[Dihydropyrimidine dehydrogenase gene expression in patients with hepatic metastases from colorectal cancer].
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-FU catabolism. Recently, much interest has been taken in the relation between the antitumor effect of 5-FU and DPD expression in gastrointestinal cancers. In this study, we compared DPD mRNA of 11 hepatic metastatic foci with that of 50 primary foci in colorectal cancer patients. DPD mRNA levels in hepatic metastatic foci were significantly higher than those in primary foci (median DPD/GAPDH ratio 0.79 vs 0.44, p = 0.035). Even in 6 cases available to compare DPD mRNA expression in matched primary and metastatic foci, the same significant difference was obtained (median DPD/GAPDH ratio 0.80 vs 0.36, p = 0.028). Our results suggested that the efficacy of intra-arterial infusion for metastatic liver tumor is mainly due to the fact that the high concentration of 5-FU is enough to overcome the high clearance of 5-FU, which is caused by DPD.
Shirota
Y
Y
Second Dept. of Surgery, Tokyo Medical and Dental University.
Ichikawa
W
W
Yamada
H
H
Uetake
H
H
Nihei
Z
Z
Sugihara
K
K
D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000556:secondary*; D010088:Oxidoreductases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP)