[Correlation between 5-fluorouracil (5-FU) sensitivity as measured by collagen gel droplet embedded culture drug sensitivity test (CD-DST) and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer].
The levels of OPRT, DPD, and TS were determined in colorectal cancer tissue specimens, and 5-FU sensitivity was measured by CD-DST. The correlation between enzyme activity and 5-FU sensitivity was then studied. Six patients with colorectal carcinoma who had undergone surgical resection in our institution between May and August 2000 were studied. The CD-DST method was used to measure the sensitivity to 5-FU under three sets of conditions: 0.2 microgram/ml x 5 days (A), 1.0 microgram/ml x 1 day (B), and 10.0 micrograms/ml x 3 h (C). The coefficients of correlation of tumor sensitivity to 5-FU and OPRT activity were A: 0.8246, B: 0.7670, and C: 0.7856, and to DPD activity were A: 0.2525, B: 0.3928, and C: 0.4337, while the coefficients of correlation to TS enzyme levels were A: -0.5240, B: -0.4770, and C: -0.6131. These findings demonstrate a high degree of correlation between OPRT activity at the tumor site and tumor sensitivity to 5-FU under a variety of conditions, suggesting that OPRT activity can be a useful indicator in predicting the anti-tumor effectiveness of 5-FU for a specific tumor.
Ochiai
T
T
Dept. of Surgery, Toubu Chiiki Hospital, Tokyo Metropolitan, Health and Medical Treatment Corporation.
Sugitani
M
M
Nishimura
K
K
Noguchi
H
H
Watanabe
T
T
Sengoku
H
H
Kihara
A
A
Okano
M
M
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil