2002 Fiscal Year Final Research Report Summary
Enhancement of chemosensitivity with the molecule that selectively abrogate G2 check point of the cell cycle
Project/Area Number |
12671277
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Fujita Health University |
Principal Investigator |
SAKURAI Yoichi Fujita Health Univ., School of Medicine, Associate Professor, 医学部, 助教授 (60170651)
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Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Yasuko Fujita Health Univ., School of Medicine, Assistant, 医学部, 助手 (50308871)
MATSUBARA Toshiki Fujita Health Univ., School of Medicine, Assistant Professor, 医学部, 講師 (50257622)
OCHIAI Masahiro Fujita Health Univ., School of Medicine, Professor, 医学部, 教授 (00051772)
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Project Period (FY) |
2000 – 2002
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Keywords | chemosensitivity test / G2 check point / Gastrointestinal cancers / CD-DST |
Research Abstract |
In vitro chemosensitivity tests with a collagen-gel droplet chemosensitivity test (CD-DST) and MTT assay were performed using cancer tissues obtained by the surgical resection of gastrointestinal cancer patients. The chemosensitivity against bleomycin (BLM) and TAT-S216, which is a novel synthetic peptide that selectivity abrogate G2 checkpoint of cell cycle were examined to evaluate the potentiation of anti-cancer effect of BLM with TAT-S216. Colon cancer cell lines, HCT-116, SW-620, and pancreatic cancer cell line, PANC-1, were used to evaluate the chemosensitivity against bleomcin alone and BLM plus TAT-S216 by exposing these cell lines for 72 hours in collagen-gel droplet and in 96-well microtiter plates. The preliminary results indicated that IC-50 of HCT-116 was the lowest among these cell lines, and HCT-116 was thus selected to be used for further studies. The results of the dose response of the final drug concentrations and the drug exposure time indicated that optimal final concentration of BLM was determined to be 5.0 μg/ml. The chemosensitivity tests against BLM were performed using a CD-DST method as well as MTT assay. TAT-S216 was used at 200μM of final concentration. Time dependent anticancer effects were evaluated after exposing these cells for 24, 48, 72 h. There were no difference of the anticancer effects of BLM alone, BLM plus TAT-S216, and BLM plus DMSO in any of the exposure time in these experimental conditions. From these data, in vitro potentiation of anticancer effect with TAT-S216 was not reproducible in CD-DST method and/or MTT assay. Further preliminary experiments of chemosensitivity tests are required to obtain an optimal experimental condition and to substantiate clinical application.
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