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Novel Approaches to Selective Treatments of Human Solid Tumors pp 125–131Cite as

Increasing the Efficacy of 5-Fluorouracil with Interferons: Preclinical, Clinical, and Pharmacokinetic Studies

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

Abstract

The interferons are a family of glycoproteins which possess potent antiviral, immunomodulatory, and antiproliferative effects in vivo 1. The interferons also additively or synergistically enhance the efficacy of many cytotoxic agents against a number of cultured human adenocarcinoma, squamous cell carcinoma, and lymphoid tumor cell lines in vivo 1. In particular, interferon-α synergistically augments the antineoplastic effect of 5-fluorouracil (5-FU) in cultured human colonic adenocarcinoma cell lines in vivo.2 At the cellular level, the interferons act in a variety of ways to augment the antineoplastic effect of 5-FU by: (1) increasing the activity of thymidine Phosphorylase 3, thereby augmenting the anabolism of 5-FU to its active metabolite, fluorodeoxyuridylate monophosphate, (2) enhancing inhibition of thymidylate synthase, the target enzyme of 5-FU, at the post-transcriptional level 4, (3) inhibiting thymidine salvage pathways 3, and (4) by enhancing 5-FU induced DNA damage 5.

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Authors and Affiliations

  1. Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York, USA

    Joseph A. Sparano & Scott Wadler

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  1. Joseph A. Sparano
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  2. Scott Wadler
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  1. Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York, USA

    Youcef M. Rustum

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© 1993 Springer Science+Business Media New York

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Sparano, J.A., Wadler, S. (1993). Increasing the Efficacy of 5-Fluorouracil with Interferons: Preclinical, Clinical, and Pharmacokinetic Studies. 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_14

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  • DOI: https://doi.org/10.1007/978-1-4615-2488-5_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6060-5

  • Online ISBN: 978-1-4615-2488-5

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