| Project/Area Number |
18591389
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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 | Nara Medical University |
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Principal Investigator |
OHNISHI Ken Nara Medical University, School of Medicine, Department of Biology, Associate Professor (50152195)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | radiation / apoptosis / cell death signal transduction / cell survival signal transduction / DNA-repair / cell survival / sensitization / RNA干渉 / siRNA / 担がんマウス / 腫瘍増殖抑制 |
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| Research Abstract |
Interference with anti-apoptosis and/or cellular proliferation signal transduction is regarded to result in effective radiation cancer therapy. This study examined the effectiveness of siRNA targeting key factors (NBS1 and XIAP) in DNA repair and signal transduction for anti-apoptosis and/or cellular proliferation after radiation using cultured human cancer cells and tumor-transplanted nude mica Radiation sensitivity and apoptosis were analyzed with colony formation assay, Western blot, fluorescent immuno-cytochemistry and hoechst staining using wild-type p53 or mutated p53 gene-transfected human lung and tongue cancer cells. Further the cancer cells were transfected with plasmids which were inserted with NBS1-siRNA expressing DNA cassette and radiation, sensitivity of the plasmid-transfected cells was examined. siRNAs targeting NBS1 and XIAP enhanced radiation sensitivity p53 independently and even more pronounced in mutated p53 cells compared with wild-type p53 cells. Enhanced radiation sensitivity was not observed in several clones from NBS1-siRNA expressing plasmid-transfected cells at this time. Our results suggest that t NBS1-siRNA and XIAP siRNA might contribute to high curative efficiency in radiation cancer therapy for malignant cancer leading to enhanced p53 independent radiation sensitivity. In addition, it was suggested that further experiments are required for study on the effectiveness of siRNAs in vivo system.
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