| Project/Area Number |
11470295
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
IMAHORI Yoshio KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR., 医学部, 助教授 (80191899)
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| Co-Investigator(Kenkyū-buntansha) |
SASAJIMA Yiroyasu KYOTO PREFECTURAL UNIVERSITY OF MEDICINE ASSISTANT PROFESSOR., 医学部, 講師 (80196188)
ONO Koji KYOTO UNIVERSITY, RESEARCH REACTOR INSTITUTE, PROFESSOR., 原子炉実験所, 教授 (90122407)
MINEURA Katsuyoshi KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, PROFESSOR., 医学部, 教授 (70134103)
OWADA Kei KYOTO PREFECTURAL UNIVERSITY OF MEDICINE ASSISTANT PROFESSOR., 医学部, 助手
小堀 信秀 京都府立医科大学, 医学部, 助手 (00254334)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | Glioma / apoptosis / antisense / Radiation injury / gene expression / telomerase / BNCT / PET / 高LET放射線 / PI3 kinase / Wortmannin / 脳腫瘍 / 高LET放射線治療 / 放射線壊死 / イノシトールリン脂質 / スフィンゴミエリン代謝 / ジアシルグリセロール / ポジトロンCT |
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| Research Abstract |
(1) Molecular biological clarification of the mechanism of induction of radiation necrosis in the brain by high-LET radiation
This study attempted to diagrammatically represent cell death due to DNA injury caused by high-LET radiation therapy and cell death not due to DNA injury, i.e. apoptosis due to death signals from the cell membrane, using a molecular biological technique. In an experiment using ^<11>C-ceramide, an increase in the uptake of labeled ceramide was observed 6 hours or more after high-LET irradiation therapy in neutron capture therapy. This finding is considered to represent a very early stage of apoptosis in consideration of the first detection of apoptosis by the TUNEL method 18 hours after irradiation. One of the greatest accomplishments of this study was the establishment of new techniques using positron-labeled antisense oligonucleotides. New techniques for imaging of gene expression such as in vivo imaging of GFAP mRNA expression in brain tumors and in vivo imagin
… More
g of telomerase mRNA were made possible by this study.
(2) Relationship between radioresponsive tissue and recurrence of tumor
Growth factors caused rapid changes in the turnover of inositol phospholipid in the normal rat brain. This finding suggests that re-proliferation occurs if responsive cells induced by radiation injury secrete excessive growth factors. Moreover, when inositol phospholipid metabolism was measured in the normal rat brain after irradiation at 10 Gy, the activity increased 6 hours after irradiation and remained increased. Therefore, rapid changes in inositol phospholipid turnover due to growth factors may be involved in recurrence.
(3) Development of preventive methods against radiation necrosis
PI3 kinase (PI3K) was shown to play an important role in the development of preventive medications against radiation necrosis. PI3K was involved in survival signals, and the survival-promoting effect of NGF was suppressed by a PI3K inhibitor (wortmannin). Therefore, it was found that suppression of PI3K increases the radiosensitivity and causes dominance of death signals while activation of PI3K with an agent such as NGF causes dominance of survival signals. Less
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