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

Publication ,  Journal Article
Moynihan, K; Elion, GB; Pegram, C; Reist, CJ; Wellner, D; Bigner, DD; Griffith, OW; Friedman, HS
Published in: Cancer Chemother Pharmacol
1997

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.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1997

Volume

39

Issue

3

Start / End Page

179 / 186

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Melphalan
  • Male
  • L-Amino Acid Oxidase
  • Humans
  • Glioma
 

Citation

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Moynihan, K., Elion, G. B., Pegram, C., Reist, C. J., Wellner, D., Bigner, D. D., … Friedman, H. S. (1997). L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma. Cancer Chemother Pharmacol, 39(3), 179–186. https://doi.org/10.1007/s002800050557
Moynihan, K., G. B. Elion, C. Pegram, C. J. Reist, D. Wellner, D. D. Bigner, O. W. Griffith, and H. S. Friedman. “L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma.Cancer Chemother Pharmacol 39, no. 3 (1997): 179–86. https://doi.org/10.1007/s002800050557.
Moynihan K, Elion GB, Pegram C, Reist CJ, Wellner D, Bigner DD, et al. L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma. Cancer Chemother Pharmacol. 1997;39(3):179–86.
Moynihan, K., et al. “L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma.Cancer Chemother Pharmacol, vol. 39, no. 3, 1997, pp. 179–86. Pubmed, doi:10.1007/s002800050557.
Moynihan K, Elion GB, Pegram C, Reist CJ, Wellner D, Bigner DD, Griffith OW, Friedman HS. L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma. Cancer Chemother Pharmacol. 1997;39(3):179–186.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1997

Volume

39

Issue

3

Start / End Page

179 / 186

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Melphalan
  • Male
  • L-Amino Acid Oxidase
  • Humans
  • Glioma