2003 Fiscal Year Final Research Report Summary
Molecular target for radiation-induced cell killing that are associated with tumor microenvironment
| Project/Area Number |
13670916
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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, Graduated School of Medicine, Assistant professor, 医学部, 講師 (10261851)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Radiosensitivity / Molecular target / radiation / tumor microenvironment / survival signal / 生存シグナル伝達 |
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| Research Abstract |
The purpose of this research project is to explore the role of activation of the signal transduction pathway originated from tumor environment including tumor hypoxia, interaction between tumor cell and extracellular matrix, and so on. The results of this research project revealed that activation of survival signal transduction induced by acute tumor hypoxia or interaction between tumor cell and extracellular matrix decreased radiosensitivity of cancer cells, and Extracellular stimulation of the survival signal transduction pathways using epidermal growth factor also decreased radiation-induced apoptosis. Inhibition of activation of these signal transduction enhanced radiation-induced cell killing in variety cancer cells that have wild or mutant p53 gene. These results indicated that activation the survival signal transduction pathways induced by intrinsic and extrinsic factors may be associated with radioresistant profile of cancer cells.
In the analysis regarding the role of epigenetic factors such as acetylation of histone on radiosensitivity, we found that hyperacetylation of histone by histone deacetylase (HDAC) inhibitor combined with radiation greatly enhanced radiation-induced cell killing through p53-independent apoptosis induction. In this mechanism, acetylation of Hsp90 was also involved by reducing binding of Hsp90 to client proteins including Raf-1 or Akt. Further research is needed to explore the molecular targets for determination of radiosensitivity, because enhancement of radiation-induced cell killing would provide great advantage for cancer treatment in clinics.
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Research Products
(26 results)
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[Publications] Sakurai H, Mitsuhashi N, Tamaki Y, Kurosaki H, Akimoto T, Ishikawa H, Saitoh J, Muramatsu H, Yamakawa M, Hayakawa K, Niibe H: "Clinical application of low dose-rate brachytherapy combined with simultaneous mild temperature hyperthermia."Anticancer Res.. 21. 679-684 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Sakurai H, Mitsuhashi N, Takahashi M, Akimoto T, Muramatsu H, Ishikawa H, Imai R, Yamakawa M, Hasegawa M, Niibe H.: "Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone : patterns of recurrence, latent periods, and prognosis."Int J Radiat Oncol Biol Phys.. 50. 1136-1144 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Sakurai H, Hayakawa K, Mitsuhashi N, Tamaki Y, Nakayama Y, Kurosaki H, Nasu S, Ishikawa H, Saitoh JI, Akimoto T, Niibe H.: "Effect of hyperthermia combined with external radiation therapy in primary non-small cell lung cancer with direct bony invasion."Int J Hyperthermia.. 18. 472-483 (2002)
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[Publications] Saitoh J, Sakurai H, Suzuki Y, Muramatsu H, Ishikawa H, Kitamoto Y, Akimoto T, Hasegawa M, Mitsuhashi N, Nakano T.: "Correlations between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by beta-D-iodinated azomycin galactopyranoside (beta-D-IAZGP), and radiation sensitivity."Int J Radiat Oncol Biol Phys. 54. 903-907 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Akimoto T, Kitamoto Y, Saito J, Harashima K, Nakano T, Ito K, Yamamoto T, Kurokawa K, Yamanaka H, Takahashi M, Mitsuhashi N, Niibe H.: "External beam radiotherapy for clinically node-negative, localized hormone-refractory prostate cancer : impact of pretreatment PSA value on radiotherapeutic outcomes."Int J Radiat Oncol Biol Phys.. 59(2). 372-379 (2004)
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「研究成果報告書概要(欧文)」より
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[Publications] Akimoto T, Muramatsu H, Takahashi M, Saitoh J, Kitamoto Y, Miyazawa Y, Yamada M, Ito K, Kurokawa K, Yamanaka H, Nakano T, Mitsuhashi N, Niibe H.: "Rectal bleeding after hypofractionated radiotherapy for prostate cancer : Correlation between clinical and dosimetric parameters and the incidence of grade 2 or higher rectal bleeding."Int J Radiat Oncol Biol Phys. (in press).
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「研究成果報告書概要(欧文)」より
