Search

The paper discusses the relationship between Commons, Social Capital, and sustainability in terms of resources used, tools available, and goals to be achieved. The conceptual framework differs from the traditional one, which considers Commons and Social Capital as different resources. The paper considers Commons and Social Capital as homogeneous assets defined by the rights related to the access, use, and reproduction of collective resources, material or immaterial, which are essential to reduce the difference between private and social costs in the economic processes. This approach derives from a definition of sustainability as a private and social responsibility in reproducing all the resources used in the life processes, minimizing the waste caused by their exhaustion and loss of fertility. The paper refers to the model of Commons by the school of Elinor Ostrom to explain the nature and role of Social Capital and to observe it in different units of analysis, with particular attention to the forms of cooperative enterprise. The last part of the work outlines field research on the Parmigiano Reggiano supply chain as a natural laboratory to test the theoretical hypotheses.

Additional file 1: Supplemental Fig. 1. General description of phosphotyrosine-enriched analysis. a. Pearson correlation of technical replicates showed good correlation, replicate 1 represents a technical replicate in one dataset, while replicate 2 and 3 represent interexperiment replicates. b. Pie chart of all RTKs and non-RTKS identified in the discovery dataset show high coverage of the kinome. c. Unsupervised clustering of phosphorylated kinases identify an abundance of kinase activity. Supplemental Fig. 2. Evaluation of kinases and FAK in PDAC. a. Outlier analysis of kinases in the discovery dataset showed no outlier phosphorylation (Grubbs’ test, threshold 1%) in the top 10 phosphorylated kinases. Bar shows median with range. b. Phosphorylated FAK represents a significant quantity of total kinases identified. c. Sensitivity curves of VS-4718 and d. TAE226 confirms effectiveness of FAK inhibition in PDAC. (Error bars are SEM of biological replicates, n = 3). Supplemental Fig. 3. Defactinib is a potent FAK inhibitor. a. Unsupervised clustering of Suit-2 cells treated with vehicle or defactinib after two hours showed different clusters. b. Heatmap of INKA score upon treatment with defactinib. c. INKA score comparison of FAK activity d. Bar graph of significantly downregulated phosphopeptides (PP) of FAK substrates (Error bars are SD of biological replicates, n = 2, t-test *

Radiotherapy is one of the main treatment modalities in oncology. The therapeutic effectiveness of irradiation is dependent on the balance between the tumour control probability (TCP) and the normal tissue complication probability (NTCP), i.e. the induction of side effects. Combination treatment of irradiation with chemotherapy, targeted or immune-modulating agents could significantly benefit from nanotechnology strategies, allowing localized delivery of therapeutic compounds to the irradiated tumour volume. When used in combination with irradiation, drugs should be selected on their interaction with the 6 R’s, the six Hallmarks of Radiobiology, to sensitize for the radiation effect on the molecular, cellular and tissue level, and therewith positively impact the TCP/NTCP balance. In this chapter, preclinical data on the combination of irradiation and nanocarrier delivered drugs in brain, pancreatic, and liver cancer are presented and discussed. Before implementation into the clinical practice, nanotechnology demands for further technical and biological studies on topics such as drug loading efficacy, drug release, cellular and tissue uptake, biodistribution, tumour targeting methods and administration routes to the patient. Notwithstanding those challenges, the combination of local radiotherapy with tumour targeted nanocarrier delivered radiosensitizers as well as the use of radiosensitizing nanoparticles are exciting developments with great clinical prospect.

Ittai B Muller,1 Adrianus J de Langen,2,3 Elisa Giovannetti,4,5 Godefridus J Peters4 1Department of Clinical Chemistry, 2Department of Pulmonology, VU University Medical Center, 3Department of Thoracic Oncology, Netherlands Cancer Institute, 4Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands; 5Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy Abstract: A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors. Keywords: crizotinib, acquired resistance, alectinib, anaplastic lymphoma kinase, tyrosine kinase inhibitors, non-small cell lung cancer