Gewerkschaften in Zypern : Geschichte der Teilung, gemeinsame Herausforderungen in der Zukunft

Gregoris Ionnou & Sertac Sona

Detection of somatostatin receptors in human osteosarcoma

Background: The location of osteosarcoma in the metaphysis as well as the age of the patients during the most rapid tumour growth suggest that factors related to skeletal growth are involved in the pathogenesis of this tumour. In this aspect this study aims to detect somatostatin receptors in human osteosarcomas and correlate this finding with the clinical outcome of the tumour. Patients and methods: Immunohistochemical staining for the presence of somatostatin receptors as well as overall survival and disease free survival rates were retrospectively studied in twenty-nine osteosarcoma patients. Results: Four osteosarcomas with several aggressive biologic behaviour expressed somatostatin receptors. In these four young patients the event free rate was 0% and the overall survival rate was 50% at 4, 3 years. In contrast the event free survival rate of the twenty-five patients with negative somatostatin receptor status was 72% with an overall survival rate of 76% at 4,3 years. Conclusion: The present study demonstrates the existence of somatostatin receptors in human osteosarcoma. Tumours expressing somatostatin receptors seemed to be aggressive with a very low disease free and overall survival rate compared to osteosarcoma with negative receptor status. © 2008 Ioannou et al; licensee BioMed Central Ltd

Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses

Small extracellular vesicle (sEV, or exosome) communication among cells in the tumor microenvironment has been modeled mainly in cell culture, whereas their relevance in cancer pathogenesis and progression in vivo is less characterized. Here we investigated cancer-microenvironment interactions in vivo using mouse models of chronic lymphocytic leukemia (CLL). sEVs isolated directly from CLL tissue were enriched in specific miRNA and immune-checkpoint ligands. Distinct molecular components of tumor-derived sEVs altered CD8+ T-cell transcriptome, proteome, and metabolome, leading to decreased functions and cell exhaustion ex vivo and in vivo. Using antagomiRs and blocking antibodies, we defined specific cargo-mediated alterations on CD8+ T cells. Abrogating sEV biogenesis by Rab27a/b knockout dramatically delayed CLL pathogenesis. This phenotype was rescued by exogenous leukemic sEV or CD8+ T-cell depletion. Finally, high expression of sEV-related genes correlated with poor outcomes in CLL patients, suggesting sEV profiling as a prognostic tool. In conclusion, sEVs shape the immune microenvironment during CLL progression.Fil: Gargiulo, Ernesto. Luxembourg Institute Of Health; LuxemburgoFil: Viry, Elodie. Luxembourg Institute Of Health; LuxemburgoFil: Morande, Pablo Elías. Luxembourg Institute Of Health; Luxemburgo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Largeot, Anne. Luxembourg Institute Of Health; LuxemburgoFil: Gonder, Susanne. Luxembourg Institute Of Health; LuxemburgoFil: Xian, Feng. Luxembourg Institute Of Health; LuxemburgoFil: Ionnou, Nikolaos. Centre Hospitalier de Luxembourg; LuxemburgoFil: Benzarti, Mohaned. Luxembourg Institute Of Health; LuxemburgoFil: Borgmann, Felix Kleine. University of Luxembourg; Luxemburgo. Luxembourg Institute Of Health; LuxemburgoFil: Mittelbronn, Michel. University of Luxembourg; LuxemburgoFil: Dittmar, Gunnar. Luxembourg Institute Of Health; LuxemburgoFil: Nazarov, Petr V.. Luxembourg Institute Of Health; LuxemburgoFil: Meiser, Johannes. Luxembourg Institute Of Health; LuxemburgoFil: Stamatopoulos, Basile. Université Libre de Bruxelles; BélgicaFil: Ramsay, Alan G.. King's College London; Reino Unid