5-Fluorouracil and UFT-sensitive gastric carcinoma has a high level of thymidylate synthase.
The authors examined the relationship between the level of thymidylate synthase (TS) and the sensitivity to 5-fluorouracil (5-FU) and UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil in a molar ratio of 1:4. For the studies we used the subrenal capsule (SRC) assay and 15 human gastric cancer tissues. The TS levels were assayed by the ligand-binding technique, using [6-3H]FdUMP. The relative variation of tumor size (delta TuS/TuS0) was calculated to be as follows: delta TuS/TuS0 = [(TuS6 - TuS0)/TuS0] x 100 (%), where TuS6 was the tumor size on day 6 and TuS0 on day 0. The chemosensitivity was considered to be positive when delta TuS/TuS0 in the treated group decreased to below -10%. Decrease in tumor size was marked in case of exposure to UFT (-19.8 +/- 13.0%) (mean +/- standard deviation), compared with that to 5-FU (-9.0 +/- 7.2%), with a statistically significant difference (P less than 0.001). The TS level varied from 1.7 to 30.8 pmol/g gastric cancer tissue and the mean was 7.1 +/- 7.2 pmol/g tissue. A correlation was noted between the TS level and decrease in size of the tumor exposed to 5-FU (r = -0.671) or UFT (r = -0.758): gastric cancer tissue with higher level of TS is more sensitive to 5-FU and UFT than is that with a lower TS level. These findings show that the sensitivity to 5-FU and UFT of gastric cancer tissue is related to the TS level and that UFT shows promise for the treatment of patients with gastric cancer.
Maehara
Y
Y
Cancer Center of Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kusumoto
T
T
Kusumoto
H
H
Anai
H
H
Sakaguchi
Y
Y
Kido
Y
Y
Okamura
T
T
Korenaga
D
D
Sugimachi
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D013370:Subrenal Capsule Assay; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000378:metabolism*; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D005472:Fluorouracil