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The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft.

Publication ,  Journal Article
Rich, JN; Elion, GB; Wellner, D; Colvin, OM; Groothuis, DR; Hilton, JH; Schlageter, KE; Bigner, DD; Griffith, OW; Friedman, HS
Published in: Cancer Chemother Pharmacol
1995

We have previously shown that diet restriction-induced depletion of large neutral amino acids (LNAAs) in murine plasma to 46% of control significantly enhances intracranial delivery of melphalan without enhancing delivery to other organs. Studies have now been conducted to determine whether more substantial LNAA depletion could further enhance intracranial delivery of melphalan. Treatment with L-amino acid oxidase (LOX) significantly depleted murine plasma LNAAs: phenylalanine, leucine, and tyrosine (> 95%); methionine (83%); isoleucine (70%); and valine (46%). Experiments evaluating the intracellular uptake of melphalan and high-pressure liquid chromatography quantitation of melphalan metabolites revealed, however, that melphalan is rapidly degraded in the presence of LOX, and that the timing of the administration of melphalan following the use of LOX to deplete LNAAs is crucial. Conditions were found under which LOX-mediated degradation of melphalan was minimized and LNAA depletion was maximized, resulting in a potentiation of the antitumor effect of melphalan on human glioma xenografts in nude mice. Such potentiation could not be obtained using diet restriction alone.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1995

Volume

36

Issue

5

Start / End Page

379 / 384

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Survival Analysis
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Melphalan
  • Male
  • L-Amino Acid Oxidase
  • Glioma
 

Citation

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Rich, J. N., Elion, G. B., Wellner, D., Colvin, O. M., Groothuis, D. R., Hilton, J. H., … Friedman, H. S. (1995). The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft. Cancer Chemother Pharmacol, 36(5), 379–384. https://doi.org/10.1007/BF00686186
Rich, J. N., G. B. Elion, D. Wellner, O. M. Colvin, D. R. Groothuis, J. H. Hilton, K. E. Schlageter, D. D. Bigner, O. W. Griffith, and H. S. Friedman. “The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft.Cancer Chemother Pharmacol 36, no. 5 (1995): 379–84. https://doi.org/10.1007/BF00686186.
Rich JN, Elion GB, Wellner D, Colvin OM, Groothuis DR, Hilton JH, et al. The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft. Cancer Chemother Pharmacol. 1995;36(5):379–84.
Rich, J. N., et al. “The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft.Cancer Chemother Pharmacol, vol. 36, no. 5, 1995, pp. 379–84. Pubmed, doi:10.1007/BF00686186.
Rich JN, Elion GB, Wellner D, Colvin OM, Groothuis DR, Hilton JH, Schlageter KE, Bigner DD, Griffith OW, Friedman HS. The effect of L-amino acid oxidase on activity of melphalan against an intracranial xenograft. Cancer Chemother Pharmacol. 1995;36(5):379–384.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1995

Volume

36

Issue

5

Start / End Page

379 / 384

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Survival Analysis
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Melphalan
  • Male
  • L-Amino Acid Oxidase
  • Glioma