Interfacial Thermal Resistive Switching in (Pt,Cr)/SrTiO₃ Devices

The operation of oxide-based memristive devices relies on the fast accumulation and depletion of oxygen vacancies by an electric field close to the metal–oxide interface. Here, we show that the reversible change of the local concentration of oxygen vacancies at this interface also produces a change in the thermal boundary resistance (TBR), i.e., a thermal resistive switching effect. We used frequency domain thermoreflectance to monitor the interfacial metal–oxide TBR in (Pt,Cr)/SrTiO3 devices, showing a change of ≈20% under usual SET/RESET operation voltages, depending on the structure of the device. Time-dependent thermal relaxation experiments suggest ionic rearrangement along the whole area of the metal/oxide interface, apart from the ionic filament responsible for the electrical conductivity switching. The experiments presented in this work provide valuable knowledge about oxide ion dynamics in redox-based memristive devices

Additional file 2: of Biological compatibility between two temperate lineages of brown dog ticks, Rhipicephalus sanguineus (sensu lato)

Partial cytochrome c oxidase subunit 1 (cox1) gene sequences generated in this study. (FAS 60 kb

Combination of nilotinib, but not imatinib, with doxorubicin displayed a synergistic effect on apoptosis in leiomyosarcoma SK-UT-1 cells.

<p>A, <i>left</i>, DNA content of cells was measured by flow cytometry. Representative histograms of vehicle-treated (DMSO), DXR (0.05 µM)-treated, nilotinib (5 µM)-treated and pre-nilotinib 24 h+DXR-treated cells are shown. The fluorescence values used to calculate the peak corresponding to the sub-G1 phase are indicated on each histogram. <i>Right</i>, Columns show percentage of apoptotic cells in the absence (vehicle, V) or presence of DXR and nilotinib as single agents or combined (pre-Nilotinib+DXR). Each column represents mean ± SEM of four independent experiments. ^**<i>P</i><0.01 and ^***<i>P</i><0.001 versus DXR-treated cells. B) Antiproliferative effect of imatinib as single compound or combined with DXR (0.05 µM) (pre-Imatinib+DXR) for 72 h. Each column represents mean ± SEM of three independent experiments. C) Panels show the immunoreactive bands of procaspase 8 and 3, cleaved caspase 8 and 3, and PARP fragmentation in representative immunoblots of leiomyosarcoma cells treated as in A.</p

Nilotinib plus doxorubicin-treated leiomyosarcoma SK-UT-1 cells showed prolonged inhibition of cell growth after drug withdrawal.

<p>Cells were pre-treated with vehicle or nilotinib for 24 h, and DXR (0.05 µM) was then added to the corresponding wells and treatment continued for another 72 h. Cells were then recovered, diluted and reseeded at a density of 1.8×10⁴ cell per well with culture medium without any further compounds. After 12 days, cells were counted using a hemocytometer. Values are mean ± SEM of three independent experiments. ^*<i>P</i><0.05 and ^**<i>P</i><0.01 versus DXR-treated cells.</p

Nilotinib, but not imatinib, increased intracellular doxorubicin in human STS cells.

<p>Synovial sarcoma SW982 and leiomyosarcoma SK-UT-1 cells were incubated with vehicle (DMSO) or DXR (1 µM) in the absence (vehicle, V) or presence of nilotinib (1–10 µM) or imatinib (1–10 µM) as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037735#s2" target="_blank">Material and Methods</a> section. After 24 h incubation, intracellular DXR was measured by its fluorescence intensity with flow cytometry. <i>Left</i>, Median of intracellular DXR fluorescence in the absence (V) or presence of TK inhibitors normalized to vehicle-treated cells (taken as 100%). Each column represents mean ± SEM of seven independent experiments. <i>Right</i>, Representative flow cytometry analysis of the intracellular DXR fluorescence detected with excitation at 488 nm and emission at 580 nm in both cell lines. ^***<i>P</i><0.001 versus DXR-treated cells.</p

Nilotinib decreased fetal bovine serum-induced AKT activation and fully blocked ERK1/2 and p38 MAPK activation.

<p>Sub-confluent synovial sarcoma SW982 cells were deprived of fetal bovine serum (FBS) for 4 h. Cells were then stimulated for 30 min with 10% FBS in the absence (vehicle, V) or presence of imatinib (10 µM) or nilotinib (5 and 10 µM) as single compounds. <i>Upper panels</i> show representative immunoblots of four independent experiments. Columns represent the phosphorylated ratio of AKT, ERK1/2 and p38 MAPK. Each column represents mean ± SEM of four independent experiments normalized to FBS-depleted cells (-FBS, taken as 100%). ^*<i>P</i><0.05; ^**<i>P</i><0.01 and ^***<i>P</i><0.001 versus vehicle-treated cells stimulated with FBS.</p

Combination of nilotinib, but not imatinib, with doxorubicin (DXR) displayed a synergistic effect on growth inhibition and apoptosis in synovial sarcoma SW982 cells.

<p>A) Antiproliferative effect of nilotinib as single compound or combined with DXR. Synovial sarcoma cells were treated with vehicle or nilotinib (0.1–40 µM) alone or combined simultaneously with DXR (0.1, 0.3 and 0.5 µM) for 72 h. Each value represents mean ± SEM of four individual experiments performed in triplicate. B) Subsequent isobolographic analyses were performed as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037735#s2" target="_blank">Material and Methods</a> section. Drug combination was synergistic at all concentrations (CI<1), as shown in the isobologram. C) Apoptotic effect of nilotinib as single compound or combined with DXR (0.1 µM) for 72 h. <i>Upper panels</i> show the immunoreactive bands of procaspase 3, cleaved caspase 3 and PARP fragmentation in representative immunoblots. DNA content of cells was measured by flow cytometry. Columns show percentage of apoptotic cells in the absence (vehicle, V) or presence of DXR and nilotinib as single compounds or combined (DXR+nilotinib). Each column represents mean ± SEM of four independent experiments. ^***<i>P</i><0.001 versus DXR-treated cells. D) Antiproliferative effect of imatinib (0.5–10 µM) as single compound or combined with DXR (0.1 µM) for 72 h. Each column represents mean ± SEM of three independent experiments.</p

RG7112, a Small-Molecule Inhibitor of MDM2, Enhances Trabectedin Response in Soft Tissue Sarcomas

<div><p>ABSTRACT</p><p>MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Selected sarcoma subtypes are being treated with Trabectedin in second line, which promotes DNA damage and p53-dependent apoptosis. The aim of this study was to evaluate the improvement of Trabectedin response with MDM2 inhibitors in soft tissue sarcomas. The antitumor effects of Trabectedin, Nutlin-3A and RG7112 as single agents or in combination were examined <i>in vitro</i>. RG7112 significantly synergized with Trabectedin in MDM2-amplified liposarcoma cells, representing a promising new therapeutic strategy for the treatment of sarcomas with MDM2 amplification.</p></div

Nilotinib inhibited P-gp activity in human STS cells.

<p>Intracellular Rho-123 fluorescence (0.5 or 0.05 µM) was estimated by flow cytometry in synovial sarcoma SW982 cells after 2 h treatment or in leiomyosarcoma SK-UT-1 cells after 24 h treatment with vehicle (DMSO), imatinib (1–10 µM), nilotinib (1–10 µM) or verapamil (10 µM). <i>Left</i>, Median of intracellular Rho-123 fluorescence in the absence (vehicle, V) or presence of TK inhibitors normalized to vehicle-treated cells (taken as 100%). Each column represents mean ± SEM of five independent experiments. <i>Right</i>, Representative flow cytometry analysis of the intracellular Rho-123 fluorescence in the absence (vehicle) or presence of imatinib (10 µM) or nilotinib (10 µM) detected with excitation at 488 nm and emission at 580 nm. T0 was the intracellular Rho-123 fluorescence measured at t = 0. ^*<i>P</i><0.05 and ^***<i>P</i><0.001 versus vehicle-treated cells.</p

Nilotinib inhibited MRP-1 activity in human STS cells.

<p>Intracellular 5(6)-CFDA fluorescence was estimated by flow cytometry in synovial sarcoma SW982 and leiomyosarcoma SK-UT-1 cells after 2 h treatment with vehicle (V), imatinib (1–10 µM), nilotinib (1–10 µM) or probenecid (250 µM). <i>Left</i>, Median of intracellular CFDA fluorescence in the absence or presence of TK inhibitors normalized to vehicle-treated cells (taken as 100%). Each column represents mean ± SEM of three independent experiments. <i>Right</i>, Representative flow cytometry analysis of the intracellular CFDA fluorescence in the absence (vehicle) or presence of imatinib (10 µM) or nilotinib (10 µM) detected with excitation at 488 nm and emission at 530 nm. T0 was the intracellular CFDA fluorescence measured at t = 0. ^***<i>P</i><0.001 versus vehicle-treated cells.</p