PREFERENTIAL EFFECT OF SYNCHROTRON MICROBEAM RADIATION THERAPY ON INTRACEREBRAL 9L GLIOSARCOMA VASCULAR NETWORKS
PREFERENTIAL EFFECT OF SYNCHROTRON MICROBEAM RADIATION THERAPY ON INTRACEREBRAL 9L GLIOSARCOMA VASCULAR NETWORKS
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DOI：
10.1016/j.ijrobp.2010.06.021
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发表时间：
2010-12-01
影响因子：
7
通讯作者：
Serduc, Raphael
中科院分区：
文献类型：
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作者：
Bouchet, Audrey;Lemasson, Benjamin;Serduc, Raphael
目的 同步加速器微束放射治疗 (MRT) 依赖于将入射光子束空间分割成平行的微米宽光束 我们的目的是分析 MRT 对正常脑和 9L 胶质肉瘤组织的影响，特别是对血管的影响 方法和材料 使用 MRI 在 6 周内研究了对 MRT（两个阵列，一个横向，一个前后向 (2 x 400 Gy)，在肿瘤区域正交相交）的反应，结果 MRT 增加了受照射大鼠的中位生存时间 ( x 3 25)，显着增加了血管通透性，并抑制了肿瘤生长，在照射后 5 天检测到对 9L 细胞的细胞毒性作用 免疫化学检测到，由于肿瘤内皮细胞的损失，从照射后 8 天开始，测量到肿瘤血容量分数和血管直径显着下降。照射后约 6 周，两种阵列交叉发射 这种水肿与血管形态的变化和血管内皮生长因子的过度表达有关。相反，暴露于两种阵列之一的脑区域的血管参数和血管形态没有受损，并且没有血管内皮细胞的损失。结论我们首次表明，与保留抗辐射的正常脑血管相比，MRT 对肿瘤血管的优先损伤有助于有效缓解 9L 胶质肉瘤MRT 后正常和肿瘤血管网络修复机制的分子途径可能对于改善脉管系统的这种差异效应至关重要 (C) 2010 Elsevier Inc
Purpose Synchrotron microbeam radiation therapy (MRT) relies on spatial fractionation of the incident photon beam into parallel micron wide beams Our aim was to analyze the effects of MRT on normal brain and 9L gliosarcoma tissues, particularly on blood vesselsMethods and Materials Responses to MRT (two arrays, one lateral, one anteroposterior (2 x 400 Gy), intersecting orthogonally in the tumor region) were studied during 6 weeks using MRI, immunohistochemistry, and vascular endothelial growth factor Western blotResults MRT increased the median survival time of irradiated rats ( x 3 25), significantly Increased blood vessel permeability, and inhibited tumor growth, a cytotoxic effect on 9L cells was detected 5 days after irradiation Significant decreases in tumoral blood volume fraction and vessel diameter were measured from 8 days after irradiation, due to loss of endothelial cells in tumors as detected by immunochemistry Edema was observed in the normal brain exposed to both crossfired arrays about 6 weeks after irradiation This edema was associated with changes in blood vessel morphology and an overexpression of vascular endothelial growth factor Conversely, vascular parameters and vessel morphology in brain regions exposed to one of the two arrays were not damaged, and there was no loss of vascular endotheliaConclusions We show for the first time that preferential damage of MRT to tumor vessels versus preservation of radioresistant normal brain vessels contributes to the efficient palliation of 9L gliosarcomas in rats Molecular pathways of repair mechanisms in normal and tumoral vascular networks after MRT may be essential for the improvement of such differential effects on the vasculature (C) 2010 Elsevier Inc