ArticleMed (New York, N.Y.)2022
Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment.
Article in Med (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Melatonin Attenuates Heat Stress-Induced Metabolic Labeling Remodeling in Primary Goat Sertoli Cells.Veterinary sciences · 2026Article
- GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells.Nature cancer · 2026Article
- 18F-FDG-PET/CT-negative gastric cancer employs glutamine-based gluconeogenesis and fatty acid oxidation to support tumor growth.Cell death & disease · 2026Article
- NF-κB and STAT3 signaling uniquely stratify survival in female glioblastoma patients.iScience · 2026Article
- Steroid-dependent metabolic rewiring reveals novel therapeutic and imaging approaches for glioblastoma.Science advances · 2026Article
- Daily locomotor activity declines with tumor growth and disease progression in glioblastoma.JCI insight · 2026Article
- Spatiotemporal and metabolic heterogeneity of tumor-associated macrophages in glioblastoma: from single-cell insights to therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- The expression pattern and prognostic relevance of p120-catenin, COL4A2 and SOX10 in glioma.Frontiers in oncology · 2026Article
- Global, regional, and national burden of brain and central nervous system cancer in children and adolescents, 1990-2021: A systematic analysis of the Global Burden of Disease study 2021.Pediatric investigation · 2025Article
- High-Resolution Mapping of Tumor and Peritumoral Glutamate and Glutamine in Gliomas Using 7-T MRSI.Radiology. Imaging cancer · 2025Article
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- Recognition of cancer chemotherapy adverse effect by patients: a cross-sectional study from Palestine.BMC cancer · 2025Article
- Sex-related changes in lactate dehydrogenase A expression differently impact the immune response in melanoma.The FEBS journal · 2025Article
- GLIO-Select: Machine Learning-Based Feature Selection and Weighting of Tissue and Serum Proteomic and Metabolomic Data Uncovers Sex Differences in Glioblastoma.International journal of molecular sciences · 2025Article
- Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.Neuro-oncology · 2025Article
- The global, regional, and national brain and central nervous system cancer burden and trends from 1990 to 2021: an analysis based on the Global Burden of Disease Study 2021.Frontiers in neurology · 2025Article
- Impact of Sex Hormones on Glioblastoma: Sex-Related Differences and Neuroradiological Insights.Life (Basel, Switzerland) · 2024Review
- Volumetric body composition analysis of the Cancer Genome Atlas reveals novel body composition traits and molecular markers Associated with Renal Carcinoma outcomes.Scientific reports · 2024Article
- Metabolic Characteristics of Gut Microbiota and Insomnia: Evidence from a Mendelian Randomization Analysis.Nutrients · 2024Article
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBrain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue.
methodsUsing positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity.
findingsWe found that male glioblastoma surgical specimens are enriched for amino acid metabolites, including glutamine. Fluoroglutamine PET imaging analyses showed that gliomas in affected male individuals exhibit significantly higher glutamine uptake. These sex differences were well modeled in murine transformed astrocytes, in which male cells imported and metabolized more glutamine and were more sensitive to glutaminase 1 (GLS1) inhibition. The sensitivity to GLS1 inhibition in males was driven by their dependence on glutamine-derived glutamate for α-ketoglutarate synthesis and tricarboxylic acid (TCA) cycle replenishment. Females were resistant to GLS1 inhibition through greater pyruvate carboxylase (PC)-mediated TCA cycle replenishment, and knockdown of PC sensitized females to GLS1 inhibition.
conclusionOur results show that clinically important sex differences exist in targetable elements of metabolism. Recognition of sex-biased metabolism may improve treatments through further laboratory and clinical research.
fundingThis work was supported by NIH grants, Joshua's Great Things, the Siteman Investment Program, and the Barnard Research Fund.
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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.