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V M Fazio

Publications and source records attributed to V M Fazio.

43 records · Page 3Linked to original sources
PubMedDate not supplied

Development of a multigenic plasmid vector for HCV DNA immunization.

HCV viral nucleocapsid protein (C), non-structural protein 3 (NS3) and the envelope glycoproteins E1 and E2 are candidate immune targets for developing anti-HCV DNA vaccine. Nevertheless, the immune response elicited by these antigens often appears weak and/or transient. Different approaches have been studied for enhancing and/or modulating the immune response of the DNA vaccine. On the basis of a prototype multigenic plasmid vector constituted of two different transcription cassettes (pRC100), we have developed a plasmid vector that allows the independent and simultaneous expression of murine IL2 and of an antigenic domain of the HCV NS3 C terminus (pRC112-HCV). The highly conserved NS3 region spans from nt 4403 to nt 4829 and contains two putative B and T epitopes. The development of this multigenic plasmid vector may combine the expression and local production of an immunomodulatory molecule (mIL2) together with the possibility of addressing the host immune response to the most immunogenic and conserved epitopes, specifically tailored in the plasmid vector.

Animals↗
PubMedDate not supplied

Apolipoprotein E genotype in sporadic early- and late-onset Alzheimer's disease.

The 84 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for Alzheimer's disease (AD), while the possible role of the epsilon2 allele in AD is controversial. We have studied the ApoE genotype in 38 patients with early-onset AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the EOAD group we observed a significant increase of epsilon4 allele frequency as compared with normal controls, while there was a more than 3-fold decrease of epsilon2 allele frequency that did not reach statistical significance. In the LOAD group we found a highly significant increase of epsilon4 allele frequency as compared with normal controls, while there was a significant decrease of epsilon2 allele frequency. In both the EOAD and LOAD groups, no significant difference was observed between epsilon4 carriers and epsilon4 noncarriers as for age at disease onset, disease duration, and Mini-Mental State score at observation. However, in both EOAD and LOAD groups a statistical trend towards a longer disease duration was observed in epsilon4 carriers. In both the EOAD and LOAD groups, disease severity was compared in epsilon4 carriers versus epsilon4 noncarriers by means of analyses of covariance, with disease duration as covariate. No significant difference between epsilon4 carriers and epsilon4 noncarriers was observed in both EOAD and LOAD. The results of the present study confirm that epsilon4 allele seems to be associated with an increased risk for sporadic AD, while the significant decrease of epsilon2 allele frequency in the LOAD group supports the hypothesis of a possible protective role of epsilon2 allele in AD.

Age of Onset↗
PubMedDate not supplied

Effect of 4-hydroxynonenal, a product of lipid peroxidation, on natural cell mediated cytotoxicity.

Lipid peroxidation of cell membrane yields a variety of final products whose a quantitatively important component is 4-hydroxynonenal (HNE). Previous studies performed in our laboratory suggest that HNE may play a physiological role in the control of cellular proliferation and/or differentiation. This appears to be further supported by our recent findings showing that pre-treatment of K562 cells with a physiological concentration of HNE leads to a marked reduction of susceptibility of NK cells. The observed regulatory effects of HNE on tumor cell growth and susceptibility to natural immune resistance, led us to try to better understand the immunotoxicological properties of this aldehyde. The present study analyses the effects of HNE on NK-mediated cytotoxicity. Treatment of MNC as effector cells with concentrations of HNE ranging from 0.001 to 1 microM for 1 h, did not produce noticeable effects on NK activity. Therefore, this aldehyde at physiological concentrations is able to differentiate tumor cells and to down-regulate target susceptibility to NK effectors from one side. On the other side, it is not able to modify the efficiency of the NK function. Moreover, HNE concentrations higher than 1 microM showed significant and concentration-dependent inhibition of NK activity. However, this effect is reversible and can be antagonized, at least in part, by treatment of effector cells with HNE in combination with beta-interferon.

Aldehydes↗
PubMedDate not supplied

[Genetic therapy in oncology: ethical aspects].

The more advanced oncologic therapies are directing toward new frontiers, on account of the remarkable undesirable effects of chemio- and radio-therapies. This new therapeutic experiences are of type biological (vaccines), or genic (substitution again genes with shutters meaning-tumoral). This therapies involve, to be effected, some ethical shrewdnesses: choice of the patient, the engineering modality of the genes, the transfer of the genes in cells of the exclusively somatic line, the elimination of the pathogenic risk of the vector virus, the obligatory use of sterile rooms, the attention to the administration of the drug, a legal issue of the judgment of notoriety.

Bioethical Issues↗
PubMedDate not supplied

Molecular organization of oncogenes and potentially oncogenic regulatory genes in primary human brain tumors.

We review here results obtained from a wide screening of 72 primary human brain tumors, in order to investigate the molecular organization of proto-oncogenes and potentially oncogenic genes. We demonstrated alterations in the restriction pattern of c-sis oncogene in 1 anaplastic astrocytoma and in 1 endotheliomatous meningioma, and amplifications of c-myc oncogene in 2 endotheliomatous meningiomas. In the same screening of primary brain tumors, we have recently published evidences for a specific alteration in the restriction pattern of estrogen receptor gene sequences which code for the DNA binding domain of the protein. These results, although preliminary and not still sufficient for a conclusive determination of the role in brain tumor growth and/or development, provided evidences of relatively frequent molecular alterations of genes involved in the control of cell proliferation and differentiation.

Blotting, Southern↗
PubMedDate not supplied

Effect of 4-hydroxynonenal, a product of lipid peroxidation, on NK susceptibility of human K562 target cells.

4-Hydroxynonenal (HNE) is one of the major breakdown products generated by lipid peroxidation of cellular membranes. The level of lipid peroxidation and the concentration of its products are inversely related to the rate of cell proliferation and directly related to the level of cell differentiation. It has been reported that HNE inhibits DNA synthesis, ornithine decarboxylase (ODC) activity and c-myc expression in different leukemic cells lines. It has also been demonstrated that HNE inhibits proliferation and induces differentiation in HL60 cell line. In the present study the effects of HNE, at concentrations close to those found in the normal tissues, on the NK susceptibility of human K562 target cells were analyzed. Repeated treatments at 45 minutes intervals with 1 microM HNE were performed to maintain the cells in the presence of the aldehyde for 12 hours. The effect of HNE was compared with that obtained in Haemin-treated cells. HNE causes a strong inhibition of cells growth (53% vs. 34% with Haemin) without affecting cell viability. We further investigated the NK susceptibility of K562 cell line upon in vitro treatment with HNE. Cytotoxic activity of mononuclear cells (MNC) from peripheral blood of healthy donors was determined by 4 hours Cr51-release assay. The results obtained, expressed in terms of percentage of specific lysis at different E:T ratios and in terms of KC (10(6)) at the E:T ratio of 50:1, show that HNE treatment of K562 cells leads to a marked reduction of susceptibility to NK cells; this decrease is very close to that found in the K562 cells treated with Haemin used as inducer. Similar results were obtained using MNC pre-treated with beta-interferon (IFN) as effector cells. MNC show a reduced capacity to lyse HNE-treated cells also under the enhancing cytolytic effect of IFN. These results are in line with data obtained with several common inducers of differentiation such as DMSO, retinoic acid or others.

Aldehydes↗