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

1)根据辐射诱导凋亡率，碳离子束对未成熟神经元的辐射效应是X射线的10倍左右。2）对于胶质细胞，未成熟细胞和成熟细胞的X射线辐射敏感性差异不大。胶质细胞对X线的放射敏感性略低于神经细胞。3）X线联合TMZ的抗肿瘤作用是不联合TMZ的1.6倍。在脑移植模型中，X射线联合TMZ和GYKI 52466的效果比单独使用TMZ高10%。对于RBE，当同时使用TMZ时，碳离子束对X射线的RBE估计约为3，与体内模型中不使用TMZ的RBE相似。TMZ的组合效应为加性效应。对于细胞运动性，单纯X射线虽能增强肿瘤细胞的运动性，但TMZ或GYKI 52466能完全抑制肿瘤细胞的运动性。4）TMZ与碳离子束联合应用并不能增强放射效应。5）X射线照射后，恶性脑肿瘤细胞Akt和PDK1表达增加，且PDK1表达增加与细胞运动性激活有关。在临床上，活化Akt和PDK1的高表达是胶质母细胞瘤放疗患者预后不良的重要因素。

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..