Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

<p>Abstract</p> <p>Background</p> <p>Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown <it>in vivo</it>. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells.</p> <p>Results</p> <p>Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma <it>in situ</it>, but not in low-grade and noninvasive phenotypes.</p> <p>Conclusions</p> <p>COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.</p

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

Measurement of Trilinear Gauge Couplings in e+e−e^+ e^- Collisions at 161 GeV and 172 GeV

Trilinear gauge boson couplings are measured using data taken by DELPHI at 161~GeV and 172~GeV. Values for $WWV$ couplings ($V=Z, \gamma$) are determined from a study of the reactions \eeWW\ and \eeWev, using differential distributions from the $WW$ final state in which one $W$ decays hadronically and the other leptonically, and total cross-section data from other channels. Limits are also derived on neutral $ZV\gamma$ couplings from an analysis of the reaction \eegi

Search for neutral heavy leptons produced in ZZ decays

Weak isosinglet Neutral Heavy Leptons (νm) have been searched for using data collected by the DELPHI detector corresponding to 3.3 × 106 hadronic Z0 decays at LEP1. Four separate searches have been performed, for short-lived νm production giving monojet or acollinear jet topologies, and for long-lived νm giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio BR(Z0 → νmν̄) of about 1.3 × 10-6 at 95% confidence level for νm masses between 3.5 and 50 GeV/c2. Outside this range the limit weakens rapidly with the νm mass. The results are also interpreted in terms of limits for the single production of excited neutrinos. © Springer-Verlag 1997

Study of B0_s anti-B0_s oscillations and B0_s lifetimes using hadronic decays of B0_s mesons

Oscillations of B0s mesons have been studied in samples selected from about 3.5 million hadronic Z decays detected by DELPHI between 1992 and 1995. One analysis uses events in the exclusive decay channels: B0s -> Ds- pi+ or Ds- a1+ and B0s -> anti-D0 K- pi+ or anti-D0 K- a1+, where the D decays are completely reconstructed. In addition, B0s anti-B0s oscillations have been studied in events with an exclusively reconstructed Ds accompanied in the same hemisphere by a high momentum hadron of opposite charge. Combining the two analyses, a limit on the mass difference between the physical B0s states has been obtained: Delta(m_B0s) > 4.0 ps^{-1} at the 95% C.L. with a sensitivity of Delta(m_B0s) = 3.2 ps^{-1}. Using the latter sample of events, the B0s lifetime has been measured and an upper limit on the decay width difference between the two physical B0s states has been obtained: tau(B0s) = 1.53^{+0.16}_{-0.15}(stat.) +/- {0.07}(syst.) ps \Delta\Gamma(B0s)/\Gamma(B0s) < 0.69 at the 95% C.L. The combination of these results with those obtained using Ds+- lepton-+ sample gives: Delta(m_B0s) > 4.9 ps^{-1} at the 95% C.L. with a sensitivity of Delta(m_B0s) = 8.7 ps^{-1}. tau(B0s) = 1.46 +/- 0.11 ps and \Delta\Gamma(B0s)/\Gamma(B0s) < 0.45 at the 95% C.L.Comment: 42 pages, 13 figure

ICAR: endoscopic skull‐base surgery

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Search for B → μ μ And B0 → μ+ μ- Decays

A search for the rare decays B → μ μ and B → μ μ is performed in pp collisions at ps = 7TeV, with a data sample corresponding to an integrated luminosity of 5 fb collected by the CMS experiment at the LHC. In both decays, the number of events observed after all selection requirements is consistent with the expectation from background plus standard model signal predictions. The resulting upper limits on the branching fractions are B(B → μ μ-) < 7:7 × 10 and B(B → μ μ ) < 1:8 × 10 at 95% confidence level