Abstract | OBJECT: METHODS: RESULTS:
Thiamphenicol showed little effects on proliferation of 9L gliosarcoma cells in vitro and did not change glutamate transporter levels in these cells. However, when delivered locally in an experimental glioma model in rats, thiamphenicol dose dependently (10-5000 μM) significantly increased survival up to 7 days and concomitantly decreased tumor size from 46.2 mm(2) to 10.2 mm(2) when compared with lesions in nontreated controls. Furthermore, immunohistochemical and biochemical analysis of peritumoral tissue confirmed an 84% increase in levels of glutamate transporter protein and a 72% increase in the number of neuronal cells in the tissue adjacent to the tumor. CONCLUSIONS: These results show that increasing glutamate transporter expression in peritumoral tissue is neuroprotective. It suggests that glutamate transporter upregulation for the treatment of gliomas should be further investigated and potentially be part of a combination therapy with standard chemotherapeutic agents.
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Authors | Rita Sattler, Betty Tyler, Benjamin Hoover, Luke T Coddington, Violette Recinos, Lee Hwang, Henry Brem, Jeffrey D Rothstein |
Journal | Journal of neurosurgery
(J Neurosurg)
Vol. 119
Issue 4
Pg. 878-86
(Oct 2013)
ISSN: 1933-0693 [Electronic] United States |
PMID | 23909244
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Excitatory Amino Acid Transporter 2
- Slc1a2 protein, rat
- Thiamphenicol
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Topics |
- Animals
- Astrocytes
(drug effects, metabolism, pathology)
- Brain
(drug effects, metabolism, pathology)
- Brain Neoplasms
(drug therapy, metabolism, pathology)
- Cell Death
(drug effects)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Disease Models, Animal
- Excitatory Amino Acid Transporter 2
(genetics, metabolism)
- Gliosarcoma
(drug therapy, metabolism, pathology)
- Neurons
(drug effects, metabolism, pathology)
- Rats
- Rats, Inbred F344
- Thiamphenicol
(pharmacology, therapeutic use)
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