Rewiring innate and adaptive immunity with TLR9 agonist to treat osteosarcoma

Background Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60-70% of event-free survival for localized disease at diagnosis. However, for metastatic disease, the prognosis is dismal. Exploiting immune system activation in the setting of such unfavorable mesenchymal tumors represents a new therapeutic challenge. Methods In immune competent OS mouse models bearing two contralateral lesions, we tested the efficacy of intralesional administration of a TLR9 agonist against the treated and not treated contralateral lesion evaluating abscopal effect. Multiparametric flow cytometry was used to evaluate changes of the tumor immune microenviroment. Experiments in immune- deficient mice allowed the investigation of the role of adaptive T cells in TLR9 agonist effects, while T cell receptor sequencing was used to assess the expansion of specific T cell clones. Results TLR9 agonist strongly impaired the growth of locally-treated tumors and its therapeutic effect also extended to the contralateral, untreated lesion. Multiparametric flow cytometry showed conspicuous changes in the immune landscape of the OS immune microenvironment upon TLR9 engagement, involving a reduction in M2-like macrophages, paralleled by increased infiltration of dendritic cells and activated CD8 T cells in both lesions. Remarkably, CD8 T cells were needed for the induction of the abscopal effect, whereas they were not strictly necessary for halting the growth of the treated lesion. T cell receptor (TCR) sequencing of tumor infiltrating CD8 T cells showed the expansion of specific TCR clones in the treated tumors and, remarkably, their selected representation in the contralateral untreated lesions, providing the first evidence of the rewiring of tumor-associated T cell clonal architectures. Conclusions Overall these data indicate that the TLR9 agonist acts as an in situ anti-tumor vaccine, activating an innate immune response sufficient to suppress local tumor growth while inducing a systemic adaptive immunity with selective expansion of CD8 T cell clones, which are needed for the abscopal effect

Emungimento delle acque e cedimenti nell'abitato di Sarno: analisi preliminare

Nel Comune di Sarno (SA) si sta verificando un fenomeno di subsidenza che ha già causato gravi danni ad alcuni edifici. Per individuarne le cause e seguirne l’evoluzione sono state intraprese indagini in situ e in laboratorio. Nel presente lavoro si riporta un inquadramento delle problematiche sulla base dei dati disponibili. I risultati, ancorché preliminari, permettono d’individuare una stretta correlazione fra lo sfruttamento delle acque sotterranee praticato intensamente in tutto il comprensorio e gli abbassamenti dei livelli di falda. Questi ultimi, pur essendo contenuti, hanno prodotto cedimenti notevoli del sottosuolo a causa della presenza di torbe molto deformabili che, sottoposte a prove di laboratorio, hanno mostrato caratteristiche di marcata viscosità e grande sensibilità alla composizione del fluido interstiziale

Vi-cloth (Virtual-clothing)

Nel presente articolo viene illustrato un ambiente per la progettazione virtuale 3D capi di abbigliamento anche su misura, simulando e validando virtualmente il loro comportamento in funzione delle proprietà meccaniche del tessuto e della configurazione del manichino e/o corpo umano. Tale ambiente prevede l’integrazione di diverse tecnologie e sistemi software, e precisamente: sistemi di digitalizzazione ed acquisizione di misure del corpo umano, sistemi per la modellazione di manichini, sistemi per la modellazione e simulazione di capi di abbigliamento e strumenti per la caratterizzazione meccanica dei tessuti. VI-CLOTH viene sviluppato nell’ambito del progetto PRIN03 - Studio e Sviluppo di un Ambiente Integrato Tridimensionale per la Progettazione Virtuale di Tessuti e Capi di Abbigliamento, denominato VI-CLOTH (Virtual Clothing), al quale partecipano quattro gruppi di ricerca operanti presso l’Universita degli Studi di Bergamo (coordinatore nazionale), Università degli Studi di Brescia, Universita degli Studi di Firenze e Politecnico di Milano

Systematic innovation practices for SMEs

Innovation is the main goal for small and medium enterprises as well as for big companies; nevertheless, while the latter are used to the introduction of new methodologies and tools for increasing the competitive potential of their product development cycle, SMEs usually give a greater relevance to personal talent and expertise of few employees. Moreover they have to face a continuous lack of resources, so that an investment on high level education is often prohibitive.Nevertheless small companies have the opportunity to play an even more relevant role for the economy of EU due to their greater flexibility and potential capability to adapt to market needs more easily.Therefore a customized approach must be adopted for providing innovation means to SMEs. According to this perspective, the authors are experiencing a 360 degrees cooperation with several small companies in order to develop a comprehensive roadmap. This paper first analyzes basic constraints of the SMEs world and some relevant differences with bigger companies; then the integrated approach for enhancing innovation capabilities is presented together with the main actions already accomplished.The authors in the past have collected several successful experiences about innovation and problem solving tasks working with different medium/large size companies, by integrating TRIZ theory and tools with PLM (Product Lifecycle Management) systems. On the base of the positive feedbacks gained through those collaborations, a special program has been started aimed at introducing systematic innovation practices even in SMEs.This paper describes the guidelines defined so far to achieve such a goal, supported by three concurrent pillars: monitoring, support, education. In order to demonstrate the efficiency of the proposed approach two case studies are presented: the redesign of a hinge for household appliances and the re-engineering of the production for an industrial mixer

Downregulation of Pro-Inflammatory and Pro-Angiogenic Pathways in Prostate Cancer Cells by a Polyphenol-Rich Extract from Olive Mill Wastewater

Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed ‘olive mill wastewater’ (OMWW) that have been reported to contain water-soluble polyphenols. Prostate cancer (PCa) is considered as an ideal cancer type for chemopreventive approaches, due to its wide incidence but relatively long latency period and progression time. Here, we investigated activities associated with potential preventive properties of a polyphenol-rich olive mill wastewater extract, OMWW (A009), on three in vitro models of PCa. A009 was able to inhibit PCa cell proliferation, adhesion, migration, and invasion. Molecularly, we found that A009 targeted NF-κB and reduced pro-angiogenic growth factor, VEGF, CXCL8, and CXCL12 production. IL-6/STAT3 axis was also regulated by the extract. A009 shows promising properties, and purified hydroxytyrosol (HyT), the major polyphenol component of A009, was also active but not always as effective as A009. Finally, our results support the idea of repositioning a food waste-derived material for nutraceutical employment, with environmental and industrial cost management benefits

Very High Resolution and Frequent Revisiting SAR Systems Applied to the Environmental Protection: a contribution based on the use of COSMO-SkyMed Interferometric Data

Since the early nineties SAR has been developed to provide contributions to several areas of the environmental risk monitoring. With the launch of X-Band Very High Resolution sensors, a significant advance in the extension of the applications to the monitoring of deformation affecting the built environment exposed to hazards has been achieved. In this work we summarize the outcomes of the studies resulting from the application of our interferometric chain developed for the processing of data acquired by the COSMO-SkyMed constellation. Applications regard geophysical processes of seismic and volcanic genesis, as well as areas affected by landslides and cultural heritage