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Palma G.,Struttura Semplice Dipartimentale Sperimentazione Animale | Palma G.,National Research Council Italy | Barbieri A.,Struttura Semplice Dipartimentale Sperimentazione Animale | Bimonte S.,Struttura Semplice Dipartimentale Sperimentazione Animale | And 6 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2013

In the last few years, the field of tumor immunology has significantly expanded and its boundaries, never particularly clear, have become less distinct. Although the immune system plays an important role in controlling tumor growth, it has also become clear that tumor growth can be promoted by inflammatory immune responses. A good example that exemplifies the ambiguous role of the immune system in cancer progression is represented by interleukin 18 (IL-18) that was first identified as an interferon-γ-inducing factor (IGIF) involved in T helper type-1 (Th1) immune response. The expression and secretion of IL-18 have been observed in various cell types from immune cells to circulating cancer cells. In this review we highlighted the multiple roles played by IL-18 in immune regulation, cancer progression and angiogenesis and the clinical potential that may result from such understanding. © 2013 Elsevier B.V.

Sharma A.,The Second University of Naples | Costantini S.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | Colonna G.,The Second University of Naples
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2013

Protein-protein interaction networks are useful for studying human diseases and to look for possible health care through a holistic approach. Networks are playing an increasing and important role in the understanding of physiological processes such as homeostasis, signaling, spatial and temporal organizations, and pathological conditions. In this article we show the complex system of interactions determined by human Sirtuins (Sirt) largely involved in many metabolic processes as well as in different diseases. The Sirtuin family consists of seven homologous Sirt-s having structurally similar cores but different terminal segments, being rather variable in length and/or intrinsically disordered. Many studies have determined their cellular location as well as biological functions although molecular mechanisms through which they act are actually little known therefore, the aim of this work was to define, explore and understand the Sirtuin-related human interactome. As a first step, we have integrated the experimentally determined protein-protein interactions of the Sirtuin-family as well as their first and second neighbors to a Sirtuin-related sub-interactome. Our data showed that the second-neighbor network of Sirtuins encompasses 25% of the entire human interactome, and exhibits a scale-free degree distribution and interconnectedness among top degree nodes. Moreover, the Sirtuin sub interactome showed a modular structure around the core comprising mixed functions. Finally, we extracted from the Sirtuin sub-interactome subnets related to cancer, aging and post-translational modifications for information on key nodes and topological space of the subnets in the Sirt family network. © 2013 Elsevier B.V.

Vettoretto N.,Laparoscopic Surgical Unit | Cirocchi R.,St Maria Hospital | Randolph J.,Mercer University | Parisi A.,St Maria Hospital | And 2 more authors.
Colorectal Disease | Year: 2014

Aim: A meta-analysis was performed to compare the outcome of single incision laparoscopic right hemicolectomy with standard multiport laparoscopic right hemicolectomy. Method: A systematic search of databases was carried out to extract comparative studies (randomized and non-randomized, prospective and retrospective). Data were analysed according to Cochrane Collaboration guidelines. A meta-analysis was performed when the data permitted this form of analysis. Results: Nine comparative studies were retrieved comprising 241 patients with single incision and standard laparoscopy. None of these was randomized. There was no significant difference between the two methods for the primary end-points of mortality, morbidity and cancer-specific parameters and for the secondary end-points of operation time, blood loss, ileus, hospital stay and conversion. It was not possible to analyse pain and cosmetics data owing to insufficient information. Conclusion: Single incision laparoscopic right hemicolectomy is comparable with standard multiport laparoscopic right hemicolectomy in primary and secondary outcomes. Given current information it is justified to use single incision laparoscopic right hemicolectomy, but there is a need for a prospective randomized study. © 2013 The Association of Coloproctology of Great Britain and Ireland.

Del Pup L.,Italian National Cancer Institute | Di Francia R.,Hematology Oncology and Stem Cell Transplantation Unit | Cavaliere C.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | Facchini G.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | And 3 more authors.
Anti-Cancer Drugs | Year: 2013

Urogenital symptoms resulting from estrogen deficiency are common problems that impair quality of life and sexuality. Potentially, one out of three postmenopausal women could benefit from a vaginal estrogen therapy, but the fear of systemic absorption limits its use. Promestriene used vaginally to relieve vaginal atrophy is a locally effective estrogen that has not shown systemic estrogenic effects. Thus, it could be a first-line option for those who necessitate a minimal or ideally no vaginal absorption, particularly in symptomatic cancer patients. There are little data available in the literature, mostly consisting of small, open-label, short duration studies, and few randomized-controlled studies. After a long-term market experience (almost 40 years), in 34 countries, and millions of pieces prescribed, the side effects were very rarely reported in pharmacovigilance data, whereas the effectiveness to relieve atrophy was good. To further improve promestriene safety, especially in estrogen-sensitive cancer patients, a very low dose is used from the beginning, starting from half or less of the usual dose, and then gradually increased till the minimum effective dose, which could further reduce its already minimal vaginal absorption. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Abate A.A.,Temple University | Pentimalli F.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | Esposito L.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | Giordano A.,Temple University | Giordano A.,University of Siena
Expert Opinion on Investigational Drugs | Year: 2013

Introduction: Cyclin-dependent kinases (CDKs) are the key drivers of cell cycle progression and are often deregulated in cancer, therefore, targeting CDKs has long been pursued as a therapeutic strategy to tackle cancer. Unfortunately, however, none of the first-generation CDK inhibitors has yielded the expected efficacy to be successfully translated to the clinic mostly because, by targeting the very conserved kinase ATP-binding site resulted to be poorly specific and quite toxic. Areas covered: Here, the authors review recent approaches aimed at developing more specific CDK inhibitors mostly through the aid of computational drug design studies and report various small molecules and peptides, which resulted in promising CDK ATP-noncompetitive inhibitors. Expert opinion: Despite few successes, these new approaches still need additional considerations to generate effective antitumoral agents. The authors discuss some of the hurdles to overcome for a successful clinical translation. © 2013 Informa UK, Ltd.

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