BackgroundCD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes.MethodsExosomes were isolated and characterized from both liver CD90+ cells and hepatoma cell lines. Endothelial cells were treated with exosomes, as well as transfected with a plasmid containing the full length sequence of the long non-coding RNA (lncRNA) H19. Molecular and functional analyses were done to characterize the endothelial phenotype after treatments.ResultsExosomes released by CD90+ cancer cells, but not by parental hepatoma cells, modulated endothelial cells, promoting angiogenic phenotype and cell-to-cell adhesion. LncRNA profiling revealed that CD90+ cells were enriched in lncRNA H19, and released this through exosomes. Experiments of gain and loss of function of H19 showed that this LncRNA plays an important role in the exosome-mediated phenotype of endothelial cells.ConclusionsOur data indicate a new exosome-mediated mechanism by which CSC-like CD90+ cells could influence their tumor microenvironment by promoting angiogenesis. Moreover, we suggest the lncRNA H19 as a putative therapeutic target in hepatocellular carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0426-x) contains supplementary material, which is available to authorized users.

Abstract Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs.

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Bullying is defined as systematic exposure to humiliation as well as hostile and violent behaviors against one or more individuals. These behaviors are a serious, growing problem, which affects a significant proportion of health care professionals. To support the hospital's risk management policy, a cross-sectional study was undertaken to determine the prevalence of bullying in this institution and identify the determinants of bullying. Bullying was measured using the Negative Acts Questionnaire-Revised, Portuguese version (NAQ-R), a self-administered tool. The questionnaire was made available in digital format on the hospital's internal network (Intranet) and in hard copy; questionnaires were returned via nonidentified internal mail addressed to the occupational health unit or deposited in suggestion boxes located throughout the hospital. Multiple questionnaire delivery methods guaranteed data anonymity and confidentiality. The prevalence of bullying in this hospital was 8% (95% confidence interval [CI] = [6.2, 10.2]). Reported bullying was predominantly vertical and more frequently occurring among nurses, clerical staff, and health care assistants (12.5%, 7.6%, 6.4%, respectively; p = .005). After adjusting for gender, age, occupation, type of contract, and work schedule, only type of contract was significantly associated with bullying in the workplace; the risk of bullying was twice as high among government employees compared to workers with indefinite duration employment contracts ( p = .038). This study identified a high prevalence of bullying among health professionals; hence a program to prevent and control this phenomenon was implemented in this institution.

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