1998 Fiscal Year Final Research Report Summary
The significance of metabolic enzymes for fluolo-pyrimidine anticancer drugs and its clinical application
| Project/Area Number |
09671297
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
KASAI Yasushi School of Medicine, Nagoya University, Res.Assoc., 医学部, 助手 (10273244)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Katsuki School of Medicine, Nagoya University, Asst.Prof., 医学部, 講師 (90184647)
AKIYAMA Seiji School of Medicine, Nagoya University, Res.Assoc., 医学部, 助手 (40202551)
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| Project Period (FY) |
1997 – 1998
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| Keywords | fluolo-pyrimidine derivatives / 5-fluorouracil / thymidylate synthase / dihydropyrimidine dehydrogenase / PCR |
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| Research Abstract |
To estimate effectiveness and sensitivity of fluoro-pyrimidine derivatives of anticancer drug such as 5-fluorouracil (5-FU), we try to measure the enzyme activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) which is a target enzyme and a main metabolic enzyme of 5-FU respectively.
First, samples were collected before the chemotherapy from the carcinoma tissue of 21 advanced stomach cancer patients and m-RNA value of TS and DPD was quantified by the competitive polymerase chain reaction. The m-RNA value of TS and DPD was significantly lower in the effective patients who showed more than 50% reduction of tumors compared to ineffective patients. Furthermore, the prognosis of high-valued patients of TS and DPD tended to be bad.
Next, thymidylate synthase for the resected samples of gastric cancer was stained by the immunostaining method (ABC method) using the polyclonal antibody for TS. Total of 76 gastric cancer samples (34 of differentiated type and 42 of undifferentiated type) in 1989〜1997 were examined. They were classified into 4 groups (-, ± and 1+ and 2+) according to the staining intensity of TS. And the life span of gastric cancer patients was proportional as a staining intensity, and the high TS expression was responsible for the poor prognosis of advanced gastric cancer.
Both TS and DPD reflected the effectiveness of fluoro-pyrimidine anticancer drugs and seemed to be clinically significant to predict the prognosis of gastric cancer patients and to introduce the proper treatment for the anticancer drug.
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