Beyond the immune suppression: the immunotherapy in prostate cancer

Prostate cancer (PCa) is the second most common cancer in men.Aswell in many other human cancers, inflammation and immune suppression have an important role in their development.We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression.Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapie

The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis

Folate-based single cell screening using surface enhanced Raman microimaging

Recent progress in nanotechnology and its application to biomedical settings have generated great advantages in dealing with early cancer diagnosis. The identification of the specific properties of cancer cells, such as the expression of particular plasma membrane molecular receptors, has become crucial in revealing the presence and in assessing the stage of development of the disease. Here we report a single cell screening approach based on Surface Enhanced Raman Scattering (SERS) microimaging. We fabricated a SERS-labelled nanovector based on the biofunctionalization of gold nanoparticles with folic acid. After treating the cells with the nanovector, we were able to distinguish three different cell populations from different cell lines (cancer HeLa and PC-3, and normal HaCaT lines), suitably chosen for their different expressions of folate binding proteins. The nanovector, indeed, binds much more efficiently on cancer cell lines than on normal ones, resulting in a higher SERS signal measured on cancer cells. These results pave the way for applications in single cell diagnostics and, potentially, in theranostic

Searching for Young M Dwarfs with GALEX

The census of young moving groups in the solar neighborhood is significantly incomplete in the low-mass regime. We have developed a new selection process to find these missing members based on the GALEX All-Sky Imaging Survey. For stars with spectral types >K5 and younger than 300~Myr, we show that near-UV and far-UV emission is greatly enhanced above the quiescent photosphere, analogous to the enhanced X-ray emission of young low-mass stars seen by ROSAT but detectable to much larger distances with GALEX. By combining GALEX data with optical (HST Guide Star Catalog) and near-IR (2MASS) photometry, we identified an initial sample of 34 young M dwarf candidates in a 1000 sq.~deg.~region around the 10-Myr TW Hydra Association (TWA). Low-resolution spectroscopy of 30 of these found 16 which had H_alpha in emission, which were then followed-up at high resolution to search for spectroscopic evidence of youth and to measure radial velocities. Four objects have low surface gravities, photometric distances and space motions consistent with TWA, but the non-detection of Li indicates they may be too old to belong to this moving group. One object (M3.5, 93 pc) appears to be the first known accreting low-mass member of the 15~Myr Lower Centaurus Crux OB association. Two objects exhibit all the characteristics of the known TWA members, and thus we designate them as TWA 31 (M4.2, 110 pc) and TWA 32 (M6.3, 53 pc). TWA 31 shows extremely broad (447 km/s) H_alpha emission, making it the sixth member of TWA found to have ongoing accretion. TWA 32 is resolved into a 0.6" binary in Keck laser guide star adaptive optics imaging. Our search should be sensitive down to spectral types of at least M4-M5 in TWA and thus the small numbers of new member is puzzling. This may indicate TWA has an atypical mass function or that the presence of Li may be too restrictive a criteria for selecting young low-mass stars.Comment: Accepted to Ap

Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines

n/

An All-Sky Catalog of Bright M Dwarfs

We present an all-sky catalog of M dwarf stars with apparent infrared magnitude J<10. The 8,889 stars are selected from the ongoing SUPERBLINK survey of stars with proper motion >40 mas/yr, supplemented on the bright end with the TYCHO-2 catalog. Completeness tests which account for kinematic (proper motion) bias suggest that our catalog represents ~75% of the estimated ~11,900 M dwarfs with J<10 expected to populate the entire sky. Our catalog is, however, significantly more complete for the Northern sky (~90%) than it is for the South (~60%). Stars are identified as cool, red M dwarfs from a combination of optical and infrared color cuts, and are distinguished from background M giants and highly-reddened stars using either existing parallax measurements or, if such measurements are lacking, on their location in an optical-to-infrared reduced proper motion diagram. These bright M dwarfs are all prime targets for exoplanet surveys using the Doppler radial velocity or transit methods; the combination of low-mass and bright apparent magnitude should make possible the detection of Earth-size planets on short-period orbits using currently available techniques. Parallax measurements, when available, and photometric distance estimates are provided for all stars, and these place most systems within 60 parsecs of the Sun. Spectral type estimated from V-J color shows that most of the stars range from K7 to M4, with only a few late M dwarfs, all within 20 pc. Proximity to the Sun also makes these stars good targets for high-resolution exoplanet imaging searches, especially if younger objects can be identified on the basis of X-ray or UV excess. For that purpose, we include X-ray flux from ROSAT and FUV/NUV ultraviolet magnitudes from GALEX for all stars for which a counterpart can be identified in those catalogs.Comment: 16 pages, accepted for publication in the Astronomical Journa

Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes

Introduction: The problem of organs’ shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques’ combination to develop hybrid scaffolds with increased performing properties was also evaluated.Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features.Results: Hybrid scaffolds showed the best properties in terms of viability (&gt;100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1–10 MPa).Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted

Properties of planets in binary systems. The role of binary separation

The statistical properties of planets in binaries were investigated. Any difference to planets orbiting single stars can shed light on the formation and evolution of planetary systems. As planets were found around components of binaries with very different separation and mass ratio, it is particularly important to study the characteristics of planets as a function of the effective gravitational influence of the companion. A compilation of planets in binary systems was made; a search for companions orbiting stars recently shown to host planets was performed, resulting in the addition of two further binary planet hosts (HD 20782 and HD 109749). The probable original properties of the three binary planet hosts with white dwarfs companions were also investigated. Using this updated sample of planets in binaries we performed a statistical analysis of the distributions of planet mass, period, and eccentricity, fraction of multiplanet systems, and stellar metallicity for planets orbiting components of tight and wide binaries and single stars. The only highly significant difference revealed by our analysis concerns the mass distribution of short-period planets. Massive planets in short period orbits are found in most cases around the components of rather tight binaries. The properties of exoplanets orbiting the components of wide binaries are compatible with those of planets orbiting single stars, except for a possible greater abundance of high-eccentricity planets. The previously suggested lack of massive planets with P>100 days in binaries is not confirmed. We conclude that the presence of a stellar companion with separation smaller than 100-300 AU is able to modify the formation and/or migration and/or the dynamical evolution history of giant planets while wide companions play a more limited roleComment: A&A, in pres

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London