background : leishmaniasis is an endemic disease in 88 countries. reports on leishmania drug resistance are growing in number. the mechanism of unresponsiveness against glucantime in iranian cutaneous leishmaniasis has not yet been characterized. to begin the first step in finding an anti- leishmania chemotherapy, we prepared recombinant l. major ptr1 enzyme and characterized its activity by en...

BACKGROUND Methotrexate is a chemotherapeutic agent used to treat a variety of cancers. However, the occurrence of resistance limits its effectiveness. Cytochrome c in its reduced state is less capable of triggering the apoptotic cascade. Thus, we set up to study the relationship among redox state of cytochrome c, apoptosis and the development of resistance to methotrexate in MCF7 human breast ...

An assay system was developed for the detection and classification of methotrexate resistance in fresh human leukemic cells. Mechanisms of resistance to be identified were: overexpression of dihydrofolate reduc Ã-ase, decreased cellular uptake of methotrexate, decreased affinity of dihydrofolate reducÃ-ase for methotrexate, decreased polyglutamylation of methotrexate, and low thymidylate syntha...

ABCG2 is an ATP-binding cassette transporter that confers resistance to various chemotherapeutic agents. Recent studies have established that an Arg (wild-type) to Gly mutation at amino acid 482 in ABCG2 alters substrate specificity. Here, we explored the role of this G482 mutation in antifolate resistance using a clinically relevant 4-hour drug exposure. Stable transfectants overexpressing the...

Development of drug resistance is a major factor that limits the effectiveness of chemotherapy treatments. In this study, we determined whether estradiol or its metabolites 2-, 4- and 16alpha-hydroxyestrone could enhance the development of methotrexate resistance in the breast carcinoma cell line, MCF-7. Cells were incubated with the estrogens at a concentration of 10(-8) M for 12 cell doubling...

ABCG2 is an ATP-binding cassette transporter that confers resistance to various chemotherapeutic agents. Recent studies have established that an Arg (wild-type) to Gly mutation at amino acid 482 in ABCG2 alters substrate specificity. Here, we explored the role of this G482 mutation in antifolate resistance using a clinically relevant 4-hour drug exposure. Stable transfectants overexpressing the...

Three human squamous carcinoma cell lines (FaDu, A253, and SQCC/Y1) were tested for sensitivity to methotrexate (MTX) and trimetrexate, a second generation folate antagonist in clinical trials. Two of the three cell lines (A253 and SQCC/Y1) showed inherent resistance to methotrexate, when cytotoxicity was evaluated after short term exposure (4 and 24 h). In contrast, all three cell lines were m...

Multidrug resistance (MDR) is a complex phenomenon in which many different genes regulating drug transport, cellular repair, detoxification and drug metabolism are involved. Nevertheless, in most drug resistant cell lines and cancer patients up-regulation of ABC-transporter genes such as MDR associated Protein (MRP1) gene could be at the basis of the drug resistance phenotype. We aimed to decre...

Drug resistance is a consequence of how most modern medicines work. Drugs exert pressure on cells that causes death or the evolution of resistance. Indeed, highly specific drugs are rendered ineffective by a single DNA mutation. In this study, we apply the drug methotrexate, which is widely used in cancer and rheumatoid arthritis, and perform evolution experiments on Baker's yeast to ask the di...

Two methotrexate-resistant sublines, CCRF-CEM R3/7 and CCRF-CEM R30/6, were selected from the human leukemia T-lymphoblast cell line, CCRF-CEM, after repeated exposures (7 and 6 times, respectively) for 24 h to constant concentrations (3 and 30 microM) of the drug. Analysis of the mechanism of resistance revealed no differences in levels of dihydrofolate reductase activity, its binding affinity...