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Articles you may be interested inImaging of variation in charge/orbital/spin ordering structure in Sm 1 − x Sr x MnO 3 ( x = 0.55 and 0.6) Appl. Phys. Lett. 94, 082509 (2009); Role of the A-site size and oxygen stoichiometry in charge ordering commensurability of Ln 0.50 Ca 0.50 MnO 3 manganites

Using atomically resolved electron energy-loss spectroscopy, the atomic-plane-by-atomic-plane, unit-cellby-unit-cell stoichiometry, and charge characteristics of the oxide interface (Nd 0.35 Sr 0.65)MnO 3 /SrTiO 3 , with a primitive polar discontinuity of (Nd 0.35 Sr 0.65 O) 0.35+-(TiO 2) 0 , were thoroughly investigated. (Nd 0.35 Sr 0.65)MnO 3 is a strongly correlated insulator and the interface was characterized to be insulating. The cell-specific stoichiometric evaluation unveiled an extensive interdiffusion across the interface. The plane-specific charge characterization revealed that the interdiffusion grades the primitive polar discontinuity. Despite the graded polar discontinuity, a charge transfer inversely into (Nd 0.35 Sr 0.65)MnO 3 was firmly resolved with a length scale of ∼2 nm and a charge density on the order of ∼10 13 /cm 2 and is effectively mediated by an asymmetric Ti interdiffusion. The intricate electronic correlations of the interfacial (Nd 0.35 Sr 0.65)MnO 3 unit cells and the interdiffusion-induced chemical disorder tend to render the charges localized, resulting in a localized two-dimensional electron density and thus the insulating interface, in distinct contrast to the conventional understanding of a vanishing charge density for an insulating interface and the metallic two-dimensional electron gas found at other classical polar-discontinuous interface systems. A potential strain manipulation on the electronic localization of the electron density was also proposed.

Epidermal growth factor receptor (EGFR), which promotes cell survival and division, is found at abnormally high levels on the surface of many cancer cell types, including many cases of non-small cell lung cancer. Erlotinib (Tarceva), an oral small-molecule tyrosine kinase inhibitor, is a so-called targeted drug that inhibits the tyrosine kinase domain of EGFR, and thus targets cancer cells with some specificity while doing less damage to normal cells. However, erlotinib resistance can occur, reducing the efficacy of this treatment. To develop more effective therapeutic interventions by overcoming this resistance problem, we combined the histone deacetylase inhibitor, MPT0E028, with erlotinib in an effort to increase their antitumor effects in erlotinib-resistant lung adenocarcinoma cells. This combined treatment yielded significant growth inhibition, induced the expression of apoptotic proteins (PARP, γH2AX, and caspase-3), increased the levels of acetylated histone H3, and showed synergistic effects in vitro and in vivo. These effects were independent of the mutation status of the genes encoding EGFR or K-Ras. MPT0E028 synergistically blocked key regulators of the EGFR/HER2 signaling pathways, attenuating multiple compensatory pathways (e.g., AKT, extracellular signal-regulated kinase, and c-MET). Our results indicate that this combination therapy might be a promising strategy for facilitating the effects of erlotinib monotherapy by activating various networks. Taken together, our data provide compelling evidence that MPT0E028 has the potential to improve the treatment of heterogeneous and drug-resistant tumors that cannot be controlled with single-target agents.