Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

<p>Abstract</p> <p>Background</p> <p>Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma.</p> <p>Methods</p> <p>HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration.</p> <p>Results</p> <p>17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration.</p> <p>Conclusions</p> <p>Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in <it>in vivo </it>induction of HIF. <it>In vitro </it>data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.</p

Proceedings of the 1st Seminar on Higher Education Rankings and E-learning

First International Seminar on Higher Education Rankings and e-Learning. ProceedingsPrimer Seminari Internacional d'Educació Superior. Les classificacions i aprenentatge virtual. ProceedingsPrimer Seminario Internacional de Educación Superior. Las clasificaciones y e-learning. Proceeding

Proceedings of the 1st Seminar on Higher Education Rankings and E-learning

First International Seminar on Higher Education Rankings and e-Learning. ProceedingsPrimer Seminari Internacional d'Educació Superior. Les classificacions i aprenentatge virtual. ProceedingsPrimer Seminario Internacional de Educación Superior. Las clasificaciones y e-learning. Proceeding

Rankings and Accountability in Higher Education : Uses and Misuses

University Rankings: The Many Sides of the Debate / Marope, Mmantsetsa; Wells, Peter -- The Academic Ranking of World Universities and its future direction / Liu, Nian Cai An evolving methodology: the Times Higher Education World University Rankings / Baty, Phil -- Issues of transparency and applicability in global university rankings / Sowter, Ben -- World-class universities or world-class systems? Rankings and higher education policy choices / Hazelkorn, Ellen -- Rankings and online learning: a disruptive combination for higher education? / Daniel, John -- Ranking higher education institutions: a critical perspective / Scott, Peter -- Rankings, new accountability tools and quality assurance / Eaton, Judith -- An African perspective on rankings in higher education / Okebukola, Peter A. -- Rankings and information on Japanese universities / Yonezawa, Akiyoshi -- The national and institutional impact of university rankings : the case of Malaysia / Hapsah, Sharifah -- What’s the use of rankings? / Downing, Kevin -- A decade of international university rankings : a critical perspective from Latin America / Ordorika, Imanol; Lloyd, Marion -- If ranking is the disease, is benchmarking the cure? / Salmi, Jamil -- U-Multirank: a user-driven and multi-dimensional ranking tool in global higher education and research / Vught, Frans van; Ziegele, Frank -- Towards an international assessment of higher education learning outcomes : The OECD-led AHELO initiative / Yelland, Richard; Castañeda Valle, RodrigoIt brings together both promoters and opposers of rankings, to reflect the wide range of views that exist in the higher education community on this highly controversial topic. If learners, institutions and policy-makers are to be responsible users of ranking data and league table lists, it is vital that those compiling them make perfectly clear what criteria they are using to devise them, how they have weighted these criteria, and why they made these choices. It is hoped that this information will enable stakeholders to take informed decisions on higher education institutions