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Stefano Lazzi,
Cristiana Bellan,
Teresa Amato,
Nazzareno Palummo, Concetta Cardone,
Alessandro D'Amuri,
Fabio De Luca,
Medard Beyanga,
Fabio Facchetti,
Piero Tosi,
Lorenzo Leoncini
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ABSTRACT: We set out to analyze the presence of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in different neoplasms occurring in East Africa, a region characterized by a high KSHV/HHV-8 seroprevalence rate and endemic Kaposi's sarcoma (KS). Our results suggest that, in endemic regions of Africa, KSHV/HHV-8 is predominantly associated with KS, independently of HIV status. During the course of this study, other important information came to light. We found the presence of KSHV/HHV-8 in 2 cases of lymph nodes partially involved by Burkitt's lymphoma and KS and in 1 case of multicentric Castleman disease. Our immunophenotypic and molecular data seem to suggest 2 different mechanisms of viral infection are at work in lymphoid cells. On one hand, when B cells show a latent phase infection with KSHV/HHV-8, after the germinal center reaction, naive B cells become resting memory B cells, similarly to Epstein-Barr virus-infected B cells. On the other hand, when lytic genes such as vIL6 are expressed in naive B cells, they may be driven to differentiate into plasmablasts without undergoing germinal center reaction. Interestingly, among KSHV/HHV-8-positive cases, in those in which there was also lymphoma, the neoplastic cells were negative for KSHV/HHV-8. This further confirms that KSHV/HHV-8 is involved in the neoplastic transformation of only certain types of lymphoma, probably in relation to their precursor infected cell. In conclusion, the maturation stage of KSHV/HHV-8-positive B cells as well as the type of viral infection may well determine the morphological, phenotypic, and clinical characteristics of KSHV/HHV-8-associated lymphomas.
Human Pathlogy 02/2006; 37(1):23-31. · 2.88 Impact Factor
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Maria Grazia Cusi,
Maria Teresa Del Vecchio,
Chiara Terrosi,
Gianni Gori Savellini,
Giuseppa Di Genova,
Marco La Placa,
Francesca Fallarino,
Christian Moser, Concetta Cardone,
Giorgio Giorgi,
Guido Francini,
Pierpaolo Correale
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ABSTRACT: The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation. This process can be exploited to significantly improve the efficacy of cancer vaccines and the outcome of a possible cancer vaccine-induced, Ag-specific CTL response. Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV). Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype. In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
The Journal of Immunology 07/2005; 174(11):7210-6. · 5.79 Impact Factor
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Clelia Miracco,
M Margherita De Santi,
Pietro Luzi,
Anna Vittoria Lalinga,
Lorella Laurini,
Maria Caterina De Nisi,
Giuseppina Angeloni,
Marco Brogi, Concetta Cardone,
Antonietta Carducci,
Felice Arcuri,
Piero Tosi,
Giovanni Rubino,
Luigi Pirtoli
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ABSTRACT: Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.
International Journal of Oncology 01/2004; 23(6):1529-35. · 2.40 Impact Factor
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ABSTRACT: To test CD-34 immunoreactivity in stromal cornea cells in normal and pathologic samples obtained from penetrating keratoplasty.
Prospective, consecutive histopathologic human tissue study.
One hundred two cornea buttons from patients with different diseases, submitted for cornea transplant, were examined. Controls were expired corneas from healthy donor patients who died (n = 4), and globes enucleated for primitive intraocular neoplasias, that is, retinoblastomas (n = 8), and malignant choroidal melanomas (n = 2).
The expression of CD-34 in stromal cornea cells was examined by immunohistochemistry analysis. Other immunohistochemical stains included an endothelial cell marker (CD-31), common leukocyte antigen, and alpha-smooth muscle actin.
Different diseases that may cause blindness and require penetrating keratoplasty have been tested for CD-34 immunoreactivity.
In control corneas, keratocytes present strong and consistent CD-34 immunoreactivity. Diseases leading to the loss of transparency and penetrating keratoplasty, such as keratoconus, herpes keratitis, trauma, and heredofamilial dystrophies, are associated with focal or diffuse loss of CD-34 expression, whereas pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy show normal CD-34 immunoreactivity in most cases and patchy unstained stromal areas in a few cases.
Scar tissue formation in the cornea, as in herpes keratitis and trauma, is always associated with loss of CD-34 immunoreactivity, which may otherwise be a primary event in keratoconus and heredofamilial dystrophies. Both in the pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy, CD-34 immunoreactivity may be normal or lost, hence these two diseases may be considered as one and part of the same group with regard to CD-34 expression, as revealed by immunohistochemistry analysis.
Ophthalmology 07/2002; 109(6):1167-71. · 5.45 Impact Factor
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ABSTRACT: Benign lymphoepithelial lesions (BLEL) are usually found in salivary glands in autoimmune disorders. Some LEL are recognized to already be, or may progress to become, lymphomas. Skin lesions similar to LEL have been described in lymphomas, and are caused by neoplastic lymphocytes which infiltrate adnexal structures. To date, BLEL have not widely been recognized in the skin.
We describe skin lesions similar to BLELs, at the periphery of squamous cell carcinomas (SCC) in 8 healthy patients, in one of whom the lesion recurred. Immunocharacterization of both epithelial and lymphocytic components and molecular genetic investigation was performed. Polymerase chain reaction (PCR) analysis was done to detect IgH chain gene, and T-cell receptor beta and gamma gene rearrangements. Association with Epstein-Barr virus (EBV) was also tested by in situ hybridization (ISH) for EBV-encoded RNAs (EBERs).
Epithelial cells showed the immunophenotype of eccrine sweat gland ducts. Infiltrating lymphocytes expressed overwhelming B antigens and CD5. Neither clonal B and/or T proliferations nor EBERs signals were demonstrable.
We observed skin lesions similar to BLELs, showing modifications of sweat gland duct and CD5+, B lymphocytic expansion. In our cases there were no associated autoimmune disorders; the local immunoresponse to SCC might have caused BLEL.
Journal of Cutaneous Pathology 02/2002; 29(1):33-7. · 1.56 Impact Factor
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ABSTRACT: This study evaluated the levels and the enzymatic characteristics of 11β-hydroxysteroid dehydrogenase activity (11β-HSD) of chorionic villi isolated from first trimester human placenta. The results demonstrated a predominant expression of the NAD-dependent dehydrogenase isoform (11β-HSD2) over the NADP-dependent oxoreductase (11β-HSD1). Thus, in tissue homogenates exogenous NAD increased the conversion of corticosterone to 11-dehydrocorticosterone of about 14-fold while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11β-HSD2 in villous tissue while 11β-HSD1 mRNA levels were undetectable. In addition, immunohistochemical staining localized the 11β-HSD2 protein to syncytiotrophoblasts and cell columns of the chorionic villi. These results suggest roles for the trophoblast-associated 11β-HSD2 oxidative activity in modulating the exposure of the embryo to active glucocorticoids in the early gestation and in regulating trophoblasts invasion of the uterine wall.
Molecular and Cellular Endocrinology.
