The objective of this study was to investigate whether polymorphisms of genes that are involved in one-carbon metabolism (dihydrofolate reductase, methionine synthase reductase, methylenetetrahydrofolate reductase, reduced folate carrier 1 and transcobalamin II) influence DNA methylation in 106 patients with alcoholism. In the multivariate model no genotype showed significant effects on DNA met...

High-dose methotrexate is a major component of current protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resistance include decreased transport through the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade o...

Intestinal folate transport has been well characterized, and rat small intestinal epithelial (IEC-6) cells have been used as a model system for the study of this process on the cellular level. The major intestinal folate transport activity has a low-pH optimum, and the current paradigm is that this process is mediated by the reduced folate carrier (RFC), despite the fact that this carrier has a...

Methods Genotypes were determined in an observational cohort of 183 JIA patients that had been systematically followed at 3 months intervals. The following SNPs were determined: methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TS) 2R/3R and Reduced Folate Carrier (RFC) 80G>A. MTX efficacy and adverse effects were c...

INTRODUCTION Methotrexate (MTX) enters cells via the reduced folate carrier SLC19A1, suggesting that SLC19A1 is associated with the efficacy of MTX. We here examined the relationship between the efficacy of MTX and the expression of SLC19A1 in glucose 6-phosphate isomerase (GPI)-induced arthritis. We found that interleukin-6 (IL-6) regulated the expression of SLC19A1, so we studied the effect o...

PURPOSE The purpose of this study was to analyze whether gene expression levels of folate enzymes in adjacent mucosa were associated with outcome of colorectal cancer patients. EXPERIMENTAL DESIGN Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and t...

Although methotrexate (MTX) is mainly transported by reduced folate carrier, P-gp and MRP1 may also be involved in its transport. In our previous study, a potent P-gp and MRP1 modulator, Cyclosporine A, potentiated MTX concentration in rat brain. Since it is important for MTX therapy for brain tumor to clarify which transporter is dominant, we herein determined whether the specific P-gp substra...

Received 26 January 2011 Revised 28 January 2011 Accepted 29 January 2011 Early online 29 January 2011 Print 31 January 2011 This study addresses the issues in translating the laboratory derived data obtained during discovery phase of research to a clinical setting using a breast cancer model. Laboratory-based risk assessment indicated that a family history of breast cancer, reduced folate carr...

The role of a membrane-associated folate binding protein (mFBP) in transport of folate analogues was investigated in three epithelial cell lines that were grown in high folate medium and folate-conditioned medium and express different levels of mFBP: human nasopharyngeal KB cells, monkey kidney MA 104 cells, and IGROV-I ovarian carcinoma cells. Folate analogues were selected for which mFBP exhi...

BACKGROUND To evaluate the impact of dihydrofolate reductase (DHFR) and reduced folate carrier (RFC) genes on methotrexate (MTX) resistance in osteosarcoma cells in relation to retinoblastoma (RB1) gene status. MATERIALS AND METHODS A series of human osteosarcoma cell lines-either sensitive or resistant to MTX-and 16 osteosarcoma tumour samples were used in this study. RESULTS In U-2OS MTX-...