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Background Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (T regs ) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and T regs . Methods This nested case‐control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163‐positive M2 macrophages and FOXP3/CD4‐positive T regs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and T regs were assessed using Spearman's rank‐order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts. Results The number of M2 macrophages and T regs showed a significant correlation ( P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23‐3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis. Conclusions Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as T regs , promote an immunosuppressive environment.

Longitudinal studies of traumatized refugees are needed to study changes in mental health over time and to improve health-related and social interventions. The aim of this study was to examine changes in symptoms of PTSD, depression, and anxiety, and in health-related quality of life during treatment in traumatized refugees. The study group comprises 55 persons admitted to the Rehabilitation and Research Centre for Torture Victims in 2001 and 2002. Data on background, trauma, present social situation, mental symptoms (Hopkins Symptom Checklist-25, Hamilton Depression Scale, Harvard Trauma Questionnaire), and health-related quality of life (WHO Quality of Life-Bref) were collected before treatment and after 9 months. No change in mental symptoms or health-related quality of life was observed. In spite of the treatment, emotional distress seems to be chronic for the majority of this population. Future studies are needed to explore which health-related and social interventions are most useful to traumatized refugees.

Some of the most frequently reported mental health problems in traumatized refugees are depression, anxiety and post-traumatic stress disorder (PTSD). The aim of this paper is to describe a group of tortured refugees referred to the Rehabilitation and Research Centre for Torture Victims (RCT) and to study the importance of past trauma/torture and post-migratory factors for the present symptoms of PTSD, depression, anxiety and for health-related quality of life. The sample comprises 63 male tortured refugees admitted to a pre-treatment assessment at RCT. Data on personal background, trauma, present situation in Denmark, symptoms of depression, anxiety (Hopkins Symptom Checklist-25, HSCL-25, and Hamilton Depression Scale, HDS), PTSD (Harvard Trauma Questionnaire, HTQ), and on health-related quality of life (WHO Quality of life-Bref, WHOQOL-Bref) were collected through self-administered questionnaires and structured and semi-structured interviews. The scores in the questionnaires measuring emotional distress were high. Previous torture and trauma, lower education, fewer social contacts, no occupation and pain were identified as significant predictors of emotional distress. Few social contacts was a significant predictor of a lower health-related quality of life. Even after many years, past torture is significantly associated with emotional distress. Post-migratory factors are also significantly associated with emotional distress and health-related quality of life, and potentially modifiable factors, such as social relations and occupation, are of special interest.

Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n ¼ 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n ¼ 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro, inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.

The aim of the study was to identify predictors of mental symptoms (posttraumatic stress disorder, depression, and anxiety), and of health-related quality of life in refugees 10 years after referral to the Rehabilitation and Research Centre for Torture Victims, and to study changes in mental health over time. The study sample comprises 139 tortured refugees admitted to a pretreatment assessment in 1991 to 1994. Data on background and trauma, and in a subsample on mental symptoms, were collected at baseline. In 2002 and 2003, data on mental symptoms, health-related quality of life, and the participants' social situation were collected. The level of emotional distress was high at follow-up. Social relations and unemployment at follow-up were important predictors of mental health symptoms and low health-related quality of life. A significant decrease in mental symptoms was observed in the subsample. Social relations and unemployment should be taken into account when developing health-related and social interventions.

BackgroundProstate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.MethodsWe included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient’s prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.ResultsThe results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93–11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.ConclusionThe present study provides further evidence for a role of P. acnes in prostate cancer development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0074-9) contains supplementary material, which is available to authorized users.

Low-density arrays for quantitative real-time PCR (qPCR) are increasingly being used as an experimental technique for miRNA expression profiling. As with gene expression profiling using microarrays, data from such experiments needs effective analysis methods to produce reliable and high-quality results. In the pre-processing of the data, one crucial analysis step is normalization, which aims to reduce measurement errors and technical variability among arrays that might have arisen during the execution of the experiments. However, there are currently a number of different approaches to choose among and an unsuitable applied method may induce misleading effects, which could affect the subsequent analysis steps and thereby any conclusions drawn from the results. The choice of normalization method is hence an important issue to consider. In this study we present the comparison of a number of data-driven normalization methods for TaqMan low-density arrays for qPCR and different descriptive statistical techniques that can facilitate the choice of normalization method. The performance of the normalization methods was assessed and compared against each other as well as against standard normalization using endogenous controls. The results clearly show that the data-driven methods reduce variation and represent robust alternatives to using endogenous controls.