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      Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma

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          Abstract

          Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy.

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          Most cited references38

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          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            The role of CXC chemokines and their receptors in cancer.

            Chemokines, or chemotactic cytokines, and their receptors have been discovered as essential and selective mediators in leukocyte migration to inflammatory sites and to secondary lymphoid organs. Besides their functions in the immune system, they also play a critical role in tumor initiation, promotion and progression. There are four subgroups of chemokines: CXC, CC, CX(3)C, and C chemokine ligands. The CXC or alpha subgroup is further subdivided in the ELR(+) and ELR(-) chemokines. Members that contain the ELR motif bind to CXC chemokine receptor 2 (CXCR2) and are angiogenic. In contrast, most of the CXC chemokines without ELR motif bind to CXCR3 and are angiostatic. An exception is the angiogenic ELR(-)CXC chemokine stromal cell-derived factor-1 (CXCL12/SDF-1), which binds to CXCR4 and CXCR7 and is implicated in tumor metastasis. This review is focusing on the role of CXC chemokines and their receptors in tumorigenesis, including angiogenesis, attraction of leukocytes to tumor sites and induction of tumor cell migration and homing in metastatic sites. Finally, their therapeutic use in cancer treatment is discussed.
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              Versatile functions for IL-6 in metabolism and cancer.

              Owing to its abundance in inflammatory settings, interleukin IL-6 is frequently viewed as a proinflammatory cytokine, with functions that parallel those of tumor necrosis factor (TNF) and IL-1β in the context of inflammation. However, accumulating evidence points to a broader role for IL-6 in a variety of (patho)physiological conditions, including functions related to the resolution of inflammation. We review recent findings on the complex biological functions governed by IL-6 signaling, focusing on its role in inflammation-associated cancer and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We propose that the anti-inflammatory functions of IL-6 may extend to multiple settings and cell types, and suggest that these dimensions should be incorporated in therapeutic approaches to these diseases. Finally, we outline important areas of inquiry towards understanding this pleiotropic cytokine.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                12 July 2016
                14 June 2016
                : 7
                : 28
                : 44236-44251
                Affiliations
                1 CNRS UMR 7284/INSERM U1081, Institute for Research on Cancer and Aging of Nice, University of Nice Sophia Antipolis, Nice, France
                2 Biomedical Department, Centre Scientifique de Monaco, Principality of Monaco
                3 Odontology Department, Nice University Hospital, University of Nice Sophia Antipolis, Nice, France
                4 Central Laboratory of Pathology, University of Nice Sophia Antipolis, Nice, France
                5 Department of Pathology, Research and Statistics, Centre Antoine Lacassagne, Nice, France
                6 Cancer Genetics and Translational Oncology Laboratory, S. Croce & Carle Teaching Hospital, Cuneo, Italy
                7 Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy
                Author notes
                Correspondence to: Gilles Pagès, gpages@ 123456unice.fr
                Article
                10005
                10.18632/oncotarget.10005
                5190092
                27329590
                4981953c-d183-4ecc-a6ba-5d3f2a4fe849
                Copyright: © 2016 Benhamou et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 January 2016
                : 4 May 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                prognostic factor,predictive factor,oral cancer,tumor microenvironment,targeted therapies

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