Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma

临床前 VM-M3 实验性胶质母细胞瘤中能量代谢的无毒靶向

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作者:Zachary M Augur, Catherine M Doyle, Mingyi Li, Purna Mukherjee, Thomas N Seyfried

Conclusion

This study provides evidence for a potentially novel therapeutic regimen of hyperbaric oxygen, oxaloacetate, and the KD-R for managing growth and progression of VM-M3/Fluc GBM.

Methods

Our proposed approach for inhibiting tumor metabolism involved various combinations of the KD-R, oxaloacetate (2 mg/g), hyperbaric oxygen, and TMZ (20 mg/kg). This combinatorial therapy was tested on adult VM/Dk mice bearing the VM-M3/Fluc preclinical GBM model grown orthotopically. After 14 days, tumor growth was quantified via bioluminescence. A survival study was performed and the data were analyzed and portrayed in a Kaplan Meier plot. Preliminary dosage studies were used and strict diet and drug administration was maintained throughout the study.

Results

The therapeutic effect of all treatments was powerful when administered under KD-R. The most promising survival advantage was seen in the two groups receiving oxaloacetate without TMZ. The survival of mice receiving TMZ was diminished due to its apparent toxicity. Among all groups, those receiving TMZ had the most significant reduction in tumor growth. The most powerful therapeutic effect was evident with combinations of these therapies.

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