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Picascia A.,The Second University of Naples | Sabia C.,The Second University of Naples | Grimaldi V.,The Second University of Naples | Montesano M.L.,The Second University of Naples | And 4 more authors.
Immunology Letters | Year: 2014

Recently, management of patients awaiting solid organ transplantation has taken advantages after the development of more sensitive and accurate solid phase assays which have supported the historic complement dependent cytotoxicity. This approach has allowed the detection of antibodies in patients previously considered negative. The use of the single antigen beads resulted in a more accurate anti-human leukocyte antigen (HLA) antibody characterization. The detection of anti-HLA antibodies specific for C, DQ and DP loci that were not so well characterized has been possible through the implementation of the single antigen assay. The assessment of HLA compatibility has been expanded through the introduction of "epitope matching" concept and the definition of the unacceptable antigens for a more adequate evaluation of donor-recipient compatibility. However, the clinical impact of pre-formed and de novo anti-HLA antibodies detected by solid phase assays is still controversial due to the drawback related to result interpretation. Until today, the unresolved issues concern if all antibodies affect the medium and long term clinical outcome. An open debate on the clinical relevance of anti-HLA antibodies detected by single-antigen beads highlights needing to further investigations. Here, we describe the novel applications and the improvements of the solid-phase assay use. © 2014 Elsevier B.V.


de Nigris F.,The Second University of Naples | Schiano C.,The Second University of Naples | Infante T.,Institute of Diagnostic and Nuclear Development SDN | Napoli C.,The Second University of Naples | Napoli C.,Institute of Diagnostic and Nuclear Development SDN
Recent Patents on Anti-Cancer Drug Discovery | Year: 2012

CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform (Mozobil® by Genzyme), is approved for stem cell mobilisation in patients with leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054 (ChemoCentryx) are currently in clinical trials in combination with chemotherapy for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx) is still in preclinical studies. We have also considered other strategies, such RNA interference and miRNA, which could be tested for solid tumor adjuvant therapy. © 2012 Bentham Science Publishers.


Napoli C.,The Second University of Naples | Napoli C.,Institute of Diagnostic and Nuclear Development SDN | Sessa M.,The Second University of Naples | Infante T.,Institute of Diagnostic and Nuclear Development SDN | Casamassimi A.,The Second University of Naples
Biochimie | Year: 2012

Mediator (MED) is a fundamental component of the RNA polymerase II-mediated transcription machinery. This multiprotein complex plays a pivotal role in the regulation of eukaryotic mRNA synthesis. The yeast Mediator complex consists of 26 different subunits. Recent studies indicate additional pathogenic roles for Mediator, for example during transcription elongation and non-coding RNA production. Mediator subunits have been emerging also to have pathophysiological roles suggesting MED-dependent therapeutic targets involving in several diseases, such as cancer, cardiovascular disease (CVD), metabolic and neurological disorders. © 2011 Elsevier Masson SAS. All rights reserved.


Schiano C.,Institute of Diagnostic and Nuclear Development SDN | Casamassimi A.,The Second University of Naples | Vietri M.T.,The Second University of Naples | Rienzo M.,The Second University of Naples | And 2 more authors.
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

Despite recent treatment advances, an increase in cardiovascular diseases (CVD) mortality is expected for the next years. Mediator (MED) complex plays key roles in eukaryotic gene transcription. Currently, while numerous studies have correlated MED alterations with several diseases, like cancer or neurological disorders, fewer studies have investigated MED role in CVD initiation and progression. The first finding of MED involvement in these pathologies was the correlation of missense mutations in MED13L gene with transposition of the great arteries. Nowadays, also MED13 and MED15 have been associated with human congenital heart diseases and others could be added, like MED12 that is involved in early mouse development and heart formation. Interestingly, a missense mutation in MED30 gene causes a progressive cardiomyopathy in homozygous mice suggesting a potential role for this subunit also in human CVDs. Moreover, several subunits like MED1, MED13, MED14, MED15, MED23, MED25 and CDK8 exert important roles in glucose and lipid metabolism. Although these evidences derive from in vitro and animal model studies, they indicate that their deregulation may have a significant role in human CVD-related metabolic disorders. Finally, alternative transcripts of MED12, MED19 and MED30 are differently expressed in circulating endothelial progenitor cells thus suggesting they can play a role in the field of regenerative medicine. Overall, further functional studies exploring MED role in human CVD are warranted. The results could allow identifying novel biomarkers to use in combination with imaging techniques for early diagnosis; otherwise, they could be useful to develop targets for novel therapeutic approaches. © 2014 Elsevier B.V.


Grimaldi V.,The Second University of Naples | Vietri M.T.,The Second University of Naples | Schiano C.,Institute of Diagnostic and Nuclear Development SDN | Picascia A.,The Second University of Naples | And 5 more authors.
Current Atherosclerosis Reports | Year: 2015

Recent data support the involvement of epigenetic alterations in the pathogenesis of atherosclerosis. The most widely investigated epigenetic mechanism is DNA methylation although also histone code changes occur during the diverse steps of atherosclerosis, such as endothelial cell proliferation, vascular smooth muscle cell (SMC) differentiation, and inflammatory pathway activation. In this review, we focus on the main genes that are epigenetically modified during the atherogenic process, particularly nitric oxide synthase (NOS), estrogen receptors (ERs), collagen type XV alpha 1 (COL15A1), vascular endothelial growth factor receptor (VEGFR), and ten-eleven translocation (TET), which are involved in endothelial dysfunction; gamma interferon (IFN-γ), forkhead box p3 (FOXP3), and tumor necrosis factor-α (TNF-α), associated with atherosclerotic inflammatory process; and p66shc, lectin-like oxLDL receptor (LOX1), and apolipoprotein E (APOE) genes, which are regulated by high cholesterol and homocysteine (Hcy) levels. Furthermore, we also discuss the role of non-coding RNAs (ncRNA) in atherosclerosis. NcRNAs are involved in epigenetic regulation of endothelial function, SMC proliferation, cholesterol synthesis, lipid metabolism, and inflammatory response. © 2014, Springer Science+Business Media New York.


Schiano C.,Institute of Diagnostic and Nuclear Development SDN | Casamassimi A.,The Second University of Naples | Rienzo M.,The Second University of Naples | de Nigris F.,The Second University of Naples | And 3 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2014

Mediator complex (MED) is an evolutionarily conserved multiprotein, fundamental for growth and survival of all cells. In eukaryotes, the mRNA transcription is dependent on RNA polymerase II that is associated to various molecules like general transcription factors, MED subunits and chromatin regulators. To date, transcriptional machinery dysfunction has been shown to elicit broad effects on cell proliferation, development, differentiation, and pathologic disease induction, including cancer. Indeed, in malignant cells, the improper activation of specific genes is usually ascribed to aberrant transcription machinery. Here, we focus our attention on the correlation of MED subunits with carcinogenesis. To date, many subunits are mutated or display altered expression in human cancers. Particularly, the role of MED1, MED28, MED12, CDK8 and Cyclin C in cancer is well documented, although several studies have recently reported a possible association of other subunits with malignancy. Definitely, a major comprehension of the involvement of the whole complex in cancer may lead to the identification of MED subunits as novel diagnostic/prognostic tumour markers to be used in combination with imaging technique in clinical oncology, and to develop novel anti-cancer targets for molecular-targeted therapy. © 2013.


Picascia A.,The Second University of Naples | Grimaldi V.,The Second University of Naples | Pignalosa O.,The Second University of Naples | De Pascale M.R.,The Second University of Naples | And 3 more authors.
Clinical Immunology | Year: 2015

Genome-wide association studies have revealed several genes predisposing to autoimmunity, however, concordance rates in monozygotic twins are significantly below 50% for several autoimmune diseases. The limited presence of a strong genetic association only in some patients supports that other non-genetic mechanisms are active in these pathologies. Epigenetic modifications such as DNA methylation, histone modification, and microRNA signaling regulate gene expression and are sensitive to external stimuli and they might be as bridging between genetic and environmental factors. Some evidence has highlighted the involvement of epigenetic alterations in the pathogenesis of various autoimmune diseases giving rise to great expectations among clinicians and researchers. The direct role of these alterations in the initiation/progression of autoimmune diseases is still unclear. The knowledge in depth of these pathogenic and epigenetic mechanisms will increase the possibility of the control and/or prevention of autoimmune diseases through the use of drugs that target epigenetic pathways. Moreover, we could use epigenetic-related biomarkers to follow this complicated framework (for example H3K4me3 and miRNA-155 are among those proposed biomarkers). This article reviews current understanding of the epigenetic involvement in the field of autoimmune diseases especially in systemic lupus erythematosus, rheumatoid arthritis, sclerosis multiple and type 1 diabetes. © 2015 Elsevier Inc.


Crudele V.,The Second University of Naples | Picascia A.,The Second University of Naples | Infante T.,Institute of Diagnostic and Nuclear Development SDN | Grimaldi V.,The Second University of Naples | And 3 more authors.
Immunology Letters | Year: 2011

The clinical transplantation outcome is related to both effects of immunological and non immunological factors degenerating into hyperacute, acute and chronic rejection. Modern immunosuppressive treatments have resolved most events linked to acute rejection while long-term survival still remains the major problem after heart transplantation. The goal of personalized immunosuppressive therapy is to prevent rejection without inducing toxic effects. The aim of future studies could be to clarify the pathogenesis of chronic rejection and develop new and less toxic therapeutic approaches to induce "tolerance" to the graft without major side effects. © 2011 Elsevier B.V.


Schiano C.,Institute of Diagnostic and Nuclear Development SDN | Rienzo M.,The Second University of Naples | Casamassimi A.,Institute of Diagnostic and Nuclear Development SDN | Casamassimi A.,The Second University of Naples | Napoli C.,The Second University of Naples
Medical Oncology | Year: 2013

Mediator complex (MED) is an essential multi-subunit component of the transcription apparatus and plays a key role in the transcription regulation of many genes involved in several diseases, including cancer. Recently, numerous MED subunits have been implicated in cancer development and metastasis, and specific alterations in their coding genes have been found to correlate with some malignancies. It is conceivable that a specific MED alteration pattern can characterize each cancer type. However, to date, no study has reported the complete picture of MED subunits in a specific tumor. Thus, the aim of this study was to investigate for the first time the gene expression profile of the whole MED complex in human osteosarcoma (OS). To this purpose, we have examined all the MED subunit genes in three OS cell lines compared to normal osteoblasts by real-time RT-PCR. Interestingly, our findings indicate that the expression of most of the MED genes is altered in OS. Moreover, a very high overexpression of MED20 and MED31 can be observed in all the analyzed OS cells, thus suggesting for the first time a potential role of these subunits in human malignancies. Overall, this study may open the way to other functional studies exploring the role of the whole complex in cancer development and progression. These findings may lead to the identification of novel biomarkers, which can be used also in combination with imaging techniques for early detection, and/or to develop novel targets for innovative therapeutic approaches. © 2013 Springer Science+Business Media New York.


PubMed | Institute of Diagnostic and Nuclear Development SDN and The Second University of Naples
Type: Journal Article | Journal: International journal of STD & AIDS | Year: 2016

Serological assays are still considered the most useful tests in the diagnosis of syphilis. Since no single serological assay is able to provide a satisfactory result, in our laboratory we have evaluated the usefulness of a commercially-available immunoblot to diagnose syphilis infection among blood donors. From October 2012 to June 2013, 4572 blood donors were screened for syphilis with an automated chemiluminescent microparticle immunoassay (CMIA). To confirm the presence of treponemal antibodies, CMIA-reactive sera were tested by standard Treponema pallidum haemagglutination assay (TPHA). In addition, an alternative confirmatory test - the immunoblot INNO-LIA assay was introduced in our laboratory. Since two additional positives among CMIA-reactive-TPHA-negative samples were found, we concluded that the INNO-LIA immunoblot allowed a better detection of syphilis compared to TPHA. A confirmatory strategy based on the use of two treponemal assays could meet the screening requirements for blood donors as well as in our centre.

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