Detail of "14110-97-5"

Reference

Some molecular characteristics of methotrexate resistance in human lymphoblastoid cells

Some molecular characteristics of methotrexate resistance in human lymphoblastoid cells. Niethammer, D.; Jackson, R. C. (Dep. Kinderheilkd., Ulm, Ger.). Mol. Base Malig., Sel. Pap. Int. Symp., 90-7. Edited by: Deutsch, Erwin; Moser, Kurt; Rainer, Hugo. Thieme: Stuttgart, Ger. (English) 1976. CODEN: 36KKAT. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacodynamics) The growth of W1-L2 human lymphoblastoid cells in continuous suspension culture with increasing concns. of methotrexate (I) [59-05-2] resulted in a variety of mechanisms of drug resistance. Membrane transport of folates and antifolates and the activity of folate dependent enzymes were studied. In these mutants, as in mouse leukemia cells, elevated cellular activities of dihydrofolate reductase [9002-03-3] were found; in some sublines activity increased over 200-fold. A relatively high frequency of mutants was found with impaired membrane transport of I; these mutants appeared rather late in the course of development of resistance, and in all these cases enzyme and transport mutations occurred together. Transport of 5-methyltetrahydrofolate [134-35-0], 5-formyltetrahydrofolic acid [58-05-9] and I in these cells shared a common pathway; this system was inhibited by p-chloromercuribenzene sulphonate Na salt (pCMS) [14110-97-5]. The concn. dependence of the pCMS effect was the same for I and 5-methyltetrahydrofolate transport. NaF and iodoacetate [64-69-7] did not change the rate of transport but increased the steady state cellular level of I. As in mouse tumor cells, folic acid [59-30-3] utilized a different uptake mechanism which was unaffected by pCMS. Serine hydroxymethyltransferase [9029-83-8], 10-formyltetrahydrofolate synthetase [9023-66-9] and 5,10-methylenetetrahydrofolate dehydrogenase [9029-14-5] were very active in this cell line. Thymidylate synthetase [9031-61-2] and serine hydroxymethyltransferase were both inhibited by I but these inhibitions were weak and probably did not contribute significantly to the cytotoxicity of I. Resistance involving impaired I transport during treatment of human malignant disease may be a more frequent phenomenon than in mouse leukemia, and may occur together with changes in tumor dihydrofolate reductase activity.

The synergistic effects of concurrent administration to rats of EDTA and sodium salicylate on the rectal absorption of sodium cefoxitin and the effects of inhibitors

The synergistic effects of concurrent administration to rats of EDTA and sodium salicylate on the rectal absorption of sodium cefoxitin and the effects of inhibitors. Nishihata, Toshiaki; Lee, Chia Shun; Rytting, J. Howard; Higuchi, Takeru (Pharm. Chem. Dep., Univ.Chemicals with cas numbers 630-60-4 and 35607-66-0 also play role. Kansas, Lawrence, KS 66045, USA). J. Pharm. Pharmacol., 39(3), 180-4 (English) 1987. CODEN: JPPMAB. ISSN: 0022-3573. DOCUMENT TYPE: Journal CA Section: 63 (Pharmaceuticals) Section cross-reference(s): 1 Plasma levels of cefoxitin (I) [35607-66-0], as enhanced by rectal coadministration of salicylate [69-72-7], were reduced by concurrent administration of <0.5 mg mL-1 N-ethylmaleimide (NEM) [128-53-0] or Na p-chloromercuriphenylsulfonate (p-CMP) [14110-97-5]. Concns. of these inhibitors above 1 mg mL-1 resulted in enhanced peak plasma values of I. This did not occur after coadministration with either di-Na EDTA [139-33-3] or polyoxyethylene-23 lauryl ether (POE) [9002-92-0]. Ouabain [630-60-4] and 2,4-dinitrophenol (DNP) [51-28-5] suppressed plasma I levels in the presence of salicylate and the enhancing effects of EDTA and POE when EDTA and POE were administered at low doses. At higher concns. of EDTA and POE, DNP had little effect, while ouabain had little effect on POE and only partially suppressed the effects of EDTA. I plasma concns. after coadministration with salicylate and POE together, or with EDTA and POE together, were about the same as expected from summing the plasma levels resulting from coadministration of each adjuvant individually at the same concns. However, combined administration of salicylate and EDTA with I yielded plasma I concns. which were much higher than expected from the sum of their individual actions. .