451 research outputs found
Chloroquine supplementation increases the cytotoxic effect of curcumin against Her2/neu overexpressing breast cancer cells in vitro and in vivo in nude mice while counteracts it in immune competent mice
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ). We found that TUBO cell death induced by CUR was increased in vitro by CQ and slightly in vivo in nude mice. Conversely, CQ counteracted the Cur cytotoxic effect in immune competent mice, as demonstrated by the lack of in vivo tumor regression and the reduction of overall mice survival as compared with CUR-treated mice. Immunohistochemistry analysis revealed the presence of a remarkable FoxP3 T cell infiltrate within the tumors in CUR/CQ treated mice and a reduction of T cytotoxic cells, as compared with single CUR treatment. These findings suggest that autophagy is important to elicit anti-tumor immune response and that autophagy inhibition by CQ reduces such response also by recruiting T regulatory (Treg) cells in the tumor microenvironment that may be pro-tumorigenic and might counteract CUR-mediated anti-cancer effects
Ion counting efficiencies at the IGISOL facility
At the IGISOL-JYFLTRAP facility, fission mass yields can be studied at high
precision. Fission fragments from a U target are passing through a Ni foil and
entering a gas filled chamber. The collected fragments are guided through a
mass separator to a Penning trap where their masses are identified. This
simulation work focuses on how different fission fragment properties (mass,
charge and energy) affect the stopping efficiency in the gas cell. In addition,
different experimental parameters are varied (e. g. U and Ni thickness and He
gas pressure) to study their impact on the stopping efficiency. The simulations
were performed using the Geant4 package and the SRIM code. The main results
suggest a small variation in the stopping efficiency as a function of mass,
charge and kinetic energy. It is predicted that heavy fragments are stopped
about 9% less efficiently than the light fragments. However it was found that
the properties of the U, Ni and the He gas influences this behavior. Hence it
could be possible to optimize the efficiency.Comment: 52 pages, 44 figure
In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.
Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has
been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog
(Shh) and NF-ÎşB expression in 51 breast cancer (ductal carcinoma) tissues using
immunohistochemistry. We found a positive correlation between nuclear GLI1
expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining
significantly correlated with a lower tumor grade. Next, the in vitro effects of two
Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the
Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61.
GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer
cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing
the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation
of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-
Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased
the nuclear translocation of NF-ÎşB. However, GANT-61 exerted these effects more
effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-
61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse
breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of
TUBO cells in BALB/c mice to different extents. These findings suggest that targeting
the Hh pathway using antagonists that act downstream of SMO is a more efficient
strategy than using antagonists that act upstream of SMO for interrupting Hh signaling
in breast cancer
Characterization of a Be(p,xn) neutron source for fission yields measurements
We report on measurements performed at The Svedberg Laboratory (TSL) to
characterize a proton-neutron converter for independent fission yield studies
at the IGISOL-JYFLTRAP facility (Jyv\"askyl\"a, Finland). A 30 MeV proton beam
impinged on a 5 mm water-cooled Beryllium target. Two independent experimental
techniques have been used to measure the neutron spectrum: a Time of Flight
(TOF) system used to estimate the high-energy contribution, and a Bonner Sphere
Spectrometer able to provide precise results from thermal energies up to 20
MeV. An overlap between the energy regions covered by the two systems will
permit a cross-check of the results from the different techniques. In this
paper, the measurement and analysis techniques will be presented together with
some preliminary results.Comment: 3 pages, 3 figures, also submitted as proceedings of the
International Conference on Nuclear Data for Science and Technology 201
Surfactant-like Effect and Dissolution of Ultrathin Fe Films on Ag(001)
The phase immiscibility and the excellent matching between Ag(001) and
Fe(001) unit cells (mismatch 0.8 %) make Fe/Ag growth attractive in the field
of low dimensionality magnetic systems. Intermixing could be drastically
limited at deposition temperatures as low as 140-150 K. The film structural
evolution induced by post-growth annealing presents many interesting aspects
involving activated atomic exchange processes and affecting magnetic
properties. Previous experiments, of He and low energy ion scattering on films
deposited at 150 K, indicated the formation of a segregated Ag layer upon
annealing at 550 K. Higher temperatures led to the embedding of Fe into the Ag
matrix. In those experiments, information on sub-surface layers was attained by
techniques mainly sensitive to the topmost layer. Here, systematic PED
measurements, providing chemical selectivity and structural information for a
depth of several layers, have been accompanied with a few XRD rod scans,
yielding a better sensitivity to the buried interface and to the film long
range order. The results of this paper allow a comparison with recent models
enlightening the dissolution paths of an ultra thin metal film into a different
metal, when both subsurface migration of the deposit and phase separation
between substrate and deposit are favoured. The occurrence of a surfactant-like
stage, in which a single layer of Ag covers the Fe film is demonstrated for
films of 4-6 ML heated at 500-550 K. Evidence of a stage characterized by the
formation of two Ag capping layers is also reported. As the annealing
temperature was increased beyond 700 K, the surface layers closely resembled
the structure of bare Ag(001) with the residual presence of subsurface Fe
aggregates.Comment: 4 pages, 3 figure
Controlling Hydrogen Activation, Spillover, and Desorption with Pd-Au Single-Atom Alloys
Key descriptors in hydrogenation catalysis are the nature of the active sites for H2 activation and the adsorption strength of H atoms to the surface. Using atomically resolved model systems of dilute Pd-Au surface alloys and density functional theory calculations, we determine key aspects of H2 activation, diffusion, and desorption. Pd monomers in a Au(111) surface catalyze the dissociative adsorption of H2 at temperatures as low as 85 K, a process previously expected to require contiguous Pd sites. H atoms preside at the Pd sites and desorb at temperatures significantly lower than those from pure Pd (175 versus 310 K). This facile H2 activation and weak adsorption of H atom intermediates are key requirements for active and selective hydrogenations. We also demonstrate weak adsorption of CO, a common catalyst poison, which is sufficient to force H atoms to spill over from Pd to Au sites, as evidenced by low-temperature H2 desorption
Imaging of metabolic bone disease
Osteoporosis is the most important metabolic bone disease, with a wide distribution among the elderly. It is characterized by low bone mass and micro architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Identify bone weakening with an appropriate and accurate use of diagnostic imaging is of critical importance in the diagnosis and follow-up of osteoporotic patients. The aim of this review is to evaluate the detection rates of the different imaging modalities in the evaluation of bone strength, in the assessment of fracture risk and in the management of fragility fractures
Randomized trial of an education and support intervention to preventreadmission of patients with heart failure
AbstractObjectivesWe determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure (HF).BackgroundDisease management programs for patients with HF including medical components may reduce readmissions by 40% or more, but the value of an intervention focused on education and support is not known.MethodsWe conducted a prospective, randomized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF.ResultsAmong the 88 patients (44 intervention and 44 control) in the study, 25 patients (56.8%) in the intervention group and 36 patients (81.8%) in the control group had at least one readmission or died during one-year follow-up (relative risk = 0.69, 95% confidence interval [CI]: 0.52, 0.92; p = 0.01). The intervention was associated with a 39% decrease in the total number of readmissions (intervention group: 49 readmissions; control group: 80 readmissions, p = 0.06). After adjusting for clinical and demographic characteristics, the intervention group had a significantly lower risk of readmission compared with the control group (hazard ratio = 0.56, 95% CI: 0.32, 0.96; p = 0.03) and hospital readmission costs of $7,515 less per patient.ConclusionsA formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF
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