53. Basic Science

Title: ADJUVANT USE OF THE KETOGENIC DIET FOR THE TREATMENT OF MALIGNANT BRAIN TUMORS INHIBITS CYCLOOXYGENASE-2 EXPRESSION AND REDUCES TUMOR-ASSOCIATED EDEMA

Author: Adrienne C Scheck PhD
Co-authors Eric C. Woolf, Gregory Turner, Vikram D. Kodibagkar, Rohini Vidya Shankar, Mark C. Preul, Mohammed G. Abdelwahab, Julie A. Charlton. Phoenix, AZ Keywords: glioma, edema, cyclooxygenase 2, mouse model

Malignant gliomas are uniformly fatal despite treatment including surgery, chemotherapy and radiation. One source of morbidity is brain edema caused by tumor growth and/or treatment. This can have a variety of sequelae including headaches, seizures and steroid dependence. We previously used a bioluminescent intracranial mouse model of malignant glioma to demonstrate that a ketogenic diet (KD) extends survival following tumor implantation, and potentiates the therapeutic effects of radiation and chemotherapy. The KD also prevents the increased expression of Cyclooxygenase 2 (COX2) seen in tumors from animals fed standard rodent chow (SD). COX2 is a mediator of inflammation and we hypothesize that KD is reducing tumor-associated edema through its inhibition and concomitant downstream effects. Bioluminescence is a quantitative measure of live tumor cells and we have found that animals maintained on KD have more tumor-associated bioluminescence when they succumb! to their disease than do animals maintained on SD. Survival is a function of overall tumor burden consisting of the tumor and peritumoral edema. The increased bioluminescence in tumor from animals fed KD suggests that the diet may be reducing the contribution of peritumoral edema to the overall tumor burden. Taken together, our data demonstrates that metabolic alteration not only affects tumor bioenergetics, it alters the expression of genes involved in other aspects of tumor growth and therapy response. The adjuvant use of KD for brain tumor therapy may improve the patients? quality of life in addition to extending survival.

Supported by Students Supporting Brain Tumor Research and Arizona Biomedical Research Commission.