<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Perri, Paolo</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Milani, Daniela</style></author><author><style face="normal" font="default" size="100%">Celeghini, Claudio</style></author><author><style face="normal" font="default" size="100%">Lamberti, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TNF-related apoptosis inducing ligand in ocular cancers and ocular diabetic complications.</style></title><secondary-title><style face="normal" font="default" size="100%">Biomed Res Int</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Biomed Res Int</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Complications</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus</style></keyword><keyword><style  face="normal" font="default" size="100%">Eye Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, TNF-Related Apoptosis-Inducing Ligand</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">2015</style></volume><pages><style face="normal" font="default" size="100%">424019</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/25834817?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Celeghini, Claudio</style></author><author><style face="normal" font="default" size="100%">Monasta, Lorenzo</style></author><author><style face="normal" font="default" size="100%">Martinelli, Monica</style></author><author><style face="normal" font="default" size="100%">Luppi, Stefania</style></author><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Grill, Vittorio</style></author><author><style face="normal" font="default" size="100%">Ricci, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Soluble TRAIL is present at high concentrations in seminal plasma and promotes spermatozoa survival.</style></title><secondary-title><style face="normal" font="default" size="100%">Reproduction</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Reproduction</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Enzyme-Linked Immunosorbent Assay</style></keyword><keyword><style  face="normal" font="default" size="100%">Flow Cytometry</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infertility, Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, TNF-Related Apoptosis-Inducing Ligand</style></keyword><keyword><style  face="normal" font="default" size="100%">Semen</style></keyword><keyword><style  face="normal" font="default" size="100%">Sperm Capacitation</style></keyword><keyword><style  face="normal" font="default" size="100%">Sperm Motility</style></keyword><keyword><style  face="normal" font="default" size="100%">Spermatozoa</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">148</style></volume><pages><style face="normal" font="default" size="100%">191-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL(TNFSF10)) and of its receptors (TRAILR1, TRAILR2, TRAILR3, and TRAILR4) have been documented in testis, but the presence of soluble TRAIL in seminal fluid, as well as the potential physiopathological role of the TRAIL/TRAILR system in spermatozoa, has not been previously investigated. Male donors (n=123) among couples presenting for infertility evaluation were consecutively enrolled in this study. The presence of soluble TRAIL was analyzed in seminal samples by ELISA, while the surface expression of TRAIL receptors was investigated by flow cytometry. High levels of soluble TRAIL were detected in seminal plasma (median, 11 621 pg/ml and mean±s.d., 13 371±8367 pg/ml) and flow cytometric analysis revealed a variable expression of TRAIL receptors in the sperm cellular fraction among different subjects. In addition, the effect of physiologically relevant concentrations of recombinant TRAIL was investigated on survival and motility of spermatozoa. Of interest, the in vitro exposure of capacitated spermatozoa to recombinant TRAIL (10 ng/ml) significantly preserved their overall survival. Therefore, the present study demonstrates for the first time the presence of elevated levels of the anti-inflammatory cytokine TRAIL in seminal fluids. Moreover, the demonstration that recombinant TRAIL promotes spermatozoa survival after capacitation suggests potential therapeutic implications.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24825910?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Rimondi, Erika</style></author><author><style face="normal" font="default" size="100%">di Iasio, Maria Grazia</style></author><author><style face="normal" font="default" size="100%">Voltan, Rebecca</style></author><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Activation of the p53 pathway induces α-smooth muscle actin expression in both myeloid leukemic cells and normal macrophages.</style></title><secondary-title><style face="normal" font="default" size="100%">J Cell Physiol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Cell. Physiol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Actins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Movement</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Endothelial Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibroblasts</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Imidazoles</style></keyword><keyword><style  face="normal" font="default" size="100%">Leukemia, Myeloid</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">Mesenchymal Stromal Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Piperazines</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins c-mdm2</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Small Interfering</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Transforming Growth Factor beta1</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Suppressor Protein p53</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 May</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">227</style></volume><pages><style face="normal" font="default" size="100%">1829-37</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;A range of cell types of mesenchymal origin express α-smooth muscle actin (α-SMA), a protein that plays a key role in controlling cell motility and differentiation along the fibrocyte and myofibroblast lineages. Although α-SMA is often expressed in stromal cells associated to a variety of cancers including hematological malignancies, up to now the role of anti-cancer drugs on α-SMA has not been deeply investigated. In this study, we demonstrated that Nutlin-3, the small molecule inhibitor of the MDM2/p53 interactions, significantly up-regulated the mRNA and protein levels of α-SMA in normal macrophages as well as in p53(wild-type) but not in p53(mutated/null) myeloid leukemic cells. The p53-dependence of α-SMA up-regulation induced by Nutlin-3 was demonstrated in experiments performed with siRNA for p53. Of note, Nutlin-3 mediated up-regulation of α-SMA in OCI leukemic cells was accompanied by cell adhesion to plastic substrate and by reduced cell migratory response in transwell assays. Notably, the role of α-SMA induction in the modulation of myeloid cell migration was clearly documented in α-SMA gene knockdown experiments. In addition, Nutlin-3 significantly up-regulated α-SMA expression in primary endothelial cells, but not in fibroblasts and mesenchymal stem cells (MSC). Conversely, transforming growth factor-β1 up-regulated α-SMA in fibroblasts and MSC, but not in macrophages and endothelial cells. Taken together, these data indicate that Nutlin-3 is a potent inducer of α-SMA in both normal and leukemic myeloid cells as well as in endothelial cells.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21732354?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rimondi, Erika</style></author><author><style face="normal" font="default" size="100%">di Iasio, Maria Grazia</style></author><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Celeghini, Claudio</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Hydrogen sulfide down-regulates the expression and release of osteoprotegerin (OPG) by vascular endothelial cells.</style></title><secondary-title><style face="normal" font="default" size="100%">Invest New Drugs</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Invest New Drugs</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Cell Death</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytostatic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Down-Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Human Umbilical Vein Endothelial Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hydrogen Sulfide</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Necrosis Factor-alpha</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">30</style></volume><pages><style face="normal" font="default" size="100%">1731-5</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21541705?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Radillo, Oriano</style></author><author><style face="normal" font="default" size="100%">Drioli, Sara</style></author><author><style face="normal" font="default" size="100%">Rimondi, Erika</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Maria Bonora, Gian</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL.</style></title><secondary-title><style face="normal" font="default" size="100%">Invest New Drugs</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Invest New Drugs</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Caspase 3</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Movement</style></keyword><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">HL-60 Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Leukemia</style></keyword><keyword><style  face="normal" font="default" size="100%">Mesenchymal Stromal Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitogen-Activated Protein Kinase 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitogen-Activated Protein Kinase 3</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphorylation</style></keyword><keyword><style  face="normal" font="default" size="100%">Polyethylene Glycols</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Fusion Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Time Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Apr</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">30</style></volume><pages><style face="normal" font="default" size="100%">828-32</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;To improve the pharmacokinetic profile of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) an N-terminal specific pegylation was performed to generate pegylated TRAIL (PEG-TRAIL). In in vitro experiments, we found that although PEG-TRAIL was slightly less efficient than recombinant TRAIL in promoting leukemic cell apoptosis, it showed an improved ability to promote migration of bone-marrow mesenchymal stem cells and to elicit the ERK1/2 intracellular signal transduction pathway. Overall, these data suggest that TRAIL pegylation retains, or even enhances, the biological activities of TRAIL relevant for its therapeutic applications.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21125311?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Corallini, Federica</style></author><author><style face="normal" font="default" size="100%">Celeghini, Claudio</style></author><author><style face="normal" font="default" size="100%">Rimondi, Erika</style></author><author><style face="normal" font="default" size="100%">di Iasio, Maria Grazia</style></author><author><style face="normal" font="default" size="100%">Gonelli, Arianna</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Trail down-regulates the release of osteoprotegerin (OPG) by primary stromal cells.</style></title><secondary-title><style face="normal" font="default" size="100%">J Cell Physiol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Cell. Physiol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Bone Marrow Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Death</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Coculture Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Down-Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Endothelial Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Enzyme Activation</style></keyword><keyword><style  face="normal" font="default" size="100%">Enzyme-Linked Immunosorbent Assay</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibroblasts</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">MAP Kinase Signaling System</style></keyword><keyword><style  face="normal" font="default" size="100%">Mesenchymal Stromal Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">p38 Mitogen-Activated Protein Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Binding</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Stromal Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Necrosis Factor-alpha</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">226</style></volume><pages><style face="normal" font="default" size="100%">2279-86</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The soluble member of the TNF-R superfamily osteoprotegerin (OPG) is abundantly released under basal conditions by both mesenchymal stem cells (MSC) and fibroblasts and by endothelial cells upon stimulation with inflammatory cytokines. Since MSC, fibroblasts and endothelial cells represent key elements of the normal and tumor microenvironment and express detectable levels of surface TRAIL receptors, we investigated the effect of TRAIL on OPG release. Unexpectedly, recombinant TRAIL decreased the spontaneous OPG release in all cell types examined. Moreover, TRAIL decreased OPG release also in stromal cells co-cultured with lymphoma cells and counteracted the OPG induction by TN-alpha in HUVEC and MSC. Such down-regulation was not due to a masking effect in the ELISA quantification of the OPG released in the culture supernatants due to binding of OPG to its ligands (TRAIL and RANKL), as demonstrated by competition experiments with recombinant TRAIL and by the lack of RANKL release/induction. In addition, OPG down-regulation was not due to induction of cytotoxic effects by TRAIL, since the degree of apoptosis in response to TRAIL was negligible in all primary cell types. With regards to the possible molecular mechanism accounting for the down-regulation of OPG release by TRAIL, we found that treatment of MSC with TRAIL significantly decreased the phosphorylation levels of p38/MAPK. There is a suggestion that this pathway is involved in the stabilization of OPG mRNA. In this respect, the ability of TRAIL to decrease the release of OPG, in the absence of cell cytotoxicity, was mimicked by the p38/MAPK inhibitor SB203580.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21660951?dopt=Abstract</style></custom1></record></records></xml>