| Project/Area Number |
14370784
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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 |
応用薬理学・医療系薬学
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| Research Institution | Kyushu University |
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Principal Investigator |
HIGUCHI Shun Kyushu University, Faculty of Pharmaceutical Sciences, Prof., 大学院・薬学研究院, 教授 (40218699)
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| Co-Investigator(Kenkyū-buntansha) |
OHDO Shigehiro Kyushu University, Faculty of Pharmaceutical Sciences, Asso.Prof., 大学院・薬学研究院, 助教授 (00223884)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2002: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | irinotecan hydrochloride / chronotherapy / biological rhythm marker / cancer chemotherapy / 時計遺伝子 |
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| Research Abstract |
Time-restricted feeding(TRF) is known as a technique to manipulate 24-hr rhythm of locomotor activity, plasma corticosterone level, etc. in rodents. In the present study, we investigated the influence of feeding schedule on the dosing time-dependent toxicity induced by CPT-11 and its possible mechanism. In the TRF, the loss in body weight and leukopenia were significantly severer in mice injected with CPT-11 at 17:00(active phase) than those at 05:00(rest phase)(P<0.01,respectively). The manipulation of feeding schedule can modify the dosing time-dependent toxicity of CPT-11. The CPT-11-induced toxicity was reduced in rest phase of mice under both feeding conditions. As the mechanism, plasma concentrations showed no clear difference between mice injected with the drug at 05:00 and 17:00. In the TRF, the S-phase of cell cycle in bone marrow cells of non-treated mice showed a significant 24-hr rhythm with a peak at 01:00 and a trough at 09:00(P<0.01). The leukopenia was severe in mice injected with CPT-11 at 17:00 when DNA synthesis(S-phase) of bone marrow cells increased. The 24-hr variation in leukopenia corresponded to that in S-phase of bone marrow cells. Therefore, choosing the optimal timing associated with individual biological rhythm rather than time of day may lead to decrease the adverse effect of CPT-11.
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