Advertisement

Modulation of Arabinosyladenine Metabolism by 2′-Deoxycoformycin in the Therapy of Human Acute Leukemia

  • W. Plunkett
  • B. Nowak
  • L. G. Feun
  • R. S. Benjamin
  • M. Keating
  • E. J. Freirich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Arabinosyladenine (araA) is a functional analog of deoxy-adenosine that exhibits antiviral activity but only weak antitumor activity in humans. The therapeutic efficacy of araA against human malignancies is known to be limited by its deamination to arabinosylhypoxanthine by adenosine deaminase. Although the likelihood of increasing the activity of araA after inhibition of adenosine deaminase had been speculated upon, it was not until potent adenosine deaminase inhibitors such as 2′-deoxyco-formycin (dCF) became available that the potential for such combination chemotherapy could be evaluated. It is now well established that both the toxicity to cells in culture and therapeutic activity of araA in tumor-bearing mice are increased by coadministration with pharmacologically active, but otherwise nontoxic doses of a deaminase inhibitor (1–3)

Keywords

Leukemic Cell Adenosine Deaminase Cellular Concentration Bolus Infusion Functional Analog 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. Plunkett, and S.S. Cohen, Cancer Res. 35:1547–1554, 1975.PubMedGoogle Scholar
  2. 2.
    C.E. Cass and T. AuYeung, Cancer Res. 36:1508–1513, 1976.Google Scholar
  3. 3.
    G.A. LePage, L.S. Worth and A.P. Kimball, Cancer Res. 36: 1481–1485, 1976.PubMedGoogle Scholar
  4. 4.
    W. Plunkett, R.S. Benjamin, M.J. Keating and E.J Freireich, Cancer Res. 42: 2092–2096, 1982.PubMedGoogle Scholar
  5. 5.
    R.A. Dicioccio and B.I.S. Srivastava, Europ. J. Biochem. 79: 411–418, 1977.PubMedCrossRefGoogle Scholar
  6. 6.
    R. Hartwick, A. Jeffries, A. Krstulovic, and P.R. Brown, J. Chrom. Sci. l6:427–435, 1978.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • W. Plunkett
    • 1
  • B. Nowak
    • 1
  • L. G. Feun
    • 1
  • R. S. Benjamin
    • 1
  • M. Keating
    • 1
  • E. J. Freirich
    • 1
  1. 1.Department of Developmental TherapeuticsThe University of Texas System Cancer Center M.D. Anderson Hospital and Tumor InstituteHoustonUSA

Personalised recommendations