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Endothelium-derived relaxing factors: a focus on endothelium-derived hyperpolarizing factor(s).
- J. McGuire, H. Ding, C. Triggle
- Chemistry, Medicine
- Canadian journal of physiology and pharmacology
- 1 June 2001
There is no agreement as to the nature of the cellular processes that mediates the non-NO/PGI2 mediated hyperpolarization of vascular smooth muscle cells, but an attractive hypothesis is that EDH is mediated via both chemical and electrical transmissions. Expand
Anticancer antifolates: current status and future directions.
- J. McGuire
- Biology, Medicine
- Current pharmaceutical design
- 30 November 2003
Detailed examination of the mechanisms of cytotoxicity and selectivity of MTX showed that inhibition of both dTMP synthesis and de novo purine synthesis, secondary to DHFR inhibition, led to DNA synthesis inhibition and subsequent cell death; inhibition of other folate-dependent pathways did not appear necessary for cell death. Expand
Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products.
- J. McGuire, P. Hsieh, J. Coward, J. Bertino
- Medicine, Chemistry
- The Journal of biological chemistry
- 25 June 1980
Inhibition by the pentaglutamate derivative offers a means by which folylpolyglutamates could regulate their own synthesis and indicate that the predominant chain length of folates in rat liver may be determined solely by the substrate specificity of the rat liver synthetase. Expand
Enzymatic synthesis and function of folylpolyglutamates
The most universal functions of folylpolyglutamates appear to be as the actual cofactors in vivo for folate dependent enzymes, as inhibitors of folatedependent enzymes for which they are not substrates, and to increase retention of folates after they are transported into cells as monoglutamate. Expand
Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug.
This is the first example of a cell line which displays resistance which is solely attributable to defective methotrexate polyglutamate synthesis, and the development of resistance to metotrexate was associated with a marked decrease in the intracellular level of methotRexate polyGLutamates. Expand
Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7 breast cancer cell line is attributable to enhanced energy-dependent drug efflux.
The data suggest that a novel MTX-specific efflux pump may be involved in this unusual cross-resistance phenotype, and members of the MRP protein family of transport proteins, which had previously been implicated in MTX resistance, were not found to be overexpressed in the MCF7/MX cells. Expand
The endothelium in health and disease--a target for therapeutic intervention.
- C. Triggle, M. Hollenberg, +9 authors Malarvannan Pannirselvam
- Journal of smooth muscle research = Nihon…
- 1 December 2003
The administration of tetrahydrobiopterin, an important co-factor for nitric oxide synthase (NOS) partially restores endothelial function in leptin-deficient mice (db/db) with spontaneous type II diabetes, as well as in human vascular tissue harvested for coronary artery bypass grafting (CABG). Expand
2-Furoyl-LIGRLO-amide: A Potent and Selective Proteinase-Activated Receptor 2 Agonist
- J. McGuire, M. Saifeddine, C. Triggle, Kimberly Sun, M. Hollenberg
- Biology, Medicine
- Journal of Pharmacology and Experimental…
- 1 June 2004
2-furoyl-LI-GRLO-NH2 represents the most potent and selective activator of PAR2 in biological systems described to date. Expand
Enzymatic synthesis of polyglutamate derivatives of 7-hydroxymethotrexate.
It was shown that the relative substrate activity of folate analogs for folylpolyglutamate synthetase is dependent on the source of the enzyme, and it was proposed that 7-hydroxymethotrexate polyglutamates may be formed by initial hydroxylation of methotrexate and subsequent polyglUTamate formation or by direct hydroxYLation of meethotrexates polygluttamates. Expand
Design, synthesis, and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent.
- A. Gangjee, J. Yu, +4 authors S. Queener
- Chemistry, Medicine
- Journal of medicinal chemistry
- 13 September 2000
Metabolite protection studies and folylpoly-gamma-glutamate synthetase studies suggest that the antitumor activity of 3a against the growth of tumor cells in culture is a result of dual inhibition of TS and DHFR. Expand