Head and Neck Medicine by Alexandros G.Sfakianakis

This study addresses the hypothesis that IL-6/STAT3 signaling is of clinical relevance in oropharyngeal squamous cell carcinoma (OPSCC). We evaluated relationships between key components of this pathway in tumors from a unique cohort of n = 59 fully annotated, treatment-naïve patients with OPSCC. The multiplex Opal platform was utilized for immunofluorescence (IF) analysis of tissues to detect IL-6 and phosphorylated STAT3 (pSTAT3), taking into consideration its nuclear versus cytoplasmic localization. Abundant staining for both IL-6 and pSTAT3 was evident in tumor-rich regions of each specimen. IL-6 correlated with cytoplasmic pSTAT3 but not nuclear or total pSTAT3 in this cohort of OPSCC tumors, regardless of p16 status (r = 0.682, p < 0.0001). There was a significant association between increased total pSTAT3, nuclear pSTAT3, cytoplasmic pSTAT3 and IL-6 in p16 negative tumors. Our data indicate STAT3 phosphorylation was a key feature in p16-negative OPSCC tumors. When IL-6 data was stratified by median expression in tumors, there was no association with overall survival. In contrast, both total and nuclear pSTAT3 were significant predictors of poor overall and disease free survival. This strong inverse relationship with overall survival was present in p16 negative tumors for both total and nuclear pSTAT3, but not in p16 positive OPSCC tumors. Together these data indicate that activation of the STAT3 signaling pathway is a marker of p16 negative tumors and relevant to OPSCC prognosis and a potential target for treatment of this more aggressive OPSCC sub-population.

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What is new in HIES? Recent insights from the interface of primary immune deficiency and atopy

Purpose of review Understanding the pathophysiology of monogenic primary immunodeficiency (PID) with atopic presentation has pivotal implications for intervention strategies and potentially wider polygenic atopic-related traits. This review will discuss advances in gene discovery arising from monogenic defects at the interface between PID and atopy, notably the hyper-IgE syndromes. Recent findings Key molecular pathways underlying development of primary atopic diseases have recently been proposed. We test this classification through reviewing novel genes reported in the last 2 years and compare insights from pathway-analysis of genome-wide association studies (GWAS) of atopic-related traits. Growing access to next-generation sequencing (NGS) has resulted in a surge in gene discovery, highlighting the utility and some pitfalls of this approach in clinical practice. The variability of presenting phenotypes reveals important gene-dosage effects. This has important implications for therapeutic strategies such as protein stabilization and modulators of JAK-STAT or TH2-cytokine signalling. We also consider the therapeutic implications raised by CARD11 deficiency, and wider applications of NGS including polygenic risk score in atopy. Summary Disorders presenting at the interface between PID and allergy are often difficult to diagnose, with serious consequences if missed. Application of NGS has already provided critical insights to pathways enabling targeted therapeutic interventions, and potential wider translation to polygenic disorders. Correspondence to Mark J. Ponsford, Immunodeficiency Centre for Wales, University Hospital of Wales; Cardiff University, Cardiff, UK. E-mail: ponsfordm@cardiff.ac.uk Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-allergy.com). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Head and Neck Medicine by Alexandros G.Sfakianakis

Αρχειοθήκη ιστολογίου

Πέμπτη 6 Σεπτεμβρίου 2018

Recognition of the peripheral airway impairment phenotype in well controlled asthmatic children

Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population

Interleukin-6/STAT3 Signaling is Prominent and Associated with Reduced Overall Survival in p16 Negative Oropharyngeal Squamous Cell Carcinoma

Abstract

What is new in HIES? Recent insights from the interface of primary immune deficiency and atopy

Adverse effects of fillers

Commentary on adverse effects of isotretinoin article by Brezenski et al.

Commentary on article on clinical efficacy of oral finasteride by Won, Lew, and Sim