855 research outputs found
Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment
Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.
Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination.
Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% \ub1 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression.
Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients
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
A Cylindrical GEM Inner Tracker for the BESIII experiment at IHEP
The Beijing Electron Spectrometer III (BESIII) is a multipurpose detector
that collects data provided by the collision in the Beijing Electron Positron
Collider II (BEPCII), hosted at the Institute of High Energy Physics of
Beijing. Since the beginning of its operation, BESIII has collected the world
largest sample of J/{\psi} and {\psi}(2s). Due to the increase of the
luminosity up to its nominal value of 10^33 cm-2 s-1 and aging effect, the MDC
decreases its efficiency in the first layers up to 35% with respect to the
value in 2014. Since BESIII has to take data up to 2022 with the chance to
continue up to 2027, the Italian collaboration proposed to replace the inner
part of the MDC with three independent layers of Cylindrical triple-GEM (CGEM).
The CGEM-IT project will deploy several new features and innovation with
respect the other current GEM based detector: the {\mu}TPC and analog readout,
with time and charge measurements will allow to reach the 130 {\mu}m spatial
resolution in 1 T magnetic field requested by the BESIII collaboration. In this
proceeding, an update of the status of the project will be presented, with a
particular focus on the results with planar and cylindrical prototypes with
test beams data. These results are beyond the state of the art for GEM
technology in magnetic field
Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment
Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets
This document is the Technical Design Report covering the two large
spectrometer magnets of the PANDA detector set-up. It shows the conceptual
design of the magnets and their anticipated performance. It precedes the tender
and procurement of the magnets and, hence, is subject to possible modifications
arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti
Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski,
Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy),
Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy
MCM2 - a promising marker for premalignant lesions of the lung: a cohort study
BACKGROUND: Because cells progressing to cancer must proliferate, marker proteins specific to proliferating cells may permit detection of premalignant lesions. Here we compared the sensitivities of a classic proliferation marker, Ki-67, with a new proliferation marker, MCM2, in 41 bronchial biopsy specimens representing normal mucosa, metaplasia, dysplasia, and carcinoma in situ. METHODS: Parallel sections were stained with antibodies against MCM2 and Ki-67, and the frequencies of staining were independently measured by two investigators. Differences were evaluated statistically using the two-sided correlated samples t-test and Wilcoxon rank sum test. RESULTS: For each of the 41 specimens, the average frequency of staining by anti-MCM2 (39%) was significantly (p < 0.001) greater than by anti-Ki-67 (16%). In metaplastic lesions anti-MCM2 frequently detected cells near the epithelial surface, while anti-Ki-67 did not. CONCLUSIONS: We conclude that MCM2 is detectable in 2-3 times more proliferating premalignant lung cells than is Ki-67. The promise of MCM2 as a sensitive marker for premalignant lung cells is enhanced by the fact that it is present in cells at the surface of metaplastic lung lesions, which are more likely to be exfoliated into sputum. Future studies will determine if use of anti-MCM2 makes possible sufficiently early detection to significantly enhance lung cancer survival rates
Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR
Simulation results for future measurements of electromagnetic proton form
factors at \PANDA (FAIR) within the PandaRoot software framework are reported.
The statistical precision with which the proton form factors can be determined
is estimated. The signal channel is studied on the basis
of two different but consistent procedures. The suppression of the main
background channel, , is studied.
Furthermore, the background versus signal efficiency, statistical and
systematical uncertainties on the extracted proton form factors are evaluated
using two different procedures. The results are consistent with those of a
previous simulation study using an older, simplified framework. However, a
slightly better precision is achieved in the PandaRoot study in a large range
of momentum transfer, assuming the nominal beam conditions and detector
performance
Observation and study of the decay
We report the observation and study of the decay
using events
collected with the BESIII detector. Its branching fraction, including all
possible intermediate states, is measured to be
. We also report evidence for a structure,
denoted as , in the mass spectrum in the GeV/
region. Using two decay modes of the meson ( and
), a simultaneous fit to the mass spectra is
performed. Assuming the quantum numbers of the to be , its
significance is found to be 4.4, with a mass and width of MeV/ and MeV, respectively, and a
product branching fraction
. Alternatively, assuming , the
significance is 3.8, with a mass and width of MeV/ and MeV, respectively, and a product
branching fraction
. The angular distribution of
is studied and the two assumptions of the
cannot be clearly distinguished due to the limited statistics. In all
measurements the first uncertainties are statistical and the second systematic.Comment: 10 pages, 6 figures and 4 table
Observation of in
Using a sample of events recorded with
the BESIII detector at the symmetric electron positron collider BEPCII, we
report the observation of the decay of the charmonium state
into a pair of mesons in the process
. The branching fraction is measured for the first
time to be , where the first uncertainty is
statistical, the second systematic and the third is from the uncertainty of
. The mass and width of the are
determined as MeV/ and
MeV.Comment: 13 pages, 6 figure
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