Level of 5-fluorodeoxyuridine 5'-monophosphate in cancerous tissue in patients with gastric cancer under preoperative administration of TS-1. A preliminary study.
Metabolizing enzymes such as thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have long been known to be useful for predicting response and outcome in patients receiving 5-fluorouracil (5-FU). However, few studies have examined the cancerous tissue levels of 5-fluorodeoxyuridine 5'-monophosphate (FdUMP), a metabolite of 5-FU that has an important role in inhibiting DNA synthesis. In this study, for the first time to our knowledge, we measured concentrations of FdUMP in tumor specimens and surrounding non-cancerous tissue obtained at operation in 10 patients with gastric cancer who received TS-1 before surgery (80 mg/m2, 3 days). The FdUMP level in the cancerous tissue was significantly higher than that in the non-cancerous tissue (153.0 +/- 85.7 pmol/g tissue vs. 53.0 +/- 47.0 pmol/g tissue)(p = 0.0046). Furthermore, the TS level in tumor was significantly higher than that in non-cancerous tissue (6.362 +/- 5.106 pmol/g tissue vs. 2.092 +/- 2.050 pmol/g tissue) (p = 0.0310). The mean ratios of TS-bound FdUMP to TS and FdUMP concentrations in the cancerous tissues were 45.9% and 2.00%, respectively. Our results demonstrate that in cancerous tissue, TS-1 may produce high FdUMP concentration and suppress about half FdUMP concentration by forming ternary complexes.
Yamamoto
S
S
Dept. of Gastroenterological Surgery, Dokkyo University School of Medicine, Tochigi, Japan.
Kubota
K
K
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005467:Floxuridine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D011300:Preoperative Care; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000378:metabolism
D000970:Antineoplastic Agents; D004338:Drug Combinations; D011725:Pyridines; D005467:Floxuridine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D013940:Thymidylate Synthase