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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.

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.

Picascia A.,The Second University of Naples | Grimaldi V.,The Second University of Naples | Casamassimi A.,The Second University of Naples | De Pascale M.R.,The Second University of Naples | And 3 more authors.
Journal of Cardiovascular Translational Research | Year: 2014

Considerable advances in heart transplantation outcome have been achieved through the improvement of donor-recipient selection, better organ preservation, lower rates of perioperative mortality and the use of innovative immunosuppressive protocols. Nevertheless, long-term survival is still influenced by late complications. We support the introduction of HLA matching as an additional criterion in the heart allocation. Indeed, allosensitization is an important factor affecting heart transplantation and the presence of anti-HLA antibodies causes an increased risk of antibody-mediated rejection and graft failure. On the other hand, the rate of heart-immunized patients awaiting transplantation is steadily increasing due to the limited availability of organs and an increased use of ventricular assist devices. Significant benefits may result from virtual crossmatch approach that prevents transplantation in the presence of unacceptable donor antigens. A combination of both virtual crossmatch and a tailored desensitization therapy could be a good compromise for a favorable outcome in highly sensitized patients. Here, we discuss the unresolved issue on the clinical immunology of heart transplantation. © Springer Science+Business Media New York 2014.

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.

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