Gene expression analysis of head and neck cancer development

Microarray analysis was performed on 32 head and neck keratinocytes cultures using Affymetrix U133A/B genechips. The panel of cultures included normal cells, mortal and immortal cultures of dysplastic keratinocytes and mortal and immortal cultures from carcinomas, all grown to a standard protocol. The overall GEP revealed that many of the well-established HNSCC molecular markers associated with motility and invasion were up-regulated in the mortal cells, particularly in the mortal carcinomas. Immortal NHSCC cells showed elevated expression of cell-cycle markers and loss of differentiation markers. In addition, a small number of common changes in gene expression in all the carcinomas, regardless of replicative fate, were identified. This included several transcription factors. A series of 49 novel gene expression changes consistently associated with immortality in dysplastic keratinocytes and SCCs were identified. The list included genes involves in cell cycle control, signalling, cellular metabolism and maintenance of cellular structure. Validation of the expression of these genes by western blot demonstrated that, in general, the protein expression of genes agreed with the RNA expression level from the microarray data. However, some heterogeneity was evident. The mortal and immortal gene expression signatures were validated by IHC in the tumours from which the cultures were derived. The tumours that gave rise to immortal cell cultures demonstrated a relatively uniform pattern of staining in relation to the novel markers of immortality. However, those tumours which gave rise to mortal cultures exhibited significant heterogeneity of gene expression pattern, with areas characteristic of both the mortal and immortal phenotype present. These novel markers give us further insight into the mechanisms and importance of keratinocytes immortalization. Surrogate markers of immortality could therefore be valuable for assessment of prognosis and therapy if confirmed in larger in vivo studies

A Reflective Hybrid Approach to Connecting Leadership Style and Stakeholder Perspective

Using quantitative analysis and reflection techniques, we examine employee perception of leadership style and perceived results within organizations based in Whistler, Canada. We are primarily concerned with results in terms of organizational culture towards 3 key stakeholder groups, customers, community, and employees. The observed differences in results between transformational and transactional leadership provide a basis for enriching the mapping of leadership style to desired outcomes

Positive Effects of Peer-Led Reflection on Undergraduates\u27 Concept Integration and Synthesis During Service Learning

Service learning that features mutually constructed community-based service can enhance the understanding of a range of concepts (Butin, 2006). However, such service is often seen as “charity” as opposed to a dually constructed experience that is central to real learning (Howard, 2000; Tellis, 2011). This project was designed to determine whether the early interjection of peer-led reflections into an undergraduate course would result in students having gained a dual partnership perspective by mid-semester. Exploratory results suggest that peer-led reflections may have both increased student understanding of service learning and contributed to the quantity and quality of theoretical course concepts cited

The Communication Conundrum Exercise: Pedagogy for Project-Based Learning

Many professionals spend a significant amount of their time managing and supporting project teams. To help students learn how to work in this environment, we present the Communication Conundrum Exercise (CCE). The CCE challenges students to solve a symbol-identification problem with tension from hierarchical controls and narrowly defined rules for communication. Students assume roles that correspond to the major roles found on real-life hybrid project teams, and work with the triple constraint triangle common in project management. We provide the rationale for the CCE and the method and results of our analyses from 126 management students in 26 groups, and provide the details of exercise setup, execution, and debrief. The CCE delivers a high-energy, high-impact experience for students on the nature of hybrid project teams and their communication challenges

Waterproofing Membrane for Concrete Boxes and Culverts

In 2019 a new INDOT Specification went into effect for waterproofing on concrete pipes and three- and four-sided boxes. The new specification decreased the leakage at these structures joints from 95% to less than 5%. This presentation will provide the background on why the change was needed and the solution, complete with construction examples and results

Overexpression of S100A4 as a biomarker of metastasis and recurrence in oral squamous cell carcinoma

S100A4, a biomarker of epithelial mesenchymal transition (EMT), plays an important role in invasion and metastasis by promoting cancer cell motility. In oral squamous cell carcinoma (OSCC), metastasis results in 90% of cancer associated mortality. Objective: To investigate the role of S100A4 expression as an important component of the epithelial mesenchymal transition (EMT) program in oral squamous cell carcinoma (OSCC). Material and Methods: S100A4 protein expression was assessed semi-quantitatively by immunohistochemistry in 47 histologically confirmed cases of oral squamous cell carcinoma (OSCC) and 10 normal oral mucosal biopsies. The association between the S100A4 overexpression and the aggressive features of OSCC were analyzed by X2 test. Results: Moderate to strong cytoplasmic expression of S100A4 was observed in 30 out of 47 specimens of OSCC (64%). Overexpression of S100A4 was significantly associated with the clinical stage, lymph node involvement, metastases, pattern of invasion and recurrence (

IL-1/IL-1R Signaling in head and neck cancer

Decades ago, the study of cancer biology was mainly focused on the tumor itself, paying little attention to the tumor microenvironment (TME). Currently, it is well recognized that the TME plays a vital role in cancer development and progression, with emerging treatment strategies focusing on different components of the TME, including tumoral cells, blood vessels, fibroblasts, senescent cells, inflammatory cells, inflammatory factors, among others. There is a well-accepted relationship between chronic inflammation and cancer development. Interleukin-1 (IL-1), a potent pro-inflammatory cytokine commonly found at tumor sites, is considered one of the most important inflammatory factors in cancer, and has been related with carcinogenesis, tumor growth and metastasis. Increasing evidence has linked development of head and neck squamous cell carcinoma (HNSCC) with chronic inflammation, and particularly, with IL-1 signaling. This review focuses on the most important members of the IL-1 family, with emphasis on how their aberrant expression can promote HNSCC development and metastasis, highlighting possible clinical applications

Malignant odontogenic tumours : a systematic review of cases reported in literature

Background: Malignant odontogenic tumours (MOTs) arise either de novo from the tooth forming tissues, their developmental residues or from existing odontogenic epithelial or mesenchymal neoplasms in the jaws. Their management requires extensive surgery due to their infiltrative nature and risk of metastasis. There is a need to understand the clinical and pathological features of MOTs to inform both treatment algorithms and prognostication. This is an area of diagnostic pathology which presents substantial difficulties in diagnosis, compounded by inconsistent use of terminology. Thus, this systematic review aimed to describe the clinical and pathological features of MOTs with a view to consolidating the literature and defining problematic areas in diagnosis and classification. Methods: An electronic database search was conducted in Web of Science, PubMed/Medline, and Embase. Additionally, the grey literature and reference lists of selected papers searched for completeness. Nine hundred and sixty articles were initially identified. Following removal of duplicates and application of inclusion/exclusion criteria, 312 articles were included for qualitative analysis. Results: The 312 articles encompassed a total of 507 patients with most lesions located within the mandible (74.3%). The most common first histological diagnosis was ameloblastic carcinoma (25.7% of all diagnoses), but there is considerable variation in how and when various diagnostic terms are used, and several misdiagnoses were reported. An initial benign diagnosis was made in 24.7% of patients, followed by a later malignant diagnosis and in this sub-group, the most common benign first diagnosis was ameloblastoma (42.4%). Cervical lymph nodes were the most common site of metastasis (9.3% of patients). With respect to distant metastasis (DM), the lungs were the most common organ affected (11.2% of DM patients) with metastasising ameloblastoma the most commonly reported tumour which metastasised to the lungs. Overall, 26.8% of patients developed recurrence. Conclusion: Overall, the quality of the literature on MOTs is poor. This review of the literature has highlighted variations in diagnostic terms and criteria which has resulted in areas of confusion with potential for misdiagnosis. This consolidation of primary data has identified key areas for targeted research including further discussion on the malignant potential of ameloblastoma