EGFR and EGFRvIII Promote Angiogenesis and Cell Invasion in Glioblastoma: Combination Therapies for an Effective Treatment

Keller, Stefanie; Schmidt, Mirko H. H.

doi:10.3390/ijms18061295

Cited by 97 publications

(82 citation statements)

References 111 publications

(120 reference statements)

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“…The major reason that therapeutic treatments fail are due to the highly invasive nature of the tumor cells and the occurrence of increased angiogenesis [26]. GBM harbors a subpopulation of self-renewing, therapy-resistant cells, GICs.…”

Section: Discussionmentioning

confidence: 99%

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling

Long

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear. Methods: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells’ invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis. Results: High expression of Jagged1 in human glioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling. Conclusion: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs.

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Section: Discussionmentioning

confidence: 99%

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling

Long

Liu

et al. 2018

Cell Physiol Biochem

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“…This could be due to receptor interference and associations with multiple transduction pathways and proteins of invasion and angiogenesis regulation and the development of resistance mechanisms. Therefore, new therapies are focused on a combination of targeted gene therapy against EGFR and EGFRvIII and transduction pathways and proteins related to this pathway [22]. Recently new EGFR-targeted therapies have been proposed (e.g.…”

Section: Discussionmentioning

confidence: 99%

Retrospective and Randomized Analysis of Influence and Correlation of Molecular and Clinical Prognostic Factors in a Mono-Operative Series of 122 Patients with Glioblastoma Treated with STR or GTR

Salvati¹,

Bruzzaniti²,

Rilucenti³

et al. 2019

Preprint

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Glioblastoma is a solid, infiltrating and the most frequent highly malignant primary brain tumor. Our aim was to find the prognostic value of mutations of IDH1, MGMT, EGFR, p53, ATRX, Ki67 genes and the correlation between sex, age, presenting with seizures, number of interventions, extent of resection with Overall Survival (OS), Progression Free Survival (PFS) and Karnofsky performance status (KPS) score. A randomized retrospective analysis of 122 patients treated by a single operator at Sapienza University of Rome, was carried out. After surgery patients followed standard treatment Stupp protocol [6]. Exclusion criteria were: patients with primitive brainstem and spinal cord gliomas and patients who underwent partial resections (resection < 90%) and cases of brain biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried on by SPSS 25 ® (IBM) program. Results showed statistically significant survival increase in four groups: 1) patients treated with gross total resection (p< 0.03); 2) patients with methylated MGMT promoter (p<0.005); 3) patients with non Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: EGFR amplification or EGFRvIII mutation (p<0.035); 4) mutated IDH1/IDH2 (p<0.0161). Higher survival rates (but not statistically significant) were observed also in patients with: age < 75 years, Ki 67 <10%, lesions in non eloquent areas, ATRX gene mutation and presentation with seizures.

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“…The induction of neovascularization is a complex process that is dependent on multiple factors, including stem cells, intermediate signalling (nitric oxide‐cGMP), and growth factors (VEGF and EGF) . Signalling through EGFR is generally believed to be angiogenic in cancer . In our study, we found that injection of AG1478 (2 μg/μL, 2 μL) significantly reduced the formation of neovascular tufts (Figure D), indicating that EGFR signalling was causally linked to the development of neovascular tufts.…”

Section: Discussionmentioning

confidence: 99%

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Yang

Yan

et al. 2018

Clin Exp Pharma Physio

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Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

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EGFR and EGFRvIII Promote Angiogenesis and Cell Invasion in Glioblastoma: Combination Therapies for an Effective Treatment

Cited by 97 publications

References 111 publications

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling

Retrospective and Randomized Analysis of Influence and Correlation of Molecular and Clinical Prognostic Factors in a Mono-Operative Series of 122 Patients with Glioblastoma Treated with STR or GTR

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

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