Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy
| Autor: | Lawrence Karl Olson, Kenneth A. Schwartz, Howard T. Chang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Medicine (miscellaneous) Biology PKM2 Internal medicine Glioma medicine BDH2: 3-hydroxybutyrate dehydrogenase 2 Anaplastic Oligoastrocytoma OXCT1 Nutrition and Dietetics Research PKM2: Pyruvate kinase M2 isoform medicine.disease HK2: Hexokinase-II Endocrinology Cancer research Immunohistochemistry BDH1: 3-hydroxybutyrate dehydrogenase 1 OXCT1: Succinyl CoA: 3-oxoacid CoA transferase 1 (SCOT EC 2.8.3.5 locus symbol OXCT) Energy source ACAT1: acetyl-CoA acetyltransferase 1 Ketogenic diet Anaplastic astrocytoma |
| Zdroj: | Nutrition & Metabolism |
| ISSN: | 1743-7075 |
| DOI: | 10.1186/1743-7075-10-47 |
| Popis: | Background Recent studies in animal models, based on the hypothesis that malignant glioma cells are more dependent on glycolysis for energy generation, have shown promising results using ketogenic diet (KD) therapy as an alternative treatment strategy for malignant glioma, effectively starving glioma cells while providing ketone bodies as an energy source for normal neurons and glial cells. In order to test this treatment strategy in humans, we investigated the relative expression of several key enzymes involved in ketolytic and glycolytic metabolism in human anaplastic glioma (WHO grade III) and glioblastoma (GBM, WHO grade IV). Methods Immunohistochemistry was performed on formalin fixed paraffin embedded sections from 22 brain biopsies (17 GBM, 3 anaplastic astrocytoma and 2 anaplastic oligoastrocytoma) using antibodies raised against glycolytic and ketolytic enzymes. The glycolytic enzymes included hexokinase-II (HK2) and pyruvate kinase M2 isoform (PKM2). The ketone body metabolic enzymes included: succinyl CoA: 3-oxoacid CoA transferase (OXCT1), 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and BDH2), and acetyl-CoA acetyltransferase 1 (ACAT1). The immunoreactivities were graded using a semi-quantitative scale based on the percentage of positive cells: POS (>20%), LOW (5-20%), and very low (VLOW) ( |
| Databáze: | OpenAIRE |
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