[Choice of chemotherapeutic drugs for colorectal cancers by DPD and OPRT activities in cancer tissues].
5-FU is the most widely used anticancer drug for digestive system cancers, and it has been recently reported that the effect of 5-FU varies with the amount of enzymes that are involved in the drug metabolism in the cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of chemotherapy for colorectal cancers. Forty-six patients with colorectal carcinoma (28 colon and 18 rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and cancer tissues, whereas OPRT showed significantly higher activity in the cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of tumor, and mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated adenocarcinoma. The DPD activity of mucinous adenocarcinoma is related to catabolism of 5-FU is equal to that of adenocarcinoma, however, the OPRT activity is related to a main pathway of 5-FU phosphorylation is significantly lower. Thus, mucinous adenocarcinoma of the colon was more resistant to 5-FU than the differentiated adenocarcinoma. Therefore, for chemotherapy of mucinous adenocarcinoma, anticancer agents other than 5-FU should be selected.
Dept. of Gastroenterological Surgery, Osaka City University Graduate School of Medicine.
Masashi
M
Takemura
Harushi
H
Osugi
Shigeru
S
Lee
Masahiro
M
Kaneko
Yoshinori
Y
Tanaka
Yushi
Y
Fujiwara
Satoshi
S
Nishizawa
Hiroshi
H
Iwasaki
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil