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Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology. Cancer Prev Res; 4(12); 2062–71. ©2011 AACR.

Green tea may prevent cancer, partially by inhibiting tumor angiogenesis. Our previous studies showed that green tea extract was effective in inhibiting breast cancer and endothelial cell proliferation in vitro, and suppressed xenograft size and decreased the tumor vessel density in vivo. Here, we set out to further investigate the molecular mechanisms of this observed angiogenesis suppression. We utilized cDNA microarray technology to profile the global changes in endothelial cellular gene expression in response to green tea. HUVEC (human umbilical vein endothelial cells) were exposed in vitro to green tea for either 6 or 48 h. Only statistically significantly differentially expressed genes were analyzed. Gene profiling demonstrated a global down-regulation of multiple genes involved in endothelial cell growth, signal transduction and oxidation, accompanied by up-regulation of several apoptotic genes. We validated these observations by showing positive correlations with biological assays of cellular proliferation, cell cycle, and apoptosis. The anti-oxidant characteristics of green tea and its metabolites were confirmed in the ORAC (oxygen radical absorbance capacity) assay. cDNA microarray revealed that green tea has an overall suppressive effect on multiple pathways in endothelial cells. This study contributes to the comprehensive analysis of the molecular effects of green tea on endothelial cells, and provides insight into genes that may be important in chemoprevention.

The interference of the polypeptide antibiotic nisin with membrane function and murein synthesis was studied. The inhibition of the in vivo synthesis of murein in Bacillus subtilis and the resistance of Mycoplasma mycoides to nisin, suggest that the membrane may be excluded as a target. On the other hand a general inhibition of macromolecule syntheses in Micrococcus luteus supports the assumption that the cytoplasmic membrane is a target. In addition, an antagonistic effect on growth inhibition by nisin with both, cytoplasmic membranes and isolated phospholipid components of membranes was demonstrated. The lysis of phospholipid liposomes by nisin and the sensitivity at increased concentration of antibiotic of organisms lacking murein in their cell walls provide further evidence for the cytoplasmic membrane as a target. We therefore assume that the antimicrobial effect of nisin is caused by its interaction with phospholipid components of the cytoplasmic membrane followed by an interference with the membrane function. The sensitivity against nisin is increased in organisms with murein in their cell walls because the inhibition of this polymer causes an additional, inhibitory effect synergistic to the disturbance of the membrane function.

The activities of the LD-carboxypeptidases of Escherichia coli K 12 and of a mutant strain 155 with reduced activities were studied with the aid of ether treated cells. Evidence was obtained that was consistent with the suggestion that in both strains two LD-carboxypeptidase activities are present. Activity I degrades the nucleotide activated precursor UDP-MurNAc-tetrapeptide and activity II splits off D-alanine residues from position 4 of the peptide subunits in the nascent murein. In the mutant strain activity I is reduced 10fold compared with strain K 12, whereas activity II is not affected. The two activities could be distinguished with regard to their sensitivity to D-amino acids and the beta-lactam antibiotic thienamycin.

The in vitro synthesis of murein from the precursors UDP-N-acetylglucosamine, L-alanine, D-glutamic acid and meso-diaminopimelic acid was performed with the aid of ether treated Escherichia coli. This synthesis was sensitive to representative inhibitors of early reactions in the cytoplasm as well as of late reactions in the membrane or the cell wall. The sensitivity was higher than in in vitro systems starting with UDP-N-acetylmuramic acid or UDP-N-acetylmuramyl-pentapeptide.

Kunstpädagogik ist eine wissenschaftliche Disziplin mit vielen Facetten und Berührungspunkten. Die Beiträge des Sammelbandes sind ein Versuch, das vielfältige Fach durch Überschneidungen und Abgrenzungen zu anderen Disziplinen neu zu konturieren. Aus Perspektive der Philosophie, Architektur, Literatur, Kunstgeschichte, Kunstvermittlung, der künstlerischen Praxis und der Kunstpädagogik untersuchen die Autor:innen Gemeinsamkeiten und Anknüpfungspunkte. Zentrale Bezugspunkte der Beiträge sind dabei die verschiedenen Positionen zur Theorie und Praxis der Kunstpädagogik. Die Autor:innen zeigen, wie stark die Diskurse von den berufsbiografischen Perspektiven, den persönlichen Blicken der Akteur:innen, ihren wissenschaftlichen und künstlerischen Schwerpunkten beeinflusst werden. Mit diesen Betrachtungen eröffnet der Band eine Alternative zu den „Richtungen' der Kunstpädagogik, die als fest umrissene „Positionen' einiger Protagonist:innen in der Kunstpädagogik teilweise nebeneinander existieren. Die Beiträge machen die Differenz der unterschiedlichen Positionen nachvollziehbar und geben Raum für die Entwicklung didaktischer Theorien.