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评估啮齿动物模型中放射性心脏毒性的方法。

Methods to assess radiation-induced cardiotoxicity in rodent models.

机构信息

Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States.

Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States.

出版信息

Methods Cell Biol. 2023;180:127-146. doi: 10.1016/bs.mcb.2023.02.014. Epub 2023 Apr 24.

Abstract

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.

摘要

癌症幸存者在接受主要治疗时接受过胸部放疗,由于心脏意外受到辐射,他们有发生放射性心脏毒性(RICT)的风险。在最近几十年中,放射治疗的进步极大地提高了放射治疗的治疗比率(有效地靶向恶性肿瘤,同时保护心脏);然而,在许多患者中,心脏的意外辐射无法完全避免。心脏辐射暴露会导致长期发病,并导致癌症患者的生存率降低。严重的心脏影响可能在治疗后 2 年内发生。目前,尚无法预测谁患放射性心脏毒性的风险更高或更低,并且尚未明确确定改变放射性心脏毒性的关键因素。因此,临床前研究是更好地预防、检测和管理癌症幸存者放射性心脏毒性的重要步骤。本章的总体目标是为研究人员提供使用小鼠和大鼠进行放射性心脏毒性研究的基础和技术知识。在简要概述放射性心脏毒性的病理生理学和临床表现之后,我们讨论了放射性心脏毒性研究设计的重要考虑因素,包括动物选择和放射规划。然后,我们提供了用于鼠组织收获和处理的示例方案,这些方案可以支持读者选择的下游应用。

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