Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells.

Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers. Two effector-to-target cell ratios (12.5:1 and 25:1) were used by two independent investigators with a focus on the concentration-dependent effect (0.5 vs. 1 ng/ml aviscumine), reproducibility (first vs. second investigator) and the specificity of the effect by comparison to a heat-inactivated aliquot and interleukin 2 (IL-2) stimulation (10 ng/ml). The mediation of the effect via degranulation was demonstrated by flow cytometric analyses of CD107α expression. Statistics were performed with SPSS using Student's t-tests for normally distributed data. Aviscumine induced a significant and reproducible, concentration-dependent increase in NK cell cytotoxicity (n=22; P<0.01 for both concentrations and ratios), which was also demonstrated when administered in combination with IL-2 (n=12; 12.5:1 ratio, P<0.001; 25:1 ratio, P=0.025) and when compared with the heat-inactivated aliquots (n=12; 12.5:1, P=0.004; 25:1 ratio, P=0.007). The mediation of its effect via interferon γ degranulation was demonstrated by significantly enhanced CD107α expression (n=7; P=0.005). Taken together, the results indicate that aviscumine induced an increase in NK cell anticancer cytotoxicity. These results highlight its clinical potential as an immunostimulatory agent, particularly with regard to combined use with chemotherapeutics or immune checkpoint inhibitors. However, further studies are required.

Assessment of tumor heterogeneity in treatment-naïve adrenocortical cancer patients using (18)F-FDG positron emission tomography.

As an orphan malignancy, only limited treatment options are available in adrenocortical carcinoma (ACC). Non-invasive risk assessment has not been described but may be of value to stratify patients for treatment. We aimed to evaluate the potential value of intra-individual tumor heterogeneity as assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for outcome prediction in treatment-naïve ACC patients. Ten patients with primary diagnosis of ACC were included in this study. Prior to any treatment initiation, baseline (18)F-FDG PET scans were performed. Tumor staging was performed using the European Network for the Study of Adrenal Tumors (ENS@T). Intratumoral heterogeneity of the primary tumor was assessed by manual segmentation using conventional PET parameters (standardized uptake values and tumor-to-liver ratios) and textural features. The impact of tumoral heterogeneity based on pre-therapeutic (18)F-FDG PET to predict progression-free (PFS) and overall survival (OS) was evaluated by receiver operating characteristic analysis. On average, tumor recurrence or progression was detected after median of 561 days (range 71-1434 days) after the pre-therapeutic baseline PET scan. 50 % of the patients died of ACC within the follow-up period (mean 983 ± 404 days). Pre-therapeutic tumor volume was associated with PFS (r = -0.67, p = 0.05) and Ki67 index with OS (r = -0.66, p = 0.04). ENS@T tumor stage was the only parameter to correlate with both PFS and OS (r = -0.82, p = 0.001, and r = -0.72, p = 0.01, respectively). In the subgroup of patients without distant metastases (ENS@T stages II and III), age and pre-therapeutic tumor volume correlated significantly with PFS (r = 0.96, p = 0.01 and r = -0.93, p = 0.02, respectively) and OS (r = 0.95, p = 0.02 and r = -0.90, p = 0.04, respectively). None of the investigated classic or textural PET parameters predicted PFS or OS. In this pilot study in treatment-naïve ACC patients, conventional (18)F-FDG PET-derived parameters and textural tumor heterogeneity features were not suitable to identify high-risk patients.

Video games do affect social outcomes: a meta-analytic review of the effects of violent and prosocial video game play.

Whether video game play affects social behavior is a topic of debate. Many argue that aggression and helping are affected by video game play, whereas this stance is disputed by others. The present research provides a meta-analytical test of the idea that depending on their content, video games do affect social outcomes. Data from 98 independent studies with 36,965 participants revealed that for both violent video games and prosocial video games, there was a significant association with social outcomes. Whereas violent video games increase aggression and aggression-related variables and decrease prosocial outcomes, prosocial video games have the opposite effects. These effects were reliable across experimental, correlational, and longitudinal studies, indicating that video game exposure causally affects social outcomes and that there are both short- and long-term effects.