Frontiers | Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic M... - 0 views
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press-pulse therapy hyperbaric ketogenic metabolic therapy cancer ketogenic diet Glioblastoma glioblastoma multiforme HBOT nutrition
shared by Nathan Goodyear on 01 Apr 18
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The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
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the greatest therapeutic benefit for patients (near 1.0)
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The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
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Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
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Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
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The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
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A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
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Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
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therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
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we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
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EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
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Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
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HBOT to increase oxidative stress in the tumor cells
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As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
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Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
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Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
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KD (increased to 1,500 kcal/day at day 22
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the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
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Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
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This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
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Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
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less than 20% of younger adults generally survive beyond 24 months
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glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
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Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
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The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
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Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
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The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
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These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
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dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
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Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
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Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
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hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
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The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism
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Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.