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Published in: Cancer Chemotherapy and Pharmacology 3/2007

01-08-2007 | Original Article

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

Authors: Elham Fakhrejahani, Akiko Miyamoto, Nobuhiko Tanigawa

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2007

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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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Metadata
Title
Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer
Authors
Elham Fakhrejahani
Akiko Miyamoto
Nobuhiko Tanigawa
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2007
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0448-1

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