Oncological study for brain tumors by using Proton radiosurgery and enhanced drugs to oxidative stress

使用质子放射外科和增强氧化应激药物对脑肿瘤进行肿瘤学研究

• 批准号: 06671372
• 负责人: YOSHII Yoshihiko
• 金额: $ 1.41万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06671372/
• 关键词: Proton Beam; lonizing Radiation; Oxidative Stress (Oxidants); Antioxidants; in vitro; in vivo; Immunohistochemistry; Scavengers; ラジカル; DCFHDA; SOD; GST-Tc; Immunohistochemical; ラジカル刺激剤; スカベンジャー薬剤; 蛍光測定; U251細胞; CDDP; 細胞致死効果; 神経膠腫細胞

Stereotactic radiosurgery has proven to be a useful adjunct to surgery and external beam radiotherapy in the treatment of malignant brain tumors. Proton beams have both characteristic Bragg peak and sharp fall-off effect, therefore proton radiosurgery is a very useful modality as a therapeutic tool or malignant brain tumors. Radiation have a cytotoxic effect by oxidative stress producing in the tumor-cells by irradiation.Some chemotherapeutic drugs also have same effect.On the other hand, there is scavenge mechanism as a cell-protection for cytotoxity by the oxidative effect in vivo. Interaction between scavengers and oxidants in the cell were very important for cytotoxic effect.The aim of this study is to develop the combination therapy of anticancer drugs or radical enhancement drugs and proton radiosurgery.(1) We made a simple head-fixing instrument referring to the Komai's head-fixing frame using the CT guided stereotaxy surgery Target-error by this instrument is a 2mm width in the … More simulated proton dosimetry.(2) We could successfully visualize the oxidizing free radicals produced by radiation and CDDP in the glioblastoma cells. The surviving fraction of the cells stimulated by radiation and CDDP was specifically correlated to the ratio of the fluorescent cells reacted with DCFHDA and active oxygen in the early period after stimulation. There was a time lag from the appearance of fluorescence to cell death after stimulation. In all probability, those oxidative stresses relate dose-dependently to the cell death and those will take time to induce the cell death by the catalytic effect of the cellular enzymes and metabolisms containing DNA strand damage.(3) The scavenger-drugs and/or enhanced drugs for the oxidative stress in the normal and/or tumor cells did not always show dose-dependently the protection to the cytotoxity.(4) In human brain tumors, the tumor cells with high SOD (scavenger) activity tended to radiotherapy and anticancer drugs.However, the presence of the fluorescent cells after stimulation was different in a same experimented group and furthermore there were few fluorescent cells in comparison with the number of the dead cells. These may suggest to further investigate the number of the DCFHDA-loaded cells and/or the DCFHDA trapping method.Evaluation of scavenger activity among tumor cells should be helpful in choosing oxidative cytotoxic treatments like proton radiosurgery and gamma knife in brain tumors.The mechanism responsible for variation in immunohistochemically reactive scavenger materials in human brain tumors remains a matter for further study. Less

立体定向放射外科已被证明是外科手术和外照射治疗恶性脑肿瘤的有效辅助手段。质子束既具有布拉格峰的特性，又具有急剧下降的效应，因此质子放射外科是一种非常有用的治疗手段或恶性脑肿瘤。辐射通过辐射在肿瘤细胞中产生氧化应激而产生细胞毒作用，一些化疗药物也具有同样的作用。另一方面，体内存在清除机制，通过氧化作用保护细胞毒作用。细胞内清除剂和氧化剂之间的相互作用是细胞毒作用的重要因素。本研究的目的是发展抗癌药物或自由基增强药物与质子放射外科的联合治疗。(1)利用CT引导的立体定向手术制作了一台简易的头部固定器，该仪器的目标误差是…中的2 mm宽更多的模拟质子剂量学。(2)我们成功地显示了辐射和顺铂在胶质母细胞瘤细胞中产生的氧化自由基。辐射和顺铂刺激的细胞存活率与刺激后早期荧光细胞与DCFHDA和活性氧反应的比例呈正相关。刺激后从出现荧光到细胞死亡有一段时间。这些氧化应激与细胞死亡呈剂量依赖关系，这些氧化应激需要时间才能通过细胞酶和含有DNA链损伤的代谢的催化作用而诱导细胞死亡。(3)在正常和/或肿瘤细胞中，针对氧化应激的清除剂和/或增强药物并不总是表现出剂量依赖的保护作用。(4)在人脑肿瘤中，具有高SOD(清除剂)活性的肿瘤细胞倾向于放射治疗和抗癌药物。然而，在人类脑肿瘤中，具有较高SOD活性的肿瘤细胞倾向于放疗和抗癌药物同一实验组刺激后的荧光细胞数不同，且与死亡细胞数相比，荧光细胞数较少。这可能建议进一步研究DCFHDA负载细胞的数量和/或DCFHDA捕捉法。肿瘤细胞中清除剂活性的评估将有助于选择脑肿瘤的氧化细胞毒治疗方案，如质子放射外科和伽玛刀。导致人脑肿瘤免疫组织化学反应性清除剂物质变化的机制仍有待进一步研究。较少

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