| Project/Area Number |
17201015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Nara Medical University |
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Principal Investigator |
OHNISHI Takeo Nara Medical University, Department of Biology, professor (60094554)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Ken Nara Medical University School of Medicine, Department of Biology, Associate Professor (50152195)
TAKAHASHI Akihisa Nara Medical University School of Medicine, Department of Biology, Assistant Professor (60275336)
松本 英樹 福井大学, 医学部, 助教授 (40142377)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000)
Fiscal Year 2007: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2006: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2005: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
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| Keywords | radiation / apoptosis / cell death signal transduction / cell survival signal transduction / molecular targeting / p53 / 生存シグナル / 放射線増感 |
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| Research Abstract |
To develop more efficient regimens for various malignant tumors the attention has focused on searching for substances to sensitize cell lethality of tumors by radiation. Inhibitors against anti-apoptosis and/or cellular Proliferation signal transductions are as good candidates for enhancers of radiation Sensitivity on human cancer calls This study examined whether siRNAs or chemical inhibitors targeting key factors (NBS1, XIAP, P13-K, MAPK, Akt and heat proteins) in DNA repair and survival Signal transductions for anti-apoptosis and/or cellular, proliferation after radiation enhance radiation induced apoptosis, Further, it was examined whether; heavy-ion bin effectively, induce apoptosis p53 independently. We analyzed radiation/heat sensitivity apoptosis with colony formation assay, Western blot, fluorescent immuno-cytochemistry, arid hoechst staining using wild-type p53 or mutated p53 gene-transfected human lung and tongue cancer cells. We showed siRNAs targeting NBS1 and XIAP enhanced radiation sensitivity more efficiently in mutated p53 cells than the wild-type p53 cell Furthermore, LY294002 (inhibitor of PI3-K) enhanced radiation/heat sensitivity and radiation/heat-induced apoptosis p53 independently. PD98059 (inhibitor of MEK) and-SB203580 (inhibitor of p38) enhanced heat sensitivity but not radiation Sensitivity, Heavy-ion beams induced p53 independent apoptosis. Our results suggest that these siRNAs, chemical inhibitors and heavy-ion beams might contribute to high curative efficiency in radiation/heat cancer therapy for malignant cancer leading to enhanced, p53 independent radiation/heat sensitivity.
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