Full metadata record
DC Field | Value | Language |
---|---|---|
dc.creator | Patiño-García, A. (Ana) | - |
dc.creator | Zalacain, M. (Marta) | - |
dc.creator | Marrodán, L. (Lucía) | - |
dc.creator | San-Julian, M. (Mikel) | - |
dc.creator | Sierrasesumaga, L. (Luis) | - |
dc.date.accessioned | 2012-11-22T12:46:40Z | - |
dc.date.available | 2012-11-22T12:46:40Z | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Patiño-García A, Zalacaín M, Marrodán L, San-Julián M, Sierrasesúmaga L. Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression. J Pediatr. 2009 May;154(5):688-93. | es_ES |
dc.identifier.issn | 0022-3476 | - |
dc.identifier.uri | https://hdl.handle.net/10171/23770 | - |
dc.description.abstract | To determine the influence of the genotype and the level of expression of different enzymes involved in folate metabolism on the response to and toxicity of high-dose methotrexate treatment in pediatric osteosarcomas. STUDY DESIGN: DHFR and Reduced folate carrier 1 (RFC1) semiquantitative expression was analyzed in 34 primary and metastatic osteosarcoma tissues by real-time polymerase chain reaction. The following polymorphisms were also analyzed in peripheral blood from 96 children with osteosarcoma and 110 control subjects: C677T, A1298C (MTHFR), G80A (RFC1), A2756G (MTR), C1420T (SHMT), the 28bp-repeat polymorphism, and 1494del6 of the TYMS gene. Treatment toxicity was scored after each cycle according to criteria from the World Health Organization. RESULTS: DHFR and RFC1 expression was lower in initial osteosarcoma biopsy specimens than in metastases (P = .024 and P = .041, respectively). RFC1 expression was moderately decreased in samples with poor histologic response to preoperative treatment (P = .053). Patients with osteosarcoma with G3/G4 hematologic toxicity were more frequently TT than CT/CC for C677T/MTHFR (P = .023) and GG for A2756G/MTR (P = .048 and P = .057 for gastrointestinal and hematologic toxicity, respectively). CONCLUSIONS: The role of C677T/MTHFR and A2756G/MTR on chemotherapy-induced toxicity should be further investigated in pediatric osteosarcomas receiving high-dose methotrexate. Altered expression of DHFR and RFC1 is a feasible mechanism by which osteosarcoma cells become resistant to methotrexate. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Methotrexate/administration & dosage/adverse effects | es_ES |
dc.subject | Polymerase Chain Reaction | es_ES |
dc.subject | Osteosarcoma/drug therapy/genetics/mortality | es_ES |
dc.title | Methotrexate in Pediatric Osteosarcoma: Response and Toxicity in Relation to Genetic Polymorphisms and Dihydrofolate Reductase and Reduced Folate Carrier 1 Expression | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.type.driver | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | http://dx.doi.org/10.1016/j.jpeds.2008.11.030 | es_ES |
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