1993 Fiscal Year Final Research Report Summary
A Model for Sensitivity Determination of Anticancer Agents against Chemical-induced Colon Cancer in Rats
Project/Area Number |
04807095
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
消化器外科学
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Research Institution | SHOWA UNIVERSITY |
Principal Investigator |
TSUNODA Akira Showa University, School of Medicine, Assistant, 医学部, 助手 (10183485)
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Co-Investigator(Kenkyū-buntansha) |
SHIBUSAWA Miki Showa University, Shool of Medicine, Assistant Professor, 医学部, 助教授 (90138496)
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Project Period (FY) |
1992 – 1993
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Keywords | Dimethylhydrazine / Colon tumor / Tumor doubling time / Barium enema / Second screening / Anticancer drug / Colostomy |
Research Abstract |
1.Chemically-induced autochthonous colon cancer was used to test the sensitivity of tumors to chemotherapeutic agents. Seventy-one Sprague-Dawley rats received dimethylhydrazine(20mg/kg)s.c. once weekly for 20wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into three groups that were subjected to the following treatments : 5-fluorouracil(5-FU) ; 1-(2-tetrahydrofury1)-5-FU(FT) ; and a mixture of FT and uracil(UFT). After 5wk of treatment, the barium enema was repeated. For evaluation of the efficacy of the treatment, colon tumors smaller than 10mm at the first barium examination were selected, because the doubling time of this size tumor tends to be constant. The mean tumor doubling time in this condition is 17days<plus-minus>10(SD). "Response" was judged as effective when tumor doubling time in the treatment groups exceeded 37 days, calculated from the mean+2SDs in the control group. Response rates i
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n the 5-FU,FT,and UFT groups were 25%, 33%, and 36%, respectively, and this reflects the clinical data of those drugs. The present system may be a predictive model for screening anticancer drugs for human colorectal cance Accoding to our previous studies, tumor doubling time of autochthonous colon cancer had a considerable variation. The possible reason for the variation is fecal stream mechanically causing the cell loss from the tumor. Based on the hypothesis that the growth rate of the tumor in the absence of fecal stream, we developed an experimental system making a colostomy and evaluated the tumor growth by the seanetial barium examination. The mean duobling time in this condition is 9.8days<plus-minus>4.0(SD). Response to UFT treatment was judged as effective when the doubling time exceeded 17.8days, calculated from the mean+2SDs in the control group. The response rate of UFT treatment was 48%. The sensitivity of UFT treatment against colon cancer in the present study was higher than that in the previous study(36% Less
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