FAK Inhibition Decreases Hepatoblastoma Survival Both In Vitro and In Vivo

AbstractHepatoblastoma is the most frequently diagnosed liver tumor of childhood, and children with advanced, metastatic or relapsed disease have a disease-free survival rate under 50%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumor development and progression. FAK has been found in other pediatric solid tumors and in adult hepatocellular carcinoma, leading us to hypothesize that FAK would be present in hepatoblastoma and would impact its cellular survival. In the current study, we showed that FAK was present and phosphorylated in human hepatoblastoma tumor specimens. We also examined the effects of FAK inhibition upon hepatoblastoma cells using a number of parallel approaches to block FAK including RNAi and small molecule FAK inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and migration and increased apoptosis. Further, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse xenograft model of hepatoblastoma. The findings from this study will help to further our understanding of the regulation of hepatoblastoma tumorigenesis and may provide desperately needed novel therapeutic strategies and targets for aggressive, recurrent, or metastatic hepatoblastomas

Institutions for Asian Connectivity

To make Asia more economically sustainable and resilient against external shocks, regional economies need to be rebalanced toward regional demand- and trade-driven growth through increased regional connectivity. The effectiveness of connectivity depends on the quality of hard and soft infrastructure. Of particular importance in terms of soft infrastructure which makes hard infrastructure work are the facilitating institutions that support connectivity through appropriate policies, reforms, systems, and procedures and through promoting effective coordination and cooperation. Asia has many overlapping subregional institutions involved in national and regional energy, transport, and telecommunications infrastructure connectivity. However, these institutions are characterized as being less effective, informal, and lacking a clear and binding system of rules and policies. This paper draws linkages between connectivity, growth and development, governance, and institutions. It details the benefits the region could achieve by addressing needed connectivity enhancements and the connectivity and financing challenges it faces. In addition, it presents various institutional options for regional infrastructure financing. To build seamless Asian connectivity, Asia needs an effective, formal, and rules-based institutional framework. The paper presents a new institutional framework together with the organizational structures of two new regional institutional mechanisms, namely the Pan-Asian Infrastructure Forum and the Asian Infrastructure Fund

Politicising government engagement with corporate social responsibility: “CSR” as an empty signifier

Governments are widely viewed by academics and practitioners (and society more generally) as the key societal actors who are capable of compelling businesses to practice corporate social responsibility (CSR). Arguably, such government involvement could be seen as a technocratic device for encouraging ethical business behaviour. In this paper, we offer a more politicised interpretation of government engagement with CSR where “CSR” is not a desired form of business conduct but an element of discourse that governments can deploy in structuring their relationships with other social actors. We build our argument through a historical analysis of government CSR discourse in the Russian Federation. Laclau and Mouffe's (Hegemony and socialist strategy: Towards a radical democratic politics,Verso Books, London, 1985) social theory of hegemony underpins our research. We find that “CSR” in the Russian government’s discourse served to legitimise its power over large businesses. Using this case, we contribute to wider academic debates by providing fresh empirical evidence that allows the development of critical evaluation tools in relation to governments’ engagement with “CSR”. We find that governments are capable of hijacking CSR for their own self-interested gain. We close the paper by reflecting on the merit of exploring the case of the Russian Federation. As a “non-core”, non-western exemplar, it provides a useful “mirror” with which to reflect on the more widely used test-bed of Western industrial democracies when scrutinising CSR. Based on our findings, we invite other scholars to adopt a more critical, politicised stance when researching the role of governments in relation to CSR in other parts of the world