| Project/Area Number |
26670555
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
Hiraoka Masahiro 京都大学, 医学(系)研究科(研究院), 教授 (70173218)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Hiroshi 京都大学, 白眉センター, 特定准教授 (80362531)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | がん / 放射線治療 / がん幹細胞 / 低酸素 / HIF-1 / 腫瘍内低酸素 / 放射線抵抗性 |
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| Outline of Final Research Achievements |
Accumulating evidence has suggested that cancer cells acquire radioresistance in hypoxic regions of solid tumors with the help of a transcription factor, HIF-1. However, there is no direct evidence for the involvement of HIF-1-active cancer cells in tumor recurrence after radiotherapy so far. Here, we established a novel system to specifically eliminate HIF-1-active hypoxic cells from a tumor xenograft by combining a HIF-1-dependent promoter (5HRE) with a diphtheria toxin receptor (DTR) and establishing breast cancer cell line, EMT6, with the plasmid (EMT6/5HRE-DTR), and approached the problem. Immunohistochemical analyses demonstrated that, when xenografted into immunodeficient nude mice, the EMT6/5HRE-DTR stable transfectant exhibited TUNEL-positive nuclei after DT treatment in HIF-1-active hypoxic regions. Growth delay assay demonstrated a possibility that the tumor recurrence after radiotherapy is influenced by the elimination of HIF-1-active hypoxic cells from tumor xenografts.
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