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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2008

01-04-2008 | Original Article

Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity with low dose and long duration in primary colorectal cancer

Authors: Kenji Okumura, Eiji Mekata, Hisanori Shiomi, Hiroyuki Naitoh, Hajime Abe, Yoshihiro Endo, Yoshimasa Kurumi, Tohru Tani

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2008

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Abstract

Objectives

To investigate the prognostic marker for the adjuvant chemotherapy of primary colorectal carcinoma.

Methods

Primary colorectal cancer tissue from 24 patients was investigated to evaluate the relationship between the mRNA expression level of several 5-fluorouracil (5-FU)-related metabolic enzymes (thymidylate synthase, TS; dihydropyrimidine dehydrogenase, DPD; and thymidine phosphorylase, TP) and chemosensitivity to two different 5-FU doses and duration (1: 5-FU concentration 1.0 μg/mL (7.68 μM), 24 h exposure and 2: 5-FU concentration 0.3 μg/mL (2.30 μM), 144 h exposure). Chemosensitivity and mRNA expression levels were measured using collagen gel droplet embedded culture drug sensitivity tests and real-time quantitative reverse transcription-polymerase chain reaction. Clinicopathological features and chemosensitivity were also compared.

Results

The TS mRNA expression level was significantly higher in the 5-FU resistant group (T/C > 60%) compared with the 5-FU sensitive group (T/C < 60%) in both 5-FU regimens (1: 5.03 ± 0.92 vs. 1.58 ± 0.76, p < 0.01, 2: 4.88 ± 0.91 vs. 0.96 ± 0.20, p < 0.001). The group with the higher TS mRNA expression level (>3.83, the average) were more resistant to both 5-FU regimens than those with lower TS mRNA (<3.83) (1: T/C = 80 vs. 66%, p = 0.11, 2: T/C = 89 vs. 64%, p < 0.005). The TS mRNA expression level inversely correlated with the sensitivity to the latter 5-FU regimen (R = 0.577, p < 0.01). There were no relationships between chemosensitivity to 5-FU and the mRNA expression level of DPD and TP and clinicopathological factors.

Conclusions

The TS mRNA expression level might be a good marker of chemosensitivity to 5-FU in primary colorectal cancer, especially the sensitivity to low dose 5-FU with a long duration.
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Metadata
Title
Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity with low dose and long duration in primary colorectal cancer
Authors
Kenji Okumura
Eiji Mekata
Hisanori Shiomi
Hiroyuki Naitoh
Hajime Abe
Yoshihiro Endo
Yoshimasa Kurumi
Tohru Tani
Publication date
01-04-2008
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0511-y

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