A Multifaceted Approach Identifies ErbB2 and ErbB3 proteins and microRNA-125b as Key Contributors to Prostate Cancer Progression

Prostate cancer is the most common cancer affecting men today. Therefore, there is a strong need for accurate biomarkers and successful therapeutic treatments. A novel approach combining a computationally built protein-protein interaction network of proven microRNA protein targets with high throughput proteomics identified ErbB2 and ErbB3 as key proteins in prostate cancer. These results coupled with microRNA array screening of an androgen-independent prostate cancer progression model, substantiated by single microRNA analysis, suggested miR125b as a key tumor suppressor contributing to prostate cancer progression. miR125b expression was shown to be substantially increased in the non-tumorigenic P69 cell line compared to its highly tumorigenic, metastatic M12 variant. Luciferase reporter gene assays including the entire 3’UTR of either ErbB2 or ErbB3 revealed a 2.8- and 2.4-fold decrease (respectively) compared to control vector. Thus, this combinatorial approach has suggested an additional microRNA and its target involved in prostate tumor progression

Exercise dependence and muscle dysmorphia in novice and experienced female bodybuilders

Background and aims: Extensive research has shown that male bodybuilders are at high risk for exercise dependence, but few studies have measured these variables in female bodybuilders. Prior research has postulated that muscular dysmorphia was more prevalent in men than women, but several qualitative studies of female bodybuilders have indicated that female bodybuilders show the same body image concerns. Only one study has compared female bodybuilders with control recreational female lifters on eating behaviors, body image, shape pre-occupation, body dissatisfaction, and steroid use. The purpose of this study was to compare exercise dependence and muscle dysmorphia measures between groups of female weight lifters. Methods: Seventy-four female lifters were classified into three lifting types (26 expert bodybuilders, 10 or more competitions; 29 novice bodybuilders, 3 or less competitions; and 19 fitness lifters, at least 6 months prior lifting) who each completed a demographic questionnaire, the Exercise Dependence Scale (EDS), the Drive for Thinness scale (DFT) of the Eating Disorder Inventory-2, the Bodybuilding Dependence Scale (BDS), and the Muscle Dysmorphia Inventory (MDI). Results: Female bodybuilders scored higher than fitness lifters for EDS Total, BDS Training and Social Dependence, and on Supplement Use, Dietary Behavior, Exercise Dependence, and Size Symmetry scales of the MDI. Discussion and conclusions: Female bodybuilders seem to be more at risk for exercise dependence and muscle dysmorphia symptoms than female recreational weight lifters

A Case of Metastatic Melanoma Presenting as a Small Bowel Obstruction

Small bowel obstructions are most commonly caused by adhesion. Less common causes arise from malignant pathology. Here we present a relatively rare case of a small bowel obstruction due to malignant melanoma. Melanoma involving the gastrointestinal tract is relatively rare with most cases occurring as metastatic spread from a cutaneous primary. The treatment typically requires a surgical resection or palliative bypass. When a patient presents with a small bowel obstruction but without prior abdominal surgeries or hernias a malignant obstruction must be on the differential

A networks method for ranking microRNA dysregulation in cancer

Background Despite the lack of agreement on their exact roles, it is known that miRNAs contribute to cancer progression. Many studies utilize methods to detect differential regulation of miRNA expression. It is prohibitively expensive to examine all potentially dysregulated miRNAs and traditionally, researchers have focused their efforts on the most extremely dysregulated miRNAs. These methods may overlook the contribution of less differentially expressed but more functionally relevant miRNAs. The purpose of this study was to outline a method that not only utilizes differential expression but ranks miRNAs based on the functional relevance of their targets. This work uses a networks based approach to determine the sum node degree for all experimentally verified miRNA targets to identify potential regulators of prostate cancer initiation, progression and metastasis. Results Here, we present a method for identifying functionally relevant miRNAs that contribute to prostate cancer development. This paper shows that miRNAs preferentially regulate highly connected, central proteins within a protein-protein interaction network. Known targets of miRNAs differentially regulated during prostate cancer progression are enriched in pathways with known involvement in tumorigenesis. To demonstrate the applicability of our method, we utilized a unique model of prostate cancer progression to identify five miRNAs that may contribute to the oncogenic state of the cell. Three of these miRNAs have been shown by other studies to have a role in cancer but their exact role in prostate cancer remains undefined. Conclusion Developing methods to determine which miRNAs to carry forward into biological and biochemical analyses is important as traditional approaches often overlook miRNAs that contribute to oncogenesis. Our method applied to a model of prostate cancer progression was able to identify miRNAs with roles in prostate cancer development

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was confirmed in human prostate tumor samples as compared to adjacent benign glandular epithelium collected through laser capture microdissection from radical prostatectomies. In fact, alterations in hsa-miR-125b expression appeared to be an early event in tumorigenesis. Reverse phase microarray proteomic analysis revealed ErbB2/3 and downstream members of the PI3K/AKT and MAPK/ERK pathways as well as PTEN to be protein targets differentially expressed in the M12 tumor cell compared to its parental p69 cell. Relevant luciferase+3’-UTR expression studies confirmed a direct interaction between hsa-miR-125b and ErbB2 and between hsa-miR-22 and PTEN. Restoration of hsa-miR-125b or inhibition of hsa-miR-22 expression via an antagomiR resulted in an alteration of M12 tumor cell behavior in vitro. Thus, the dual action of hsa-miR-125b as a tumor suppressor and hsa-miR-22 as an oncomiR contributed to prostate tumorigenesis by modulations in PI3K/AKT and MAPK/ERK signaling pathways, key pathways known to influence prostate cancer progression

Non-Participants in Policy Efforts to Promote Evidence-Based Practices in a Large Behavioral Health System

Background: System-wide training initiatives to support and implement evidence-based practices (EBPs) in behavioral health systems have become increasingly widespread. Understanding more about organizations who do not participate in EBP training initiatives is a critical piece of the dissemination and implementation puzzle if we endeavor to increase access in community settings. Methods: We conducted 30 1-h semi-structured interviews with leaders in non-participating agencies who did not formally participate in system-wide training initiatives to implement EBPs in the City of Philadelphia, with the goal to understand why they did not participate. Results: We found that despite not participating in training initiatives, most agencies were adopting (and self-financing) some EBP implementation. Leadership from agencies that were implementing EBPs reported relying on previously trained staff to implement EBPs and acknowledged a lack of emphasis on fidelity. Most leaders at agencies not adopting EBPs did not have a clear understanding of what EBP is. Those familiar with EBPs in agencies not adopting EBPs reported philosophical objections to EBPs. When asked about quality assurance and treatment selection, leaders reported being guided by system audits. Conclusions: While it is highly encouraging that many agencies are adopting EBPs on their own, significant questions about fidelity and implementation success more broadly remain