title: Thymidylate synthase and dihydropyrimidine dehydrogenase activities in non-small cell lung cancer tissues: relationship with in vitro sensitivity to 5-fluorouracil.
abstract: We examined enzymatic activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in non-small cell lung cancer (NSCLC) tissues to determine the relationship to tumor sensitivity to 5-fluorouracil (5-FU). TS and DPD activities were measured in 60 surgically resected primary NSCLC tissues using a TS-binding assay and a radioenzyme assay, respectively. In vitro tumor sensitivity to 5-FU was assayed using a collagen gel droplet embedded culture drug test (CD-DST). DPD activities slightly correlated with in vitro sensitivity to 5-FU (r=0.402,P=0.013), such that tumors with higher DPD activity were more resistant to 5-FU. In contrast, no correlation was observed in TS activities. Thus, it was suggested that only DPD activity in NSCLC tissues is a potential indicator in predicting tumor sensitivity to 5-FU. Based on these results, further study is needed to evaluate the clinical significance of these enzymes in 5-FU-based chemotherapy for patients with NSCLC.
authors.affiliation: Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinariku, Osaka 537-8511, Japan. higashiyama@rj8.so-net.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Higashiyama
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Yokouchi
authors.forename: K
authors.initials: K
authors.lastname: Takami
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: K
authors.initials: K
authors.lastname: Minamigawa
authors.forename: T
authors.initials: T
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology*; D042943:Dihydrouracil Dehydrogenase (NADP); D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil