The role of the microenvironment in tumor immune surveillance.

The evidence appears compelling that the microenvironment, and associated biological cellular and molecular factors, may contribute to the progression of a variety of tumors. The effects of the microenvironment may directly influence the plasticity of T cell lineages, which was recently discussed (O'Shea & Paul, 2010 [4]). To review the putative role of the microenvironment in modulating the commitment of tumor immune surveillance, we use the model of oral premalignant lesions.

From Systematic Reviews to Clinical Recommendations for Evidence-Based Health Care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.

Research synthesis seeks to gather, examine and evaluate systematically research reports that converge toward answering a carefully crafted research question, which states the problem patient population, the intervention under consideration, and the clinical outcome of interest. The product of the process of systematically reviewing the research literature pertinent to the research question thusly stated is the "systematic review".The objective and transparent approach of the systematic review aims to minimize bias. Most systematic reviews yield quantitative analyses of measurable data (e.g., acceptable sampling analysis, meta-analysis). Systematic reviews may also be qualitative, while adhering to accepted standards for gathering, evaluating, and reporting evidence. Systematic reviews provide highly rated recommendations for evidence-based health care; but, systematic reviews are not equally reliable and successful in minimizing bias.Several instruments are available to evaluate the quality of systematic reviews. The 'assessment of multiple systematic reviews' (AMSTAR) was derived from factor analysis of the most relevant items among them. AMSTAR consists of eleven items with good face and content validity for measuring the methodological quality of systematic reviews, has been widely accepted and utilized, and has gained in reliability, reproducibility. AMSTAR does not produce quantifiable assessments of systematic review quality and clinical relevance. In this study, we have revised the AMSTAR instrument, detracting nothing from its content and construct validity, and utilizing the very criteria employed in the development of the original tool, with the aim of yielding an instrument that can quantify the quality of systematic reviews. We present validation data of the revised AMSTAR (R-AMSTAR), and discuss its implications and application in evidence-based health care.

LCK, survivin and PI-3K in the molecular biomarker profiling of oral lichen planus and oral squamous cell carcinoma.

T cell signaling is critical in oral lichen planus (OLP) based on the pathogenesis of this chronic inflammatory autoimmune mucocutaneous lesion. Lck plays a key role in T cell signaling; ultimately this signaling affects other targets such as PI-3K. Excessive activity in PI-3K inhibits apoptosis and promotes uncontrolled cell growth. Molecular biomarker profiling in OLP, Chronic Interface Mucosities (CIM), Epithelial Dysplasia (EpD) and Oral Squamous Cell Carcinoma (SCCA) with application of the principle of biomarker voting may represent a new frontier in the diagnosis, assessment and the arguable debate of OLP transformation to cancer. The presence of Lck, PI-3K and Survivin, a cancer specific anti-apoptotic protein was assessed, using immunohistochemistry and tissue micro-array on patient samples, in OLP, SCCA, CIM and EpD. Lck expression was very 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. CIM cases may be slightly different molecularly to OLP. Taken together, our data suggest that biomarker protein voting can be effectively used to isolate high-risk OLP cases. Specifically, we show data with four remarkable cases demonstrating that molecular factors are predictive of histopathology. We conclude that it is safer to treat OLP as premalignant lesions, to adopt aggressive treatment measure in histopathologic described well and moderately differentiated SCCA, and to monitor progress of these diseases molecularly using individualized auto-proteomic approach. The use of Lck inhibitors in OLP management needs to be investigated in the future.