Mechanisms of radiation-induced brain toxicity and implications for future clinical trials
Mechanisms of radiation-induced brain toxicity and implications for future clinical trials
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DOI：
10.1007/s11060-008-9520-x
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发表时间：
2008-05-01
影响因子：
3.9
通讯作者：
Ryu, Samuel
中科院分区：
文献类型：
--
作者：
Kim, Jae Ho;Brown, Stephen L.;Ryu, Samuel
放射治疗广泛用于治疗原发性恶性脑肿瘤和脑转移瘤，具有治愈或姑息的目的。癌症放射治疗的局限性并不在于不能消融肿瘤，而是不能在不过度损伤患者的情况下消融肿瘤。在各种辐射引起的脑毒性中，迟发效应导致严重和不可逆转的神经系统后果。辐射暴露后，CNS内的迟发性效应可归因于涉及少突胶质细胞、神经祖细胞和内皮细胞的实质和血管损伤。这些反映了一个动态过程，涉及辐射诱导的靶细胞死亡和随后的继发性反应性神经炎症过程，据信这些过程会导致选择性细胞丢失、组织损伤和功能缺陷。大剂量辐射后脑的进行性、迟发性损伤被认为是由辐射诱导的长寿命自由基、活性氧和促炎细胞因子引起的。实验研究表明，放射性脑损伤可以成功地减轻和治疗与几个公认的药物在广泛的临床使用，发挥其作用，通过阻断促炎细胞因子和活性氧。这篇综述强调了可用于未来临床试验的临床前和早期临床数据。
Radiation therapy is widely used in the treatment of primary malignant brain tumors and metastatic tumors of the brain with either curative or palliative intent. The limitation of cancer radiation therapy does not derive from the inability to ablate tumor, but rather to do so without excessively damaging the patient. Among the varieties of radiation-induced brain toxicities, it is the late delayed effects that lead to severe and irreversible neurological consequences. Following radiation exposure, late delayed effects within the CNS have been attributable to both parenchymal and vascular damage involving oligodendrocytes, neural progenitors, and endothelial cells. These reflect a dynamic process involving radiation-induced death of target cells and subsequent secondary reactive neuroinflammatory processes that are believed to lead to selective cell loss, tissue damage, and functional deficits. The progressive, late delayed damage to the brain after high-dose radiation is thought to be caused by radiation-induced long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines. Experimental studies suggest that radiation-induced brain injury can be successfully mitigated and treated with several well established drugs in wide clinical use which exert their effects by blocking pro-inflammatory cytokines and reactive oxygen species. This review highlights preclinical and early clinical data that are translatable for future clinical trials.