1,850 research outputs found

    Room temperature radio-frequency plasma-enhanced pulsed laser deposition of ZnO thin films

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    [[abstract]]In this study, we compared the crystalline structures, optical properties, and surface morphologies of ZnO thin films deposited on silicon and glass substrates by conventional pulsed laser deposition (PLD) and radio-frequency (RF) plasma-enhanced PLD (RF-PEPLD). The depositions were performed at room temperature under 30-100 mTorr pressure conditions. The RF-PEPLD process was found to have deposited a ZnO structure with preferred (0 0 2) c-axis orientation at a higher deposition rate; however, the RF-PEPLD process generated more defects in the thin films. The application of oxygen pressure to the RF-PEPLD process reduced defects effectively and also increased the deposition rate. (c) 2012 Elsevier B.V. All rights reserved.[[note]]SC

    Suppression of Radiation Induced Pulmonary Metastasis by Yc-1 through Inhibition of Cancer Cell Invasion and Adhesion Capabilities in a Mouse Model

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    Purpose/Objective: Metastasis has been the lethal factor in cancer patients. YC-1, 3-(5′-hydroxymethyl-2′-furyl)-1- benzylindazole, an agent developed for circulatory disorders by inhibiting platelet aggregation and vascular contraction , was found to inhibit hypoxia inducible factor-1 (HIF-1) activity. HIF-1 is a stress protein during radiation and modulates genes associated with cancer invasion and metastasis. With HIF-1 as a molecular target of YC-1, we try to clarify the therapeutic effect and mechanism of YC-1 on radiation induced cancer metastasis. Materials/Methods: An established animal model with radiation induced pulmonary metastasis was used in this study. The right thighs of thirty-two C57BL/6 mice were injected subcutaneously with 1× 106 Lewis lung carcinoma (LLC-LM) cells. Animals were randomized to one of the four groups, including no treatment (Control), radiation with 50 Gy in five 10 Gy daily fractions (RT), radiation with 50 Gy in five 10 Gy daily fractions and YC-1 (RT+YC-1), and YC-1 alone (YC-1). Radiation with cobalt -60 started 7 days after LLC-LM cell implantation. YC-1 (10mg/kg/day) was given orally from 3 days before radiation to the last day of the study. The animals were sacrificed 14 days after radiation. The serial sections of both lungs in each mouse were taken for the number of pulmonary metastasis. Besides, LLC-LM cells were in vitro treated with 5 to 20 uM of YC-1 for cytotoxicity test in MTT assay, with non-toxic dose of YC-1 used in the subsequent adhesion and invasion assay. Metalloprotease (MMP )-2 activities were determined by gelatin zymography assay and RT-PCR. Level of focal adhesion kinase (FAK) phosphorylation was determined by western blot. Results: The eradication of a primary LLC-LM was followed by the rapid growth of pulmonary metastasis within 14 days after radiation. Radiation to the thigh tumor induced pulmonary metastasis significantly ( Control vs. RT, p<0.001). Pulmonary metastases was significantly reduced with the addition of YC-1 to radiation (RT vs. RT+YC-1, p<0.001). YC- 1 itself did not have any impact on pulmonary metastasis ( Control vs. YC-1, p=0.883). The body weight of mice with radiation alone was lower than the other groups, but the difference was not statistically significant. The gelatin zymography with mouse urine samples showed that the level of MMP-2 activity, correlated with tumor growth, was much lower in YC-1 treated groups. The in vitro study showed YC-1 significantly inhibited radiation induced LLC-LM cell invasion on matrigel coated Boyden chamber, MMP-2 expression , and serum induced FAK phosphorylation. Conclusions: YC-1 inhibited radiation induced lung metastasis not only through the mechanism of HIF-1 related tumor angiogenesis but also by inhibiting cancer cell invasion and adhesion capabilities

    YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK

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    BACKGROUND AND PURPOSE YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells. EXPERIMENTAL APPROACH In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1. KEY RESULTS YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration-and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2. CONCLUSION AND IMPLICATIONS We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer
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