Donna Boarman

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Drug therapy studies imply that Pneumocystis carinii and Toxoplasma gondii possess the enzymes necessary for de novo folate synthesis. To verify this, incorporation of [3H]paraaminobenzoic acid [( 3H]PABA) into reduced folates by P. carinii and T. gondii was investigated. Both organisms synthesized tritiated reduced folates. In P. carinii,(More)
Toxoplasma gondii is a common protozoan disease that often causes life-threatening disease, particularly among patients with the acquired immunodeficiency syndrome. This study demonstrates that the dihydropteroate synthase in T. gondii is kinetically distinct from the enzyme characterized from other sources and can be highly purified with a high yield using(More)
The antiproliferative effects and pharmacological interactions of 5-fluorouracil (5-FU) in combination with gamma interferon (IFN-gamma) were determined against the human colon carcinoma H630 cell line in vitro. H630 was 9-fold more resistant to 5-FU, as compared to a relatively sensitive human colon line (C1). IFN-gamma showed modest antiproliferative(More)
This report describes the intracellular metabolism of 5-formyltetrahydrofolate into the various one-carbon substituted folate and polyglutamate pools in a human breast (MCF-7) and colon (HCT 116) carcinoma cell line. Metabolism into the one-carbon substituted pools was found to be time and dose dependent over a concentration range up to 50 microM. A 3-fold(More)
We have studied the roles of 5,10-methylenetetrahydrofolate (5,10-methylene-H4PteGlu) depletion and dihydrofolate (H2PteGlu) accumulation in the inhibition of de novo thymidylate synthesis by methotrexate (MTX) in human MCF-7 breast cancer cells. Using both a high pressure liquid chromatography system and a modification of the(More)
Leucovorin and interferon are capable of modulating the cytotoxicity of fluorouracil (5-FU). Preclinical studies demonstrate that d,l-leucovorin is rapidly metabolized in human breast and colon cells into the various one-carbon substituted folate pools and to the polyglutamated state. While increases in intracellular folate pools are proportional to the(More)
Previous studies have suggested that metabolic inhibition by methotrexate (MTX) is multifactorial and that cytotoxicity can be reversed by the reduced folate leucovorin. In this report we investigated the mechanism of leucovorin rescue in the MCF-7 human breast cancer cell line. Cells were exposed to various concentrations of MTX (0.5, 1.0, 3.0, and 10.0(More)
Previous investigations have suggested that high-dose methotrexate with leucovorin rescue is a potentially useful strategy for overcoming antifolate resistance. Interactions between methotrexate (MTX) and leucovorin and their respective metabolites appear to occur at multiple intracellular sites, including dihydrofolate reductase (MTX/MTX polyglutamates(More)
Previous investigations have suggested that high-dose methotrexate with leucovorin rescue is a potentially useful strategy for overcoming antifolate resistance. Interactions between methotrexate (MTX) and leu covorin and their respective metabolites appear to occur at multiple intracellular sites, including dihydrofolate reducÃ-ase(MTX/MTX polyglutamates(More)
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