A Pyrazolo[3,4-d]pyrimidine compound inhibits Fyn phosphorylation and induces apoptosis in natural killer cell leukemia

Natural killer (NK) cell neoplasms are characterized by clonal proliferation of cytotoxic NK cells. Since there is no standard treatment to date, new therapeutic options are needed, especially for NK aggressive tumors. Fyn tyrosine kinase has a key role in different biological processes, such as cell growth and differentiation, being also involved in the pathogenesis of hematologic malignancies. Our previous studies led us to identify 4c pyrazolo[3,4-d]pyrimidine compound capable of inhibiting Fyn activation and inducing apoptosis in different cancer cell lines. Here we investigated the presence of Fyn and the effect of its inhibitor in NK malignant cells. Firstly, we showed Fyn over-expression in NK leukemic cells compared to peripheral blood mononuclear cells from healthy donors. Subsequently, we demonstrated that 4c treatment reduced cell viability, induced caspase 3-mediate apoptosis and cell cycle arrest in NK cells. Moreover, by inhibiting Fyn phosphorylation, 4c compound reduced Akt and P70 S6 kinase activation and changed the expression of genes involved in cell death and survival in NK cells. Our study demonstrated that Fyn is involved in the pathogenesis of NK leukemia and that it could represent a potential target for this neoplasm. Moreover, we proved that Fyn inhibitor pyrazolo[3,4-d]pyrimidine compound, could be a started point to develop new therapeutic agents

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

ACTIVE FLOW CONTROL USING PLASMA ACTUATORS IN GAS TURBINE ENGINE

This study is focused on the active flow control in the internal flow of turbo-jet engines by Dielectric Barrier Discharges Actuators. In particular the application of this techniques has been studied with the aim of improving the aerodynamic behavior of compressor blades by reducing, or even eliminating, flow separation. A numerical electrostatic model has been implemented in the CFD code, to investigate the aerodynamic behaviour of a transonic compressor rotor with and without plasma actuators

ACTIVE FLOW CONTROL TECHNIQUES ON A STATOR COMPRESSOR CASCADE: A COMPARISON BETWEEN SYNTHETIC JET AND PLASMA ACTUATORS

In this work it is applied a CFD analysis to study the suppression of the boundary layer separation in to a highly - loaded subsonic compressor stator cascade, by active flow control techniques, as zero net mass flux Synthetic Jet (SJA) actuation and Plasma actuation. Active flow control techniques have the potential to delay separation and to increase the pressure ratio. Several works have investigated the use of synthetic jet and plasma actuators on the airfoil, but only few studies have compared the effect of these two devices. Concerning the synthetic jet actuator, a suction/blowing type boundary condition is used, imposing a prescribed sinusoidal velocity depending on velocity amplitude, jet frequency and jet angle of ejection with respect to the wall. Concerning the plasma actuation, the effect is modeled into numerical flow solvers by adding the paraelectric force that represents the plasma force into the momentum equation. The plasma, generated by Dielectric Barrier Discharge, acts as a momentum source to the boundary layer allowing it to remain attached throughout a larger portion of the airfoil. The timeaveraged body force component, acting on the fluid, depends on the frequency and on the applied voltage, the charge density, the electrical field and the dimensional properties of the actuator, like width of the electrodes and gap between the electrodes. Using this numerical model, the effect of plasma actuators to suppress the flow separation over the blade has been investigated, increasing the turbo-machinery performance too. Finally, the comparison between these two devices shows that, reducing the secondary flow structures, both actuation techniques beneficially affect the performance of the stator compressor cascade, even if in the steady jet the costs are relevant

A comparison between micro linear plasma synthetic jets and conventional dbd plasma actuators for separation control in a low pressure turbine

At high altitudes the boundary layer of the blades of low-pressure turbine of small gas turbines for aircraft propulsion could be dominated by laminar flow and susceptible to flow separation and secondary vortices, with a reduction of turbine performance. The present study concerns the active flow control using plasma actuators to reattach the simulated separation flow over the suction surface of a low-pressure turbine blade at low Reynolds number. Different actuator geometries have been studied: a macro single dielectric barrier discharge (SDBD), a micro SDBD and a micro linear plasma synthetic jet (L-PSJ) with and without thrust vectoring. In particular, the micro plasma actuator was realized and experimentally characterized by measuring the induced wall-jet with Particle Image Velocimetry (PIV) and by evaluating the electrical power consumption. The numerical modelling was used to assess and compare the performances of the different configurations in the separation control. In presence of these active flow control devices the separated flow was successfully reduced

Epidermoid cyst of the coronal sulcus mimicking penile cancer: A case report

INTRODUCTION: Epidermoid cysts represent common benign tumors occurring anywhere in the body but very rarely in the penis. Only a few cases of penile localization have been reported in the literature so far, most of them being congenital and/or idiopathic, usually presenting in children as slow-growing, solitary, well-delimited cystic lesions. Here, we describe the case of a patient with a penile epidermoid cyst presenting as an ulcerated lesion of the coronal sulcus, thus mimicking penile cancer. CASE PRESENTATION: A 36-year-old Caucasian man presented with a three-month history of a rapidly growing asymptomatic ulcerated lesion in the ventral portion of the penile coronal sulcus. At surgical exploration, the area under the ulcerated lesion had a well-demarcated cystic shape; following its wide excision, an intraoperative histological examination revealed an epidermoid cyst. No recurrence had occurred at nine years of follow-up. CONCLUSIONS: Rare benign tumors of the penis, like the described epidermoid cyst, may mimic cancer. Nevertheless, penile ulcerated lesions should always be surgically explored as wide excision and intraoperative histological examination remain the only means of obtaining a precise disease definition and, consequently, administering the appropriate treatment

Vasoactive intestinal polypeptide (VIP) is not an androgen-dependent neuromediator of penile erection.

The effects of castration on vasoactive intestinal polypeptide (VIP) immunostaining in human corpus cavernosum (CC) and the relationship between VIP immunostaining and erectile function were studied in patients with localised prostate cancer who had (Group 1 = castrated) or had not (Group 2 = control) undergone 3-month neoadjuvant chemical castration before radical prostatectomy. Evaluation of erectile function included medical and sexual history, physical examination, and measurement of total serum testosterone. CC biopsies were taken at the end of radical prostatectomy and samples immunostained with anti-human VIP antibody. Specific staining was quantified by image analysis and expressed in arbitrary units (AU). Chemical castration induced erectile function deterioration in 70% of patients due to loss of sexual interest and confidence in the ability of having an erection rather than reduced ability of obtaining sexually induced erections. Average VIP content was 34.5 AU in Group 1 and 39 AU in Group 2 and this difference was not statistically significant. Chemical castration does not influence VIP immunostaining of human CC, suggesting that VIP is not an androgen-dependent neuromediator of penile erection and that it can be responsible for sexually induced erections in castrated patients