ArticleNeuro-oncology2013
Implications of Dll4-Notch signaling activation in primary glioblastoma multiforme.
Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review.World journal of surgical oncology · 2022Pooled it
- Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma.Oncogene · 2026Article
- Targeting NOTCH-immune crosstalk in gliomas: from mechanisms to therapeutics.Frontiers in oncology · 2026Review
- CaMKK2 as a therapeutic target to combat metastasis in glioblastoma.Molecular biology reports · 2025Review
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- Exploring the Dual Roles of Neural Stem Cells in Glioblastoma: Therapeutic Implications and Opportunities.Current stem cell research & therapy · 2025Review
- Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024Review
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- Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.Heliyon · 2023Review
- Development and validation of an immune infiltration/tumor proliferation-related Notch3 nomogram for predicting survival in patients with primary glioblastoma.Frontiers in genetics · 2023Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- Monocentric evaluation of Ki-67 labeling index in combination with a modified RPA score as a prognostic factor for survival in IDH-wildtype glioblastoma patients treated with radiochemotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2022Article
- Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma.Cells · 2022Review
- Characterization of Temozolomide Resistance Using a Novel Acquired Resistance Model in Glioblastoma Cell Lines.Cancers · 2022Article
- POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling.Journal of bioenergetics and biomembranes · 2021Article
- Contradictory Effect of Notch1 and Notch2 on Phosphatase and Tensin Homolog and its Influence on Glioblastoma Angiogenesis.Galen medical journal · 2021Article
- Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by massive neovascularization, necrosis, and intense resistance to therapy. Deregulated Notch signaling has been implicated in the formation and progression of different malignancies. The present study attempted to investigate the activation status of Dll4-Notch signaling in primary human GBM and its association with vascular and clinical parameters in patients.
methodsMajor components of Dll4-Notch signaling were examined by real-time reverse-transcription polymerase chain reaction (PCR), Western blotting, and immunohistochemistry in GBM (n = 26) and control (n = 11) brain tissue. The vascular pattern (VP) and microvascular density (MVD) were analyzed after laminin immunostaining. O6-Methylguanine-methyltransferase (MGMT) promoter methylation in GBM samples was detected by methylation-specific PCR.
resultsThe mRNA levels of Dll4, Jagged1, Notch1, Notch4, Hey1, Hey2, Hes1, and VEGF were 3.12-, 3.58-, 3.37-, 5.77-, 4.89-, 3.13-, 6.62-, and 32.57-fold elevated, respectively, in GBM samples, compared with the controls. Western blotting revealed a 4-, 3.7-, and 45.6-fold upregulation of Dll4, Notch1, and Hey1, respectively, accompanied by a downregulation of PTEN expression and an increase in the expression of p-Akt and VEGF. Immunostaining located the immunoreactivity of Dll4 and Notch1 in endothelial cells, microglia/macrophages, tumor cells, and astrocytes. Furthermore, the upregulation of Dll4-Notch signaling components was correlated to a low MVD and was potentially related to a classic VP, tumor edema, and MGMT promoter methylation.
conclusionsThe upregulation of Dll4-Notch signaling components was found in a subset of GBM samples and was associated with some angiogenic and clinical parameters. These findings highlight this signaling pathway as a potential therapeutic target for patients with GBM who show an activation of Dll4-Notch signaling.
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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.