Epidermal Growth Factor Receptor's Function in Cutaneous Squamous Cell Carcinoma and Its Role as a Therapeutic Target in the Age of Immunotherapies.

OPINION STATEMENT: Recent studies have evidenced the potential of combining anti-EGFR therapies with anti-PD-1/PD-L1 checkpoint therapies. Both anti-EGFR and anti-PD-1/PD-L1 have been separately tested in the treatment of cutaneous SCC (cSCC). Here, we review recent data on EGFR in the context of cancer progression, as a prognostic and as a therapeutic target in cSCC. Anti-EGFR/checkpoint immunotherapy and other combination therapy approaches are discussed. With the advent of immunotherapy, EGFR is still a valid cSCC target.

Effect of eosinophil cationic protein on human oral squamous carcinoma cell viability.

The exact function of eosinophils in cancer, particularly in oral squamous cell carcinoma (OSCC), has not yet been elucidated and the possible antitumor effect of these leukocytes is associated with the release of cytotoxic proteins, particularly eosinophil cationic protein (ECP). The aim of this study was to evaluate the effect of ECP on human OSCC lines and to provide novel insights into the role of eosinophils in these tumors. The viability of the SCC-4 and SCC-25 OSCC cell lines was assessed by colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The cells were plated into 96-well plates in Dulbecco's modified Eagle's medium/Ham's nutrient mixture F12 supplemented with 10% fetal bovine serum. After 24 h, the indicated concentration of ECP (0-10 µ M) was added to each sample. The plate was read using a microplate reader at a wavelength of 570 nm. The association between variables was estimated by linear regression analysis. There was a significant inverse association between ECP concentrations with SCC-4 (ß=0.16, P=0.019) and SCC-25 cell viability (ß=0.24, P=0.006). To the best of our knowledge, the present study was the first to investigate the effects of ECP on OSCCs and to demonstrate a significant inverse association between ECP concentrations with SCC-4 and SCC-25 cell viability.

Effects of digoxin and Na, K-ATPase immunoexpression on human oral squamous carcinomas.

AIM: The present study evaluated the expression of α1 and ß1 Na,K-ATPase, as well as the effects of digoxin (DGX) on oral squamous cell carcinomas (OSCCs). PATIENTS AND METHODS: Immunohistochemical expression of α1 and ß1 Na,K-ATPase were evaluated in 60 patients who underwent treatment at the São João de Deus Hospital. SCC-25 viability was assessed by the colorimetric assay. Chi-square or Fisher's exact tests were used to analyze the association of α1 and ß1 Na,K-ATPase expression with the variables. RESULTS: Immunoexpression of α1 and ß1 Na,K-ATPase were observed in 28% and 55% of the tumors, however these proteins were not significant prognostic factors. Tobacco was significantly associated with α1 expression. SCC-25 viability decreased significantly after treatment with 1 µM DGX at 24 h. CONCLUSION: The smoking status of OSCC patients was significantly associated with α1 expression and DGX affected the SCC-25 viability in a dose- and duration-dependent manner.

Hypoxic condition and prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinomas (OSCCs) have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumours and contribute to cancer progression, resistance to therapy and poor outcome. Out of all proteins induced by hypoxia, hypoxia-inducible factors (HIFs) and their target genes have been most extensively studied. HIF1 is a heterodimeric transcriptional complex that functions as the main regulator of systemic and cellular oxygen homeostasis; it is composed of HIF1α and HF1ß subunits. At physiological concentrations of oxygen, prolyl hydroxylases (PHDs) modify HIF1α and prepare it for proteasomal degradation. In hypoxia, PHDs are inhibited and HIF1α dimerises with HIF1ß to form HIF1, which is responsible for the activation of several genes involved in multiple aspects of tumor biology. Among these genes, vascular endothelial growth factor (VEGF) is essential as a regulatory gene of angiogenesis in the adaptation to a hypoxic microenvironment. Previous studies have shown the correlation between HIF1α and VEGF in OSCC and high levels of HIF1α expression appear to predict a poor prognosis. The purpose of the present article is to review the hypoxic condition in OSCC and its correlation with prognosis.

Eosinophil cationic protein: overview of biological and genetic features.

The eosinophil cationic protein (ECP) is a small polypeptide that originates from activated eosinophil granulocytes. A wide range of stimuli has been shown to induce the secretion of ECP. The gene that encodes the human ECP is located on chromosome 14, and the protein shares the overall three-dimensional structure and the RNase active-site residues with other proteins in the RNase A superfamily. Several single-nucleotide polymorphisms in the human ECP gene have been currently described. ECP has many biological functions, including an immunoregulatory function, the regulation of fibroblast activity, and the induction of mucus secretion in the airway. Additionally, the protein is a potent cytotoxic molecule and has the capacity to kill mammalian and nonmammalian cells. The purpose of this article was to review the known biological and genetic characteristics of ECP that contribute to the understanding of this protein's role in the development and progression of a wide variety of diseases.