| Project/Area Number |
62570680
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
TOMITA Katsuro Associate Professor, 医学部・助教授(整形外科学) (00092792)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIHARA Makoto Kanazawa University Hospital, 医学部附属病院, 医員(整形外科学)
YASUTAKE Hidetoshi Kanazawa University Hospital, 医学部附属病院, 医員(整形外科学)
SHIMOZAKI Eiji School of Medicine, Kanazawa University, 医学部, 助手(整形外科学) (00196552)
土屋 弘行 金沢大学, 医学部附属病院, 医員(整形外科学)
青竹 康雄 金沢大学, 附属病院・整形外科学, 医員
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Caffeine / Drug resistance / Anticancer agents / Human tumor clonogenic assay / Flow cytometry / Athymic mice / Human tumor clonogenic assay / シスプラチン / ヌードマウス / ヒト骨肉腫 / human tumor clonogenic assay / フローサイトメトリー |
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| Research Abstract |
In this study the combined effect of anticancer agents and caffeine, which inhibits DNA repair, on human sarcomas was examined with various assay techniques. In human tumor clonogenic assay, the combined use of caffeine produced synergistic effects with four DNA-damaging agents (cisplatin, mitomycin C, cyclophosphamide and adriamycin). Particularly by the combination of cisplatin with caffeine, marked synergistic effects were observed in 14 out of 18 specimens (78%) of fresh human tumor specimens. Caffeine markedly increased the cytocidal effect of cisplatin following mitosis. At this time, the accumulation of S and G2/M phase was reduced on the DNA histogram, and nuclear fragmentations of tumor cells were frequently observed. In assay, using athymic mice, the combination of caffeine and cisplatin showed prominent antitumor effect without significant toxicity. These findings suggest the possibility that caffeine could be a useful drug capable of overcoming drug resistance to sarcomas, as caffeine enhanced the effect of DNA-damaging agents.
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