Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board-approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed. Conclusion This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC

Novel method for hit-position reconstruction using voltage signals in plastic scintillators and its application to Positron Emission Tomography

Currently inorganic scintillator detectors are used in all commercial Time of Flight Positron Emission Tomograph (TOF-PET) devices. The J-PET collaboration investigates a possibility of construction of a PET scanner from plastic scintillators which would allow for single bed imaging of the whole human body. This paper describes a novel method of hit-position reconstruction based on sampled signals and an example of an application of the method for a single module with a 30 cm long plastic strip, read out on both ends by Hamamatsu R4998 photomultipliers. The sampling scheme to generate a vector with samples of a PET event waveform with respect to four user-defined amplitudes is introduced. The experimental setup provides irradiation of a chosen position in the plastic scintillator strip with an annihilation gamma quanta of energy 511~keV. The statistical test for a multivariate normal (MVN) distribution of measured vectors at a given position is developed, and it is shown that signals sampled at four thresholds in a voltage domain are approximately normally distributed variables. With the presented method of a vector analysis made out of waveform samples acquired with four thresholds, we obtain a spatial resolution of about 1 cm and a timing resolution of about 80 p

The Straw Tube Trackers of the PANDA Experiment

The PANDA experiment will be built at the FAIR facility at Darmstadt (Germany) to perform accurate tests of the strong interaction through bar pp and bar pA annihilation's studies. To track charged particles, two systems consisting of a set of planar, closed-packed, self-supporting straw tube layers are under construction. The PANDA straw tubes will have also unique characteristics in term of material budget and performance. They consist of very thin mylar-aluminized cathodes which are made self-supporting by means of the operation gas-mixture over-pressure. This solution allows to reduce at maximum the weight of the mechanical support frame and hence the detector material budget. The PANDA straw tube central tracker will not only reconstruct charged particle trajectories, but also will help in low momentum (< 1 GeV) particle identification via dE/dx measurements. This is a quite new approach that PANDA tracking group has first tested with detailed Monte Carlo simulations, and then with experimental tests of detector prototypes. This paper addresses the design issues of the PANDA straw tube trackers and the performance obtained in prototype tests.Comment: 7 pages,16 figure

Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX-Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model

Background/Aims: The effect of impaired intracellular proline availability for proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis was studied. Methods: We generated a constitutively knocked-down PRODH/POX MCF-7 breast cancer cell line (MCF-7(shPRODH/POX)) as a model to analyze the functional consequences of impaired intracellular proline levels. We have used inhibitor of proline utilization in collagen biosynthesis, 2-metoxyestradiol (MOE), inhibitor of prolidase that generate proline, rapamycin (Rap) and glycyl-proline (GlyPro), substrate for prolidase. Collagen and DNA biosynthesis were evaluated by radiometric assays. Cell viability was determined using Nucleo-Counter NC-3000. The activity of prolidase was determined by colorimetric assay. Expression of proteins was assessed by Western blot and immunofluorescence bioimaging. Concentration of proline was analyzed by liquid chromatography with mass spectrometry. Results: PRODH/POX knockdown decreased DNA and collagen biosynthesis, whereas increased prolidase activity and intracellular proline level in MCF-7(shPRODH/POX) cells. All studied compounds decreased cell viability in MCF-7 and MCF-7(shPRODH/POX) cells. DNA biosynthesis was similarly inhibited by Rap and MOE in both cell lines, but GlyPro inhibited the process only in MCF-7(shPRODH/POX) and MOE+GlyPro only in MCF-7 cells. All the compounds inhibited collagen biosynthesis, increased prolidase activity and cytoplasmic proline level in MCF-7(shPRODH/POX) cells and contributed to the induction of pro-survival mode only in MCF-7(shPRODH/POX) cells. In contrast, all studied compounds upregulated expression of pro-apoptotic protein only in MCF-7 cells. Conclusion: PRODH/POX was confirmed as a driver of apoptosis and proved the eligibility of MCF-7(shPRODH/POX) cell line as a highly effective model to elucidate the different mechanisms underlying proline utilization or generation in PRODH/POX-dependent pro-apoptotic pathways. (C) 2017 The Author(s) Published by S. Karger AG, Base

Partial Wave Analysis of the Reaction p(3.5GeV)+p→pK+Λp(3.5 GeV)+p \to pK^+\Lambda to Search for the "ppK−ppK^-" Bound State

Employing the Bonn-Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction $p(3.5GeV)+p\to pK^{+}\Lambda$. This reaction might contain information about the kaonic cluster "$ppK^-$" via its decay into $p\Lambda$. Due to interference effects in our coherent description of the data, a hypothetical $\overline{K}NN$ (or, specifically "$ppK^-$") cluster signal must not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectra like $p\Lambda$. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a $\overline{K}NN$ cluster. At a confidence level of CL$_{s}$=95\% such a cluster can not contribute more than 2-12\% to the total cross section with a $pK^{+}\Lambda$ final state, which translates into a production cross-section between 0.7 $\mu b$ and 4.2 $\mu b$, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.Comment: 7 Pages, 5 Figure

Deep sub-threshold Ξ−\Xi^- production in Ar+KCl reactions at 1.76A GeV

We report first results on a deep sub-threshold production of the doubly strange hyperon $\Xi^-$ in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar+KCl was studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. A high-statistics and high-purity $\Lambda$ sample was collected, allowing for the investigation of the decay channel $\Xi^- \to \Lambda \pi^-$. The deduced $\Xi^-/(\Lambda+\Sigma^0)$ production ratio of $(5.6 \pm 1.2 ^{+1.8}_{-1.7})\cdot 10^{-3}$ is significantly larger than available model predictions.Comment: 4 pages, including 4 figure

Inclusive pion and eta production in p+Nb collisions at 3.5 GeV beam energy

Data on inclusive pion and eta production measured with the dielectron spectrometer HADES in the reaction p+93Nb at a kinetic beam energy of 3.5 GeV are presented. Our results, obtained with the photon conversion method, supplement the rather sparse information on neutral meson production in proton-nucleus reactions existing for this bombarding energy regime. The reconstructed e+e-e+e- transverse-momentum and rapidity distributions are confronted with transport model calculations, which account fairly well for both pi0 and eta production.Comment: 12 pages, 9 figures, submitted to Physical Review