Background:Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. Objective: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficac...

Patients with acute leukemia were given repeated cycles consisting of infusions of methotrexate followed by "rescue" with folinic acid. Peripheral blood leukemic cells were harvested from patients before cyclical treatment, and the rates of incorporation of thymidine and of deoxyuridine into deoxyribonucleic acid (DNA) were measuared in vitro. There was no relationship between the pretreatment ...

The biochemical factors determining resistance to the antifolate, methotrexate, were quantitatively evaluated for a methotrexate-resistant L1210 cell line. The concentration needed for 50% inhibition of C3H]deoxyuridine incorporation into DNA was increased 60-fold, as compared to a sensitive cell line. Properties of the membrane transport system for methotrexate were unchanged. Dihydrofolate re...

Dihydrofolate reductase (DHFR) cDNA sequences were isolated from a methotrexate-resistant mouse L5178Y cell line previously shown to contain methotrexate-resistant dihydrofolate reductase enzyme activity. Specifically-primed reverse transcription products were amplified using the polymerase chain reaction and then cloned into a mammalian expression plasmid. Candidate clones were identified by r...

The effect of hepatocarcinogen administration in vivo on the induction of pleiotropic drug resistance was studied in primary monolayer cultures of adult rat hepatocytes using a cytotoxicity assay in vitro. Dietary 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, aflatoxin B1, ethionine, and diethylnitrosamine rapidly induced resistance to doses of Adriamycin, methotrexate, cyclohexim...

Chinese hamster ovary (CHO) cells, maintained and treated in log-phase growth, are extremely sensitive to Adniamycin but are very resistant to methotrexate-induced cell killing. The survival response to Adniamycin is biphasic, with the sensitive population showing a D0 of 0.08 pg/mI for 1 hr, while essen tially no cell killing is produced by methotrexate treatments of up to 500 @.tg/mI for eith...

The rate of dihydrofolate reductase synthesis in the AT3000 line of methotrexate-resistant murine Sarcoma 180 cells is approximately 200to 250-fold greater than that of the sensitive, parental line. We have purified cDNA sequences complementary to dihydrofolate reductase mRNA and subsequently used this probe to quantitate dihydrofolate reductase mRNA and gene copies in each of these lines. Anal...

The rate of dihydrofolate reductase synthesis in the AT3000 line of methotrexate-resistant murine Sarcoma 180 cells is approximately 200to 250-fold greater than that of the sensitive, parental line. We have purified cDNA sequences complementary to dihydrofolate reductase mRNA and subsequently used this probe to quantitate dihydrofolate reductase mRNA and gene copies in each of these lines. Anal...

conclusions single dose therapy of mtx has sufficient power and efficacy in the treatment of ectopic pregnancy, however in patients with higher serum level of β-hcg, the successful treatment increases by using double dose method. using double dose also could decrease the necessity of operation, re-administration of mtx, and duration of hospitalization. results results showed that the rate of su...