649 research outputs found
Transcriptional dissection of pancreatic tumors engrafted in mice.
BACKGROUND: Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient-derived xenograft (PDX) models is a promising platform for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine tumor environment on the gene expression of the engrafted human tumoral cells.
METHODS: We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data of 18 PDX models, 53 primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC system were further compared with public available microarray data from 42 PDX models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC). We developed a robust analysis protocol to explore the gene expression space. In addition, we completed the analysis with a functional characterization of PDX models, including if changes were caused by murine environment or by serial passing.
RESULTS: Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable from each other based on their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models can be separated into two different groups that share some partial similarity with their corresponding original primary tumors. Our results point to the lack of human stromal involvement in PDXs as a major factor contributing to their differences from the original primary tumors. The main functional differences between pancreatic PDX models and human PDAC are the lower expression of genes involved in pathways related to extracellular matrix and hemostasis and the up- regulation of cell cycle genes. Importantly, most of these differences are detected in the first passages after the tumor engraftment.
CONCLUSIONS: Our results suggest that PDX models of PDAC and HCC retain, to some extent, a gene expression memory of the original primary tumors, while this pattern is not detected in conventional cancer cell lines. Expression changes in PDXs are mainly related to pathways reflecting the lack of human infiltrating cells and the adaptation to a new environment. We also provide evidence of the stability of gene expression patterns over subsequent passages, indicating early phases of the adaptation process
Evaluation of compliance with the Spanish Code of self-regulation of food and drinks advertising directed at children under the age of 12 years in Spain, 2012
OBJECTIVE: To evaluate compliance levels with the Spanish Code of self-regulation of food and drinks advertising directed at children under the age of 12 years (Publicidad, Actividad, Obesidad, Salud [PAOS] Code) in 2012; and compare these against the figures for 2008. STUDY DESIGN: Cross-sectional study. METHODS: Television advertisements of food and drinks (AFD) were recorded over 7 days in 2012 (8am-midnight) of five Spanish channels popular to children. AFD were classified as core (nutrient-rich/low-calorie products), non-core (nutrient-poor/rich-calorie products) or miscellaneous. Compliance with each standard of the PAOS Code was evaluated. AFD were deemed to be fully compliant when it met all the standards. RESULTS: Two thousand five hundred and eighty-two AFDs came within the purview of the PAOS Code. Some of the standards that registered the highest levels of non-compliance were those regulating the suitability of the information presented (79.4%) and those prohibiting the use of characters popular with children (25%). Overall non-compliance with the Code was greater in 2012 than in 2008 (88.3% vs 49.3%). Non-compliance was highest for advertisements screened on children's/youth channels (92.3% vs. 81.5%; P < 0.001) and for those aired outside the enhanced protection time slot (89.3% vs. 86%; P = 0.015). CONCLUSIONS: Non-compliance with the PAOS Code is higher than for 2008. Given the lack of effectiveness of self-regulation, a statutory system should be adopted to ban AFD directed at minors, or at least restrict it to healthy products.S
Leucine-Rich Alpha-2-Glycoprotein as a non-invasive biomarker for pediatric acute appendicitis: a systematic review and meta-analysis
The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric
acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography.
Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using
the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were
performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls)
were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant
mean difference (95% CI) of 46.76 ÎŒg/mL (29.26â64.26). The random-effect meta-analysis for unadjusted urinary LRG1
(PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 ÎŒg/mL (0.30â0.93). The random-effect metaanalysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95%
CI) of 0.89 g/mol (0.11â1.66).
Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand,
due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study
that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings
Photovoltaic LiNbO3particles: Applications to Biomedicine/Biophotonics
Recently, a novel method to trap and pattern ensembles of nanoparticles has been proposed and
tested. It relies on the photovoltaic (PV) properties of certain ferroelectric crystals such as LiNbO3 [1,2].
These crystals, when suitably doped, develop very high electric fields in response to illumination with
light of suitable wavelength. The PV effect lies in the asymmetrical excitation of electrons giving rise to
PV currents and associated space-charge fields (photorefractive effect). The field generated in the bulk
of the sample propagates to the surrounding medium as evanescent fields. When dielectric or metal
nanoparticles are deposited on the surface of the sample the evanescent fields give rise to either
electrophoretic or dielectrophoretic forces, depending on the charge state of the particles, that induce
the trapping and patterning effects [3,4].
The purpose of this work has been to explore the effects of such PV fields in the biology and
biomedical areas. A first work was able to show the necrotic effects induced by such fields on He-La
tumour cells grown on the surface of an illuminated iron-doped LiNbO3 crystal [5]. In principle, it is
conceived that LiNbO3 nanoparticles may be advantageously used for such biomedical purposes
considering the possibility of such nanoparticles being incorporated into the cells. Previous experiments
using microparticles have been performed [5] with similar results to those achieved with the substrate.
Therefore, the purpose of this work has been to fabricate and characterize the LiNbO3 nanoparticles and
assess their necrotic effects when they are incorporated on a culture of tumour cells.
Two different preparation methods have been used: 1) mechanical grinding from crystals, and 2)
bottom-up sol-gel chemical synthesis from metal-ethoxide precursors. This later method leads to a more
uniform size distribution of smaller particles (down to around 50 nm). Fig. 1(a) and 1(b) shows SEM
images of the nanoparticles obtained with both method.
An ad hoc software taking into account the physical properties of the crystal, particullarly donor
and aceptor concentrations has been developped in order to estimate the electric field generated in
noparticles. In a first stage simulations of the electric current of nanoparticles, in a conductive media,
due to the PV effect have been carried out by MonteCarlo simulations using the Kutharev 1-centre
transport model equations [6] . Special attention has been paid to the dependence on particle size and
[Fe2+]/[Fe3+]. First results on cubic particles shows large dispersion for small sizes due to the random
number of donors and its effective concentration (Fig 2).
The necrotic (toxicity) effect of nanoparticles incorporated into a tumour cell culture subjected to
30 min. illumination with a blue LED is shown in Fig.3. For each type of nanoparticle the percent of cell
survival in dark and illumination conditions has been plot as a function of the particle dilution factor. Fig.
1a corresponds to mechanical grinding particles whereas 1b and 1c refer to chemically synthesized
particles with two oxidation states. The light effect is larger with mechanical grinding nanoparticles, but
dark toxicity is also higher. For chemically synthesized nanoparticles dark toxicity is low but only in
oxidized samples, where the PV effect is known to be larger, the light effect is appreciable.
These preliminary results demonstrate that Fe:LiNbO· nanoparticles have a biological damaging
effect on cells, although there are many points that should be clarified and much space for PV
nanoparticles optimization. In particular, it appears necessary to determine the fraction of nanoparticles
that become incorporated into the cells and the possible existence of threshold size effects.
This work has been supported by MINECO under grant MAT2011-28379-C03
Constraints on the steady and pulsed very high energy gamma-ray emission from observations of PSR B1951+32/CTB 80 with the MAGIC Telescope
We report on very high energy gamma-observations with the MAGIC Telescope of
the pulsar PSR B1951+32 and its associated nebula, CTB 80. Our data constrain
the cutoff energy of the pulsar to be less than 32 GeV, assuming the pulsed
gamma-ray emission to be exponentially cut off. The upper limit on the flux of
pulsed gamma-ray emission above 75 GeV is 4.3*10^-11 photons cm^-2 sec^-1, and
the upper limit on the flux of steady emission above 140 GeV is 1.5*10^-11
photons cm^-2 sec^-1. We discuss our results in the framework of recent model
predictions and other studies.Comment: 7 pages, 7 figures, replaced with published versio
MAGIC upper limits on the very high energy emission from GRBs
The fast repositioning system of the MAGIC Telescope has allowed during its
first data cycle, between 2005 and the beginning of year 2006, observing nine
different GRBs as possible sources of very high energy gammas. These
observations were triggered by alerts from Swift, HETE-II, and Integral; they
started as fast as possible after the alerts and lasted for several minutes,
with an energy threshold varying between 80 and 200 GeV, depending upon the
zenith angle of the burst. No evidence for gamma signals was found, and upper
limits for the flux were derived for all events, using the standard analysis
chain of MAGIC. For the bursts with measured redshift, the upper limits are
compatible with a power law extrapolation, when the intrinsic fluxes are
evaluated taking into account the attenuation due to the scattering in the
Metagalactic Radiation Field (MRF).Comment: 25 pages, 9 figures, final version accepted by ApJ. Changet title to
"MAGIC upped limits on the VERY high energy emission from GRBs", re-organized
chapter with description of observation, removed non necessaries figures,
added plot of effective area depending on zenith angle, added an appendix
explaining the upper limit calculation, added some reference
Discovery of VHE Gamma Radiation from IC443 with the MAGIC Telescope
We report the detection of a new source of very high energy (VHE, E_gamma >=
100GeV) gamma-ray emission located close to the Galactic Plane, MAGIC
J0616+225, which is spatially coincident with SNR IC443. The observations were
carried out with the MAGIC telescope in the periods December 2005 - January
2006 and December 2006 - January 2007. Here we present results from this
source, leading to a VHE gamma-ray signal with a statistical significance of
5.7 sigma in the 2006/7 data and a measured differential gamma-ray flux
consistent with a power law, described as dN_gamma/(dA dt dE) = (1.0 +/-
0.2)*10^(-11)(E/0.4 TeV)^(-3.1 +/- 0.3) cm^(-2)s^(-1)TeV^(-1). We briefly
discuss the observational technique used and the procedure implemented for the
data analysis. The results are put in the perspective of the multiwavelength
emission and the molecular environment found in the region of IC443.Comment: Accepted by ApJ Letter
Multi-Wavelength Observations of the Blazar 1ES 1011+496 in Spring 2008
The BL Lac object 1ES 1011+496 was discovered at Very High Energy gamma-rays
by MAGIC in spring 2007. Before that the source was little studied in different
wavelengths. Therefore a multi-wavelength (MWL) campaign was organized in
spring 2008. Along MAGIC, the MWL campaign included the Metsahovi radio
observatory, Bell and KVA optical telescopes and the Swift and AGILE
satellites. MAGIC observations span from March to May, 2008 for a total of 27.9
hours, of which 19.4 hours remained after quality cuts. The light curve showed
no significant variability. The differential VHE spectrum could be described
with a power-law function. Both results were similar to those obtained during
the discovery. Swift XRT observations revealed an X-ray flare, characterized by
a harder when brighter trend, as is typical for high synchrotron peak BL Lac
objects (HBL). Strong optical variability was found during the campaign, but no
conclusion on the connection between the optical and VHE gamma-ray bands could
be drawn. The contemporaneous SED shows a synchrotron dominated source, unlike
concluded in previous work based on nonsimultaneous data, and is well described
by a standard one zone synchrotron self Compton model. We also performed a
study on the source classification. While the optical and X-ray data taken
during our campaign show typical characteristics of an HBL, we suggest, based
on archival data, that 1ES 1011+496 is actually a borderline case between
intermediate and high synchrotron peak frequency BL Lac objects.Comment: 13 pages, accepted for publication in MNRA
The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in
the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent
a series of upgrades, involving the exchange of the MAGIC-I camera and its
trigger system, as well as the upgrade of the readout system of both
telescopes. We use observations of the Crab Nebula taken at low and medium
zenith angles to assess the key performance parameters of the MAGIC stereo
system. For low zenith angle observations, the standard trigger threshold of
the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources
with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula
flux in 50 h of observations. The angular resolution, defined as the sigma of a
2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while
the energy resolution is 16%. We also re-evaluate the effect of the systematic
uncertainty on the data taken with the MAGIC telescopes after the upgrade. We
estimate that the systematic uncertainties can be divided in the following
components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for
the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle
Physic
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