A Test of the Psychometric Characteristics of the BIS-Brief Among Three Groups of Youth

The current study empirically investigates the relationships between the Dark Triad personality traits and cyber-aggression among adolescents (14–18 year old). The sample consisted of 324 participants aged 14–18 (M = 16.05, SD = 1.31). Participants completed the Short Dark Triad (SD3) as a measure of the Dark Triad personality traits, the Facebook Intensity Scale and a scale to measure cyber-aggression. Structural equation modelling was applied to investigate the relationships. Results show that only Facebook intensity and psychopathy significantly predict cyber-aggression, when controlling for age and gender. Findings are discussed regarding the potential importance to further study Dark Triad traits, and psychopathy in particular, in the context of adolescent cyber-aggression

Lineage of origin in rhabdomyosarcoma informs pharmacological response

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.Stem Cell and Regenerative Biolog

EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma affecting children and is often diagnosed with concurrent metastases. Unfortunately, few effective therapies have been discovered that improve the long-term survival rate for children with metastatic disease. Here we determined effectiveness of targeting the receptor tyrosine kinase, EphB4, in both alveolar and embryonal RMS either directly through the inhibitory antibody, VasG3, or indirectly by blocking both forward and reverse signaling of EphB4 binding to EphrinB2, cognate ligand of EphB4. Clinically, EphB4 expression in eRMS was correlated with longer survival. Experimentally, inhibition of EphB4 with VasG3 in both aRMS and eRMS orthotopic xenograft and allograft models failed to alter tumor progression. Inhibition of EphB4 forward signaling using soluble EphB4 protein fused with murine serum albumin failed to affect eRMS model tumor progression, but did moderately slow progression in murine aRMS. We conclude that inhibition of EphB4 signaling with these agents is not a viable monotherapy for rhabdomyosarcoma

Features of human xenograft model systems.

<p>Features of human xenograft model systems.</p

VasG3 treatment of Rh30 & PCB380 aRMS xenografts.

<p><i>A</i>. Experimental design of the orthotopic aRMS xenograft tumor models and VasG3 treatment regime. <i>B</i>. Immunohistochemical staining of the patient-derived PCB380 tumor to demonstrate EphB4 and EphrinB2 expression as obtained from the BioPathology Center RMS tissue microarray. Skeletal muscles sections were concurrently stained as controls. Arrow heads indicate EphB4/EphrinB2 expressing vascular/stromal cells. Mag bar = 50 μm. <i>C</i>. EphB4 protein expression in cultured aRMS cell lines. <i>D and E</i>. Kaplan-Meier survival curves post-treatment initiation of isotype control (black line) versus VasG3 (anti-human EphB4 binding antibody; red line) treated mice for both the PCB380 (<i>D</i>) and Rh30 (<i>E</i>) xenograft models. Mice were euthanized either on day 60 or when the tumor volume exceeded 1.2 cm³. n = 11–12 female mice per treatment group for both models. <i>F and G</i>. Representative western blot demonstrating loss of EphB4 protein levels with VasG3 treatment (<i>F</i>) and quantification of EphB4 loss (<i>G</i>) for the Rh30 model. n = 11–12 mice per cohort. p<0.0001.</p

EphB4 and EphrinB2 expression in model systems of human eRMS.

<p><i>A</i>. Patient survival improves with high EphB4 expression determined using the. p = 0.0033, n = 72. <i>B</i>. Human eRMS expression of EphB4 and EphrinB2, respectively, of PCB82 tissue sections from a human eRMS tissue microarray. Control skeletal muscle from the same TMA is depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183161#pone.0183161.g001" target="_blank">Fig 1B</a>. <i>C</i>. Human eRMS expression of EphB4 and EphrinB2 in Rh18 xenograft sections. Mag bar = 50 μm. <i>D</i>. Representative western blot demonstrating EphB4 and EphrinB2 protein expression in human eRMS xenograft models, PCB82 and Rh18.</p

Immunohistochemistry of embryonal rhabdomyosarcoma tissue microarrays.

<p>Immunohistochemistry of embryonal rhabdomyosarcoma tissue microarrays.</p

VasG3 treatment of PCB82 eRMS xenografts.

<p><i>A</i>. Kaplan-Meier curve demonstrating percent event-free survival based on day post-treatment. Isotype control (black line) versus VasG3 (red line). p = 0.351, n = 6 female mice per cohort. <i>B</i>. Western blot demonstrating loss of EphB4 protein levels following VasG3 treatment. <i>C</i>. Differences in EphB4 protein levels following VasG3 treatment were quantified with densitometry. **p = 0.006.</p