129 research outputs found
Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients
Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation
Nearby early-type galaxies with ionized gas VI. The Spitzer-IRS view
We present low resolution Spitzer-IRS spectra of 40 ETGs, selected from a
sample of 65 ETGs showing emission lines in their optical spectra. We
homogeneously extract the mid-infrared (MIR) spectra, and after the proper
subtraction of a "passive" ETG template, we derive the intensity of the ionic
and molecular lines and of the polycyclic aromatic hydrocarbon emission
features. We use MIR diagnostic diagrams to investigate the powering mechanisms
of the ionized gas. The mid-infrared spectra of early-type galaxies show a
variety of spectral characteristics. We empirically sub-divide the sample into
five classes of spectra with common characteristics. Class-0, accounting for
20% of the sample, are purely passive ETGs with neither emission lines nor PAH
features. Class-1 show emission lines but no PAH features, and account for
17.5% of the sample. Class-2, in which 50% of the ETGs are found, as well as
having emission lines, show PAH features with unusual ratios, e.g. 7.7
{\mu}m/11.3 {\mu}m \leq 2.3. Class-3 objects have emission lines and PAH
features with ratios typical of star-forming galaxies. 7.5% of objects fall in
this class, likely to be objects in a starburst/post-starburst regime. Class-4,
containing only 5% of the ETGs, is dominated by a hot dust continuum. The
diagnostic diagram [Ne III]15.55{\mu}m/[Ne II]12.8{\mu}m vs. [S
III]33.48{\mu}m/[Si II]34.82{\mu}m, is used to investigate the different
mechanisms ionizing the gas. If we exclude NGC 3258 where a starburst seems
present, most of our ETGs contain gas ionized via either AGN-like or shock
phenomena, or both. Most of the spectra in the present sample are classified as
LINERs in the optical window. The proposed MIR spectral classes show
unambiguously the manifold of the physical processes and ionization mechanisms,
from star formation, low level AGN activity, to shocks, present in LINER
nuclei.Comment: Accepted for publication in Astronomy and Astrophysic
Mid-infrared colour gradients and the colour-magnitude relation in Virgo early-type galaxies
We make use of Spitzer imaging between 4 and 16 micron and near-infrared data
at 2.2 micron to investigate the nature and distribution of the mid-infrared
emission in a sample of early-type galaxies in the Virgo cluster. These data
allow us to conclude, with some confidence, that the emission at 16 micron in
passive ETGs is stellar in origin, consistent with previous work concluding
that the excess mid-infrared emission comes from the dusty envelopes around
evolved AGB stars. There is little evidence for the mid-infrared emission of an
unresolved central component, as might arise in the presence of a dusty torus
associated with a low-luminosity AGN. We nonetheless find that the 16 micron
emission is more centrally peaked than the near-infrared emission, implying a
radial stellar population gradient. By comparing with independent evidence from
studies at optical wavelengths, we conclude that a metallicity that falls with
increasing radius is the principal driver of the observed gradient. We also
plot the mid-infrared colour-magnitude diagram and combine with similar work on
the Coma cluster to define the colour-magnitude relation for absolute K-band
magnitudes from -26 to -19. Because a correlation between mass and age would
produce a relation with a gradient in the opposite sense to that observed, we
conclude that the relation reflects the fact that passive ETGs of lower mass
also have a lower average metallicity. The colour-magnitude relation is thus
driven by metallicity effects. In contrast to what is found in Coma, we do not
find any objects with anomalously bright 16 micron emission relative to the
colour-magnitude relation. Although there is little overlap in the mass ranges
probed in the two clusters, this may suggest that observable ``rejuvenation''
episodes are limited to intermediate mass objects.Comment: 8 pages, 4 figure
Star Formation Histories of the LEGUS Dwarf Galaxies (I): recent History of NGC1705, NGC4449 and Holmberg II
We use HST observations from the Legacy Extragalactic UV Survey to
reconstruct the recent star formation histories (SFHs) of three actively
star-forming dwarf galaxies, NGC4449, Holmberg II and NGC1705, from their UV
color-magnitude diagrams (CMDs). We apply a CMD fitting technique using two
independent sets of stellar isochrones, PARSEC-COLIBRI and MIST, to assess the
uncertainties related to stellar evolution modelling. Irrespective of the
adopted stellar models, all the three dwarfs are found to have had almost
constant star formation rates (SFRs) in the last 100-200 Myr, with modest
enhancements (a factor of 2) above the 100 Myr-averaged-SFR. Significant
differences among the three dwarfs are found in the overall SFR, the timing of
the most recent peak and the SFRarea. The Initial Mass Function (IMF) of
NGC1705 and Holmberg II is consistent with a Salpeter slope down to 5
M, whereas it is slightly flatter, s, in NGC4449. The SFHs
derived with the two different sets of stellar models are consistent with each
other, except for some quantitative details, attributable to their input
assumptions. They also share the drawback that all synthetic diagrams predict a
clear separation in color between upper main sequence and helium burning stars,
which is not apparent in the data. Since differential reddening, significant in
NGC4449, or unresolved binaries don't appear to be sufficient to fill the gap,
we suggest this calls for a revision of both sets of stellar evolutionary
tracks.Comment: 22 pages, 17 figures, accepted for publication on Ap
The effects of cannabidiol and prognostic role of TRPV2 in human endometrial cancer
Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness. Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the effects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated. Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy
Biological function of PD-L2 and correlation with overall survival in type II endometrial cancer
In cancer, upregulation of coinhibitory B7 ligands has been associated with immune evasion. So far, anti-programmed death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies have been used in immuno-oncology, with promising outcomes; however, it is still needed to identify other markers, especially for endometrial cancer (EC). EC is a gynecological malignancy historically classified into two types: type I, with mostly estrogen-dependent endometrioid diseases, and the most aggressive type II, including mainly estrogen-independent and non-endometrioid tumors. PD ligand-2 (PD-L2) is known as the second ligand of the PD-1 receptor and, upon its binding, contributes to T-cell exhaustion. Up to now, very few information are available about PD-L2 in cancers, and no data have been reported for EC. The aim of this work was to characterize the PD-L1 and PD-L2 ligand expression profile in EC cell lines, focusing the attention on the biological role of PD-L2 and its prognostic impact in human type II EC biopsies. Using in silico analysis of TCGA data, we performed a molecular profiling in a cohort of 506 patients, both types I and II, and PD-1 ligands expression was also analyzed in different primary human EC cell lines. Moreover, PD-L2 staining was evaluated in a cohort of human type II EC samples and correlated with the overall survival (OS), progression-free survival (PFS), and additional clinicopathological data. From the in silico analysis, PD-L2 was more expressed than PD-L1 in EC cell lines. PD-L2 was found highly expressed in 64.44% of tumor specimens, predominantly in the serous subtype, in both stromal and epithelial components, while in peritumoral and normal tissues it was predominantly moderate or low. In vitro, we investigated the cell autonomous role of PD-L2 in controlling cell survival, migration, and chemoresistance
Unusual PAH Emission in Nearby Early-Type Galaxies: A Signature of an Intermediate Age Stellar Population?
We present the analysis of Spitzer-IRS spectra of four early-type galaxies,
NGC 1297, NGC 5044, NGC 6868, and NGC 7079, all classified as LINERs in the
optical bands. Their IRS spectra present the full series of H2 rotational
emission lines in the range 5--38 microns, atomic lines, and prominent PAH
features. We investigate the nature and origin of the PAH emission,
characterized by unusually low 6 -- 9/11.3 microns inter-band ratios. After the
subtraction of a passive early type galaxy template, we find that the 7 -- 9
microns spectral region requires dust features not normally present in star
forming galaxies. Each spectrum is then analyzed with the aim of identifying
their components and origin. In contrast to normal star forming galaxies, where
cationic PAH emission prevails, our 6--14 microns spectra seem to be dominated
by large and neutral PAH emission, responsible for the low 6 -- 9/11.3 microns
ratios, plus two broad dust emission features peaking at 8.2 microns and 12
microns. Theses broad components, observed until now mainly in evolved carbon
stars and usually attributed to pristine material, contribute approximately
30-50% of the total PAH flux in the 6--14 microns region. We propose that the
PAH molecules in our ETGs arise from fresh carbonaceous material which is
continuously released by a population of carbon stars, formed in a rejuvenation
episode which occurred within the last few Gyr. The analysis of the MIR spectra
allows us to infer that, in order to maintain the peculiar size and charge
distributions biased to large and neutral PAHs, this material must be shocked,
and excited by the weak UV interstellar radiation field of our ETG.Comment: ApJ accepte
Tracing the evolution of nearby early-type galaxies in low density environments. The Ultraviolet view from GALEX
We detected recent star formation in nearby early-type galaxies located in
low density environments, with GALEX Ultraviolet (UV) imaging. Signatures of
star formation may be present in the nucleus and in outer rings/arm like
structures. Our study suggests that such star formation may be induced by
different triggering mechanisms, such as the inner secular evolution driven by
bars, and minor accretion phenomena. We investigate the nature of the (FUV-NUV)
color vs. Mg2 correlation, and suggest that it relates to "downsizing" in
galaxy formation.Comment: Conference "UV Universe 2010" S. Petersburg 31 May - 3 June, 2010
Accepted for publication in Astrophysics & Space Science . The final
publication is available at http://www.springerlink.co
Patient-Reported Outcomes and Quality of Life Assessment. New Targets for New Targeted Therapy?
No abstract availabl
Novel NPM1 exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML
Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non–exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML
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