Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

There is a great interest in developing biomarkers to enhance early detection and clinical management of tongue squamous cell carcinoma (TSCC). However, the developmental path towards a clinically valid biomarker remains extremely challenging. Ideally, the initial key step in moving a newly discovered biomarker towards clinical implementation is independent replication. Therefore, the focus of this review is on biomarkers that consistently showed clinical relevance in two or more publications. We searched PubMed database for relevant papers across different TSCC sample sources, i.e., body fluids (saliva, serum/plasma) and tissues. No restriction regarding the date of publication was applied except for immunohistochemistry (IHC); only studies published between 2010 and June 2017 were included. The search strategy identified 1429 abstracts, of which 96 papers, examining 150 biomarkers, were eventually included. Of these papers, 66% were exploratory studies evaluating single or a panel of biomarkers in one publication. Ultimately, based on studies that had undergone validation for their clinical relevance in at least two independent studies, we identified 10 promising candidates, consisting of different types of molecules (IL-6, IL-8, and Prolactin in liquid samples; HIF-1α, SOX2, E-cadherin, vimentin, MALAT1, TP53, and NOTCH1 in tissue biopsies) Although more exploratory research is needed with newer methods to identify biomarkers for TSCC, rigorous validation of biomarkers that have already shown unbiased assessment in at least two publications should be considered a high priority. Further research on these promising biomarkers or their combination in multi-institutional studies, could provide new possibilities to develop a specific panel for early diagnosis, prognosis, and individualized treatments.

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A review of the most promising biomarkers for early diagnosis and prognosis prediction of tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva. We performed next-generation sequencing of the TNFα-treated OSCC cells and showed marked overexpression of over 180 genes distributed among clusters related to neutrophil recruitment, invasion, and invadopodia. At the molecular level, TNFα treatment increased phosphoinositide 3-kinase (PI3K)-mediated invadopodia formation and matrix metalloproteinase (MMP)-dependent invasion. We show here that TNFα promotes a pro-inflammatory and pro-invasion phenotype leading to the recruitment and activation of inflammatory cells in a paracrine mechanism. Increased TNFα in the tumor microenvironment tips the balance towards invasion leading to decreased overall survival and disease-free survival. This represents a significant advancement of oral cancer research and will support new treatment approaches to control OSCC invasion and metastasis.

/pdf/oral-inflammation-promotes-oral-squamous-cell-carcinoma-4s1otj7cnh.pdf

Oral inflammation promotes oral squamous cell carcinoma invasion.

BACKGROUND Inflammation and cell-mediated immunity have a key role in different stages of carcinogenesis. The aim of this prospective study was to assess serum levels of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), and MHC class I polypeptide-related sequence B (MICB) in patients with oral premalignant lesion (OPL), oral squamous cell carcinoma (OSCC), and healthy controls in a multi-biomarker approach as a potential diagnostic and prognostic tool for OSCC. MATERIAL AND METHODS A total of 205 patients (81 with OSCC, 75 with OPL, and 49 healthy controls) were included in this prospective study. Cytokine concentrations were measured by commercial enzyme linked immunoassay and chemiluminescence immunoassay. RESULTS IL-6, IL-8, and sIL-2R were significantly elevated in OSCC patients compared to healthy controls and to OPL patients. Higher T-Grade (>T2) and positive lymph node involvement resulted in significantly higher IL-6 values (P < .001 and P = .037). IL-6 serum values ≥5 pg/mL (n = 45) and sIL-2R serum values ≥623 U/mL (n = 19) indicated a significant lower survival rate compared to OSCC patients with low IL-6 (n = 36) and sIL-2R values (n = 62, P = .023 and P = .026). ROC and classification tree analyses identified the combination of IL-6 and IL-8 as diagnostic markers with good diagnostic accuracy. CONCLUSION In conclusion, IL-6, IL-8, and sIL-2R are strongly associated with OSCC oncogenesis and IL-6 and sIL-2R seem to be promising and potent biomarkers for evaluating patients' prognosis.

Proinflammatory cytokines as serum biomarker in oral carcinoma-A prospective multi-biomarker approach

Interleukin-6 (IL-6) is a proinflammatory cytokine which plays an important role in several regulatory mechanisms of cancer. Moreover, experimental and clinical studies have reported that IL-6 targeted therapies might provide significant benefits for cancer treatment. The purpose of this systematic review is to evaluate IL-6 activity in patients with head and neck squamous cell carcinoma (HNSCC). A systematic review of the association between serum, saliva and tumor IL-6 and HNSCC was developed on PubMed/Medline in the publication range from January 1995 to January 2019. Our literature analysis demonstrated that overexpression and elevated serum and/or saliva IL-6 concentrations in patients with HNSCC are related to poor survival and oncological outcomes. Although there is a correlation between IL-6 concentrations and tumorigenicity, it is noteworthy that IL-6 targeted therapies are generally performed in vitro and in experimental studies. Therefore, prospective, randomized clinical trials are required that focus on IL-6 targeted therapies for the treatment of HNSCC.

/pdf/association-between-interleukin-6-and-head-and-neck-squamous-1gmtz5th6m.pdf

Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review

Introduction: The clinical outcome of patients with squamous cell carcinoma (SCC) located in the head and neck has remained poor despite ongoing advances in diagnosis and management. Interleukin6(IL-6) is a multi-functional cytokine that plays an important role in the process of cell differentiation and is increased in several malignancies. The aim of this study was to investigate the serum levels of interleukin-6 in patients with oral tongue SCC. Materials and Methods: In a cross-sectional study, 17 patients with oral tongue SCC were compared with the same number of age- and gender-matched healthy subjects. Serum IL-6 level fluctuation was determined using an immunological technique, before detecting its possible association with the subjects’ age, gender, drinking and smoking history, cancer site, and disease severity. Results: The intensity of serum IL-6 in patients with oral tongue SCC was statistically significantly higher than that in healthy subjects (P<0.001). Serum IL-6 level was independent of the patients’ age, gender, smoking and drinking history as well as cancer stage. Conclusion: IL-6 is a valuable biomarker in the diagnosis of oral tongue SCC. Its high sensitivity makes prediction of this condition possible, while this biomarker can also be used to screen high-risk patients.

https://ijorl.mums.ac.ir/article_4250_b59e6e3d3b7a7ca72cf783e1fb3d2f5c.pdf

Rezvan Notash

Papers

Serum Level of Interleukin-6 in Patients with Oral Tongue Squamous cell Carcinoma.

Nasal septal lipoma in a child: Pai syndrome or not?

Cleft palate lateral synechia syndrome: Inhereditary or not?