Evidence map›Paper›PMID 32096068›Full record

ArticleJournal of neuro-oncology2020

The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma.

Frederic A Vallejo, Sumedh S Shah, Nicolas de Cordoba, Winston M Walters, Jeffrey Prince, Ziad Khatib, Ricardo J Komotar, Steven Vanni, Regina M Graham

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In one paragraph

Article in Journal of neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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  20. Current knowledges in pharmaconutrition: "Frontiers in nutrition · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Frederic A VallejoDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Sumedh S ShahDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Nicolas de CordobaDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Winston M WaltersDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Jeffrey PrinceDepartment of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL, 33146, USA.
Ziad KhatibNicklaus Children's Hospital, Miami, 3100 SW 62nd Ave, Miami, FL, 33155, USA.
Ricardo J KomotarDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Steven VanniDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
Regina M GrahamDepartment of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA. RGraham@med.miami.edu.ORCID http://orcid.org/0000-0003-0103-2971
University of Miami · USMiami Children's Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGlioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs).

methodsGene expression data was obtained from the online patient-histology database, GlioVis. GSC mitochondria morphology was examined by TEM. Cell viability and effect on GSC self-renewal was determined via MTS assay and neurosphere assay, respectively. Proteins were evaluated by Western Blot.

resultsEnzymes necessary for ketone catabolism (BDH1, OXCT1 and ACAT1) are significantly downregulated in adult and pediatric GBM. GSC mitochondrial ultrastructure suggested defects in oxidative phosphorylation. Treatment of both GBM and GSC cell lines resulted in dose-dependent decreases in viability in response to glycolytic inhibitor 2-deoxy-D-glucose (2-DG), and ketone body Acetoacetate (AA), but not β-hydroxybutyrate (βHB). AA induced apoptosis was confirmed by western blot analysis, indicating robust caspase activation and PARP cleavage. AA reduced neurosphere formation at concentrations as low as 1 mM. Combined treatment of low dose 2-DG (50 μM) with AA resulted in more cell death than either treatment alone. The effect was greater than additive at low concentrations of AA, reducing viability approximately 50% at 1 mM AA. AA was found to directly upregulate mitochondrial uncoupling protein 2 (UCP2), which may explain this potential drug synergism via multi-faceted inhibition of the glycolytic pathway.

conclusionTargeting the metabolic pathway of GBM via glycolytic inhibition in conjunction with ketogenic diet or exogenous ketone body supplementation warrants further investigation as a promising adjunctive treatment to conventional therapy.

Indexed as

Cell Proliferation3-Hydroxybutyric AcidAcetoacetatesAdultAntimetabolitesBrain NeoplasmsCell SurvivalChildDeoxyglucoseDrug Therapy, CombinationGlioblastomaGlycolysisHumansNeoplastic Stem CellsTumor Cells, Cultured3-Hydroxybutyric AcidAcetoacetatesacetoacetic acidAntimetabolitesDeoxyglucose2-deoxy-D-glucoseCancer stem cellsGlioblastomaGlycolysisKetogenic dietKetone bodiesMetabolism

Identifiers

PMID32096068
OpenAlexW3008847232

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.