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Novel Approaches to Selective Treatments of Human Solid Tumors pp 133–142Cite as

Enhanced Cytotoxicity of 5-Fluorouracil Combined with [6RS]Leucovorin and Recombinant Human Interferon-α2a in Colon Carcinoma Cells

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 339))

Abstract

We had proposed previously that one mechanism of intrinsic resistance to 5-fluorouracil (FUra) in colon adenocarcinomas was suboptimal concentrations of intracellular 5,10-methylenetetrahydrofolate (CH2-H4PteGlun).1 Whereas the concentration of this reduced folate may not be rate limiting for thymidylate synthesis de novo, it may be suboptimal to allow maximal interaction between the FUra metabolite, 5-fluorodeoxyuridylate (FdUMP), and thymidylate synthase.1–5 Supplementation with a reduced folate, therefore, elevates intracellular levels of CH2-H4PteGlun and enhances the rate of formation or stabilization of the ternary complex. In human colon tumor xenografts, pools of CH2-H4PteGlun and H4PteGlun expanded by 2- to 5-fold in response to 24 hr infusions of [6RS]leucovorin ([6RS]LV), elevating species containing from 2 to 5 glutamate residues.6’7

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Authors and Affiliations

  1. Department of Biochemical and Clinical Pharmacology, St. Jude Children’s Research Hospital, Memphis, TN, 38101, USA

    Janet A. Houghton, David A. Adkins & Peter J. Houghton

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  1. Janet A. Houghton
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  2. David A. Adkins
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  1. Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York, USA

    Youcef M. Rustum

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Houghton, J.A., Adkins, D.A., Houghton, P.J. (1993). Enhanced Cytotoxicity of 5-Fluorouracil Combined with [6RS]Leucovorin and Recombinant Human Interferon-α2a in Colon Carcinoma Cells. In: Rustum, Y.M. (eds) Novel Approaches to Selective Treatments of Human Solid Tumors. Advances in Experimental Medicine and Biology, vol 339. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2488-5_15

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  • DOI: https://doi.org/10.1007/978-1-4615-2488-5_15

  • Publisher Name: Springer, Boston, MA

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