Hepatocellular carcinoma (HCC) is a highly malignant cancer with poor prognosis. Inhibitors of EGFR and VEGFR for HCC treatment are currently under investigation. Gefitinib and vandetanib inhibit migration of HCC cells on Laminin-5 and Fibronectin, and invasion through matrigel. Both drugs inhibit p-EGFR after short time, while their efficacy on p-Erk1/2 and p-Akt is progressive and stable over time. PI3K/Akt and MEK/Erk1/2 inhibitors, inhibit migration and invasion as well as inducing de-phosphorylation of downstream effectors. Finally, both inhibitors, vandetanib and gefitinib down-regulated the secretion of matrix metalloproteases MMP-2 and MMP-9. All these biological effects seem to depend on the activity of gefitinib and vandetanib blocking activity towards p-EGFR mediated pathways.
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http://dx.doi.org/10.1016/j.canlet.2007.12.001 | DOI Listing |
Future Med Chem
January 2025
Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized.
Methods & Results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFR (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors.
Fundam Clin Pharmacol
February 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
Drug repurposing of well-established drugs to be targeted against lung cancer has been a promising strategy. Bosentan is an endothelin 1 (ET-1) blocker widely used in pulmonary hypertension. The current experiment intends to inspect the anticancer and antiangiogenic mechanism of bosentan targeting epidermal growth factor receptor (EGFR) /extra-cellular Signal Regulated Kinase (ERK) /c-Jun/vascular endothelial growth factor (VEGF) carcinogenic pathway.
View Article and Find Full Text PDFMedicina (Kaunas)
December 2024
Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Breast cancer is a heterogeneous disease characterized by a wide range of biomarker expressions, resulting in varied progression, behavior, and prognosis. While traditional biopsy-based molecular classification is the gold standard, it is invasive and limited in capturing tumor heterogeneity, especially in deep or metastatic lesions. Molecular imaging, particularly positron emission tomography (PET) imaging, offering a non-invasive alternative, potentially plays a crucial role in the classification and management of breast cancer by providing detailed information about tumor location, heterogeneity, and progression.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Department of Pulmonology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Japan.
: This research aims to investigate the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC), particularly focusing on the role of the epithelial-mesenchymal transition (EMT) within the tumor microenvironment (TME). : We employed an in vitro three-dimensional organoid model that mirrors the physiology of human lung cancer. These organoids consist of lung cancer cells harboring specific mutations, human mesenchymal stem cells, and human umbilical vein endothelial cells.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Ophthalmology, Muğla Training and Research Hospital, Mugla, Turkey.
Nowadays, the use of monoclonal antibodies to target angiogenic signalling pathways is common, but, unfortunately, the clinical activity of these agents is limited. Thus, the development of approaches targeting multiple pathways for anti-angiogenic effect will lead to increase the clinical benefit. For this purpose, oleuropein, hesperidin, piperine, proanthocyanidins and retinoic acid, which have previously been proven to be bioactive components, anti-angiogenic performances were experimentally tested in retinal pigment epithelial cells.
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