ArticleCellular oncology (Dordrecht, Netherlands)2017
Inhibition of histone deacetylases sensitizes glioblastoma cells to lomustine.
Article in Cellular oncology (Dordrecht, Netherlands), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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
42 citing papers in PubMed, 62 citations in OpenAlex.
- Identification of novel genetic mutations for the treatment prognostication of canine lymphoma.NPJ precision oncology · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Key genes altered in glioblastoma based on bioinformatics (Review).Oncology letters · 2025Review
- USP39 promotes retinal pathological angiogenesis in retinopathy of prematurity by stabilizing SIRT2 expression through deubiquitination.International ophthalmology · 2025Article
- The Conjugation of Chlorambucil with 4-Phenylbutanoic Acid and Valproic Acid respectively for Enhancing Anti-tumor Activity.Current organic synthesis · 2025Article
- Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.Journal of cell science · 2024Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Metabolism in the progression and metastasis of brain tumors.Cancer letters · 2022Review
- Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression.Cell death & disease · 2022Article
- Article
- Genotoxic therapy and resistance mechanism in gliomas.Pharmacology & therapeutics · 2021Review
- Differential gene expression-based connectivity mapping identified novel drug candidate and improved Temozolomide efficacy for Glioblastoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment.World journal of stem cells · 2021Review
- Clinical Significance of Histone Deacetylase (HDAC)-1, -2, -4 and -6 Expression in Salivary Gland Tumors.Diagnostics (Basel, Switzerland) · 2021Article
- Review
- Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Increased activation of HDAC1/2/6 and Sp1 underlies therapeutic resistance and tumor growth in glioblastoma.Neuro-oncology · 2020Article
- The application of histone deacetylases inhibitors in glioblastoma.Journal of experimental & clinical cancer research : CR · 2020Review
- Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin.Cancers · 2020Review
- Selective Inhibition of HDAC1 by Macrocyclic Polypeptide for the Treatment of Glioblastoma: A Binding Mechanistic Analysis Based on Molecular Dynamics.Frontiers in molecular biosciences · 2020Article
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGlioblastoma (GBM) ranks among the deadliest solid cancers worldwide and its prognosis has remained dismal, despite the use of aggressive chemo-irradiation treatment regimens. Limited drug delivery into the brain parenchyma and frequent resistance to currently available therapies are problems that call for a prompt development of novel therapeutic strategies. While only displaying modest efficacies as mono-therapy in pre-clinical settings, histone deacetylase inhibitors (HDACi) have shown promising sensitizing effects to a number of cytotoxic agents. Here, we sought to investigate the sensitizing effect of the HDACi trichostatin A (TSA) to the alkylating agent lomustine (CCNU), which is used in the clinic for the treatment of GBM.
methodsTwelve primary GBM cell cultures grown as neurospheres were used in this study, as well as one established GBM-derived cell line (U87 MG). Histone deacetylase (HDAC) expression levels were determined using quantitative real-time PCR and Western blotting. The efficacy of either CCNU alone or its combination with TSA was assessed using various assays, i.e., cell viability assays (MTT), cell cycle assays (flow cytometry, FACS), double-strand DNA break (DSB) quantification assays (microscopy/immunofluorescence) and expression profiling assays of proteins involved in apoptosis and cell stress (Western blotting and protein array).
resultsWe found that the HDAC1, 3 and 6 expression levels were significantly increased in GBM samples compared to non-neoplastic brain control samples. Additionally, we found that pre-treatment of GBM cells with TSA resulted in an enhancement of their sensitivity to CCNU, possibly via the accumulation of DSBs, decreased cell proliferation and viability rates, and an increased apoptotic rate.
conclusionFrom our data we conclude that the combined administration of TSA and CCNU eradicates GBM cells with a higher efficacy than either drug alone, thereby opening a novel avenue for the treatment of GBM.
Indexed as
Identifiers
What OpenQuestion holds
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.