We previously showed that intrathecal administration of methotrexate slowed disability progression in multiple sclerosis (MS) patients with progressive disease. In general MS patients with progressive disease respond poorly to anti-inflammatory therapies. In order to better understand the mechanism by which methotrexate is protective in progressive MS, we analyzed its impact on the non-inflamma...

[8H]Methotrexate was metabolized mainly to 4-amino-4deoxy-lo-methylpteroic acid in resting cells of ZactobaciZZus casei and a small amount of methotrexate remained inside the cells after 24 hours of incubation. Preincubation of L. casei with methotrexate inhibited the incorporation of [3H]folic acid completely and I-5-formyl-[3H]tetrahydrofolic acid partially into pteroyloctaglutamate and incre...

SUMMARY Inhibition by Methotrexate of dihydrofolate reductase and of the incorporation of deoxynucleosides into DNA has been examined in three mouse ascites cell leukemias which had differ ences in uptake and sensitivity. Dihydrofolate reductase ac tivity in all cell lines was completely inhibited in less than five minutes after the optimal therapeutic dose of Methotrexate. The rate of recovery...

In protection experiments (5-formyltetrahydrofolate or 5-methyltetrahydrofolate added to cultures in vitro at the same time as methotrexate), 5-methyltetrahydrofolate af forded the same degree of protection as did formyltetrahydrofolate for phytohemagglutinin-stimulated peripheral blood lymphocytes and for methotrexate-resistant (R) and methotrexate-sensitive (S) sublines of CCRF-CEM. Either re...

While there is still no convincing evidence that methotrexate is of benefit in primary Sjögren's syndrome, the SLE evidence on this rheumatology anchor drug is substantial. In fact, there are randomised controlled trials showing the benefit for methotrexate on overall SLE activity, reduction in glucocorticoid doses, and effects on lupus arthritis and lupus skin manifestations. In addition, meth...

Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous ...

The antitumor effects of methotrexate against early leukemia L1210 were partially reversed by the coadministration of allopurinol in vivo, even though allopurinol did not alter the growth-inhibitory effects of methotrexate against L1210 cells in culture. These data suggest that this alteration in antitumor activity results from a decreased catabolism of preformed systemic purines by allopurinol...

OBJECTIVE To evaluate the achievement of comprehensive disease control (CDC) following 1 year of treatment with adalimumab+methotrexate versus methotrexate alone and whether early achievement of remission (at week 24 or 26) is associated with CDC at week 52 in patients with either early or established rheumatoid arthritis (RA). METHODS Post hoc analyses were conducted in three clinical studie...

Teniposide (VM-26) and etoposide (VP-16-213) were eval uated for their effects on methotrexate transport and metabo lism in Ehrlich ascites tumor cells in vitro. VM-26 (10 JUM)does not alter influx of methotrexate but slows efflux of the drug which leads to an increase in the steady-state level of ex changeable antifolate. VM-26 stimulation of net methotrexate transport occurs within 5 min of e...

The modulation of methotrexate polyglutamylation by L-asparaginase has been examined in mice bearing sublines of leukemia L5178Y that have different sensitivities to asparaginase. A single i.p. injection of 200 IU/kg of asparaginase completely inhibited ascites tumor cell growth in the parental L5178Y/S+ tumor for 120 h compared to 72 and 30 h in the L5178Y/S and L5178Y/S+/- sublines, respectiv...