| Project/Area Number |
12460135
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KUWABARA Mikinori Hokkaido Univ., Grad. School of Vet. Med., Prof., 大学院・獣医学研究科, 教授 (10002081)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Toshio Hokkaido Univ., Grad. School of Vet. Med., Asso. Prof., 大学院・獣医学研究科, 助教授 (20176895)
MATSUDA Akira Hokkaido Univ., Grad. School of Pharm., Prof., 大学院・薬学研究科, 教授 (90157313)
INANAMI Osamu Hokkaido Univ., Grad. School of Vet. Med., Asso. Prof., 大学院・獣医学研究科, 助教授 (10193559)
OKADA Kosuke Iwate Univ., Fac. of Agr., Prof., 農学部, 教授 (50002077)
SATO Reeko Iwate Univ., Fac. of Agr., Asso. Prof., 農学部, 助教授 (80142892)
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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 |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥11,400,000 (Direct Cost: ¥11,400,000)
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| Keywords | LEUKEMIA / LYMPHOMA / ANTICANCER DRUG / APOPTOSIS / CASPASE / CELL DEATH / NECROSIS / TUMOR CELL LINES |
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| Research Abstract |
Clinically, the combination treatment of solid tumor cells with an anticancer drug and radiation was widely used to enhance cell killing. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd) and 2-chrolo-deoxyadenosine (Cl-Ade) was newly developed as anticancer drugs to induce cell death by inhibiting RNA synthesis. In this study, we examined whether the exposure of these anticancer drugs or /and ionizing radiation to human gastric adenocarcinoma MKN45 cells, human lekemia cell line MOLT-4 cells induce apoptosis and canine lymphoma cell line CL-1. In MOLT-4 cells, Fas expression and caspase 8/3 activation apoptotic cell death was observed after treatment of Cl-Ade, followed by apoptotic cell death. 2Cl-Ade and ECyd showed to induce apoptotic cell death in canine lymphoma cell CL-1 cells. MKN45 cells were treated with 0.1 μM ECyd for 1 h before irradiation. After irradiation with 20 Gy, apoptotic as well as swelling cells were morphologically discriminated by fluorescence microscopy
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combined with propidium iodide staining or electron microscopy and were scored. When cells were treated with ECyd alone, only 5 % of either apoptotic or necrotic cells appeared. When cells were exposed to X rays alone, about 5 % of apoptotic and about 45 % of swelling cells appeared. However, when cells were exposed to X rays in the presence of 0.1 μM ECyd, about 25 % of total cells was apoptotic cells and about 10 % of total cells was swelling cells. Apoptosis induced by treating cells with ECyd and X irradiation was significantly reduced by the treatment with Ac-DEVD-CHO (caspase 3 inhibitor) or TPCK (chymotrypsin-like protease inhibitor).
These results suggested that caspase 3 and chymotrypsin-like proteases were responsible for apoptosis induced by co-treatment with ECyd and X rays. In this study, it was demonstrated that co-treatment of MKN45 cells with ECyd and X rays activated G2-phase-linked apoptotic signaling associated with caspase 3 and chymotrypsin like protease. These data may provide useful information to develop clinical treatment of radiation combined with anticancer drugs for solid tumors. Less
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