2007 Fiscal Year Final Research Report Summary
Research for radio-sensitizers which specifically attack tumor cells
Project/Area Number |
16209036
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Radiation science
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Research Institution | National Institute of Radiological Sciences |
Principal Investigator |
RYUICHI Okayasu National Institute of Radiological Sciences, Heavy-Ion Radiobiology Research Group, Group Leader (50356135)
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Co-Investigator(Kenkyū-buntansha) |
YAMADA Shigeru National Institute of Radiological Sciences, Charged Particle Therapy Hospital, Chief Doctor (80311380)
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Project Period (FY) |
2004 – 2007
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Keywords | Radio-sensitization / Hsp90 inhibitor / 17AAG / DNA DSB repair / Homologous recombination repair / BRCA2 / siRNA / Rad51 |
Research Abstract |
We performed two specific aims on this project. Results for the individual aim are described. Aim 1) lb investigate Hsp90 inhibitors as effective radio-sensitizers which have much higher affinity for tumor cells than for normal cells. We showed that 17-AAG effectively radio-sensitized human tumor cells in vitro and in vivo, while normal cells were not affected by the drug. The cause of this sensitization was found out to be inhibition of DNA double strand break (DSB) repair by 17AAG. We also discovered that 17AAG affected the homologous recombination repair (HRR) pathway of DSB repair. Furthermore, the proteins influenced by this chemical were found out to be BRCA2 and Rad51. (Noguchi, et. al. 2006) Aim 2) lb find an efficient strategy to specifically damage tumor cells, the inhibition of HRR repair mechanism was pursued; the HRR mechanism is known to be active only at late-S and G2 phases of the cell cyde. We used RNA interference technology to knockdown the expression of BRCA2 protein, a crucial molecule for HRR pathway. After efficiently knocking down the protein expression by transfecting tumor cells by BRCA2 small interference RNA (siRNA), significant radio-sensitization was observed in HeLa cells. The cause of this sensitization was found out to be DNA DSB repair inhibition and the HRR pathway was again affected by BRCA2 siRNA transfection in tumor cells. The radio-sensitization was also observed in animal zenograft model. (Yu, et. al. 2008)
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Research Products
(55 results)
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[Journal Article] Role of the major, small, acid-soluble spore proteins and spore-specific and universal DNA repair mechanisms in resistance of Bacillus subtilis spores to ionizing radiation from X rays and high energy charged-particle bombardment2008
Author(s)
Ralf Moeller, Peter Setlow, Gerda Horneck, Thomas Berger, Gunther Reitz, Petra Rettberg, Aidan J. Doherty, Ryuichi Okayasu, Wayne L Nicholson
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Journal Title
Journal of Bacteriology 190
Pages: 1134-1140
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Role of the major, small, acid-soluble spore proteins and spore-specific and universal DNA repair mechanisms in resistance of Bacillus subtilis spores to ioninzing radiation from X rays and high energy charged-particle bombardment.2008
Author(s)
Moeller, R., Stelow, P., Horneck, G., Berger, T., Reitz, G., Rettberg, P., Doherty, A. J., Okayasu, R., Nicholson, W. L.
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Journal Title
J. Bacteriol. 190
Pages: 1134-1140
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High LET heavy ion radiation induces lower numbers of initial chromosome breaks with minimal repair than low LET radiation in normal human cells.2008
Author(s)
Sekine, E., Okada, M., Matsufuji, N., Yu, D., Furusawa, Y. ^*Okayasu, R.
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Journal Title
Mutat. Res. 652
Pages: 95-101
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans.2008
Author(s)
Fujimori, A, Bing, W., Suetomi, K., Sekine, E., Yu, D., Kato, T., Takahashi, S., Okayasu, R. et. Al
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Journal Title
Biochem. Biophys. Res. Commun. 369
Pages: 953-957
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter activity via Sp1 phosphorylation.2007
Author(s)
Niina I, Uchiumi T, Izumi H, Torigoe T, Wakasugi T, Igarashi T, Miyamoto N, Onitsuka T, Shiota M, Okayasu R, Chijiiwa K, Kohno K.
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Journal Title
Cancer Science 98
Pages: 858-863
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] ENHANCEMENT OF CHROMOSOMAL ABERRATIONS INTUMOR CELLS WITH A NON-LABELED CU-PTSM ANDIRRADIATION WITH CU-K SHELL MONOCHROMATIC X RAYS.2007
Author(s)
Takakura, K., Yaguchi, S., Kanasugi, Y., Kobayashi, K., Okayasu, R., Fujibayashi, Y.
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Journal Title
Radiat. Protec. Dosimetry 122
Pages: 188-194
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Single extreme low dose/low dose rate irradiation causes alteration in life span and genome instability in primary human cells.2007
Author(s)
Okada, M., Okabe, A., Uchihori, Y., Kitamura, H., Sekine, E., Ebisawa, S., Suzuki, M., ^*Okayasu R.
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Journal Title
Br. J. Cancer 96
Pages: 1707-1710
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter activity via Spl phosphorylation.2007
Author(s)
Niina I, Uchiumi T, Izumi H, torigoe T, Wakasugi T, Igarashi T, Miyamoto N, Onitsuka T, Shiota M, Okayasu R, Chijiiwa K, Kohno K.
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Journal Title
Cancer Sci. 98
Pages: 858-863
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Heavy ion radiation induces complex DNA damage that cannot be efficiently repaired by non-homologous end joining.2006
Author(s)
Okayasu, R., Okada, M, Okabe, A., Noguchi, M., Takakara, K., takahashi, S.
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Journal Title
Radiat. Res. 165
Pages: 59-67
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The PCC assay can be used to predict radiosensitivity in biopsy cultures irradiated with different types of radiation.2006
Author(s)
Suzuki, M., Tsuruoka, C., Nakano, T., Ohno, Y., Furusawa, Okayasu, R.
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Journal Title
Oncol. Rep. 16
Pages: 1293-1299
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition of Homologous Recombination Repair in Irradiated Tumor Cells Pretreated with Hsp90 Inhibitor 17-Allylamino-17-demethoxygeldanamycin.2006
Author(s)
Noguchi, M, Yu, D., Hirayama, R., Ninomiya, Y., Sekine, E., Kubota, N., Ando, K. Okayasu, R.
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Journal Title
Biochem. Biophys. Res. Commun. 351
Pages: 658-663
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Radio-sensitivity of the cells from amyotrophic lateral sclerosis model mice transfected with human mutant SOD1.2005
Author(s)
Iimuro, R, Takahashi, S, Ito, H, Kubota, Y, Suetomi, K, Sato, H, Okayasu, R.
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Journal Title
Journal of Radiation Research 46
Pages: 67-73
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Caffeine sensitizes non-dividing human fibroblasts to X-rays by inducing high frequency of misrepair.2005
Author(s)
Kawata, T., Ito, H., Saito, M., Uno, T., Okayasu, R, et. al.
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Journal Title
Radiation Research 164
Pages: 509-513
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Radio-sensitivity of the cells from amyotrophic lateral sclerosis model mice transfected with human mutant SOD12005
Author(s)
Iimuro, R, Takahashi, S, Ito, H, Kubota, Y, Suetomi, K, Sato, H, Okayasu, R.
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Journal Title
J. Radiat. Res. 46
Pages: 67-73
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Caffeine sensitizes non-dividing human fibroblasts to X-rays by inducing high frequency of misrepair.2005
Author(s)
Kawata, T., Ito, H., Saito, M., Uno, T., Okayasu, R., Liu, C., Kan'o, M., George, K., Cucinotta, F. A.
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Journal Title
Radiat. Res. 164
Pages: 509-513
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Extremely low-dose ionizing radiation upregulates CXC chemokines in normal human fibroblasts.2005
Author(s)
Fujjimori, A., Okayasu, R., Ishihara, H., Yoshida, S., Eguchi-Kasai, K., Nojima, K., Ebisawa, S., takahashi, S.
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Journal Title
Cancer Res. 65
Pages: 10159-10163
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Radiobiology for Heavy-Ion Radiotherapy,2008
Author(s)
Okayasu, R., Kato, T., Noguchi, M., Okada, M., Fujimori, A., Sekine, E.
Organizer
NIRS-MD Anderson Symposium on Clinical Issues for Particle Therapy
Place of Presentation
Houston,
Year and Date
20080300
Description
「研究成果報告書概要(和文)」より
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[Presentation] Radiobiology for Heavy-Ion Radiotherapy2008
Author(s)
Okayasu, R., Kato, T., Noguchi, M., Okada, M., Fujimori, A., Sekine, E.
Organizer
NIRS-MD Anderson Symposium on Clinical Issues for Particle Therapy
Place of Presentation
Houston, USA
Year and Date
20080300
Description
「研究成果報告書概要(欧文)」より
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[Presentation] High LET radiation uncovers a new aspect of DNA double strand break repair.2005
Author(s)
Okayasu, R., Okada, M., Okabe, A., Noguchi, M., Takahashi, S.
Organizer
Japan Radiation Research Society Annual Meeting and The 1st Asian Radiation Research Conference
Place of Presentation
Hiroshima, Japan,
Year and Date
20051100
Description
「研究成果報告書概要(和文)」より
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[Presentation] High Let radiation uncovers a new aspect of DNA double strand break repair.2005
Author(s)
Okayasu, R., Okada, M., Okabe, A., Noguchi, M., Takahashi, S.
Organizer
Japan Radiation Research Society Annual Meeting and The 1st Asian Radiation Research Conference
Place of Presentation
Hiroshima, Japan
Year and Date
20051100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Extreme low dose rate irradiation with heavy ions induces accelerated senescence in primary human cells.2005
Author(s)
Okayasu, R., Okada, M., Okabe, A., Uchihori, Y., Suzuki, M., Takahashi, S.
Organizer
The 52nd Radiation Research Society Annual Meeting,
Place of Presentation
Denver,
Year and Date
20051000
Description
「研究成果報告書概要(和文)」より
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[Presentation] Extreme low dose rate irradiation with heavy ions induces accelerated senescence in primary human cells.2005
Author(s)
Okayasu, R., Okada, M., Okabe, A., Uchihori, Y., Suzuki, M., Takahashi, S.
Organizer
The 52nd Radiation Research Society Annual Meeting
Place of Presentation
Denve, USA
Year and Date
20051000
Description
「研究成果報告書概要(欧文)」より
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[Book] 癌の臨床(6月号の1章執筆)2007
Author(s)
岡安 隆一、岡田 真希、岡部 篤史、野口 実穂
Total Pages
60(371-375)
Publisher
篠原出版新社
Description
「研究成果報告書概要(和文)」より
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