L -Amino acid oxidase (LOX) modulation of melphalan activity against intracranial glioma
| Autor: | Charles N. Pegram, Darell D. Bigner, Daniel Wellner, Henry S. Friedman, Gertrude B. Elion, Kate Moynihan, Owen W. Griffith, Craig J. Reist |
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| Rok vydání: | 1996 |
| Předmět: |
Male
musculoskeletal diseases Melphalan Cancer Research endocrine system diseases Transplantation Heterologous Mice Nude Phenylalanine Pharmacology Biology L-Amino Acid Oxidase Toxicology Antibodies Mice chemistry.chemical_compound In vivo Valine medicine Animals Humans Pharmacology (medical) Amino Acids Tyrosine Antineoplastic Agents Alkylating Antiserum Mice Inbred BALB C Methionine integumentary system Brain Neoplasms food and beverages Glioma enzymes and coenzymes (carbohydrates) Oncology chemistry Biochemistry Blood-Brain Barrier Female Amino Acid Oxidoreductases Leucine medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 39:179-186 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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 (P0.01) 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. |
| Databáze: | OpenAIRE |
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