The role of endothelin and RAS/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications.

Systemic sclerosis (SSc) is a disease of connective tissue with high rate of morbidity and mortality highlighted by extreme fibrosis affecting various organs such as the dermis, lungs, and heart. Until now, there is no specific cure for the fibrosis occurred in SSc disease. The SSc pathogenesis is yet unknown, but transforming growth factor beta (TGF-ß), endothelin-1 (ET-1), and Ras-ERK1/2 cascade are the main factors contributing to the tissue fibrosis through extracellular matrix (ECM) accumulation. Several studies have hallmarked the association of ET-1 with or without TGF-ß and Ras-ERK1/2 signaling in the development of SSc disease, vasculopathy, and fibrosis of the dermis, lungs, and several organs. Accordingly, different clinical and experimental studies have indicated the potential therapeutic role of ET-1 and Ras antagonists in these situations in SSc. In addition, ET-1 and connective tissue growth factor (CTGF) as a cofactor of the TGF-ß cascade play a substantial initiative role in inducing fibrosis. Once initiated, TGF-ß alone or in combination with ET-1 and CTGF can activate several kinase proteins such as the Ras-ERK1/2 pathway that serve as the fundamental factor for developing fibrosis. Furthermore, Salirasib is a synthetic small molecule that is able to inhibit all Ras forms. Therefore, it can be used as a potent therapeutic factor for fibrotic disorders. So, this review discusses the role of TGF-ß/ET-1/Ras signaling and their involvement in SSc pathogenesis, particularly in its fibrotic situation.

Hepatitis C virus in patients with squamous cell carcinoma of the head and neck in Iran: is there any relation?

Recently, some studies have noticed a large number of patients with squamous cell carcinoma of the head and neck (SCCHN), who are infected with hepatitis C virus (HCV). The aim of this study is to determine the prevalence of HCV in these patients in our population. Patients with SCCHN in four tertiary centers in different regions of Iran were checked for HCV. The prevalence of HCV in 107 patients diagnosed with head and neck squamous cell carcinoma was 0.9%, which has no significant difference with its prevalence in normal population. It seems that HCV at least in Iran could not be considered as a risk factor for SCCHN.