STAT3 Is Activated by JAK2 Independent of Key Oncogenic Driver Mutations in Non-Small Cell Lung Carcinoma

Constitutive activation of STAT3 is a common feature in many solid tumors including non-small cell lung carcinoma (NSCLC). While activation of STAT3 is commonly achieved by somatic mutations to JAK2 in hematologic malignancies, similar mutations are not often found in solid tumors. Previous work has instead suggested that STAT3 activation in solid tumors is more commonly induced by hyperactive growth factor receptors or autocrine cytokine signaling. The interplay between STAT3 activation and other well-characterized oncogenic “driver” mutations in NSCLC has not been fully characterized, though constitutive STAT3 activation has been proposed to play an important role in resistance to various small-molecule therapies that target these oncogenes. In this study we demonstrate that STAT3 is constitutively activated in human NSCLC samples and in a variety of NSCLC lines independent of activating KRAS or tyrosine kinase mutations. We further show that genetic or pharmacologic inhibition of the gp130/JAK2 signaling pathway disrupts activation of STAT3. Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations

Systematic Assessment of Carbon Emissions from Renewable Energy Access to Improve Rural Livelihoods

One way of increasing access to electricity for impoverished unconnected areas without adding significant amounts of CO2 to the atmosphere is by promoting renewable energy technologies. However, decision-makers rarely, if ever, take into account the level of in-built energy requirements and consequential CO2 emissions found in renewable energy, particularly photovoltaic cells and related equipment, which have been widely disseminated in developing countries. The deployment of solar panels worldwide has mostly relied on silicon crystalline cell modules, despite the fact that less polluting material—in particular, thin film and organic cells—offers comparatively distinct technical, environmental and cost advantages characteristics. A major scientific challenge has thus been the design of a single decision-making approach to assess local and global climate change-related impacts as well as the socio-economic effects of low-carbon technology. The article focuses on the functions of the multi-criteria-based tool SURE-DSS and environmental impact analysis focused on greenhouse gases (GHG) emissions balance to inform the selection of technologies in terms of their impact on livelihoods and CO2eq. emissions. An application in a remote rural community in Cuba is discussed. The results of this study show that while PV silicon (c-Si), thin film (CdTe) and organic solar cells may each equally meet the demands of the community and enhance people’s livelihoods, their effect on the global environment varies