The effect of methylcobalamin on 3H-methotrexate uptake by tumor and normal tissues of mice with mammary adenocarcinoma (Ca-755) was studied. Methylcobalamin stimulated the rate of 3H-methotrexate influx into the tumor and small intestine but did not change its influx into the spleen. The effect was dependent on the dose of methylcobalamin. Comparative analysis of the kinetic differences in 3H-methotrexate influx and efflux in tumor and susceptible host tissues revealed the optimal dose of methylcobalamin 0.01 mg/kg to improve the antitumor drug action.
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The reduced folate carrier gene is a novel selectable marker for recombinant protein overexpression.
Mol Pharmacol
September 2005
Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Folate cofactors are one-carbon donors essential for the biosynthesis of purines and thymidylate. Mammalian cells are devoid of folate biosynthesis and are therefore folate auxotrophs that take up folate vitamins primarily via the reduced folate carrier (RFC). In this study, we showed that the human RFC (hRFC) gene can serve as a novel selectable marker for the overproduction of recombinant proteins.
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Clin Cancer Res
March 1999
Department of Medical Oncology, University Hospital Vrije Universiteit, The Netherlands.
Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. In a panel of 13 nonselected human colon cancer cell lines, we evaluated the role of TS levels in sensitivity to 5-fluorouracil (5FU) and four folate-based TS inhibitors that have been introduced recently into the clinic: ZD1694 (Tomudex, Raltitrexed, TDX), GW1843U89 (GW), LY231514 (LY), and AG337 (Thymitaq, AG). Because the latter compounds have different transport and polyglutamylation characteristics, we also related these parameters with drug sensitivity, measured by the sulforhodamine B assay after 72 h of drug exposure.
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Biochem Pharmacol
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Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
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View Article and Find Full Text PDFRole of N-glycosylation in the structure and function of the methotrexate membrane transporter from CCRF-CEM human lymphoblastic leukemia cells.
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Developmental Therapeutics Program, Michigan Cancer Foundation, Detroit 48201.
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View Article and Find Full Text PDFIncreased expression and genomic organization of a folate-binding protein homologous to the human placental isoform in L1210 murine leukemia cell lines with a defective reduced folate carrier.
J Biol Chem
February 1994
Department of Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298.
This laboratory previously described an L1210 leukemia cell line (MTXrA) selected for resistance to methotrexate by virtue of impaired transport. In this line, the reduced folate carrier had unchanged affinity for methotrexate, was present at the cell surface in usual quantity, but did not deliver drug into the cell, indicative of a functional defect in the translocation process. In this study, we further characterize this cell line along with a subline (F2-MTXrA) selected for growth in low levels of folic acid.
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