Abstract | OBJECTIVE: METHODS: The survival of male Fischer 344 rats with intracranial 9L gliomas was measured after implantation of controlled-release polymers containing one of the following: no drug, BSO, 4-HC, or both BSO and 4-HC. The efficacy of intracranial 4-HC treatment was assessed with and without serial systemic intraperitoneal BSO injections. Tissue glutathione levels were measured in the brains, tumors, and livers of animals treated with intraperitoneal injections or local delivery of BSO. RESULTS: The median survival of animals treated with intracranial polymers containing 4-HC was 2.3 times greater than that of controls. This survival benefit was doubled by local delivery of BSO. In contrast, systemic BSO therapy did not improve survival time. In animals that were treated systemically, both liver and tumor glutathione levels were significantly lower than they were in control animals. In the locally treated animals, glutathione levels were reduced in the brain tumor but not in the liver. CONCLUSION: These results demonstrate that local but not systemic delivery of BSO enhances the antineoplastic effect of 4-HC in this rat 9L glioma model. In addition, because local delivery of BSO within the brain did not deplete glutathione levels systemically, this method of treatment may be safer than systemic administration of BSO.
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Authors | E P Sipos, T F Witham, R Ratan, P C Burger, J Baraban, K W Li, S Piantadosi, H Brem |
Journal | Neurosurgery
(Neurosurgery)
Vol. 48
Issue 2
Pg. 392-400
(Feb 2001)
ISSN: 0148-396X [Print] United States |
PMID | 11220384
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites, Antineoplastic
- Antineoplastic Agents
- Drug Combinations
- Drug Implants
- Buthionine Sulfoximine
- Cyclophosphamide
- Glutathione
- perfosfamide
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(administration & dosage, therapeutic use)
- Antineoplastic Agents
(administration & dosage, therapeutic use)
- Brain
- Brain Neoplasms
(drug therapy, metabolism, pathology)
- Buthionine Sulfoximine
(administration & dosage, therapeutic use)
- Cyclophosphamide
(administration & dosage, analogs & derivatives, therapeutic use)
- Drug Combinations
- Drug Implants
- Drug Synergism
- Glioma
(drug therapy, metabolism, pathology)
- Glutathione
(antagonists & inhibitors)
- Injections, Intraperitoneal
- Liver
(metabolism)
- Male
- Rats
- Rats, Inbred F344
- Reference Values
- Survival Analysis
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