Oncological study for brain tumors by using Proton radiosurgery and enhanced drugs to oxidative stress
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||University of Tsukuba|
YOSHII Yoshihiko Univ.of Tsukuba Inst.of Clinical Medicine Assoc.Prof., 臨床医学系, 助教授 (50110507)
OKUNO Hiroaki National Inst.of Bioscience & Human Technology Senoir Res., 生体物質部;機能科学室, 室長
TSUBOI Koji Inst.of Clinical Medicine, University of Tsukuba Assist.Prof., 臨床医学系, 講師 (90188615)
AOYAGI Kazumasa Inst.of Clinical Medicine, University of Tsukuba Assist.Prof., 臨床医学系, 講師 (40114029)
HAYAKAWA Yoshinori Inst.of Basic Medicine, University of Tsukuba Assist.Prof., 基礎医学系, 講師 (90101740)
MARUHASHI Akira Inst.of Basic Medicine, University of Tsukuba Assoc.Prof., 基礎医学系, 助教授 (30114135)
|Project Period (FY)
1994 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1996 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
|Keywords||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
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
Research Output (19results)