Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice

Pharmacological treatments for advanced hepatocellular carcinoma (HCC) have a partial efficacy. Augmented Na+ content and water retention are observed in human cancers and offer unexplored targets for anticancer therapies. Na+ levels are evaluated upon treatments with the antibiotic cation ionophore Monensin by fluorimetry, ICP-MS, Na-23-MRI, NMR relaxometry, confocal or time-lapse analysis related to energy production, water fluxes and cell death, employing both murine and human HCC cell lines, primary murine hepatocytes, or HCC allografts in NSG mice. Na+ levels of HCC cells and tissue are 8-10 times higher than that of healthy hepatocytes and livers. Monensin further increases Na+ levels in HCC cells and in HCC allografts but not in primary hepatocytes and in normal hepatic and extrahepatic tissue. The Na+ increase is associated with energy depletion, mitochondrial Na+ load and inhibition of O-2 consumption. The Na+ increase causes an enhancement of the intracellular water lifetime and death of HCC cells, and a regression and necrosis of allograft tumors, without affecting the proliferating activity of either HCCs or healthy tissues. These observations indicate that HCC cells are, unlike healthy cells, energetically incapable of compensating and surviving a pharmacologically induced Na+ load, highlighting Na+ homeostasis as druggable target for HCC therapy.The ionophore monensin is shown to have cancer-selective cytotoxic action by selectively increasing the sodium content in cultured hepatocellular carcinoma cells (HCC) and allografts, highlighting the sensitivity of HCC cells to pharmacologically induced Na+ load

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Boccaccio

In Boccaccio le attività di autore, copista, esegeta e traduttore di testi concorrono alla realizzazione di un unico progetto intellettuale. La stessa interpretazione del Decameron – opera fondativa della narrativa europea – non può prescindere dall’esame di questo complesso sistema culturale in cui tradizione e innovazione convivono in una nuova visione del mondo e della letteratura. Il volume propone un profilo di Boccaccio attraverso quindici saggi di studiose (Monica Berté, Roberta Cella, Silvia Finazzi, Irene Iocca, Carla Maria Monti, Laura Regnicoli, Valentina Rovere) e studiosi (Luca Azzetta, Renzo Bragantini, Stefano Carrai, Marco Cursi, Maurizio Fiorilla, Marco Petoletti, Angelo Piacentini, Daniele Piccini) che offrono una rilettura critica delle sue opere, insieme a percorsi dedicati ai documenti biografici, alla lingua dei testi, ai manoscritti autografi e alla biblioteca, agli scambi epistolari con Petrarca e altri corrispondenti, al culto di Dante. Tenendo conto delle prospettive attivate dalla più recente stagione di studi, il libro rilancia la figura di Boccaccio in tutta la sua profondità di autore medievale e di umanista