Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5‐fluorouracil to patients with colorectal cancer

This study explores the effect of 5‐fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate‐limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2007-06, Vol.120 (12), p.2609-2612
Main Authors: Mauritz, Robert, van Groeningen, Cees J., Smid, Kees, Jansen, Gerrit, Pinedo, Herbert M., Peters, Godefridus J.
Format: Article
Language:English
Subjects:
5‐fluorouracil
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic - therapeutic use
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Colonic Neoplasms - enzymology
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - enzymology
Colorectal Neoplasms - genetics
dihydropyrimidine dehydrogenase
Dihydrouracil Dehydrogenase (NADP) - genetics
Female
Fluorouracil - therapeutic use
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Humans
Liver Neoplasms - enzymology
Liver Neoplasms - genetics
Liver Neoplasms - secondary
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
RT‐PCR
thymidylate synthase
Thymidylate Synthase - genetics
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study explores the effect of 5‐fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate‐limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor and liver metastasis samples from patients who were either not pretreated (n = 29) or given one presurgery bolus of 5FU (n = 67). In both groups a wide variation in TS mRNA levels was observed. Median TS mRNA expression in 17 primary tumors of exposed patients was 3.0‐fold higher than in 19 primary tumors of unexposed patients (p = 0.015). TS mRNA expression in liver metastasis samples of exposed patients (n = 16) was also higher (5.2‐fold) than that of unexposed patients (n = 48; p < 0.001). Also DPD mRNA expression displayed a large degree of interpatient variation. No difference in DPD expression in liver metastasis samples was observed between exposed and unexposed patients. However, median DPD mRNA expression in 15 primary tumors of exposed patients was 3.2‐fold lower than in 18 primary tumors of unexposed patients (p = 0.027). In conclusion, administration of 5FU in vivo influences the gene expression of TS and DPD. © 2007 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.22626