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Molecular Biomarker Profiling and Translational Evidence-Based Dentistry in Oral Lichen Planus and Oral Squamous Cell Carcinoma

Posted on:2011-12-30Degree:Ph.DType:Dissertation
University:University of California, Los AngelesCandidate:Oluwadara, Oluwadayo OluwagbemigaFull Text:PDF
GTID:1444390002963087Subject:Health Sciences
Abstract/Summary:
Oral lichen planus-(OLP) is a T cell mediated disease with controversy about its transformation to oral squamous cell carcinoma-(SCCA). Caution in classifying OLP to be one of the Oral premalignant lesions-(OPM) such as epithelial dysplasia-(EpD) exists. Despite this caution, cases of OLP transforming to SCCA exists, and the incidence of SCCA is increasing. Molecular insights to complement histopathology/management of OLP and SCCA are needed.;Using immunohistochemistry on tissue microarray-(TMA) and evidence-based methods, this work demonstrated:-validity of translational evidence-based dentistry-(T-EBD) through the link of molecular biomarker profiling and evidence-based science. Lck, PI-3K and Survivin, a cancer specific anti-apoptotic protein were assessed on patient biopsy samples with OLP, Chronic interface mucosities-(CIM), EpD and SCCA. Lck expression was high in 78.6 % of OLP patients compared to 3.7% in SCCA; PI-3K was high in 63% of SCCA, 100% of EpD, and 35.7% OLP cases. Survivin was high in 64.3% of OLP cases, 96.3% of SCCA, and 100% of EpD. Biomarker protein voting among markers isolated four high risks OLP cases. This result was supported through a data mining study.;The proteomic signatures of individual patient biopsies and the usage of such information for the best-available treatment intervention for each patient serve as a link for molecular profiling and evidence-based analysis.;Evidence-based analysis revealed no superior management for OLP with limited literatures on Lck inhibitors/Pl-3K inhibitors. Most published reports were studies on animal/cell lines and were difficult to analyze with the Wong scale. The Oluwadara-Kossan (OK) scale was developed and validated to assess literatures based on animal/cell lines studies and it provides basis for numbers of samples needed to conduct a clinical trial (NNCCT).;Taken together, biomarker protein voting can be used to isolate high-risk OLP cases. It is better to treat OLP as OPM, to adopt aggressive treatment for SCCA cases, to monitor diseases molecularly using individualized auto-proteomic approach. Lck inhibitors/PI-3K inhibitors might be useful in the future management of OLP, OPM and SCCA.;The findings presented in this study validate a model of tailored personalized medicine- (PM). In the future, PM will depend on correlating information from molecular spatial segments and T-EBD.
Keywords/Search Tags:OLP, SCCA, Molecular, Oral, Evidence-based, Cell, Biomarker, Profiling
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