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[Inhibition of thymidylate synthetase and antiproliferative effect by 1-hexylcarbamoyl-5-fluorouracil].
- Source :
-
Gan to kagaku ryoho. Cancer & chemotherapy [Gan To Kagaku Ryoho] 1988 Nov; Vol. 15 (11), pp. 3109-13. - Publication Year :
- 1988
-
Abstract
- In order to estimate tumor chemosensitivity of fluoropyrimidine derivative, inhibition of thymidylate synthetase (TS) was investigated using a nude mouse experimental system. Four human tumors xenografted in nude mice; H-111, SH-8 and SH-10, each established from gastric cancer, and EH-1 from esophageal cancer, were used. When the transplanted tumor volumes reached to approximately 200 mm3, 1-hexylcarbamoyl-5-fluorouracil (HCFU) was given for 5 days. Tumors was removed for the measurement of total and free TS at 0 hr, 6 hrs and 24 hrs after the last administrations. Simultaneously, the anti-proliferative effects were investigated according to the therapeutic protocol of NCI. No positive correlation between the inhibition rate of TS and the anti-proliferative effects was observed, although the absolute values of free TS were similar to the tumor inhibition rates. The measurement of total TS provided a highest concentration in SH-8, while extremely low in EH-1. On the analysis of free TS, a significant increase of the concentration was observed at 24 hrs after the last administration compared with at 6 hrs in SH-8. These results indicate that free TS had a potentiality as a new parameter for predicting tumor chemosensitivity of fluoropyrimidine derivative and the analysis of TS should be affected strongly by the characteristics of enzymic activity of examined tumor.
- Subjects :
- Animals
Cell Division drug effects
Esophageal Neoplasms enzymology
Esophageal Neoplasms pathology
Fluorouracil pharmacology
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Stomach Neoplasms enzymology
Stomach Neoplasms pathology
Antineoplastic Agents pharmacology
Esophageal Neoplasms drug therapy
Fluorouracil analogs & derivatives
Stomach Neoplasms drug therapy
Thymidylate Synthase antagonists & inhibitors
Subjects
Details
- Language :
- Japanese
- ISSN :
- 0385-0684
- Volume :
- 15
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Gan to kagaku ryoho. Cancer & chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 3190249