ArticleJournal of neuro-oncology2012
Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor.
Article in Journal of neuro-oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Spatial Transcriptomics Meets Histochemistry: Insights from Glioblastoma as a Model System.Acta histochemica et cytochemica · 2026Review
- Novel 1,8-Naphthalimide Derivatives Inhibit Growth and Induce Apoptosis in Human Glioblastoma.International journal of molecular sciences · 2024Article
- TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?Endocrine pathology · 2023Article
- Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors.Frontiers in oncology · 2023Article
- Identification of core genes as potential biomarkers for predicting progression and prognosis in glioblastoma.Frontiers in genetics · 2022Article
- Coactosin-Like Protein (COTL1) Promotes Glioblastoma (GBM) Growth in vitro and in vivo.Cancer management and research · 2020Article
- MicroRNA-9 enhances chemotherapy sensitivity of glioma to TMZ by suppressing TOPO II via the NF-κB signaling pathway.Oncology letters · 2019Article
- Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice.Molecular neurodegeneration · 2018Article
- TRAF3IP2, a novel therapeutic target in glioblastoma multiforme.Oncotarget · 2018Article
- Cross-species transcriptional analysis reveals conserved and host-specific neoplastic processes in mammalian glioma.Scientific reports · 2018Article
- Over-expression of TOP2A as a prognostic biomarker in patients with glioma.International journal of clinical and experimental pathology · 2018Article
- Integrated mRNAseq and microRNAseq data analysis for grade III gliomas.Molecular medicine reports · 2017Article
- Identification of potential key genes associated with glioblastoma based on the gene expression profile.Oncology letters · 2017Article
- Glioblastoma-derived cellsBioscience reports · 2017Article
- Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy.International journal of clinical and experimental medicine · 2015Article
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- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
- Recurrent Glioblastomas Exhibit Higher Expression of Biomarkers with Stem-like Properties.Journal of neurosciences in rural practiceArticle
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.
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Registered trials
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