Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker?

Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF165. The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF165 for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker

Radical prostatectomy after vascular-targeted photodynamic therapy (VTP) with TOOKAD® : feasibility, early and intermediate results

Purpose: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. Materials and Methods: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. Results: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. Conclusions: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons

The SPHERE infrared survey for exoplanets (SHINE). III. The demographics of young giant exoplanets below 300 au with SPHERE

The SHINE project is a 500-star survey performed with SPHERE on the VLT for the purpose of directly detecting new substellar companions and understanding their formation and early evolution. Here we present an initial statistical analysis for a subsample of 150 stars that are representative of the full SHINE sample. Our goal is to constrain the frequency of substellar companions with masses between 1 and 75 MJup and semimajor axes between 5 and 300 au. We adopt detection limits as a function of angular separation from the survey data for all stars converted into mass and projected orbital separation using the BEX-COND-hot evolutionary tracks and known distance to each system. Based on the results obtained for each star and on the 13 detections in the sample, we use a MCMC tool to compare our observations to two different types of models. The first is a parametric model based on observational constraints, and the second type are numerical models that combine advanced core accretion and gravitational instability planet population synthesis. Using the parametric model, we show that the frequencies of systems with at least one substellar companion are $23.0_{-9.7}^{+13.5}\%$, $5.8_{-2.8}^{+4.7}\%$, and $12.6_{-7.1}^{+12.9}\%$ for BA, FGK, and M stars, respectively. We also demonstrate that a planet-like formation pathway probably dominates the mass range from 1-75 MJup for companions around BA stars, while for M dwarfs, brown dwarf binaries dominate detections. In contrast, a combination of binary star-like and planet-like formation is required to best fit the observations for FGK stars. Using our population model and restricting our sample to FGK stars, we derive a frequency of $5.7_{-2.8}^{+3.8}\%$, consistent with predictions from the parametric model. More generally, the frequency values that we derive are in excellent agreement with values obtained in previous studies.Comment: 24 pages, 14 figures, 3 tables. Accepted for publication in A&

Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis

The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis

Imaging radial velocity planets with SPHERE

We present observations with the planet finder SPHERE of a selected sample of the most promising radial velocity (RV) companions for high-contrast imaging. Using a Monte Carlo simulation to explore all the possible inclinations of the orbit of wide RV companions, we identified the systems with companions that could potentially be detected with SPHERE. We found the most favorable RV systems to observe are : HD\,142, GJ\,676, HD\,39091, HIP\,70849, and HD\,30177 and carried out observations of these systems during SPHERE Guaranteed Time Observing (GTO). To reduce the intensity of the starlight and reveal faint companions, we used Principle Component Analysis (PCA) algorithms alongside angular and spectral differential imaging. We injected synthetic planets with known flux to evaluate the self-subtraction caused by our data reduction and to determine the 5$\sigma$ contrast in the J band $vs$ separation for our reduced images. We estimated the upper limit on detectable companion mass around the selected stars from the contrast plot obtained from our data reduction. Although our observations enabled contrasts larger than 15 mag at a few tenths of arcsec from the host stars, we detected no planets. However, we were able to set upper mass limits around the stars using AMES-COND evolutionary models. We can exclude the presence of companions more massive than 25-28 \MJup around these stars, confirming the substellar nature of these RV companions.Comment: 14 pages, 11 figures, accepted by MNRA

The SPHERE Infrared Survey for Exoplanets (SHINE): II. Observations, Data Reduction and Analysis, Detection Performances, and Initial Results

Context. In recent decades, direct imaging has confirmed the existence of substellar companions (exoplanets or brown dwarfs) on wide orbits (>10 au) around their host stars. In striving to understand their formation and evolution mechanisms, in 2015 we initiated the SPHERE infrared survey for exoplanets (SHINE), a systematic direct imaging survey of young, nearby stars that is targeted at exploring their demographics. Aims. We aim to detect and characterize the population of giant planets and brown dwarfs beyond the snow line around young, nearby stars. Combined with the survey completeness, our observations offer the opportunity to constrain the statistical properties (occurrence, mass and orbital distributions, dependency on the stellar mass) of these young giant planets. Methods. In this study, we present the observing and data analysis strategy, the ranking process of the detected candidates, and the survey performances for a subsample of 150 stars that are representative of the full SHINE sample. Observations were conducted in a homogeneous way between February 2015 and February 2017 with the dedicated ground-based VLT/SPHERE instrument equipped with the IFS integral field spectrograph and the IRDIS dual-band imager, covering a spectral range between 0.9 and 2.3 μm. We used coronographic, angular, and spectral differential imaging techniques to achieve the best detection performances for this study, down to the planetary mass regime. Results. We processed, in a uniform manner, more than 300 SHINE observations and datasets to assess the survey typical sensitivity as a function of the host star and of the observing conditions. The median detection performance reached 5σ-contrasts of 13 mag at 200 mas and 14.2 mag at 800 mas with the IFS (YJ and YJH bands), and of 11.8 mag at 200 mas, 13.1 mag at 800 mas, and 15.8 mag at 3 as with IRDIS in H band, delivering one of the deepest sensitivity surveys thus far for young, nearby stars. A total of sixteen substellar companions were imaged in this first part of SHINE: seven brown dwarf companions and ten planetary-mass companions.These include two new discoveries, HIP 65426 b and HIP 64892 B, but not the planets around PDS70 that had not been originally selected for the SHINE core sample. A total of 1483 candidates were detected, mainly in the large field of view that characterizes IRDIS. The color-magnitude diagrams, low-resolution spectrum (when available with IFS), and follow-up observations enabled us to identify the nature (background contaminant or comoving companion) of about 86% of our subsample. The remaining cases are often connected to crowded-field follow-up observations that were missing. Finally, even though SHINE was not initially designed for disk searches, we imaged twelve circumstellar disks, including three new detections around the HIP 73145, HIP 86598, and HD 106906 systems. Conclusions. Nowadays, direct imaging provides a unique opportunity to probe the outer part of exoplanetary systems beyond 10 au to explore planetary architectures, as highlighted by the discoveries of: one new exoplanet, one new brown dwarf companion, and three new debris disks during this early phase of SHINE. It also offers the opportunity to explore and revisit the physical and orbital properties of these young, giant planets and brown dwarf companions (relative position, photometry, and low-resolution spectrum in near-infrared, predicted masses, and contrast in order to search for additional companions). Finally, these results highlight the importance of finalizing the SHINE systematic observation of about 500 young, nearby stars for a full exploration of their outer part to explore the demographics of young giant planets beyond 10 au and to identify the most interesting systems for the next generation of high-contrast imagers on very large and extremely large telescopes. © M. Langlois et al. 2021.SPHERE is an instrument designed and built by a consortium consisting of IPAG (Grenoble, France), MPIA (Heidelberg, Germany), LAM (Marseille, France), LESIA (Paris, France), Laboratoire Lagrange (Nice, France), INAF – Osservatorio di Padova (Italy), Observatoire de Genève (Switzerland), ETH Zürich (Switzerland), NOVA (Netherlands), ONERA (France) and ASTRON (Netherlands) in collaboration with ESO. SPHERE was funded by ESO, with additional contributions from CNRS (France), MPIA (Germany), INAF (Italy), FINES (Switzerland) and NOVA (Netherlands). SPHERE also received funding from the European CommissionSixth and Seventh Framework Programmes as part of the Optical Infrared Coordination Network for Astronomy (OPTICON) under grant number RII3-Ct-2004-001566 for FP6 (2004-2008), grant number 226604 for FP7 (2009-2012) and grant number 312430 for FP7 (2013-2016). This paper is based on observations collected at the European Southern Observatory under ESO programmes 198.C-0209, 097.C-0865, 095.C-0298, 095.C-0309,096.C-0241. This work has made use of the SPHERE Data Centre, jointly operated by OSUG/IPAG (Grenoble), PYTHEAS/LAM/CeSAM (Marseille), OCA/Lagrange (Nice), Observatoire de Paris/LESIA (Paris), and Observatoire de Lyon (OSUL/CRAL). This work is supported by the French National Research Agency in the framework of the Investissements d’Avenir program (ANR-15-IDEX-02), through the funding of the “Origin of Life” project of the Univ. Grenoble-Alpes. This work is jointly supported by the French National Programms (PNP and PNPS) and by the Action Spécifique Haute Résolution Angulaire (ASHRA) of CNRS/INSU co-funded by CNES. We also thank the anonymous referee for her/his careful reading of the manuscript as well as her/his insightful comments and suggestions. AV acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 757561). A.-M.L. acknowledges funding from French National Research Agency (GIPSE project). C.P. acknowledges financial support from Fondecyt (grant 3190691) and financial support from the ICM (Iniciativa Científica Milenio) via the Núcleo Milenio de Formación Planetaria grant, from the Universidad de Valparaíso. T.H. acknowledges support from the European Research Council under the Horizon 2020 Framework Program via the ERC Advanced Grant Origins 832428

Immune plexins and semaphorins: old proteins, new immune functions

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intra-cellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review