Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

  • Authors:
    • Jun Nakamura
    • Naohiko Kohya
    • Keita Kai
    • Kazuma Ohtaka
    • Kazuyoshi Hashiguchi
    • Masatsugu Hiraki
    • Yoshihiko Kitajima
    • Osamu Tokunaga
    • Hirokazu Noshiro
    • Kohji Miyazaki
  • View Affiliations

  • Published online on: October 1, 2010     https://doi.org/10.3892/ijo_00000735
  • Pages: 845-852
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Abstract

Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract carcinoma (BTC), although its efficacy is insufficient. Therefore, it is essential to establish new diagnostic methods, which can predict responders before the treatment. The aim of this study is to identify the most reliable chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK, RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules were investigated in 5 BTC cell lines, and correlated with gemcitabine sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly correlated with the IC50 value for gemcitabine in BTC cell lines (R=0.935, 0.771, respectively). In addition, patients with low RRM1 were significantly more sensitive to gemcitabine (p=0.033), and their survival was significantly better than patients with high RRM1 (p=0.001). In conclusion, RRM1 particularly in protein level is a reliable marker for gemcitabine resistance in BTC. Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in order to design a tailor-made chemotherapeutic regimen for BTC patients.

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October 2010
Volume 37 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nakamura J, Kohya N, Kai K, Ohtaka K, Hashiguchi K, Hiraki M, Kitajima Y, Tokunaga O, Noshiro H, Miyazaki K, Miyazaki K, et al: Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma. Int J Oncol 37: 845-852, 2010
APA
Nakamura, J., Kohya, N., Kai, K., Ohtaka, K., Hashiguchi, K., Hiraki, M. ... Miyazaki, K. (2010). Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma. International Journal of Oncology, 37, 845-852. https://doi.org/10.3892/ijo_00000735
MLA
Nakamura, J., Kohya, N., Kai, K., Ohtaka, K., Hashiguchi, K., Hiraki, M., Kitajima, Y., Tokunaga, O., Noshiro, H., Miyazaki, K."Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma". International Journal of Oncology 37.4 (2010): 845-852.
Chicago
Nakamura, J., Kohya, N., Kai, K., Ohtaka, K., Hashiguchi, K., Hiraki, M., Kitajima, Y., Tokunaga, O., Noshiro, H., Miyazaki, K."Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma". International Journal of Oncology 37, no. 4 (2010): 845-852. https://doi.org/10.3892/ijo_00000735