2,380 research outputs found
Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer
Background: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients.
Methods: CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn's post-test was used for comparisons between groups. Statistical significance was set at p < 0.05.
Results: EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis.
Conclusions: Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing
Genome-Wide Functional Divergence after the Symbiosis of Proteobacteria with Insects Unraveled through a Novel Computational Approach
Symbiosis has been among the most important evolutionary steps to generate biological complexity. The establishment of symbiosis required an intimate metabolic link between biological systems with different complexity levels. The strict endo-cellular symbiotic bacteria of insects are beautiful examples of the metabolic coupling between organisms belonging to different kingdoms, a eukaryote and a prokaryote. The host (eukaryote) provides the endosymbiont (prokaryote) with a stable cellular environment while the endosymbiont supplements the host's diet with essential metabolites. For such communication to take place, endosymbionts' genomes have suffered dramatic modifications and reconfigurations of proteins' functions. Two of the main modifications, loss of genes redundant for endosymbiotic bacteria or the host and bacterial genome streamlining, have been extensively studied. However, no studies have accounted for possible functional shifts in the endosymbiotic proteomes. Here, we develop a simple method to screen genomes for evidence of functional divergence between two species clusters, and we apply it to identify functional shifts in the endosymbiotic proteomes. Despite the strong effects of genetic drift in the endosymbiotic systems, we unexpectedly identified genes to be under stronger selective constraints in endosymbionts of aphids and ants than in their free-living bacterial relatives. These genes are directly involved in supplementing the host's diet with essential metabolites. A test of functional divergence supports a strong relationship between the endosymbiosis and the functional shifts of proteins involved in the metabolic communication with the insect host. The correlation between functional divergence in the endosymbiotic bacterium and the ecological requirements of the host uncovers their intimate biochemical and metabolic communication and provides insights on the role of symbiosis in generating species diversity
Hyperon production in Ar+KCl collisions at 1.76A GeV
We present transverse momentum spectra, rapidity distribution and
multiplicity of Lambda-hyperons measured with the HADES spectrometer in the
reaction Ar(1.76A GeV)+KCl. The yield of Xi- is calculated from our previously
reported Xi-/(Lambda+Sigma0) ratio and compared to other strange particle
multiplicities. Employing a strangeness balance equation the multiplicities of
the yet unmeasured charged Sigma hyperons can be estimated. Finally a
statistical hadronization model is used to fit the yields of pi-, K+, K0s, K-,
phi, Lambda and Xi-. The resulting chemical freeze-out temperature of T=(76+-2)
MeV is compared to the measured slope parameters obtained from fits to the
transverse mass distributions of the particles
Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment
The Double Chooz Experiment presents an indication of reactor electron
antineutrino disappearance consistent with neutrino oscillations. A ratio of
0.944 0.016 (stat) 0.040 (syst) observed to predicted events was
obtained in 101 days of running at the Chooz Nuclear Power Plant in France,
with two 4.25 GW reactors. The results were obtained from a single 10
m fiducial volume detector located 1050 m from the two reactor cores. The
reactor antineutrino flux prediction used the Bugey4 measurement as an anchor
point. The deficit can be interpreted as an indication of a non-zero value of
the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate
of the prompt positrons and their energy spectrum we find \sang = 0.086
0.041 (stat) 0.030 (syst), or, at 90% CL, 0.015 \sang 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments
Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF
The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at
the Fermilab Long-Baseline Neutrino Facility (LBNF) is described
Search for composite and exotic fermions at LEP 2
A search for unstable heavy fermions with the DELPHI detector at LEP is
reported. Sequential and non-canonical leptons, as well as excited leptons and
quarks, are considered. The data analysed correspond to an integrated
luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV
and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172
GeV and 161 GeV. The search for pair-produced new leptons establishes 95%
confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2,
depending on the channel. The search for singly produced excited leptons and
quarks establishes upper limits on the ratio of the coupling of the excited
fermio
Search for charginos in e+e- interactions at sqrt(s) = 189 GeV
An update of the searches for charginos and gravitinos is presented, based on
a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector
in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was
found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a
centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by
combining the chargino searches with neutralino searches at the Z resonance
implies a limit on the mass of the lightest neutralino which, for a heavy
sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure
Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP
Promptly decaying lightest neutralinos and long-lived staus are searched for
in the context of light gravitino scenarios. It is assumed that the stau is the
next to lightest supersymmetric particle (NLSP) and that the lightest
neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector
at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of
the production of these particles is found. Hence, lower mass limits for both
kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is
found to be greater than 71.5 GeV/c^2. In the search for long-lived stau,
masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10
to 150 \eVcc . Combining this search with the searches for stable heavy leptons
and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc
may be set for the stau mas
Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV
The DELPHI detector at LEP has collected 54 pb^{-1} of data at a
centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV
during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data
were used to measure the average charged particle multiplicity in e+e- -> b
bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the
multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183
GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85
(stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01
(syst). This result is consistent with QCD predictions, while it is
inconsistent with calculations assuming that the multiplicity accompanying the
decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure
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