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 $\sim$2) above the 100 Myr-averaged-SFR. Significant differences among the three dwarfs are found in the overall SFR, the timing of the most recent peak and the SFR$/$area. The Initial Mass Function (IMF) of NGC1705 and Holmberg II is consistent with a Salpeter slope down to $\approx$ 5 M$_{\odot}$, whereas it is slightly flatter, s$=-2.0$, 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