Basical study for curing malignant brain tumor with carbon-ion beam therapy

碳离子束治疗恶性脑肿瘤的基础研究

基本信息

批准号：
20790877
负责人：
SUZUKI Yoshiyuki
金额：
$ 2.58万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790877/
关键词：
炭素イオン線悪性脳腫瘍遊走能増感剤ニューロン

项目摘要

1) According to the rate of radiation induced apoptosis, effect of Carbon-ion beam to immature neuron was about ten times higher than that of X-ray.2) As for glial cell, there was little difference in X-ray radiosensitivity between immature and mature cells. X-ray radiosensitivity of glial cell was a little low compared with that of neuronal cell.3) As for anti-tumor effect, the effect of X-ray with concurrent TMZ was 1.6 times higher than that without TMZ. Moreover, the effect of X-ray with concurrent TMZ and GYKI52466 was 10% higher than that with TMZ alone in the brain transplant model. As for RBE, when TMZ was used concurrently, the RBE of carbon-ion beam to X-ray was estimated about 3, similar to the RBE without TMZ in in vivo model. Also, the combinational effect of TMZ was an additive effect. As for cell motility, though the motility of tumor cell was enhanced by X-ray alone, it was completely controled by the use of ether TMZ or GYKI52466.4) Concurrent use of TMZ with carbon-ion beam did not enhance the radiation effect.5) Expression of Akt and PDK1 in malignant brain tumor cell were increased by X-ray irradiation and the increased expression of PDK1 correlated to activation of cell motility. In clinical, strong expression of activated Akt and PDK1 were significant poor prognostic factor in the Glioblastoma patients treated with radiation therapy..

1）根据辐射诱导的细胞凋亡的速率，碳离子束对未成熟神经元的作用是X射线的十倍。和成熟的细胞。与神经元细胞相比，神经胶质细胞的X射线辐射敏感性略低。3）与抗肿瘤效应相比，与没有TMZ的X射线X射线的效果是X射线的效应。此外，X射线与并发TMZ和GYKI52466的效果比单独使用TMZ高10％。至于RBE，当同时使用TMZ时，估计碳离子束至X射线的RBE估计约为3，类似于在体内模型中没有TMZ的RBE。同样，TMZ的组合效应是一种加性效应。至于细胞运动性，尽管仅X射线射线可以增强肿瘤细胞的运动性，但通过使用Ether TMZ或GYKI52466.4完全控制了肿瘤细胞的动力，但同时将TMZ与碳纤维束一起使用并不能增强辐射效应。 5）通过X射线照射，AKT和PDK1在恶性脑肿瘤细胞中的表达增加，PDK1的表达与细胞运动的激活相关。在临床上，激活的Akt和PDK1的强表达在接受放射疗法治疗的胶质母细胞瘤患者中是明显较差的预后因素。