Targeting Angiogenesis with Multitargeted Tyrosine Kinase Inhibitors in the Treatment of Non-Small Cell Lung Cancer

The article reviews the current developmental status of antiangiogenic tyrosine kinase inhibitors (including vandetanib, sunitinib, axitinib, sorafenib, vatalanib, and pazopanib) in non-small cell lung cancer and discusses the need for optimal patient selection and potential future directions

HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice.

Members of the hypoxia-inducible factor (HIF) family of transcription factors regulate the cellular response to hypoxia. In non-small cell lung cancer (NSCLC), high HIF2alpha levels correlate with decreased overall survival, and inhibition of either the protein encoded by the canonical HIF target gene VEGF or VEGFR2 improves clinical outcomes. However, whether HIF2alpha is causal in imparting this poor prognosis is unknown. Here, we generated mice that conditionally express both a nondegradable variant of HIF2alpha and a mutant form of Kras (KrasG12D) that induces lung tumors. Mice expressing both Hif2a and KrasG12D in the lungs developed larger tumors and had an increased tumor burden and decreased survival compared with mice expressing only KrasG12D. Additionally, tumors expressing both KrasG12D and Hif2a were more invasive, demonstrated features of epithelial- mesenchymal transition (EMT), and exhibited increased angiogenesis associated with mobilization of circulating endothelial progenitor cells. These results implicate HIF2alpha causally in the pathogenesis of lung cancer in mice, demonstrate in vivo that HIF2alpha can promote expression of markers of EMT, and define HIF2alpha as a promoter of tumor growth and progression in a solid tumor other than renal cell carcinoma. They further suggest a possible causal relationship between HIF2alpha and prognosis in patients with NSCLC

Beyond Murphy, Films and Football: Audiovisual Content in Europe

European audiovisual policy recognises the broader societal significance of broadcast content, and professional content remains significant to policy objectives relating to the public sphere and the public interest. The digital environment has made their attainment more complex by allowing the introduction of numerous other services which aggregate and disseminate content in a range of ways. Given the value of broadcast content, tensions arise in the distribution chain as different actors seek to control and/or use that content leading to concerns on the one hand about the effect of free-riders and piracy on those producing content and, on the other, about excessive monopolisation of content, leading to barriers to those seeking either to develop new services or to the viewers. In this, the role and scope of copyright is key. This article assesses the existing European legislative framework and analyses the judgments of the Court of Justice against the objectives of ensuring that a wide range of content is available for viewers and that new services are not hindered in their development. Its thesis is that the development of legislation at Union level has led to consolidation of power in the hands of the few, which seek to exploit that position to the detriment of viewers and would be competitors, and that competition law and the essential facilities doctrine do not provide an adequate backstop level of regulation to prevent this. The article concludes with some proposals for reform