Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
July-August 2013 Volume 1 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-August 2013 Volume 1 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy

  • Authors:
    • Satoshi Nishino
    • Ayumi Itoh
    • Hiroshi Matsuoka
    • Kotaro Maeda
    • Shingo Kamoshida
  • View Affiliations / Copyright

    Affiliations: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan, Department of Surgery, School of Medicine, Fujita Health University Toyoake, Aichi 470-1192, Japan
  • Pages: 661-667
    |
    Published online on: April 15, 2013
       https://doi.org/10.3892/mco.2013.104
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Colorectal cancer is one of the most common malignancies in developed countries and chemotherapy is the standard treatment option for advanced colorectal cancer. Identification of biomarkers for predicting response to uracil̸ftorafur plus leucovorin (UFT/LV) chemotherapy is an important issue in colorectal cancer treatment. Organic anion transporter 2 (OAT2) and reduced folate carrier 1 (RFC1) are the major uptake transporters of 5-fluorouracil (5-FU) and LV, respectively. In the present study, the correlation between OAT2 and RFC1 expression and histological response to preoperative UFT-based (UFT or UFT/LV) chemotherapy was investigated. Pre‑treatment biopsy specimens obtained from 45 patients were evaluated for OAT2 and RFC1 expression levels by using an immunohistochemical approach. A high expression of OAT2 and RFC1 was significantly correlated with good response to UFT-based chemotherapy (P<0.0001 and P=0.002, respectively). In multivariate logistic regression analysis, a high OAT2 expression was an independent predictor of good response to UFT-based chemotherapy (P=0.02), unlike RFC1 expression. High expression levels of OAT2 were significantly correlated with a good response in the UFT-treated (P=0.04) as well as the UFT̸LV‑treated (P<0.0005) groups; however, RFC1 expression levels were significantly correlated with a good response only in the UFT̸LV‑treated group (P=0.02). Therefore, immunohistochemical analysis of OAT2 and RFC1 may serve as a useful tool for predicting the efficacy of UFT/LV treatment regimens in colorectal cancer patients.
View Figures

Figure 1

View References

1. 

Fujii S, Ikenaka K, Fukushima M and Shirasaka T: Effect of uracil and its derivatives on antitumor activity of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil. Gann. 69:763–772. 1978.PubMed/NCBI

2. 

Milano G, Ferrero JM and François E: Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation. Br J Cancer. 91:613–617. 2004.PubMed/NCBI

3. 

Anttila MI, Sotaniemi EA, Kairaluoma MI, Mokka RE and Sundquist HT: Pharmacokinetics of ftorafur after intravenous and oral administration. Cancer Chemother Pharmacol. 10:150–153. 1983. View Article : Google Scholar : PubMed/NCBI

4. 

Longley DB, Harkin DP and Johnston PG: 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 3:330–338. 2003. View Article : Google Scholar : PubMed/NCBI

5. 

Borner MM, Schöffski P, de Wit R, et al: Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer. 38:349–358. 2002. View Article : Google Scholar

6. 

Carmichael J, Popiela T, Radstone D, et al: Randomized comparative study of tegafur/uracil and oral leucovorin versus parenteral fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 20:3617–3627. 2002. View Article : Google Scholar

7. 

Douillard JY, Hoff PM, Skillings JR, et al: Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 20:3605–3616. 2002. View Article : Google Scholar : PubMed/NCBI

8. 

Lembersky BC, Wieand HS, Petrelli NJ, et al: Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 24:2059–2064. 2006. View Article : Google Scholar

9. 

Dobson PD and Kell DB: Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat Rev Drug Discov. 7:205–220. 2008. View Article : Google Scholar : PubMed/NCBI

10. 

Sissung TM, Baum CE, Kirkland CT, Gao R, Gardner ER and Figg WD: Pharmacogenetics of membrane transporters: an update on current approaches. Mol Biotechnol. 44:152–167. 2010. View Article : Google Scholar : PubMed/NCBI

11. 

Marzolini C, Tirona RG and Kim RB: Pharmacogenomics of the OATP and OAT families. Pharmacogenomics. 5:273–282. 2004. View Article : Google Scholar : PubMed/NCBI

12. 

You G: The role of organic ion transporters in drug disposition: an update. Curr Drug Metab. 5:55–62. 2004. View Article : Google Scholar : PubMed/NCBI

13. 

Kobayashi Y, Ohshiro N, Sakai R, Ohbatashi M, Kohyama N and Yamamoto T: Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 57:573–578. 2005.

14. 

Sirotnak FM and Tolner B: Carrier-mediated membrane transport of folates in mammalian cells. Annu Rev Nutr. 19:91–122. 1999. View Article : Google Scholar : PubMed/NCBI

15. 

Blehaut H, Mircher C, Ravel A, et al: Effect of leucovorin (folinic acid) on the developmental quotient of children with Down’s syndrome (trisomy 21) and influence of thyroid status. PLoS One. 5:e83942010.PubMed/NCBI

16. 

Japanese Society for Cancer of the Colon and Rectum: Japanese Classification of Colorectal Carcinoma. 2nd English edition. Kanehara Shuppan Co. Ltd.; Tokyo: 2009

17. 

Kamoshida S, Matsuoka H, Shiogama K, et al: Immunohistochemical analysis of thymidylate synthase, p16INK4a, cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16INK4a-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil. Pathol Int. 54:564–575. 2004.PubMed/NCBI

18. 

Ichikawa W, Uetake H, Shirota Y, et al: Both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Br J Cancer. 89:1486–1492. 2003. View Article : Google Scholar

19. 

Sadahiro S, Suzuki T, Tanaka A, Okada K, Nagase H and Uchida J: Association of right-sided tumors with high thymidine phosphorylase gene expression levels and the response to oral uracil and tegafur/leucovorin chemotherapy among patients with colorectal cancer. Cancer Chemother Pharmacol. 70:285–291. 2012. View Article : Google Scholar

20. 

Seithel A, Karlsson J, Hilgendorf C, Björquist A and Ungell AL: Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells. Eur J Pharm Sci. 28:291–299. 2006. View Article : Google Scholar : PubMed/NCBI

21. 

Odin E, Wettergren Y, Nilsson S, et al: Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients. Clin Cancer Res. 9:6012–6019. 2003.PubMed/NCBI

22. 

Hlavata I, Mohelnikova-Duchonova B, Vaclavikova R, et al: The role of ABC transporters in progression and clinical outcome of colorectal cancer. Mutagenesis. 27:187–196. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Nishino S, Itoh A, Matsuoka H, Maeda K and Kamoshida S: Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy. Mol Clin Oncol 1: 661-667, 2013.
APA
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., & Kamoshida, S. (2013). Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy. Molecular and Clinical Oncology, 1, 661-667. https://doi.org/10.3892/mco.2013.104
MLA
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., Kamoshida, S."Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy". Molecular and Clinical Oncology 1.4 (2013): 661-667.
Chicago
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., Kamoshida, S."Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy". Molecular and Clinical Oncology 1, no. 4 (2013): 661-667. https://doi.org/10.3892/mco.2013.104
Copy and paste a formatted citation
x
Spandidos Publications style
Nishino S, Itoh A, Matsuoka H, Maeda K and Kamoshida S: Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy. Mol Clin Oncol 1: 661-667, 2013.
APA
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., & Kamoshida, S. (2013). Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy. Molecular and Clinical Oncology, 1, 661-667. https://doi.org/10.3892/mco.2013.104
MLA
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., Kamoshida, S."Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy". Molecular and Clinical Oncology 1.4 (2013): 661-667.
Chicago
Nishino, S., Itoh, A., Matsuoka, H., Maeda, K., Kamoshida, S."Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy". Molecular and Clinical Oncology 1, no. 4 (2013): 661-667. https://doi.org/10.3892/mco.2013.104
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team