Molecular Signature in HCV-Positive Lymphomas

Hepatitis C virus (HCV) is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL). Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified

High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

BACKGROUND: Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. RESULTS: At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L(+ )lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. CONCLUSION: sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation

“Gli aspetti innovativi dell’informativa finanziaria nelle “entità” del settore pubblico: gli IPSAS 5, 15, 18, 19 e 21”

Per il citato lavoro, che rappresenta un contributo alla ricerca della Scuola Superiore della Pubblica Amministrazione “Principi e metodi di contabilità economico-patrimoniale per lo Stato e le Pubbliche Amministrazioni nel quadro teorico ed operativo internazionale” (coordinatore Prof. L. Anselmi, anni 2007/2008), sono stati assolti gli obblighi di pubblicazione direttamente dall’autore, ai sensi della Legge 15.4.2006 n. 106 e del D.P.R. 03.05.2006, n. 252

Antibody Vh Repertoire Differences between Resolving and Chronically Evolving Hepatitis C Virus Infections

Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion

Identification of new major histocompatibility complex‐A, ‐B, ‐C alleles in chimpanzees (Pan troglodytes)

Two new Patr-A, five new Patr-B and three new Patr-C alleles from Pan troglodytes are described

Description of two new major histocompatibility complex (MHC) class II DRB1 [Pan troglodytes (Patr)-DRB1] alleles

Sequence-based typing strategy is used to identify polymorphism of Patr-DRB1. Two new Patr-DRB1 are described

Family’s History Based on the CDH1 Germline Variant (c.360delG) and a Suspected Hereditary Gastric Cancer Form

Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome caused by germline pathogenic variant in CDH1, the gene encoding E-cadherin. The germline loss-of-function variants are the only proven cause of the cancer syndrome HDGC, occurring in approximately 10&ndash;18% of cases and representing a helpful tool in genetic counseling. The current case reports the family history based on a CDH1 gene variant, c.360delG, p.His121Thr in a suspected family for hereditary gastric cancer form. This frameshift deletion generates a premature stop codon at the amino acid 214, which leads to a truncated E-cadherin protein detecting it as a deleterious variant. The present study expands the mutational spectra of the family with the CDH1 variant. Our results highlight the clinical impact of the reported CDH1 variant running in gastric cancer families

Protein signature characterizing Helicobacter pylori strains of patients with autoimmune atrophic gastritis, duodenal ulcer and gastric cancer

Abstract Background Helicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of H. pylori isolated from gastric biopsies of patients affected by either AAG, DU or GC. Methods The H. pylori strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease. Protein profiles of H. pylori were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) for the identification of significantly different spots (Student t-test, p 1.5). These spots corresponded to 35 unique proteins. The identity of 7 protein spots was validated after one-dimensional electrophoresis and MS/MS analyses of excised gel portions. In H. pylori isolated from DU-patients a significant increase in proteins with antioxidant activity emerged (AroQ, AspA, FldA, Icd, OorA and ScoB), together with a higher content of proteins counteracting the high acid environment (KatA and NapA). In H. pylori isolated from AAG-patients proteins neutralizing hydrogen concentrations through organic substance metabolic processes decreased (GroL, TrxB and Tuf). In addition, a reduction of bacterial motility (FlhA) was found to be associated with AAG-H. pylori isolates. In GC-H. pylori strains it was found an increase in nucleic acid-binding proteins (e.g. DnaG, Tuf, RpoA, RplU) which may be involved in a higher demand of DNA- and protein-related processes. Conclusion Our data suggest the presence of specific protein signatures discriminating among H. pylori isolated from either AAG, DU or GC. Changes in protein expression profiles evaluated by DIGE succeeded in deciphering part of the molecular scenarios associated with the different H. pylori-related gastric diseases