BACKGROUND Rheumatoid Arthritis is a chronic disease leading to decreased quality of life with a rather variable response rate to Disease Modifying Anti Rheumatic Drugs. Methotrexate (MTX) is the gold standard therapy in Rheumatoid Arthritis. The Multidrug resistance Related Protein and Multi Drug Resistance protein 1, also called P-glycoprotein-170 transporters can alter the intracellular conc...

Three techniques for measuring methotrexate show various cross reactivities with methotrexate-related compounds: "high-pressure" liquid chromatography, by principle, is virtually specific for methotrexate; the enzyme-inhibition assay quantitates methotrexate, methotrexate diglutamate, and methotrexate triglutamate equally well, but has a 10% cross reactivity with 4-amino-4-deoxy-N10-methylptero...

Ohnuma et al reported a series of methotrexate-resistant MOLT-3 human T-cell acute lymphoblastic leukemia cell lines that showed decreasing methotrexate (MTX) uptake as the sublines acquired increasing MTX resistance (Cancer Res 45:1815, 1985). The alteration of MTX uptake kinetics in these cells, the intermediately resistant MOLT-3/MTX200 and the highly resistant MOLT-3/MTX10,000 cell lines, w...

PURPOSE Studies in oncology have implicated multiple molecular mechanisms as contributors to intrinsic and acquired tumor resistance to antifolate therapy. Here we show the utility of an (19)F-labeled methotrexate (FMTX) with (19)F magnetic resonance to differentiate between sensitive and resistant tumors in vivo and thus predict therapeutic response. EXPERIMENTAL DESIGN Human sarcoma xenogra...

Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette...

The efflux of methotrexate and methotrexate polyglutamates was examined with primary monolayer cultures of rat hepatocytes and also with monolayer cultures of a stable hepatocarcinoma cell line (H35 cells). In this study, the polyglutamates were considered as those species with two or more additional glutamate residues. When methotrexate polyglutamates were present in hepatocytes in excess of m...

OBJECTIVE Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therap...

a study was undertaken to evaluate the nucleolar organizing regions (nor) count and histopathological changes in rat’s liver treated with methotrexate (mtx). male wistar rats aged 4 months, maintained in our institution were used in the present study. animals were injected intraperitonealy with 3 different doses of methotrexate on alternative days for one week and the animals were sacrificed on...