Th1/Th2 Cytokine Ratio in Tissue Transudates from Patients with Oral Lichen Planus

Objective. The characteristics of oral lichen planus (OLP) provoke investigators to explore possible biomarkers by which to monitor disease activity and therapeutic efficacy. Oral fluids may provide an accessible medium for analysis of such biomarkers. Previous studies have shown that activation of nuclear factor-kappa B (NF-κ B) plays an important role in the pathogenesis of oral lichen planus (OLP), which is a chronic inflammatory disorder mediated by T cells. Prior to the present investigation, reports of the levels of NF-κ B and its dependent cytokines in oral fluids have not been forthcoming. The purpose of this study was to detect the level of NF-κ B dependent cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in tissue transudates directly from lesions of OLP, and explore the feasibility of the data for clinical application. Study design. Thirteen definitively diagnosed OLP subjects were enrolled in the study as were 13 age-sex matched controls. In each subject, lesion tissue transudates (TTs) were collected by a novel collection technique with a filter paper. The level of cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids were determined by ELISA. Results. In the tissue transudate(TT), there were significantly higher level of cytokines TNF-alpha, IL-1-alpha, IL-6, and IL-8 detected in OLP patients than in controls: (TT: 40.0 ± 9.8 versus 4.5 ± 0.7, 710 ± 114 versus 305 ± 78, 150 ± 25 versus 1.7 ± 0.5, 2800 ± 260 versus 1450 ± 130, P < .0001; unit: pg/mL). Conclusions. These results indicate that NF-κ B dependent inflammatory cytokines may be detected at increased levels in oral lesion tissue transudates which may have diagnostic and prognostic potentials for monitoring disease activity and making therapeutic decisions in patients with OLP

Exons 19 and 21 of Epidermal Growth Factor Receptor Are Highly Conserved in Squamous Cell Cancer of the Head and Neck

Objective. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI) is a promising treatment in upper aerodigestive malignancies. EGFR inhibitors might be more effective in patients whose tumors harbor specific EGFR mutations. The presence of specific EFGR mutations is predictive of over a 75% response rate to TKI therapies as compared to 10% in wild type cases of non-small cell lung cancer. Our objective was to examine whether these mutations might occur in upper aerodigestive cancers. Design. DNA was extracted from 20 head and neck squamous cell tumors and 4 squamous cell carcinoma cell lines and sequenced the receptor using published primer pairs. We then compared the results against published mutations. Results. No exon 19 or 21 mutations were found in any of the 20 tumors and 0 of 4 cell lines. Based on the tumor data we would predict that no greater than 8% of head and neck tumors (CI 97.5%) would be likely to harbor either of these mutations. Conclusions. Our findings are comparable to results recently published of Korean, Austrian, and Spanish patient populations and we conclude that exon 19 and 21 EGFR mutations are not more common in head and neck cancer than in nonsmall-cell carcinoma

Event- , politics-, and audience-driven news: a comparison of populism in European media coverage in 2016 and 2017

This chapter focuses on trends in reporting over time. It examines the presence of populist key messages in “news coverage of immigration” and “commentaries on current political events” in European newspapers at two points in time, namely spring 2016 and spring 2017. The chapter has a twofold aim. First, it will explore similarities and differences in the populist content of European newspapers between the two periods. Second, it identifies a set of extra-media and intra-media explanatory factors contributing to the understanding of the emerging differences in a year-to-year comparison. The chapter by Blassnig et al. in this volume provides more detailed information about the newspaper stories we content-analyzed. Two types of stories are analyzed: ‘news articles on immigration’, and ‘editorials commenting on current political events’ irrespective of the topic. While the chapter by Blassnig et al. pooled and jointly investigated the data from 2016 and 2017, and the chapter by Maurer et al. in this volume, used only content data from 2017, this chapter will evaluate and compare the data from 2016 and 2017. These two periods are seen as two phases of a news and policy cycle that responds to real world cues. The two phases are understood as stages of a crisis, which offer more or less favorable opportunity structures for populist discourse (Moffitt, 2015). As stated in the introduction to this volume, a whole range of contextual factors influence the populist worldview of crises and, subsequently, the use of populist communication in news reports and commentaries about theses crises

Benchmark experiments for higher-order and full-Stokes ice sheet models (ISMIP-HOM)

We present the results of the first ice sheet model intercomparison project for higher-order and full-Stokes ice sheet models. These models are compared and verified in a series of six experiments of which one has an analytical solution obtained from a perturbation analysis. The experiments are applied to both 2-D and 3-D geometries; five experiments are steady-state diagnostic, and one has a time-dependent prognostic solution. All participating models give results that are in close agreement. A clear distinction can be made between higher-order models and those that solve the full system of equations. The full-Stokes models show a much smaller spread, hence are in better agreement with one another and with the analytical solution

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells.Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early

The functional cancer map: A systems-level synopsis of genetic deregulation in cancer

<p>Abstract</p> <p>Background</p> <p>Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies.</p> <p>Methods</p> <p>Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors.</p> <p>Results</p> <p>We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'.</p> <p>Conclusion</p> <p>The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.</p

The Role of Inflammatory Mediators in the Pathogenesis of Otitis Media and Sequelae

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued