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furthermore, a complex network of signalling involving other receptors enhances the potency and endurance of c-MET downstream signalling Elevated c-MET expression/amplification has been associated with a poor clinical outcome in patients with gastro-oesophageal tumours, although conflicting reports exist with respect to a prognostic role of c-MET in colorectal cancer Structural studies of HGF and c-MET have yielded important results that paved the way for the development of anti-HGF and anti-c-MET monoclonal antibodies and specific or nonspecific c-MET tyrosine kinase inhibitors In contrast to the initial phase II studies, the phase III trials failed to show any clinical benefit from anti-HGF or anti-c-MET therapies in gastrointestinal tumours, even in patients with c-MET-positive disease Additional biomarkers should be sought, using techniques such as MET RNA in situ hybridization (ISH) and MET single/double silver ISH and 'omics'-based approaches to identify patients that are likely to derive maximal benefits from anti-HGF/c-MET therapies Abstract Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers

Protein oxidation causes odd protein structure and function, involving enzyme inactivation and distublance of cell signal transduction, straightly influencing the activity of fibroblasts and osteoblasts (Sharifi-Rad et al., 2020), ( Moreover, DNA damage activates stress response mechanisms within cells, possibly causing apoptosis or mutation, further compromising the health of gingival tissues ( 2.3.3 Depletion of antioxidant systems During the prolonged progression of chronic periodontitis, oxidative stress persists, causing depletion and imbalance of antioxidant systems (Shang et al., 2023)

10.1016/j.pathophys.2017.08.001 41 HosseinianS.Ebrahimzadeh BideskanA.ShafeiM

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