1989 Fiscal Year Final Research Report Summary
Comparative study of concentrations of antitumor agents in serum and tumor in nude mouse and human
| Project/Area Number |
62570579
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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 |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KUBOTA Tetsuro Keio University, Department of Medicine, Assistant, 医学部, 助手 (00118944)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Concentration of antitumor agents / Human tumor xenografts / Surgical specimen / Nude mouse / Comparative pharmacology |
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| Research Abstract |
The pharmacokinetic comparison between nude mouse and human beings is important to use the human tumor xenografts - nude mouse system as a screening panel of newly developed antiunor agents. Mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU), cisplatin (DDP), DWA2114R (DWA) and carboplatin (CBDCA) were administered to nude mice bearing human tumor xenografts in maximum tolerated doses and to patinets with cancer in conventionally available doses in clinics. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, high performance liquid chromatography for ADM and atom absorption method for DDP, DWA and CBDCA.
The maximum serum concentration (Cmax in ug/ml) and concentration in tumor (T in ug/g) in nude mouse and human were as follows; mmc ADM 5-FU DDP DWA CBDCA Cmax in mouse 1.09 1.44 44.7 4.8 30.3 61.2 Cmax in human 0.84 0.42 85.4 2.2 24.0 6.5 T/Cmax% (mouse) 1.3 209.1 10.4 40.6 31.0 27.9 T/Cmax% (human) 0.9 354.6 3.1 42.9 30.7 10.4 T/Cmax ratio of each agent in mouse and human was similar to each other with a statistical significance at r = 0.996 (p 0.001).
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