Thymidylate synthase inhibition after administration of XXXX with or without @entity4181 in @entity694 @entity1 : implications for treatment with @entity1487 .

@entity1 @entity4181 @entity1382 @entity5 @entity22572 @entity21726 @entity1442 @entity14 @entity694 @entity1487
PURPOSE: To determine the time-dependence of @entity1487 (5FU)-induced @entity1382 ( @entity1382 ) inhibition in @entity694 @entity1 , the effect of @entity4181 (LV), and the relation to response. @entity1 AND METHODS: A 5FU injection (500 mg/m2) was given to 47 @entity1 with advanced @entity14 ; @entity5 biopsy specimens were obtained 1 to 72 hours after laparotomy. Eleven @entity1 received LV (2-hour infusion of 500 mg/m2) with 5FU midinfusion; biopsies were obtained after 45 hours. @entity1382 inhibition was evaluated by comparing the number of total and free @entity21726 ( @entity22572 ) ( @entity21726 ) binding sites and the total and residual catalytic activity of @entity1382 . RESULTS: The total catalytic @entity1382 activity varied from 0 to 621 pmol/h/mg protein and the total number of @entity21726 binding sites varied from 0 to 976 fmol/mg protein. The residual catalytic @entity1382 activity after 2, 23, and 45 hours was 41%, 65%, and 74% of the total catalytic activity; the number of free @entity21726 binding sites was 12%, 27%, and 49% of the total number, respectively. LV enhanced @entity1382 inhibition after 45 hours; the residual catalytic activity decreased from 74% to 49%, and the number of free @entity21726 binding sites from 49% to 24%. Eleven of 19 @entity1 treated with hepatic arterial infusion of 5FU had a partial response (PR). In the nonresponding @entity1 , total @entity1382 activity was significantly higher (P < .05) than in responding @entity1 . A high @entity1382 activity with a poor inhibition correlated with no response. CONCLUSION: Residual and total @entity1382 activity are predictive for response to 5FU. The findings may be applicable for treatment of @entity1 with @entity1442 and @entity1382 should be evaluated as a prognostic factor in adjuvant chemotherapy studies.
