5-Fluorouracil-related gene expression in hepatic artery infusion-treated patients with hepatic metastases from colorectal carcinomas.
OBJECTIVE
To predict the therapeutic efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinomas, 5FU-related gene expressions were examined in primary colorectal carcinomas.


METHODS
Thirty-eight patients with liver metastases from colorectal carcinoma received HAI of 5FU. The expressions of the mRNAs for thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and oroteta phophoribosyl transferase (OPRT) in primary colorectal carcinomas were measured by RT-PCR.


RESULTS
The response rate was 52.6% (20/38). The overall median survival time was 29.1 months. DPD and TP expression was significantly higher in the progressive disease (PD) group than in the complete response (CR) or partial response (PR) group (p = 0.032, p = 0.014), respectively. The levels of DPD and TP mRNAs showed a significant correlation (r = 0.76, p = 0.0001).


CONCLUSIONS
The expression of DPD and TP mRNAs in primary colorectal carcinomas was significantly predictive of the therapeutic response to 5FU HAI.
Sameshima
Shinichi
S
Department of Surgery, Gunma Cancer Center, Ota, Gunma, Japan. shinsame@gunma-cc.jp
Tomozawa
Shigeru
S
Horikoshi
Hiroyuki
H
Motegi
Kenta
K
Hirayama
Isao
I
Koketsu
Shinichiro
S
Okada
Toshiyuki
T
Kojima
Masaru
M
Kon
Youichi
Y
Sawada
Toshio
T
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D008297:Male; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000235:genetics; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil