123
نویسندگان
Chelsea Snyder, Lanlan Yu, Tin Ngo, Daniel Sheinson, Yuda Zhu, Min Tseng, Dinah Misner, Karin Staflin,