PRIMA SEGNALAZIONE DI ALCUNI FUNGI E MYCETOZOA INTERESSANTI PER LA BASILICATA E/O LA PUGLIA

Investigations carried out over the past six years in some territories of Basilicata and Apulia (southern Italy), allowed to discover for the first time the following taxa of Fungi and Mycetozoa: Basilicata - Ascomycota: Ascocoryne sarcoides, Helvella leucomelaena, Hymenoscyphus conscriptus, Hypomyces chrysospermus, H. lateritius, H. luteovirens, Poronia punctata, Xylaria polymorpha; Basidiomycota: Clavaria vermicularis var. vermicularis, Clavulinopsis corniculata var. bispora, Cyathus olla, Hebeloma radicosum, Inonotus hispidus, Myriostoma coliforme, Panellus stypticus, Pluteus thomsonii, Scleroderma bovista, Xerocomus badius; Mycetozoa: Arcyria incarnata, Didymium clavus, Leocarpus fragilis, Lycogala epidendrum and Stemonitis axifera; Puglia - Ascomycota: Daldinia concentrica; Basidiomycota: Amanita codinae, Ceriporia purpurea, Dichomitus campestris, Perenniporia rosmarini, Polyporus arcularius, Scleroderma meridionale, Stereum subtomentosum and Tulostoma brumale. Finally, new natural stations of Amanita vittadini, Bisporella citrina, Coltricia perennis, Geastrum triplex, Gyromitra esculenta, Macrotyphula fistulosa, Morchella conica, Pycnoporus cinnabarinus, Sarcoscypha coccinea, and Xylaria hypoxylon were also found in Basilicata and, in some instances, also in Apulia

PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells

Objective: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy. Design: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance. Results: Here we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy. Conclusions: While PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting

N-3 fatty acids in patients with multiple cardiovascular risk factors

BACKGROUND: Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. METHODS: In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. RESULTS: Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. CONCLUSIONS: In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. Copyright © 2013 Massachusetts Medical Society