Gefitinib modulates stress fibers and tubular-like structure formation and attenuates angiogenesis in an in vivo chicken model of chorioallantoic membrane angiogenesis

Lin, Tsung-Chieh

doi:10.1016/j.bbrc.2020.03.102

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…The chicken CAM assay is an established paradigm for the screening of angiogenesis modulators. Bevacizumab, sunitinib, thalidomide, and other therapeutically licensed antiangiogenic drugs inhibited angiogenesis in the CAM membrane of chicken embryos. , In addition, drugs with antiangiogenic activity in the CAM assay have demonstrated anticancer potential in clinical studies . Given the advantages over traditional in vitro and in vivo research models, the in ovo research paradigm was used in the current study to assess the angiogenesis modulating effect of saroglitazar.…”

Section: Discussionmentioning

confidence: 99%

“…The results identified EGFR as the strongest and most preferred target for saroglitazar in this interactome. The EGFR inhibitor geftininb inhibited the angiogenic process in the CAM membrane in a previous study, indicating the roles of EGFR expression and EGFR-mediated angiogenesis in the CAM . Therefore, to simultaneously assess EGFR expression and its effect on the angiogenic process, IHC staining of CAMs was performed.…”

Section: Discussionmentioning

confidence: 99%

“…The EGFR inhibitor geftininb inhibited the angiogenic process in the CAM membrane in a previous study, indicating the roles of EGFR expression and EGFR-mediated angiogenesis in the CAM. 39 Therefore, to simultaneously assess EGFR expression and its effect on the angiogenic process, IHC staining of CAMs was performed. In comparison to 2D cell culture models in which monolayer cell cultures are isolated systems and lack complex physiological conditions, the chicken embryo model is unique due to its accessible CAM membrane in which blood vessels grow in a three-dimensional framework, which is advantageous as it mimics the true biological complexities.…”

Section: Discussionmentioning

confidence: 99%

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Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach

et al. 2023

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Antidiabetic drugs that have a secondary pharmacological effect on angiogenesis inhibition may help diabetic patients delay or avoid comorbidities caused by angiogenesis including malignancies. In recent studies, saroglitazar has exhibited antiangiogenic effects in diabetic retinopathy. The current study investigates the antiangiogenic effects of saroglitazar utilizing the chicken chorioallantoic membrane (CAM) assay and then identifies its precise mode of action on system-level protein networks. To determine the regulatory effect of saroglitazar on the protein–protein interaction network (PIN), 104 target genes were retrieved and tested using an acid server and Swiss target prediction tools. A string-based interactome was created and analyzed using Cytoscape. It was determined that the constructed network was scale-free, making it biologically relevant. Upon topological analysis of the network, 37 targets were screened on the basis of centrality values. Submodularization of the interactome resulted in the formation of four clusters. A total of 20 common targets identified in topological analysis and modular analysis were filtered. A total of 20 targets were compiled and were integrated into the pathway enrichment analysis using ShinyGO. The majority of hub genes were associated with cancer and PI3-AKT signaling pathways. Molecular docking was utilized to reveal the most potent target, which was validated by using molecular dynamic simulations and immunohistochemical staining on the chicken CAM. The comprehensive study offers an alternate research paradigm for the investigation of antiangiogenic effects using CAM assays. This was followed by the identification of the precise off-target use of saroglitazar using system biology and network pharmacology to inhibit angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach

et al. 2023

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“…Gefitinib, a quinazoline derivative, is a selective receptor tyrosine kinase inhibitor with oral activity. 23) In 2003, the FDA approved gefitinib for the treatment of locally advanced or metastatic NSCLC patients who had received chemotherapy or had contraindications to chemotherapy. 9) Gefitinib was not considered to have significant cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Gefitinib Increases the Incidence of QT Prolongation in Patients with Non-Small Cell Lung Cancer

et al. 2023

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Gefitinib (GEF) may increase the risk of corrected QT prolongation (QTc). We aimed to evaluate whether gefitinib increases the risk of corrected QT interval (QTc) prolongation and analyze the associated risk factors.A total of 122 cases of advanced EGFR-mutated non-small cell lung cancer (NSCLC) who received gefitinib therapy from January 2015 to December 2020 were evaluated. The results of at least two resting 12-lead electrocardiogram before and after gefitinib treatment were obtained. The Bazett and Fridericia formulas were used to calculate the QTc interval, and the changes of QTc interval values before and after treatment were evaluated. The correlation between gefitinib and QTc interval prolongation and related risk factors were analyzed.After gefitinib-targeted therapy, 23 patients (18.9%) had a prolonged QTc interval, which increased from a mean of 446 ± 25 ms at baseline to 478 ± 18 ms (P < 0.001). Three of the patients met criteria for Grade 3 QTc prolongation in the common term V5.0 for clinical adverse events. Univariate analysis showed that age (ORR, 1.054; 95% confidence interval [CI], 1.003-1.107; P = 0.038), history of hypertension (ORR, 3.409; 95% CI,; P = 0.01), CCB medication history (ORR, 0.259; 95% CI, 0.094-0.712; P = 0.009), history of lung cancer surgery (ORR, 0.231; 95% CI, 0.064-0.829; P = 0.025), and baseline QT interval (ORR, 0.978; 95% CI, 0.964-0.993; P = 0.004) were important predictors of QTc interval prolongation in patients treated with gefitinib. The results of multivariate analysis showed that the history of lung cancer surgery and the baseline QT interval were important factors affecting QTc interval prolongation in patients treated with gefitinib.Gefitinib increases the risk of QTc prolongation in NSCLC patients, which may be more pronounced in patients with advanced age, hypertension, CCB therapy, lung cancer surgery, and a long QT interval at baseline.

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Plumbagin as a preferential lead molecule to combat EGFR-driven matrix abundance and migration of cervical carcinoma cells

Krishnamoorthy,

Sabanayagam,

Periyasamy

et al. 2024

Med Oncol

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Gefitinib modulates stress fibers and tubular-like structure formation and attenuates angiogenesis in an in vivo chicken model of chorioallantoic membrane angiogenesis

Cited by 4 publications

References 19 publications

Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach

Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach

Gefitinib Increases the Incidence of QT Prolongation in Patients with Non-Small Cell Lung Cancer

Plumbagin as a preferential lead molecule to combat EGFR-driven matrix abundance and migration of cervical carcinoma cells

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