University of Duisburg-Essen

About: University of Duisburg-Essen is a education organization based out in Essen, Nordrhein-Westfalen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 16072 authors who have published 39972 publications receiving 1109199 citations.

CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth

Abstract: This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.

EPS—Then and Now

Abstract: “Slime” played a brief and spectacular role in the 19th century founded by the theory of primordial slime by Ernst Haeckel. However, that substance was never found and eventually abandoned. Further scientific attention slowly began in the 1930s referring to slime as a microbial product and then was inspired by “How bacteria stick” by Costerton et al. in 1978, and the matrix material was considered to be polysaccharides. Later, it turned out that proteins, nucleic acids and lipids were major other constituents of the extracellular polymeric substances (EPS), an acronym which was highly discussed. The role of the EPS matrix turns out to be fundamental for biofilms, in terms of keeping cells in proximity and allowing for extended interaction, resource capture, mechanical strength and other properties, which emerge from the life of biofilm organisms, including enhanced tolerance to antimicrobials and other stress. The EPS components are extremely complex and dynamic and fulfil many functional roles, turning biofilms into the most ubiquitous and successful form of life on Earth.

Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells

Abstract: Purpose: To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared with functional tumor antigen–specific T cells in patients with melanoma with distant metastasis. Experimental Design: The percentage of CD14+CD11b+HLA-DR−/low MDSCs, CD4+CD25+FoxP3+ Tregs, and the presence of NY-ESO-1- or Melan-A–specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan–Meier and log-rank tests. Multivariate analyses were performed using Cox regression models. Results: NY-ESO-1–specific T cells, the M-category, and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1–specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of >11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months versus 8 months for others ( P < 0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma antigen–specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs. Conclusions: Circulating CD14+CD11b+HLA-DR−/low MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen–specific T cells in patients with advanced melanoma. Our findings provide a rationale to investigate MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches. Clin Cancer Res; 20(6); 1601–9. ©2013 AACR . See related article by Kiessling et al., [p. 1401][1] [1]: /lookup/volpage/20/1401?iss=6

Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index.

Abstract: Background: There is not at present a suitable disease-specific health-related quality of life instrument for uninvestigated dyspepsia and functional (non-ulcer) dyspepsia Aim: To develop a new multi-dimensional disease-specific instrument Methods: The Nepean Dyspepsia Index (NDI) was designed to measure impairment of a subject’s ability to engage in relevant aspects of their life and also their enjoyment of these aspects; in addition, the individual importance of each aspect is assessed A 42-item quality of life measure was developed and tested, both in out-patients presenting to general practice with upper gastrointestinal complaints (n = 113) and in a randomly chosen population-based sample (n = 347) Results: Adequate face and content validity was documented by an expert panel Factor analysis identified four clinically relevant subscales: interference with activities of daily living, work, enjoyment of life and emotional well-being; lack of knowledge and control over the illness; disturbance to eating or drinking; and disturbance to sleep because of dyspepsia These scales had high internal consistency Both symptoms and the quality of life scores discriminated dyspepsia from health Conclusion: The Nepean Dyspepsia Index is a reliable and valid disease-specific index for dyspepsia, measuring symptoms and health-related quality of life

Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosis.

Abstract: Nitric oxide (NO) is produced by various cell types in the human respiratory tract. Endogenously produced nitric oxide is detectable in the exhaled air of healthy individuals. Exhaled NO has been shown to be increased in airway inflammation, most probably due to cytokine-mediated activation of NO synthases. To assess whether NO can serve as a marker of inflammation in cystic fibrosis (CF) lung disease, we measured exhaled NO in CF patients with a chemiluminescence analyser. Single breath measurements were performed in 27 stable CF patients (age range, 6-40 years) and 30 non-smoking controls (age range, 6-37 years). Exhaled NO concentrations were 9.1 +/- 3.6 ppb in the controls and 5.9 +/- 2.6 ppb (P < 0.001) in CF patients. To account for room air NO concentrations on the measurement of exhaled NO, we also calculated the difference between exhaled NO and ambient NO concentrations. Difference values were also significantly lower in CF compared with controls (P < 0.0001). In CF patients there was a positive correlation between exhaled NO and forced vital capacity (r = 0.43, P = 0.033), suggesting that exhaled NO is lower in patients with severe lung disease than in those with mild disease. We conclude that measurements of exhaled NO in CF does not reflect activity of CF airway inflammation. The decreased concentrations of exhaled NO may be due to inhibitory effects of inflammatory cytokines on NO syntheses in the airways and alveolar epithelial cells or to increased retention in airway secretions.