Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo

The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC-cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 μM) was tested by WST-1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice. Vandetanib significantly reduced ATC cell proliferation (P<0.01, ANOVA), induced apoptosis dose-dependently (P<0.001, ANOVA), and inhibited migration (P<0.01) and invasion (P<0.001). Furthermore, vandetanib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in ATC cells. In 8305C and AF cells, vandetanib significantly inhibited the proliferation, inducing also apoptosis. 8305C cells were injected subcutaneously in CD nu/nu mice and tumor masses became detectable after 30 days. Vandetanib (25 mg/kg/day) significantly inhibited tumor growth and VEGF-A expression and microvessel density in 8305C tumor tissues. In conclusion, the antitumor and antiangiogenic activity of vandetanib is very auspicious in ATC, opening the way to a future clinical evaluation

Lenvatinib exhibits antineoplastic activity in anaplastic thyroid cancer in vitro and in vivo

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages. The effect of lenvatinib (1 and 100 nM; and 1, 10, 25 and 50 μM) was investigated in primary ATC, 8305C and AF cells as well as in AF cells in CD nu/nu mice. Lenvatinib significantly reduced ATC cell proliferation (P<0.01, ANOVA) and increased the percentage of apoptotic ATC cells (P<0.001, ANOVA). Furthermore, lenvatinib inhibited migration (P<0.01) and invasion (P<0.001) in ATC. In addition, lenvatinib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in the ATC cells. Lenvatinib also significantly inhibited 8305C and AF cell proliferation, increasing apoptosis. AF cells were subcutaneously injected into CD nu/nu mice and tumor masses were observed 20 days later. Tumor growth was significantly inhibited by lenvatinib (25 mg/kg/day), as well as the expression of VEGF-A and microvessel density in the AF tumor tissues. In conclusion, the antitumor and antiangiogenic activities of lenvatinib may be promising for the treatment of anaplastic thyroid cancer, and may consist a basis for future clinical therapeutic applications

Tyrosine kinase inhibitors for the therapy of anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is often incurable so new therapeutic approaches are needed. Tyrosine kinases inhibitors (such as imanitib, sunitinib or sorafenib) are under evaluation for the treatment of ATC. Other vascular disrupting agents, such as combretastatin A4 phosphate, and antiangiogenic agents, such as aplidin, PTK787/ZK222584 and human VEGF monoclonal antibodies (bevacizumab, cetuximab), have been evaluated. Small-molecule adenosine triphosphate competitive inhibitors directed intracellularly at EGFRs tyrosine kinase, such as erlotinib or gefitinib, are also studied. Furthermore, new molecules have been shown to be active against ATC, such as CLM94 and CLM3. However, more research is needed to finally identify therapies able to control and to cure this disease

Numerical simulations of X-rays Free Electron Lasers (XFEL)

We study a nonlinear Schr\"odinger equation which arises as an effective single particle model in X-ray Free Electron Lasers (XFEL). This equation appears as a first-principles model for the beam-matter interactions that would take place in an XFEL molecular imaging experiment in \cite{frat1}. Since XFEL is more powerful by several orders of magnitude than more conventional lasers, the systematic investigation of many of the standard assumptions and approximations has attracted increased attention. In this model the electrons move under a rapidly oscillating electromagnetic field, and the convergence of the problem to an effective time-averaged one is examined. We use an operator splitting pseudo-spectral method to investigate numerically the behaviour of the model versus its time-averaged version in complex situations, namely the energy subcritical/mass supercritical case, and in the presence of a periodic lattice. We find the time averaged model to be an effective approximation, even close to blowup, for fast enough oscillations of the external field. This work extends previous analytical results for simpler cases \cite{xfel1}.Comment: 14 page

The LOFT Ground Segment

LOFT, the Large Observatory For X-ray Timing, was one of the ESA M3 mission candidates that completed their assessment phase at the end of 2013. LOFT is equipped with two instruments, the Large Area Detector (LAD) and the Wide Field Monitor (WFM). The LAD performs pointed observations of several targets per orbit (~90 minutes), providing roughly ~80 GB of proprietary data per day (the proprietary period will be 12 months). The WFM continuously monitors about 1/3 of the sky at a time and provides data for about ~100 sources a day, resulting in a total of ~20 GB of additional telemetry. The LOFT Burst alert System additionally identifies on-board bright impulsive events (e.g., Gamma-ray Bursts, GRBs) and broadcasts the corresponding position and trigger time to the ground using a dedicated system of ~15 VHF receivers. All WFM data are planned to be made public immediately. In this contribution we summarize the planned organization of the LOFT ground segment (GS), as established in the mission Yellow Book 1 . We describe the expected GS contributions from ESA and the LOFT consortium. A review is provided of the planned LOFT data products and the details of the data flow, archiving and distribution. Despite LOFT was not selected for launch within the M3 call, its long assessment phase (> 2 years) led to a very solid mission design and an efficient planning of its ground operations.Comment: Proc. SPIE 9144, Space Telescopes and Instrumentation 2014: Ultraviolet to Gamma Ray, 91446

ChPT tests at the NA48 and NA62 experiments at CERN

The NA48/2 Collaboration at CERN has accumulated unprecedented statistics of rare kaon decays in the Ke4 modes: Ke4(+-) ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and Ke4(00) ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. The detailed study of form factors and branching rates, based on these data, has been completed recently. The results brings new inputs to low energy strong interactions description and tests of Chiral Perturbation Theory (ChPT) and lattice QCD calculations. In particular, new data support the ChPT prediction for a cusp in the $\pi^0\pi^0$ invariant mass spectrum at the two charged pions threshold for Ke4(00) decay. New final results from an analysis of about 400 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN during low intensity runs with minimum bias trigger configurations are presented. The results include a model-independent decay rate measurement and fits to ChPT description.Comment: XIIth International Conference on Heavy Quarks and Leptons 2014, Mainz, German

Study of the a_0(980) meson via the radiative decay phi->eta pi^0 gamma with the KLOE detector

We have studied the phi->a_0(980) gamma process with the KLOE detector at the Frascati phi-factory DAPhNE by detecting the phi->eta pi^0 gamma decays in the final states with eta->gamma gamma and eta->pi^+ pi^- pi^0. We have measured the branching ratios for both final states: Br(phi->eta pi^0 gamma)=(7.01 +/- 0.10 +/- 0.20)x10^-5 and (7.12 +/- 0.13 +/- 0.22)x10^-5 respectively. We have also extracted the a_0(980) mass and its couplings to eta pi^0, K^+ K^-, and to the phi meson from the fit of the eta pi^0 invariant mass distributions using different phenomenological models.Comment: 17 pages, 6 figures, submitted to Physics Letters B. Corrected typos in eq.

GRB 081029: Understanding Multiple Afterglow Components

We present an analysis of the unusual optical light curve of the gamma-ray burst GRB~081029, which occurred at a redshift of z = 3.8479$. We combine X-ray and optical observations from the Swift X-Ray Telescope and the Swift UltraViolet/Optical Telescope with optical and infrared data obtained using the REM and ROTSE telescopes to construct a detailed data set extending from 86 s to approximately 100,000 s after the BAT trigger. Our data also cover a wide energy range, from 10 keV to 0.77 eV (1.24 Angstrom to 16,000 Angstrom). The X-ray afterglow shows a shallow initial decay followed by a rapid decay starting at about 18,000s. The optical and infrared afterglow, however, shows an uncharacteristic rise at about 5000 s that does not correspond to any feature in the X-ray light curve. Our data are not consistent with synchrotron radiation from a single-component jet interacting with an external medium. We do, however, find that the observed light curve can be explained using multi-component model for the jet.Comment: 4 pages, 3 figures, to appear in the AIP Conference Proceedings for the Gamma-Ray Burst 2010 Conference, Annapolis, MD, USA, November 201