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Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer

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An Erratum to this article was published on 08 May 2007

Abstract

Purpose

It has been suggested that the gene expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) help in the prediction of the response to 5-fluorouracil (5-FU) in vivo and in vitro in gastric cancers.

Methods

In this study, intratumoral TS and DPD gene expressions were evaluated with real time reverse transcriptional polymerase chain reaction technique to determine the correlation between the expression of these two genes and in vitro sensitivity to 5-FU, assessed by the histoculture drug response assay on 87 patients with gastric adenocarcinoma.

Results

The sensitivity to 5-FU did not show any difference in clinicopathological groups. DPD gene level was higher in undifferentiated (n = 39) than differentiated (n = 48) tumors (P = 0.043). In differentiated tumors, TS gene expression levels were higher in the tumors with relative resistance to 5-FU, while in undifferentiated cases, DPD mRNA levels were higher in tumors that showed resistance to 5-FU in vitro (P = 0.043 and 0.007, respectively). DPD also had significant predictive value for 5-FU sensitivity in undifferentiated cases [R(S) = −0.401, P = 0.011]. TS and DPD gene expression levels were more highly correlated in undifferentiated compared to differentiated cases [R(S) = 0.515 and 0.359, respectively].

Conclusions

Different gene expression might be responsible for 5-FU sensitivity in gastric cancers of different histologic origin.

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Acknowledgments

This study was supported by a grant from Taiho Pharmaceutical Company. We are grateful to Prof. Hideyuki Hayashi, Biochemistry Department of Osaka Medical College for his valuable advice in the design of this study. We also thank Drs. Hideaki Mabuchi, Tetsuhisa Yamamoto and Hua Meng for their support in conducting this work, and acknowledge Drs. Kiarash Riazi and Michael A. Galic (University of Calgary, Canada) for their thorough review of this manuscript.

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  1. Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki-shi, Osaka, 569-8686, Japan

    Elham Fakhrejahani, Akiko Miyamoto & Nobuhiko Tanigawa

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  1. Elham Fakhrejahani
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Correspondence to Nobuhiko Tanigawa.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00280-007-0501-0

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Fakhrejahani, E., Miyamoto, A. & Tanigawa, N. Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer. Cancer Chemother Pharmacol 60, 437–446 (2007). https://doi.org/10.1007/s00280-007-0448-1

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