Exploration of molecular target for potentiation of radiation-induced cell killing
| Project/Area Number |
16591185
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Gunma University |
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Principal Investigator |
AKIMOTO Tetsuo GUNMA UNIVERSITY, Dept.Radiation Oncology, Assistant Professor, 医学部, 講師 (10261851)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Molecular target / Radiosensitivity / Radiation therapy / Enhahcement effect / signal transduction / 放射線 |
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| Research Abstract |
The purpose of this project is to explore the molecular targets for potentiation of radiation-induced cell killing in various cancer cells. In regarding molecular targets for potentiation of radiosensitivity in prostate cancer cells, we obtained following results.
In hormone sensitive prostate cancer, DHT at a concentration of 1 nM caused enhancement of the proliferative activity and reduction of the radiosensitivity of the cells. Radicicol at a concentration of 500 nM abolished the DHT-induced decrease in cellular radiosensitivity and potentiated the radiation-induced cell killing synergistically. Consistent with the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and HER2/neu via reduced binding of AR to Hsp90, although selective degradation of HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect the cellular radiosensitivity. However, DHT did not change proliferative activity and radiosensitivity of hormone-independent prostate cancer cells (PC3). Radicicol at a concentration of 500 nM enhanced radiation-induced cell killing synergistically. In underlining mechanism, inhibition of survival signal transduction pathway such as PI3K-Akt pathways was closely associated with enhancement of radiation-induced cell killing in hormone-independent prostate cancer cells. The results suggest that the Hsp90 chaperone complex may be a potential molecular target for potentiation of radiation-induced cell killing in both hormone- sensitive and hormone-independent prostate cancer cell line.
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Report
(3 results)
Research Products
(36 results)
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[Journal Article] Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer : Correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity2005
Author(s)
Akimoto T, Ito K, Saitoh J, Noda S, Harashima K, Sakurai H, Nakayama Y, Yamamoto T, Suzuki K, Nakano T, Niibe H
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Journal Title
Int J Radiat Oncol Biol Phys. 63(2)
Pages: 463-471
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Attenuation of chronic thermotolerance by KNK437, a benzylidene lactam compound, enhances thermal radiosensitization in mild temperature hyperthermia combined with low dose-rate irradiation.2005
Author(s)
Sakurai H, Kitamoto Y, Saitoh J, Nonaka T, Ishikawa H, Kiyohara H, Shioya M, Fukushima M, Akimoto T, Hasegawa M, Nakano T
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Journal Title
Int J Radiat Biol. 81(9)
Pages: 711-718
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] External beam radiotherapy for clinically node-negative, localized hormone-refractory prostate cancer : impact of pretreatment PSA value on radiotherapeutic outcomes.2004
Author(s)
Akimoto T, Kitamoto Y, Saito J, Harashima K, Nakano T, Ito K, Yamamoto T, Kurokawa K, Yamanaka H, Takahashi M, Mitsuhashi N, Niibe H
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Journal Title
Int J Radiat Oncol Biol Phys. 59(2)
Pages: 372-379
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A persistent retroperitoneal synovial sarcoma -Effect of hyperthermia alone-2004
Author(s)
Saitoh, J, Sakurai H, Kiyohara H, Ishikawa H, Harashima K, Akimoto T, Nakayama Y, Hasegawa M, Watanabe H, Shinozaki T, Nakano T
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Journal Title
Jpn J Hyperthermia 20(2)
Pages: 79-85
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Rectal bleeding after hypofractionated radiotherapy for prostate cancer : correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding.2004
Author(s)
Akimoto T, Muramatsu H, Takahashi M, Saito J, Kitamoto Y, Harashima K, Miyazawa Y, Yamada M, Ito K, Kurokawa K, Yamanaka H, Nakano T, Mitsuhashi N, Niibe H
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Journal Title
Int J Radiat Oncol Biol Phys. 60(4)
Pages: 1033-1039
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] CT-fluoroscopy guided interstitial brachytherapy with image-based treatment planning for unresectable locally recurrent rectal carcinoma.2004
Author(s)
Sakurai H, Mitsuhashi N, Harashima K, Muramatsu H, Ishikawa H, Kitamoto Y, Suzuki Y, Saitoh JI, Nonaka T, Akimoto T, Nakayama Y, Hasegawa M, Nakano T
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Journal Title
Brachytherapy 3(4)
Pages: 222-230
Description
「研究成果報告書概要(欧文)」より
Related Report
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