[Effects of neo-adjuvant chemotherapy with UFT (a combination of tegafur and uracil) on DNA-synthesizing enzyme activities in human colorectal carcinomas].
Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High TS and TK activities have been observed in rapidly proliferating tissues such as foetal tissue, regenerating liver and carcinomas. TS and TK activities were measured in histologically normal colon mucosa and colorectal carcinomas with or without neo-adjuvant chemotherapy of an antitumor drug UFT (a combination of tegafur and uracil) in humans. In colorectal carcinomas, 5-FU and uracil levels were increased to 2.6- and 3.2-fold, respectively, those in normal colon mucosa by neo-adjuvant chemotherapy of UFT. In colorectal carcinomas, TS and TK activities were both increased to approximately 2- and 3-fold, respectively, those in normal colon mucosa without UFT treatment. In normal colon mucosa and colorectal carcinomas with neo-adjuvant chemotherapy of UFT, TS activities were reduced to approximately 50% and 40%, respectively, those without UFT treatment. These results indicate that neo-adjuvant chemotherapy with UFT may prevent dissemination of cancer cells during operation, and local recurrence and distant metastasis after operation, inhibiting DNA synthesis via the de novo pathway of pyrimidine synthesis in carcinomas.
Sakamoto
S
S
Kudo
H
H
Kuwa
K
K
Kawasaki
T
T
Kasahara
N
N
Okamoto
R
R
Sagara
T
T
Kawachi
Y
Y
Iwama
T
T
Hirayama
R
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D003864:Depression, Chemical; D006801:Humans; D005641:Tegafur / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*; D014498:Uracil / Q000627:therapeutic use
D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D013937:Thymidine Kinase