The Journal of Pediatrics
Volume 154, Issue 5 , Pages 688-693 , May 2009

Methotrexate in Pediatric Osteosarcoma: Response and Toxicity in Relation to Genetic Polymorphisms and Dihydrofolate Reductase and Reduced Folate Carrier 1 Expression

  • Ana Patiño-García, PhD

      Affiliations

    • Laboratory of Pediatrics, University of Navarra/University Clinic, Pamplona, Spain
    • Corresponding Author InformationReprint requests: Ana Patiño-García, PhD, Laboratory of Pediatrics, University of Navarra/University Clinic, Irunlarrea SN, Los Castaños Building, 31080 Pamplona, Spain
    • ,
  • Marta Zalacaín, PhD

      Affiliations

    • Laboratory of Pediatrics, University of Navarra/University Clinic, Pamplona, Spain
    • ,
  • Lucía Marrodán, BSc

      Affiliations

    • Laboratory of Pediatrics, University of Navarra/University Clinic, Pamplona, Spain
    • ,
  • Mikel San-Julián, MD, PhD

      Affiliations

    • Department of Traumatology and Orthopaedic Surgery, University Clinic of Navarra, Pamplona, Spain
    • ,
  • Luis Sierrasesúmaga, MD, PhD

      Affiliations

    • Laboratory of Pediatrics, University of Navarra/University Clinic, Pamplona, Spain

Received 29 April 2008 ,Revised 17 September 2008 ,Accepted 17 November 2008.

References 

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  11. Serra M, Reverter-Branchat G, Maurici D, Benini S, Shen JN, Chano T, et al. Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells. Ann Oncol. 2004;15:151–160
  12. Sowers R, Toguchida J, Qin J, Meyers PA, Healey JH, Huvos A, et al. mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma. Mol Cancer Ther. 2003;2:535–541
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  19. Berkun Y, Abou Atta I, Rubinow A, Orbach H, Levartovsky D, Aamar S, et al. 2756GG genotype of methionine synthase reductase gene is more prevalent in rheumatoid arthritis patients treated with methotrexate and is associated with methotrexate-induced nodulosis. J Rheumatol. 2007;34:1664–1669
  20. Wessels JA, Kooloos WM, De Jonge R, De Vries-Bouwstra JK, Allaart CF, Linssen A, et al. Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2006;54:2830–2839
  21. Assaraf YG. Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007;26:153–181
  22. Ifergan I, Meller I, Issakov J, Assaraf YG. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer. 2003;98:1958–1966
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 This work was partially supported by a grant from the Department of Education and Culture of the Gobierno de Navarra. The authors declare no conflicts of interest.

PII: S0022-3476(08)01041-X

doi: 10.1016/j.jpeds.2008.11.030

The Journal of Pediatrics
Volume 154, Issue 5 , Pages 688-693 , May 2009

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