Methotrexate and 6-mercaptopurine, important components of acute lymphoblastic leukemia treatment, are substrates for multidrug resistance-associated protein MRP4. Eight single nucleotide polymorphisms were analyzed in MRP4 gene, and 4 variants were identified as tagSNPs with frequency more than or equal to 5%. They were investigated for association with treatment responses in 275 children with...

Introduction Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease among children. Among patients with JIA often meets resistance to the therapy of various drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular injections and physiotherapy. For the treatment of JIA is used several groups of drugs: NSAIDs, corticosteroids (CS), immunosuppressive drugs a...

Numerous new antifolate drugs have been developed in an attempt to overcome the potential mechanisms of tumor cell resistance to methotrexate, which can include decreased drug transport into cells; decreased polyglutamation, leading to increased drug efflux from cells; decreased drug affinity for folate-dependent enzymes; mutations of dihydrofolate reductase (DHFR), a key enzyme required for th...

We have used a microtiter assay to study the toxicity of various folate analogs in a series of cultured human cell lines that exhibit different degrees of resistance to methotrexate, an inhibitor of dihydrofolate reductase. These cells retain their sensitivity to the lipophilic antifolate BW301U despite the amplification of dihydrofolate reductase genes. Because the cell lines under investigati...

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...

We have compared the relative susceptibility of resting (GO) versus exponentially growing mouse fibroblasts (line 3T6) to methotrexate (MTX) cytotoxicity. Cultures of cells were exposed to different levels of MTX for various intervals. Cloning efficiencies of the cells were then determined in medium containing hypoxanthine and thymidine. We found that growing 3T6 cells exhibit time- as well as ...

5,10-dideaza-5,6,7,8-terrahydrofolic acid (DDATHF) is a potent antiproliferative agent in cell culture systems and in vivo in a number of murine and human xenograft tumors. In contrast to classical antifolates, which are dihydrofolate reductase inhibitors, DDATHF primarily inhibits GAR transformylase, the first folate-dependent enzyme along the pathway of de novo purine biosynthesis. The (6R) d...

background: cervical pregnancy is rare and dangerous form of ectopic pregnancy which can be treated surgically or conservatively. methotrexate is reasonable conservative option with high efficiency and acceptable level of side effects. aim of this paper is to present possible treatment option in case of methotrexate failure, still keeping the postulates of minimal invasive surgery. case:  we de...

background methotrexate is a folic acid antagonist that has been in clinical use for five decades. its use in patients with brain tumors is primarily confined to primary central nervous system lymphoma (pcnsl), in which it is the cornerstone of chemotherapy. objectives a selective and sensitive high-performance liquid chromatography-electrospray ionization-mass spectrometry method was developed...

objective: to evaluate the plasma creatine phosphokinase (cpk) level after a single injection of methotrexate (mtx) as a predictor of treatment success in ectopic pregnancy (ep). materials and methods: in this prospective study, seventy nine women older than 18 years treated with methotrexate for ectopic pregnancy were evaluated for cpk and β-subunit of human chorionic gonadotropin (βhcg) level...