ArticleThe American journal of pathology2010
Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers.
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Who cites it
193 citing papers in PubMed, 353 citations in OpenAlex.
- Mimicking tumor hypoxia in a glioblastoma-on-a-chip.Materials today. Bio · 2026Article
- Forming a Precise and Reproducible Hypoxic Tumor Microenvironment in Glioblastoma by High Cell Density Bioprinting.Advanced healthcare materials · 2026Article
- Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Dissociable perfusion chip (DPC): perfusable microfluidic chip for single-cell screening of anti-cancer drugs in live glioblastoma explants.Lab on a chip · 2026Article
- Spatial heterogeneity of malignant molecular markers in glioma revealed by stereotactic biopsy.Discover oncology · 2026Article
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
- XELOX combined with sintilimab and hyperbaric oxygen therapy for advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase Ib/II clinical trial.Frontiers in immunology · 2025Article
- Hyperbaric oxygen therapy as an immunosensitizing strategy in advanced gastric hepatoid adenocarcinoma: a case report.Frontiers in immunology · 2025Article
- Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications.Frontiers in epigenetics and epigenomics · 2025Review
- Genomic, epigenomic and transcriptomic landscape of glioblastoma.Metabolic brain disease · 2024Review
- Recapitulating Glioma Stem Cell Niches Using 3D Spheroid Models for Glioblastoma Research.Biosensors · 2024Review
- Glioblastoma microenvironment-from biology to therapy.Genes & development · 2024Review
- Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review.Cancers · 2024Review
- The Impact of A3AR Antagonism on the Differential Expression of Chemoresistance-Related Genes in Glioblastoma Stem-like Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease.Cellular & molecular biology letters · 2024Review
- Impact of hypoxia on the molecular content of glioblastoma-derived exosomes.Extracellular vesicles and circulating nucleic acids · 2024Review
- Evaluating circulating tumour cell enrichment techniques to establish an appropriate method for clinical application in glioblastomas.Frontiers in neurology · 2024Article
- Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons.International journal of molecular sciences · 2023Review
- The semaphorin 3A/neuropilin-1 pathway promotes clonogenic growth of glioblastoma via activation of TGF-β signaling.JCI insight · 2023Article
133 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia promotes the expansion of non-neoplastic stem and precursor cell populations in the normal brain, and is common in malignant brain tumors. We examined the effects of hypoxia on stem-like cells in glioblastoma (GBM). When GBM-derived neurosphere cultures are grown in 1% oxygen, hypoxia-inducible factor 1alpha (HIF1alpha) protein levels increase dramatically, and mRNA encoding other hypoxic response genes, such as those encoding hypoxia-inducible gene-2, lysyl oxidase, and vascular endothelial growth factor, are induced over 10-fold. Hypoxia increases the stem-like side population over fivefold, and the percentage of cells expressing CD133 threefold or more. Notch pathway ligands and targets are also induced. The rise in the stem-like fraction in GBM following hypoxia is paralleled by a twofold increase in clonogenicity. We believe HIF1alpha plays a causal role in these changes, as when oxygen-stable HIF1alpha is expressed in normoxic glioma cells CD133 is induced. We used digoxin, which has been shown to lower HIF protein levels in vitro and in vivo, to inhibit the hypoxic response. Digoxin suppressed HIF1alpha protein expression, HIF1alpha downstream targets, and slowed tumor growth in vivo. In addition, pretreatment with digoxin reduced GBM flank xenograft engraftment of hypoxic GBM cells, and daily intraperitoneal injections of digoxin were able to significantly inhibit the growth of established subcutaneous glioblastoma xenografts, and suppressed expression of vascular endothelial growth factor.
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Registered trials
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.