623 research outputs found

    The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway

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    Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at \u3c40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers

    Differential Expression of Chemokine and Matrix Re-Modelling Genes Is Associated with Contrasting Schistosome-Induced Hepatopathology in Murine Models

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    The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis

    Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

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    The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 < pt < 70 GeV, in the rapidity intervals abs(y) < 0.6 and 0.6 < abs(y) < 1.2. The corresponding psi(2S) results cover 14 < pt < 50 GeV and include a third rapidity bin, 1.2 < abs(y) < 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored

    Measurement of the triple-differential cross section for photon plus jets production in proton-proton collisions at √s = 7 TeV

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    Evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons

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    Search for massive resonances in dijet systems containing jets tagged as W or Z boson decays in pp collisions at √s=8 TeV

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    Measurement of the t-channel single-top-quark production cross section and of the |V tb| CKM matrix element in pp collisions at √s = 8 TeV

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    Schadevergoeding bij overlijden: een stoel die een soort tafeltje is

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    In het aansprakelijkheidsrecht heeft een benadeelde in beginsel recht op volledige vergoeding van zijn schade. De gevolgen van de schadetoebrengende gebeurtenis dienen zoveel als mogelijk te worden weggenomen of te worden gecompenseerd. Daarbij wordt gekeken naar de situatie waarin de benadeelde zou hebben verkeerd indien de schadetoebrengende gebeurtenis niet zou hebben plaatsgevonden. Dat is bij overlijden per definitie problematisch. Er is iemand weggevallen, wat vele gevolgen heeft. De schade als gevolg van het overlijden komt maar beperkt voor vergoeding in aanmerking. In artikel 6:108 BW is een drietal beperkingen te vinden. Het gaat hier om beperkingen ten aanzien van de aard van de schade, de kring van gerechtigden en de omvang van de schade. Daarbij hinkt het recht op schadevergoeding bij overlijden op twee gedachten. Aan de ene kant is er het aansprakelijkheidsrecht, maar de geleden schade komt niet volledig voor vergoeding in aanmerking. Aan de andere kant is er het recht op alimentatie uit het familierecht, maar dat wordt bij overlijden niet consequent toegepast. De motieven voor de beperkingen van het recht op schadevergoeding zijn achterhaald en niet (langer) overtuigend. Het recht is niet bij de tijd, het sluit niet aan bij de maatschappelijke ontwikkelingen. De beperkingen die het recht op schadevergoeding bij overlijden in de huidige samenleving met zich meebrengt zorgen voor complexe methoden om de nabestaanden tegemoet te komen en oogsten daardoor veel kritiek. In deze bijdrage wordt die kritiek besproken. De bijdrage wordt afgesloten met enkele denkrichtingen voor nader onderzoek

    Observation of the diphoton decay of the Higgs boson and measurement of its properties

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    Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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