2000 Fiscal Year Final Research Report Summary
MOLECULAR BIOLOGICAL CLARIFICATION OF THE MECHANISM OF INDUCTION OF RADIATION NECROSIS IN THE BRAIN BY HIGH-LET RADIATION
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 |
Section | 一般 |
Research Field |
Cerebral neurosurgery
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Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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
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Project Period (FY) |
1999 – 2000
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Keywords | Glioma / apoptosis / antisense / Radiation injury / gene expression / telomerase / BNCT / PET |
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
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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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Research Products
(29 results)
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[Publications] Wakita, K., Imahori, Y., Ido, T., Fujii, R., Horii, H., Shimizu, M., Nakajima, S., Mineura, K., Nakamura, T., Kanatsuna, T.: "Simplification for measuring the input function for ^<18>FDG-PET : Investigation of one-point blood sampling method"J Nucl Med. 41 (9). 1484-1490 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chida, M., Kagaya, Y., Imahori, Y., Namiuchi, S., Fujii, R., Fukuchi, M., Takahashi, C., Tezuka, F., Ido, T., Shirato, K.: "Visualization of myocardial phosphoinositide turnover with 1-[1-^<11>C]-butyryl-2-palmitoyl-rac-glycerol in rats with myocardial infarction."J Nucl Med. 41 (12). 2063-2068 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsumoto, K., Imahori, Y., Fujii, R., Ohmori, Y., Sekimoto, T., Ueda, S., Mineura, K.: "Evaluation of phosphoinositides turnover on ischemic human brain with ^<11> C-diacylglycerol using positron emission tomography."J Nucl Med. 40. 1590-1594 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kondo, M., Imahori, Y., Mori, S., Ueda, Y., Fujii, R., Nakajima, K.: "Aberrant plasticity in Alzheimer's disease."Neuroreport. 10 (7). 1481-1484 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Ono, K., Masunaga, S., Suzuki, M., Kinashi, Y., Takagaki, M., Akaboshi, M.: "The combined effect of boronophenylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice."Int.J.Radiat.Oncol.Biol.Phys.. 43 (2). 431-436 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Masunaga, S., Ono, K., Suzuki, M., Sakurai, Y., Kobayashi, T., Takagaki, M., Kinashi, Y., Akaboshi, M.: "Reoxygenation in quescent and total intratumor cells following thermal neutron irradiation with or without 10B-compound-compred with that after X-ray irradiation."Int.J.Radiat.Oncol.Biol.Phys.. 44 (2). 391-398 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsumura, A., Shibata, Y., Yamamoto, T., Yoshida, F., Isobe, T., Nakai, K., Hayakawa, Y., Kiriya, M., Shimojo, N., Ono, K., Sakata, I., Nakajima, S., Okumura, M., Nose, T.: "A new boronated porphyrin (STA-BX909) for neutron capture therapy : an in vitro survival assay and in vivo tissue uptake study."Cancer Letter. 141. 203-209 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Masunaga, S., Ono, K., Suzuki, M., Sakurai, Y., Takagaki, M., Kobayashi, T., Kinashi, Y., Akaboshi, M.: "Repair of potentially lethal damage by total and quiescent cells in solid tumors following a neutron capture reaction."J Cancer Res Clin Oncol. 125. 609-614 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Masunaga, S., Ono, K., Suzuki, M., Sakurai, Y., Kobayashi, T., Takagaki, M., Kinashi, Y., Akaboshi, M.: "Alteration of sensitivity of intratumor quiescent and total cells to X-rays following thermal neutron irradiation with or without 10B-compound."Int.J.Radiat.Oncol.Biol.Phys.. 46 (3). 653-659 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Barth, R.F., Yang, W., Rotaru, J.H., Moeschberger, M.L., Boesel, C.P., Soloway, A.H., Joel, D.D., Nawrocky, M.M., Ono, K., Goodman, J.H.: "Boron neutron capture therapy of brain tumors : enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine."Int.J.Radiat.Oncol.Biol.Phys.. 47 (1). 209-218 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Kinashi, Y., Sakurai, Y., Masunaga, S., Suzuki, M., Akaboshi, M.Ono, K.: "Dimethyl sulfoxide protects against thermal and epithermal neutron induced cell death and mutagenesis of chinese hamster ovary (CHO) cells."Int.J.Radiat.Oncol.Biol.Phys.. 47 (5). 1371-1378 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Kinashi, Y., Sakurai, Y., Masunaga, S., Suzuki, M., Takagaki, M., Akaboshi, M.Ono, K.: "Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in chinese hamster ovary (CHO) cells."Radiat.Res.. 154 (3). 313-318 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Suzuki, M., Masunaga, S., Kinashi, Y., Takagaki, M., Sakurai, Y., Kobayashi, T., Ono, K.: "The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice."Jpn J Cancer Res.. 91 (10). 1058-1064 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Takagaki, M., Ono, K., Masunaga, S., Kinashi, Y., Sakurai, Y., Kobayashi, T., Miyatake, S., Hashimoto, N.: "10B quantitative determination in the ppm range by particle tracks reading for boron neutron capture therapy."J Radioanalytical and Nuclear Chemistry. 247 (2). 389-392 (2001)
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「研究成果報告書概要(欧文)」より
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