Malignant pleural mesothelioma : novel biomarkers and related pathways

摘要: Malignant mesothelioma is an asbestos induced cancer that difficult to diagnose. Several studies have combined biomarkers improve diagnosis, but with moderate success, and there a need for new biomarkers. The tumour often resistant treatment most patients will survive less than year. An indicator of patient survival the tumours growth pattern, which in turn influenced by expressed proteoglycans. In this thesis work, we aim possibilities diagnose malignant combining identifying ones. We also investigate driving mechanisms focus on one these suggested biomarkers, cell-bound proteoglycan syndecan-1. were able construct diagnostic two-step model based material. By implementing cut-off level thereafter focusing unresolved hyaluronan N-ERC/mesothelin (paper I), significantly increased accuracy mesothelioma. To further used mass spectrometry find identified validated galectin-1, was excellent discriminating mesotheliomas from adenocarcinomas II). same study, first describe aldo-keto reductase 1B10 as novel prognostic biomarker. Syndecan-1 has been indicated marker carcinomas. paper I how higher levels syndecan-1 indicate presence carcinoma over This verified II when downregulated fluids compared lung patients. Paper III IV proteoglycan. cell lines transfected various truncated forms affected adhesion migration, are key features invasion III). results showed domainand type specific effect cells’ motility. Regulating analysing global gene expression cells made it evident strong influence transforming factor β signalling several pathways IV). Links migration proliferation furthermore identified, along glycosaminoglycan modifying enzymes. These can shed light complex role mesenchymal cells. Taken together, work describes complement conventional diagnosis identifies Furthermore, potential biomarker shown motility proliferation. increase our understanding aggressive malignancy. LIST OF PUBLICATIONS following publications, be referred text their Roman numerals: I. Filip Mundt, Gustav Nilsonne, Sertac Arslan, Karola Csuros, Gunnar Hillerdal, Huseyin Yildirim, Muzaffer Metintas, Katalin Dobra Anders Hjerpe. Pleural effusion Manuscript. II. Henrik Johansson, Jenny Forshed, Dobra, Janne Lehtio Proteome screening galectin-1 negative predictor pleural effusions. III. Fang Zong, Eleni Fthenou, Tunde Szatmari, Ilona Kovalszky, Laszlo Szilak, David Brodin, George Tzanakakis, Hjerpe Dobra. Specific domains regulate tumor adhesion, migration. PLoS ONE 2011; 6(6): e14816. IV. Ghazal Heidari-Hamedani, Elena Ferolla, Andrey Alexeyenko, Novel genes modulated syndecan-1: implications cell-cycle regulation 2012; 7(10): e48091.