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Gargiulo P.,Swiss Group for Clinical Cancer Research Coordinating Center | Della Pepa C.,Istituto Nazionale Tumori Fondazione G. Pascale | Berardi S.,Swiss Group for Clinical Cancer Research Coordinating Center | Califano D.,Istituto Nazionale Tumori Fondazione G. Pascale | And 5 more authors.
Cancer Treatment Reviews | Year: 2016

Endometrial Cancer (EC) is still a challenge for gynecological oncologists because the treatment of the advanced disease remains an unmet need for patients. The Cancer Genome Atlas Research Network (TCGA) recently provided a comprehensive genomic and transcriptomic analysis of EC, offering a new classification of the disease, based on genetic features, which defines four subgroups of cancer rather than the two traditionally recognized. In the molecular classification two types of EC, the polymerase epsilon (POLE)-ultramutated and the microsatellite instability (MSI)-hypermutated, seem to present an enhanced immune microenvironment and a high mutation burden. The blockade of the immune checkpoints is an innovative approach that has largely demonstrated to be effective in solid malignancies, such as lung, renal and melanoma; it acts by reducing the cancer-induced immune-suppression through inhibition of the PD-1/PD-L1 (Programmed Death and PD-Ligand) axis. All available evidence supporting an over-expression of the PD-1/PD-L1 pathway in EC has been reviewed. In particular in the POLE and MSI ECs an up-regulation of this pathway was found, aiming to suggest a rationale for testing the PD-1/PD-L1 immunotherapy in these cancer subgroups. © 2016 Elsevier Ltd Source

Xie Q.,Van Andel Research Institute | Su Y.,Van Andel Research Institute | Dykema K.,Van Andel Research Institute | Johnson J.,Van Andel Research Institute | And 16 more authors.
Genes and Cancer | Year: 2013

Hepatitis B virus (HBV) is a well-known cause of hepatocellular carcinoma (HCC), but the regulators effectively driving virus production and HCC progression remain unclear. By using genetically engineered mouse models, we show that overexpression of hepatocyte growth factor (HGF) accelerated HCC progression, supporting the genomic analysis that an up-regulated HGF signature is associated with poor prognosis in HBV-positive HCC patients. We show that for both liver regeneration and spontaneous HCC development there is an inclusive requirement for MET expression, and when HGF induces autocrine activation the tumor displays sensitivity to a small-molecule Met inhibitor. Our results demonstrate that HGF is a driver of HBV-induced HCC progression and may serve as an effective biomarker for Met-targeted therapy. MET inhibitors are entering clinical trials against cancer, and our data provide a molecular basis for targeting the Met pathway in hepatitis B-induced HCC. © The Author(s) 2013. Source

Visciano M.L.,Molecular Biology and Viral Oncogenesis Unit | Tagliamonte M.,Molecular Biology and Viral Oncogenesis Unit | Stewart-Jones G.,Weatherall Institute of Molecular Medicine | Heyndrickx L.,Institute of Tropical Medicine | And 10 more authors.
Journal of Translational Medicine | Year: 2013

Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity. © 2013 Visciano et al.; licensee BioMed Central Ltd. Source

Cools N.,University of Antwerp | Petrizzo A.,Molecular Biology and Viral Oncogenesis Unit | Smits E.,University of Antwerp | Buonaguro F.M.,Molecular Biology and Viral Oncogenesis Unit | And 4 more authors.
Immunotherapy | Year: 2011

Dendritic cells (DCs) represent the bridging cell compartment between a variety of nonself antigens (i.e., microbial, cancer and vaccine antigens) and adaptive immunity, orchestrating the quality and potency of downstream immune responses. Because of the central role of DCs in the generation and regulation of immunity, the modulation of DC function in order to shape immune responses is gaining momentum. In this respect, recent advances in understanding DC biology, as well as the required molecular signals for induction of T-cell immunity, have spurred many experimental strategies to use DCs for therapeutic immunological approaches for infections and cancer. However, when DCs lose control over such 'protective' responses - by alterations in their number, phenotype and/or function - undesired effects leading to allergy and autoimmune clinical manifestations may occur. Novel therapeutic approaches have been designed and currently evaluated in order to address DCs and silence these immunopathological processes. In this article we present recent concepts of DC biology and some medical implications in view of therapeutic opportunities. © 2011 Future Medicine Ltd. Source

Tuccillo F.M.,Molecular Biology and Viral Oncogenesis Unit | De Laurentiis A.,University of Catanzaro | Palmieri C.,University of Catanzaro | Fiume G.,University of Catanzaro | And 7 more authors.
BioMed Research International | Year: 2014

Glycosylation is a posttranslational modification of proteins playing a major role in cell signalling, immune recognition, and cell-cell interaction because of their glycan branches conferring structure variability and binding specificity to lectin ligands. Aberrant expression of glycan structures as well as occurrence of truncated structures, precursors, or novel structures of glycan may affect ligand-receptor interactions and thus interfere with regulation of cell adhesion, migration, and proliferation. Indeed, aberrant glycosylation represents a hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis pathways such as the altered expression of glycosyltransferases and glycosidases. Most studies have been carried out to identify changes in serum glycan structures. In most cancers, fucosylation and sialylation are significantly modified. Thus, aberrations in glycan structures can be used as targets to improve existing serum cancer biomarkers. The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. In this review, we discuss the aberrant protein glycosylation associated with human cancer and the identification of protein glycoforms as cancer biomarkers. In particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker and the potential to exploit the UN1 monoclonal antibody (UN1 mAb) to identify aberrant CD43 glycoforms. © 2014 Franca Maria Tuccillo et al. Source

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