340 research outputs found

    Mesenchymal stem cells from tumor microenvironment favour breast cancer stem cell proliferation, cancerogenic and metastatic potential, via ionotropic purinergic signalling

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    Interaction between tumor cells and the microenvironment is key in initiation, progression, and invasiveness of cancer. In particular, mesenchymal stem cells (MSCs) are recruited to the sites of developing tumors, thus promoting metastasis formation. Although it is well known that MSCs migrate and integrate in the tumor microenvironment (TME), their fate and function inside the tumor is still not clear. In this study, we analyzed the role played by MSCs in breast cancer oncogenesis. Data indicate that interaction of breast cancer cells with MSCs results in an increased proliferation and metabolic activity of breast cancer cells, partially due to MSC-derived microvesicles that are shed in the TME. Moreover, we addressed the question of whether we could modulate such interaction by acting on P2X-mediated intercellular communication. By inhibiting P2X-mediated purinergic signaling, we succeeded in reducing both the cancerogenic as well as the metastatic potential of breast cancer cells co-cultured with MSCs, in 2D as well as in 3D in vitro models. Data obtained demonstrate for the first time that the trophic effect of MSCs on breast cancer cell growth is exerted via ionotropic purinergic signaling, thus suggesting the inhibition of the purinergic signaling system as a potential target for therapeutic intervention

    Wetting films on chemically heterogeneous substrates

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    Based on a microscopic density functional theory we investigate the morphology of thin liquidlike wetting films adsorbed on substrates endowed with well-defined chemical heterogeneities. As paradigmatic cases we focus on a single chemical step and on a single stripe. In view of applications in microfluidics the accuracy of guiding liquids by chemical microchannels is discussed. Finally we give a general prescription of how to investigate theoretically the wetting properties of substrates with arbitrary chemical structures.Comment: 56 pages, RevTeX, 20 Figure

    Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

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    Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations

    Fast, Multiphase Volume Adaptation to Hyperosmotic Shock by Escherichia coli

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    All living cells employ an array of different mechanisms to help them survive changes in extra cellular osmotic pressure. The difference in the concentration of chemicals in a bacterium's cytoplasm and the external environment generates an osmotic pressure that inflates the cell. It is thought that the bacterium Escherichia coli use a number of interconnected systems to adapt to changes in external pressure, allowing them to maintain turgor and live in surroundings that range more than two-hundred-fold in external osmolality. Here, we use fluorescence imaging to make the first measurements of cell volume changes over time during hyperosmotic shock and subsequent adaptation on a single cell level in vivo with a time resolution on the order of seconds. We directly observe two previously unseen phases of the cytoplasmic water efflux upon hyperosmotic shock. Furthermore, we monitor cell volume changes during the post-shock recovery and observe a two-phase response that depends on the shock magnitude. The initial phase of recovery is fast, on the order of 15–20 min and shows little cell-to-cell variation. For large sucrose shocks, a secondary phase that lasts several hours adds to the recovery. We find that cells are able to recover fully from shocks as high as 1 Osmol/kg using existing systems, but that for larger shocks, protein synthesis is required for full recovery
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