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Lecce nei Marsi, Italy

Vergara D.,University of Salento | Martignago R.,University of Salento | Bonsegna S.,CNR Institute of Neuroscience | De Nuccio F.,University of Salento | And 4 more authors.
Journal of Neuroimmunology

Astrocytes have a key role in the pathogenesis of several diseases, including multiple sclerosis, and are proposed as a possible target for immunotherapy.Our earlier study reported that astrocytes treated with IFN-β modified their biomechanical properties possibly due to changes in the expression of the proteins involved in cytoskeleton organization and other important physiological processes.To gain insight into the mechanism underlying IFN-β action during inflammation, we stimulated astrocytes with LPS, a bacterial wall component used as a model for both in vitro and in vivo immunological stimulation of microglia and astrocytes.We showed that IFN-β reverses the effects of LPS on the proteome of astrocytes. To better examine this result, we performed a proteomic analysis of astrocytes treated with LPS or LPS plus IFN-β. Treatment with LPS caused increases both in a series of proteins mainly involved in cytoskeletal changes and in protein degradation, as well as protective enzymes like superoxide dismutase. IFN-β reverses LPS effects on astrocyte proteome, supporting its protective role during inflammatory insults. © 2010 Elsevier B.V. Source

Vergara D.,University of Salento | Vergara D.,Laboratory of Clinical Proteomic | Simeone P.,University of Chieti Pescara | Toraldo D.,Laboratory of Clinical Proteomic | And 12 more authors.
Molecular BioSystems

Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance. © 2012 The Royal Society of Chemistry. Source

Vergara D.,University of Salento | Vergara D.,Laboratory of Clinical Proteomic | Tinelli A.,Vito Fazzi Hospital | Iannone A.,University of Modena and Reggio Emilia | And 2 more authors.
Current Cancer Drug Targets

The current therapy for ovarian cancer has advanced from alkylating agents, to a combination of carboplatinum and paclitaxel offering increased survival. Although most patients respond to this first-line therapy, initially, the majority of these patients relapse within 2 years. The mechanisms responsible for acquired drug resistance in ovarian cancer have been elucidated only in part. They include i) enhanced drug export, ii) activation/inhibition of intracellular signalling pathways, iii) molecular alterations in tubulin isotype composition. A better understanding of these mechanisms is needed, in order to develop new approaches, aimed at overcoming resistance to anticancer agents, and to reveal the complexity of causes, which contribute to drug resistance. In this review we offer an updated overview of proteomic studies on the molecular mechanisms of paclitaxel resistance. These proteomic studies also identify potential targets for modulating drug resistance, that could be predictive of response to chemotherapy in ovarian carcinomas. © 2012 Bentham Science Publishers. Source

Vergara D.,University of Salento | Vergara D.,Laboratory of Clinical Proteomic | Simeone P.,University of Chieti Pescara | Del Boccio P.,University of Chieti Pescara | And 11 more authors.
Molecular BioSystems

The epithelial to mesenchymal transition (EMT) is a cellular program associated with the organ morphogenesis but also with the disease progression. EMT in the cancer field fuels neoplastic progression promoting the resistance to cell death, the resistance to chemotherapy and the acquisition of stem cell properties. Considering the crucial role of EMT in breast cancer metastasis, a better understanding of this process may provide new therapeutic options. Here, by using a proteomic approach we identified a set of proteins differentially expressed between an epithelial and a mesenchymal breast cancer cell line. The protein-protein network of these identified proteins was determined by an in silico analysis highlighting, in the EMT program, the role of proteins involved in cell adhesion, migration, and invasion, together with protein kinases involved in proliferation and survival, with many of these emerging as possible targets of novel biological agents. Finally, the pharmacological inhibition of some of these kinases was able to reverse the mesenchymal phenotype to an epithelial phenotype. © 2013 The Royal Society of Chemistry. Source

Vergara D.,University of Salento | Vergara D.,Laboratory of Clinical Proteomic | Bellomo C.,Istituto Nanoscienze | Zhang X.,Louisiana Tech University | And 8 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine

The sonication-assisted layer-by-layer (SLBL) technology was developed to combine necessary factors for an efficient drug-delivery system: (i) control of nanocolloid size within 100 - 300 nm, (ii) high drug content (70% wt), (iii) shell biocompatibility and biodegradability, (iv) sustained controlled release, and (v) multidrug-loaded system. Stable nanocolloids of Paclitaxel (PTX) and lapatinib were prepared by the SLBL method. In a multidrug-resistant (MDR) ovarian cancer cell line, OVCAR-3, lapatinib/PTX nanocolloids mediated an enhanced cell growth inhibition in comparison with the PTX-only treatment. A series of in vitro cell assays were used to test the efficacy of these formulations. The small size and functional versatility of these nanoparticles, combined with their ability to incorporate various drugs, indicates that lapatinib/PTX nanocolloids may have in vivo therapeutic applications. From the Clinical Editor: The efficacy of Lapatinib/Paclitaxel polyelectrolyte nanocapsules is described in this study in cell cultures of multidrug-resistant ovarian cancer. If in vivo studies also result in similar efficacy and low toxicity, this may represent a viable avenue to address such malignancies. © 2012 Elsevier Inc. Source

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