| Project/Area Number |
12671223
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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 |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
YANO Masahiko (2001) Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70273646)
塩崎 均 (2000) 大阪大学, 医学系研究科, 助教授 (70144475)
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| Co-Investigator(Kenkyū-buntansha) |
ARIYOSHI Hideo Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助教授 (60294055)
FUJIWARA Yoshiyuki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40314330)
矢野 雅彦 大阪大学, 医学系研究科, 助手 (70273646)
井上 雅智 大阪大学, 医学系研究科, 講師 (80232560)
福地 成晃 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | CDC25B / esophageal cancer / radiationherapy t / cell cycle / check point / G2 / M arrst / apoptosis / p53 / P53 |
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| Research Abstract |
1) In order to investigate of the role of CDC25B as a sensitive factor for radiotherapy, its expression in the biopsy specimen were compared with the histological effect of chemoradiotherapy (CRT) for the patients with advanced esophageal cancers. The patients with high CDC25B expression showed better histological effect for preoperative CRT.
2) Among patients treated by preoperative CRT and surgery, CDC25B expression alone did not associate with the prognosis, but combined evaluation of CDC25B with p53 and metallothionein, successfully correlated with prognosis.
When comparing esophageal cancer patients with or without pre-operative CRT, survival benefit of CRT was recognized for the patients with high CDC25B expression, but not for those with low CDC25B expression. These suggest the clinical usefulness of CDC25B estimation.
3) The mechanism for increasing radiosensitivity was investigated by transfection of CDC25B gene into esophageal cancer cell line (TE8). No significant difference was observed upon CDC25B overexpression when cells were not irradiated. However, after 10 Gy irradiation, increase of apoptosis and inhibition of G2/M arrest were prominent for CDC25B transfectant. Radiation induces decline of CDC25B protein followed by increase of tyrosine phosphorylation and decrease activity of CDC2. CDC25B transfectant kept high level of CDC25B after radiation, resulting minimal change of CDC2 phsophorylation and activity after radiation.
4) Our study suggests the compounds that abrogate G2M arrest can be used as radiosensitizer. Therefore, we are planning clinical application of caffeine and UCN01 for a chemical modulator of radiation therapy.
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