88 research outputs found

    Copper chelation suppresses epithelial-mesenchymal transition by inhibition of canonical and non-canonical TGF-β signaling pathways in cancer

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    Background: Metastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance to treatments. Recent studies highlight that elevated levels of copper are implicated in cancer progression and metastasis. Clinical trials using copper chelators are associated with improved patient survival; however, the molecular mechanisms by which copper depletion inhibits tumor progression and metastasis are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Here, we propose that copper chelation inhibits metastasis by reducing TGF-β levels and EMT signaling. Given that many drugs targeting TGF-β have failed in clinical trials, partly because of severe side effects arising in patients, we hypothesized that copper chelation therapy might be a less toxic alternative to target the TGF-β/EMT axis. Results: Our cytokine array and RNA-seq data suggested a link between copper homeostasis, TGF-β and EMT process. To validate this hypothesis, we performed single-cell imaging, protein assays, and in vivo studies. Here, we used the copper chelating agent TEPA to block copper trafficking. Our in vivo study showed a reduction of TGF-β levels and metastasis to the lung in the TNBC mouse model. Mechanistically, TEPA significantly downregulated canonical (TGF-β/SMAD2&3) and non-canonical (TGF-β/PI3K/AKT, TGF-β/RAS/RAF/MEK/ERK, and TGF-β/WNT/β-catenin) TGF-β signaling pathways. Additionally, EMT markers of MMP-9, MMP-14, Vimentin, β-catenin, ZEB1, and p-SMAD2 were downregulated, and EMT transcription factors of SNAI1, ZEB1, and p-SMAD2 accumulated in the cytoplasm after treatment. Conclusions: Our study suggests that copper chelation therapy represents a potentially effective therapeutic approach for targeting TGF-β and inhibiting EMT in a diverse range of cancers

    Borgese, Salvemini, La Piana e "le systeme de l'exil"

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    L'articolo ricostruisce la trama dei rapporti intellettuali e politici tra tre grandi esuli: Borgede, Salvemini e La Pian

    Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: The LUNA16 challenge

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    Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems

    Sindrome plurienocrina autoimmune e candidiasi cronica mucocutanea (SPA di Tipo I).

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    A diverse population of introns in the nuclear ribosomal genes off ericoid mycorrhizal fungi includes elements with sequence similarity to endonuclease-coding genes

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    Ericoid mycorrhizal fungi form symbioses with the roots of members of the Ericales. Although only two genera have been identified in culture, the taxonomic diversity of ericoid symbionts is certainly wider. Genetic variation among 40 ericoid fungal isolates was investigated in this study. PCR amplification of the nuclear small-subunit ribosomal DNA (SSU rDNA) and of the internal transcribed spacer (ITS), followed by sequencing, led to the discovery of DNA insertions of various sizes in the SSU rDNA of most isolates. They reached sizes of almost 1,800 bp and occurred in up to five different insertion sites. Their positions and sizes were generally correlated with morphological and ITS-RFLP grouping of the isolates, although some insertions were found to be optional among isolates of the same species, and insertions were not always present in all SSU rDNA repeats within an isolate. Most insertions were identified as typical group I introns, possessing the conserved motifs characteristic of this group. However, other insertions lack these motifs and form a distinct group that includes other fungal ribosomal introns. Alignments with almost 70 additional sequences from fungal nuclear SSU rDNA introns indicate that introns inserted at the same site along the rDNA gene are generally homologous, but they also suggest the possibility of some horizontal transfers. Two of the ericoid fungal introns showed strong homology with a conserved motif found in endonuclease genes from nuclear rDNA introns

    Consumer assessment on sensory attributes of fresh table grapes cv 'Italia' and 'Red Globe' after long cold storage treatment

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    The impact of research that is being carried out into the relationship between food and consumers is progressively reinforced by continuous findings in literature confirming that consumers choose foods basing on their functional cognition and sensory perception, especially when buying fruit and vegetables. Therefore, it is important for table grape producers to be aware of consumers' concerns and preferences both, during the purchasing stage and after, during consumption at home, when experiential attributes have more importance. In both cases, sensory attributes play an important role in determining consumers' purchase behavior of table grape. Table grapes cv 'Italia' and 'Red Globe' are produced in South Italy (Sicily and Apulia) and appreciated by consumers for their superior taste and other intrinsic qualities, both in Italy and in other European countries. Nevertheless, harvested grapes of these cultivars deteriorate rapidly without post-harvest appropriate treatments, especially in terms of fungal rot, rachis browning, berry drop, softening, moisture loss and off flavor, and this fast deterioration is the main limitation to market acceptance. The objective of this study is to assess consumers preferences in regards to 22 sensory attributes of fresh table grapes cv 'Italia' and 'Red Globe', after a cold storage treatment of 90 days at 1\ub11 \ub0C and 90\ub12% RH, combined with low SO2 concentration. Therefore, 'In-store' consumer acceptance tests were performed, on 1000 consumers, in nine cities nearby the main Sicilian areas of table grape production. Consumers were asked to score table grape sensory attributes, using a 9-pt scale, after long storage of 30, 60 and 90d. For this study, the table grapes were harvested from two locations, Canicatt\uec and Naro during the last week of September and treated with SO2 fumigation, with SSC >14%, for prolonging shelf life. Analysis of scores revealed that consumers preferred cv 'Italia' for its uniform color and no shades of berries and for a balanced tasting sugar/acidity ratio. The cv 'Red Globe' performed good results for crunchy berries and intense berry aroma, detachment of berries and skin tannicity. No difference was observed between the two cultivars for odor descriptors
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