In order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early, implying the existence of a different, faster route to the metastatic motile phenotype. Using a spontaneous murine model of melanoma, we show that a subset of bone marrow-derived immune cells (myeloid-derived suppressor cells or MDSC) preferentially infiltrates the primary tumor and actively promotes cancer cell dissemination by inducing epithelial-mesenchymal transition (EMT). CXCL5 is the main chemokine attracting MDSC to the primary tumor. In vitro assay using purified MDSC showed that TGF-β, EGF, and HGF signaling pathways are all used by MDSC to induce EMT in cancer cells. These findings explain how cancer cells acquire a motile phenotype so early and provide a mechanistic explanation for the long recognized link between inflammation and cancer progression.

The use of silver to control infections was common in ancient civilizations. In recent years, this material has resurfaced as a therapeutic option due to the increasing prevalence of bacterial resistance to antimicrobials. This renewed interest has prompted researchers to investigate how the antimicrobial properties of silver might be enhanced, thus broadening the possibilities for antimicrobial applications. This review presents a compilation of patented products utilizing any forms of silver for its bactericidal actions in the decade 2007–2017. It analyses the trends in patent applications related to different forms of silver and their use for antimicrobial purposes. Based on the retrospective view of registered patents, statements of prognosis are also presented with a view to heightening awareness of potential industrial and health care applications.

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The structure and reactivity of the surface methoxy species on Ag{ 11 l} have been studied using a combination of reflection absorption infrared spectroscopy and temperature-programmed desorption. Methoxy can be generated by exposing a preoxidized Ag{ 11 l} surface to methanol at 180 K and adsorbs in an upright geometry possessing effective 3-fold symmetry, with its C-0 bond axis oriented normal to the surface at all coverages.This conclusion is based on a detailed symmetry analysis coupled with rigorous application of the metalsurface selection rule and careful assignment of the infrared absorption bands with the aid of deuterium substitution. It is shown that strong Fermi resonance interactions are the cause behind unusual features observed in the C-H stretching region of the infrared spectra of methoxy on many metal surfaces. Significant interadsorbate dipole coupling and chemicaUelectrostatic effects are responsible for the coverage-dependent frequency shifts exhibited by the infrared active bands. Methoxy is stable on Ag{ 11 11 up to 290 K, above which it decomposes to yield formaldehyde as the major product, which desorbs in a reaction-limited step that is consistent with first-order kinetics. Formate has been identified as a minor surface species when excess surface oxygen is present and acts as the intermediate in the further oxidation of formaldehyde to COZ and Hz.

Epithelial–mesenchymal transition (EMT) plays a critical role in the early stages of dissemination of carcinoma leading to metastatic tumors, which are responsible for over 90% of all cancer-related deaths. Current therapeutic regimens, however, have been ineffective in the cure of metastatic cancer, thus an urgent need exists to revisit existing protocols and to improve the efficacy of newly developed therapeutics. Strategies based on preventing EMT could potentially contribute to improving the outcome of advanced stage cancers. To achieve this goal new assays are needed to identify targeted drugs capable of interfering with EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial-like state. Current assays are limited to examining the dispersion of carcinoma cells in isolation in conventional 2-dimensional (2D) microwell systems, an approach that fails to account for the 3-dimensional (3D) environment of the tumor or the essential interactions that occur with other nearby cell types in the tumor microenvironment. Here we present a microfluidic system that integrates tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an endothelial monolayer. Drug candidates inhibiting receptor activation or signal transduction pathways implicated in EMT have been tested using dispersion of A549 lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate significant differences in response to drugs between 2D and 3D, and between monoculture and co-culture.

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Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

The adsorption and reaction of the surface formate species on Ag{111} have been studied using a combination of reflection absorption infrared spectroscopy and temperature programmed desorption. Four formate species with distinct bonding configurations have been identified when formic acid is deprotonated by preoxidized Ag{111} at 240 K. Bidentate bridging formate with 2-fold symmetry is present at low coverage, while monodentate formate with three different degrees of tilt are formed sequentially with increasing coverage as a result of dipolar interactions and steric crowding. Coadsorption of methoxy and formate, accomplished by nucleophilic displacement of methyl formate with surface atomic O, yields an intermixed surface phase where interadsorbate interactions are minimized and formate tilting is suppressed. Monodentate formate partially decomposes to CO2 and formic acid at 325 K and partially reverts to bidentate bridging formate which dehydrogenates at 350 K to give CO2 and H2.