Activities of thymidylate synthetase and thymidine kinase in gastric cancer.
In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.
Konishi
T
T
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
Miyama
T
T
Sakamoto
S
S
Hirata
T
T
Mafune
K
K
Hiraishi
M
M
Idezuki
Y
Y
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000453:epidemiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016014:Linear Models; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000453:epidemiology; D013937:Thymidine Kinase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D005472:Fluorouracil; D008727:Methotrexate