Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

被引:226
作者
Kim, Jae Ho [1 ]
Jenrow, Kenneth A. [1 ]
Brown, Stephen L. [1 ]
机构
[1] Henry Ford Hlth Syst, Dept Radiat Oncol, 2799 W Grand Blvd, Detroit, MI 48202 USA
来源
RADIATION ONCOLOGY JOURNAL | 2014年 / 32卷 / 03期
基金
美国国家卫生研究院;
关键词
Radiation normal tissue injury; Protectors; Mitigators;
D O I
10.3857/roj.2014.32.3.103
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.
引用
收藏
页码:103 / 115
页数:13
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