Thymosin β10 Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production

Thymosin β10 (Tβ10) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ10, that can overexpress the Tβ10 gene in cancer cells. This was accomplished by replacing the native Tβ10 gene promoter with the human TERT promoter in Ad.TERT.Tβ10. We investigated the cancer suppression activity of Tβ10 and found that Ad.TERT.Tβ10 strikingly induced cancer-specific expression of Tβ10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ10 by Ad.TERT.Tβ10 could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells

Characterizing Community-Based Mental Health Services for Children with Autism Spectrum Disorders and Disruptive Behavior Problems

This study describes the characteristics of children with autism spectrum disorders (ASD) with disruptive behavior problems served in community-based mental health clinics, characterizes psychotherapy process and outcome, and examines differences between children with ASD and a non-ASD comparison group. Results indicate that children with ASD served in this setting are high functioning and diagnostically complex. Certain research-based behavioral and cognitive behavioral psychotherapeutic strategies were observed frequently, while parent training strategies and active teaching strategies were observed less frequently. The intensity or thoroughness with which strategies were pursued was relatively low. Outcome analyses indicate improvement in child symptoms and family functioning. Treatment delivery and outcome were similar for children with and without ASD. These findings represent the first detailed observational data characterizing community-based mental health services for children with ASD

Anxiety Disorders in Children and Adolescents with Autistic Spectrum Disorders: A Meta-Analysis

There is considerable evidence that children and adolescents with autistic spectrum disorders (ASD) are at increased risk of anxiety and anxiety disorders. However, it is less clear which of the specific DSM-IV anxiety disorders occur most in this population. The present study used meta-analytic techniques to help clarify this issue. A systematic review of the literature identified 31 studies involving 2,121 young people (aged <18 years) with ASD, and where the presence of anxiety disorder was assessed using standardized questionnaires or diagnostic interviews. Across studies, 39.6% of young people with ASD had at least one comorbid DSM-IV anxiety disorder, the most frequent being specific phobia (29.8%) followed by OCD (17.4%) and social anxiety disorder (16.6%). Associations were found between the specific anxiety disorders and ASD subtype, age, IQ, and assessment method (questionnaire versus interview). Implications for the identification and treatment of anxiety in young people with ASD are discussed