The effects of extra high dose rate irradiation on glioma stem-like cells.
The effects of extra high dose rate irradiation on glioma stem-like cells.
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DOI：
10.1371/journal.pone.0202533
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Yu JS
中科院分区：
文献类型：
--
作者：
Hao J;Godley A;Shoemake JD;Han Z;Magnelli A;Yu JS
放射治疗是胶质母细胞瘤患者治疗不可或缺的一部分。直线加速器的新技术进步使超高剂量率辐射成为可能。与标准剂量率照射相比，这显著缩短了患者的治疗时间，但超高剂量率照射的生物学效应尚不清楚。胶质瘤干细胞(GSCs)对标准辐射具有抵抗力，有助于肿瘤的进展。在这里，我们评估了超高剂量率与标准剂量率照射对GSCs的治疗效果。GSC接受2、4和6GyX射线照射，剂量率分别为4.2Gymin或21.2Gymin(400个监测单位/min或2100MU/min)。通过细胞生长实验、肿瘤球体形成实验和集落形成实验分析细胞存活率。细胞杀伤和自我更新依赖于辐射总剂量。但不同剂量率照射后，GSCs的存活率和DNA损伤修复能力无明显差异。随着辐射剂量的增加，GSCs出现明显的G1期和G2/M期停滞，细胞凋亡率增加，但两种剂量率在各剂量组间无明显差异。在GSC衍生的胶质母细胞瘤临床前模型中，辐射延长了动物的存活时间，但在接受不同剂量率辐射的小鼠中，存活时间没有差异。我们的结论是，GSCs对更大比例的辐射有反应，但超高剂量率照射与标准剂量率照射相比没有显著的生物学优势。
Radiation therapy is an integral part of treatment for patients with glioblastoma. New technological advances in linear accelerators have made extra-high dose rate irradiation possible. This shortens patient treatment time significantly compared to standard dose rate irradiation, but the biologic effects of extra high dose rate irradiation are poorly understood. Glioma stem-like cells (GSCs) are resistant to standard radiation and contribute to tumor progression. Here, we assess the therapeutic effect of extra high dose rate vs. standard dose rate irradiation on GSCs. GSCs were exposed to 2, 4 and 6 Gy X-irradiation at dose rates of 4.2 Gy/min or 21.2 Gy/min (400 monitoring units (MU)/min or 2100 MU/min). We analyzed cell survival with cell growth assays, tumorsphere formation assays and colony formation assays. Cell kill and self-renewal were dependent on the total dose of radiation delivered. However, there was no difference in survival of GSCs or DNA damage repair in GSCs irradiated at different dose rates. GSCs exhibited significant G1 and G2/M phase arrest and increased apoptosis with higher doses of radiation but there was no difference between the two dose rates at each given dose. In a GSC-derived preclinical model of glioblastoma, radiation extended animal survival, but there was no difference in survival in mice receiving different dose rates of radiation. We conclude that GSCs respond to larger fractions of radiation, but extra high dose rate irradiation has no significant biologic advantage in comparison with standard dose rate irradiation.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
胶质瘤干细胞增殖和肿瘤生长由一氧化氮合酶2促进。
影响因子：
64.5
作者：
Eyler CE;Wu Q;Yan K;MacSwords JM;Chandler-Militello D;Misuraca KL;Lathia JD;Forrester MT;Lee J;Stamler JS;Goldman SA;Bredel M;McLendon RE;Sloan AE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
影响因子：
5.7
作者：
Lohse, Ines;Lang, Stephanie;Zaugg, Kathrin
通讯作者：
Zaugg, Kathrin
影响因子：
3.5
作者：
O'Brien, Catherine Adell;Kreso, Antonija;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A