Literature DB >> 17520254

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

Kenji Okumura1, Eiji Mekata, Hisanori Shiomi, Hiroyuki Naitoh, Hajime Abe, Yoshihiro Endo, Yoshimasa Kurumi, Tohru Tani.   

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 microg/mL (7.68 microM), 24 h exposure and 2: 5-FU concentration 0.3 microg/mL (2.30 microM), 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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Year:  2007        PMID: 17520254     DOI: 10.1007/s00280-007-0511-y

Source DB:  PubMed          Journal:  Cancer Chemother Pharmacol        ISSN: 0344-5704            Impact factor:   3.333


  6 in total

1.  Reliability of tumor primary cultures as a model for drug response prediction: expression profiles comparison of tissues versus primary cultures from colorectal cancer patients.

Authors:  Gregory Lucien Bellot; Wei Han Tan; Ling Lee Tay; Dean Koh; Xueying Wang
Journal:  J Cancer Res Clin Oncol       Date:  2011-12-21       Impact factor: 4.553

2.  Thymidylate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cells.

Authors:  Dimitrios J Stravopodis; Panagiotis K Karkoulis; Eumorphia G Konstantakou; Sophia Melachroinou; Angeliki Thanasopoulou; Gerasimos Aravantinos; Lukas H Margaritis; Ema Anastasiadou; Gerassimos E Voutsinas
Journal:  J Cancer Res Clin Oncol       Date:  2010-04-28       Impact factor: 4.553

3.  In vivo 5FU-exposed human medullary thyroid carcinoma cells contain a chemoresistant CD133+ tumor-initiating cell subset.

Authors:  Lucia Kucerova; Lucia Feketeova; Zuzana Kozovska; Martina Poturnajova; Miroslava Matuskova; Radim Nencka; Pavel Babal
Journal:  Thyroid       Date:  2013-12-13       Impact factor: 6.568

4.  Glycogen Synthase Kinase 3β Inhibitor (2'Z,3'E)-6-Bromo-indirubin- 3'-Oxime Enhances Drug Resistance to 5-Fluorouracil Chemotherapy in Colon Cancer Cells.

Authors:  Kun-Ping Liu; Feng Luo; Si-Ming Xie; Li-Juan Tang; Mei-Xiang Chen; Xue-Fang Wu; Xue-Yun Zhong; Tong Zhao
Journal:  Chin J Cancer Res       Date:  2012-06       Impact factor: 5.087

5.  A practical approach for assessing chemosensitivity in colorectal cancer cell lines by comparative analysis of cell viability and thymidylate synthase mRNA expression.

Authors:  Hyun Yong Hwang
Journal:  J Korean Surg Soc       Date:  2011-12-27

6.  Differences in chemosensitivity between primary and metastatic tumors in colorectal cancer.

Authors:  Katsushi Takebayashi; Eiji Mekata; Hiromichi Sonoda; Tomoharu Shimizu; Hisanori Shiomi; Shigeyuki Naka; Yoshihiro Endo; Tohru Tani
Journal:  PLoS One       Date:  2013-08-28       Impact factor: 3.240

  6 in total

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