L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma.

Published

Journal Article

These studies evaluated the efficacy of sequential pretreatment with L-amino acid oxidase (LOX) and LOX antiserum in the modulation of melphalan activity against intracranial glioma in athymic nude mice. LOX produced statistically significant (P < 0.01) depletion of the large neutral amino acids isoleucine, leucine, methionine, phenylalanine, tyrosine, and valine in murine plasma at doses of 100 and 200 micrograms administered intravenously. Polyclonal anti-LOX antibody was successfully produced in mice, rabbits, and goats subsequent to immunization with LOX. Staphylococcal protein A-purified rabbit anti-LOX serum inhibited approximately 50% of LOX activity in vitro relative to control samples. This antiserum was used in vivo to inactivate LOX after it had depleted the large neutral amino acids, thereby preventing LOX-mediated catabolism of melphalan. Inoculation of three mice with rabbit anti-LOX serum after the treatment with LOX (100 micrograms) reduced LOX activity by 100%, 89%, and 100% at 6 h compared with reductions of 80%, 59%, and 52% over the same period in animals receiving LOX alone. In three separate studies using groups of eight to ten mice bearing intracranial human glioma xenografts, pretreatment with LOX followed by anti-LOX serum increased the antitumor activity of melphalan as compared with treatments with melphalan plus LOX, melphalan plus anti-LOX serum, or melphalan alone.

Full Text

Duke Authors

Cited Authors

  • Moynihan, K; Elion, GB; Pegram, C; Reist, CJ; Wellner, D; Bigner, DD; Griffith, OW; Friedman, HS

Published Date

  • January 1997

Published In

Volume / Issue

  • 39 / 3

Start / End Page

  • 179 - 186

PubMed ID

  • 8996517

Pubmed Central ID

  • 8996517

Electronic International Standard Serial Number (EISSN)

  • 1432-0843

International Standard Serial Number (ISSN)

  • 0344-5704

Digital Object Identifier (DOI)

  • 10.1007/s002800050557

Language

  • eng