| 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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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Radiosensitivity / Molecular target / radiation / tumor microenvironment / survival signal / 生存シグナル伝達 / 放射線治療 / 増感作用 / 低酸素 / アポトーシス / 細胞外マトリックス / 増殖因子 |
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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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