Physical limits to Economic Growth

The debate on the physical limits and constraints to the economic growth of globalized society is now widespread. This book explores the physical and economic aspects of the conflict between humans, with their thoughtless focus on growth through material production, and environmental constraints. In the context of the looming shortage of material resources and the latest science on climate change, Physical Limits to Economic Growth offers new insights which provide a broad and comprehensive picture of the conflict between humans and environmental constraints. The authors’ approach goes beyond the boundaries of specialized disciplines to explore climate change, resource depletion, technical innovation and the interactions between these within the socio-economic-institutional systems we live in. This volume looks at opportunities for rethinking these systems if we moved away from fossil fuel dependence, while considering the status of current mainstream economic thinking around this subject. Physical Limits to Economic Growth provides a genuine interdisciplinary examination of the physical limits to economic growth. It will be of interest to both students and academics in various disciplines in the areas of natural sciences, climate change and economics

Anaplastic lymphoma kinase aberrations correlate with metastatic features in pediatric rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches. Moreover, to get insight into its possible therapeutic relevance, effects of ALK silencing on cell proliferation, invasion and apoptosis were studied in RMS cells. ALK IHC positivity was significantly correlated with gene copy number gain, the alveolar subtype, PAX3/7-FOXO1 rearrangements, the presence of metastasis at diagnosis and a worse overall outcome. Furthermore, EML4-ALK fusion gene associated with higher protein expression was identified in an embryonal RMS. ALK silencing in RH30 ALK positive cells strongly inhibited invasion capability. Overall, our data suggest a potential role of ALK in pediatric RMS

Microenvironment-modulated metastatic CD133+/CXCR4+/EpCAM-lung cancer-initiating cells sustain tumor dissemination and correlate with poor prognosis

Metastasis is the main reason for lung cancer-related mortality, but little is known about specific determinants of successful dissemination from primary tumors and metastasis initiation. Here, we show that CD133+/CXCR4+ cancer-initiating cells (CIC) directly isolated from patient-derived xenografts (PDX) of non-small cell lung cancer are endowed with superior ability to seed and initiate metastasis at distant organs. We additionally report that CXCR4 inhibition successfully prevents the increase of cisplatin-resistant CD133+/CXCR4+ cells in residual tumors and their metastatization. Immunophenotypic analysis of lung tumor cells intravenously injected or spontaneously disseminated to murine lungs demonstrated the survival advantage and increased colonization ability of a specific subset of CD133+/CXCR4+ with reduced expression of epithelial cell adhesion molecule (EpCAM-), which also shows the greatest in vitro invasive potential. We next prove that recovered disseminated cells from lungs of PDX-bearing mice enriched for CD133+/CXCR4+/EpCAM-CICs are highly tumorigenic and metastatic. Importantly, microenvironment stimuli eliciting epithelial-to-mesenchymal transition, including signals from cancer-associated fibroblasts, are able to increase the dissemination potential of lung cancer cells through the generation of the CD133+/CXCR4+/EpCAM-subset. These findings also have correlates in patient samples where disseminating CICs are enriched in metastatic lymph nodes (20-fold, P=0.006) and their detection in primary tumors is correlated with poor clinical outcome (diseasefree survival: P=0.03; overall survival: P=0.05). Overall, these results highlight the importance of specific cellular subsets in the metastatic process, the need for in-depth characterization of disseminating tumor cells, and the potential of therapeutic strategies targeting both primary tumor and tumor-microenvironment interactions. Cancer Res; 75(17); 3636-49