ArticleNeuro-oncology2019
Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Systematic Review of Epigenetic Therapies for Treatment of IDH-mutant Glioma.World neurosurgery · 2022Pooled it
- A systematic review of ongoing clinical trials in optic pathway gliomas.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Pooled it
- High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas.Medical gas research · 2027Review
- Glioma-induced DNMT3A reduction in microglia promotes an anti-tumoral phenotype.Cell death and differentiation · 2026Article
- Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Current and emerging therapies in IDH-mutant glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- The embedding of stress: mitophagy as a mechanism for the central nervous system (CNS) programming and lifelong disease vulnerability.Frontiers in cell and developmental biology · 2026Review
- Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.Neuro-oncology · 2025Article
- Human endogenous retroviruses (HERVs) associated with glioblastoma risk and prognosis.Cancer gene therapy · 2025Article
- Integrating Multiplex Immunohistochemistry and Machine Learning for Glioma Subtyping and Prognosis Prediction.MedComm · 2025Article
- Epigenetic crosstalk between stem cells and tumors: mechanisms and emerging perspectives.American journal of stem cells · 2025Review
- Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications.Frontiers in epigenetics and epigenomics · 2025Review
- Treatment of IDH-mutant glioma in the INDIGO era.NPJ precision oncology · 2024Review
- Review
- IDH inhibition in gliomas: from preclinical models to clinical trials.Nature reviews. Neurology · 2024Review
- Article
- RIPK3 deficiency blocks R-2-hydroxyglutarate-induced necroptosis in IDH-mutated AML cells.Science advances · 2024Article
- Epigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status.International journal of molecular sciences · 2023Article
- Therapies for IDH-Mutant Gliomas.Current neurology and neuroscience reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIsocitrate deyhydrogenase (IDH) mutant glioma comprises the majority of grades II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produce D-2-hydroxyglutarate (2HG), which interferes with cell reactions using alpha ketoglutarate, leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis.
methodsHuman IDH1 wild type (wt) and IDH1 R132H cell lines and patient-derived xenografts (PDXs) were used to evaluate the FDA-approved DNA demethylating agent 5-azacytidine (5-aza). Cell growth, protein and gene expression, chromatin immunoprecipitation, and nucleosome position assays were performed in 5-aza treated cells. To evaluate antitumor activity in vivo, 5-aza was administered alone and in combination with temozolomide (TMZ) in a PDX glioma model harboring IDH1 R132H mutation.
results5-Aza treatment has been found to reduce cell growth and increase expression of glial fibrillary acid protein (GFAP). Chromatin immunoprecipitation and nucleosome position assay showed that the mechanism of increased GFAP expression induction is associated with histone modification and nucleosome repositioning of the GFAP promoter, respectively. In vivo, 5-aza treatment extended survival in IDH1 R132H mutant but not in an IDH1 wt glioma model. Additionally, 5-aza enhances the therapeutic effect of the DNA damaging agent TMZ in both subcutaneous and orthotopic PDX models of IDH1 R132H mutant glioma.
conclusion5-Aza provided a survival benefit as a single agent but worked best in combination with TMZ in 2 different IDH1 R132H mutant glioma models.
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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.