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Biomedical subjects

A Vecchi

Publications and source records attributed to A Vecchi.

125 records · Page 7Linked to original sources
PubMedDate not supplied

Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts.

BACKGROUND: The oncosuppressive properties of some autonomous parvoviruses such as H-1 virus, together with their low pathogenicity, make them attractive vectors for tumor-directed gene therapy. Indeed, it was recently shown that these viruses became endowed with an enhanced oncosuppressive activity after they had been engineered to deliver a recognized therapeutic transgene. This prompted us to use a parvoviral vector to analyse the antineoplastic capacity of MCP-3 (monocyte chemotactic protein-3), a CC chemokine which has a broad spectrum of target cells, and can thus be considered to be a promising candidate for cancer treatment. METHODS: We explored the use of a parvovirus H-1-based vector encoding human MCP-3 for its antitumor potential on human cervical carcinoma cells. HeLa cells were infected in vitro with the recombinant virus hH1/MCP-3 at a low multiplicity [1 replication unit (RU)/cell] and we investigated the effect of parvovirus-mediated MCP-3 transduction on tumor formation and growth upon implantation of HeLa cells in nude mice. RESULTS: Infection of HeLa cells with hH1/MCP-3 led to secretion of high levels of MCP-3 and to significant retardation of tumor growth in recipient mice, as compared with HeLa cells that were either buffer-treated or infected with a MCP-3-free vector. Tumors from hH1/MCP-3-infected HeLa cells were heavily infiltrated with activated macrophages and showed increased numbers of dendritic cells. In addition, activated natural killer (NK) cells were also recruited into MCP-3-transduced tumors. CONCLUSION: These observations indicate that parvovirus H-1-transduced MCP-3 is able to exert a significant antitumor activity which is mediated, at least in part, through macrophages and NK cells, under conditions in which activated T cells are lacking.

Animals↗
PubMedDate not supplied

Effect of bacterial purified antigenic fractions on natural defence mechanisms.

The in vitro ability of bacterial purified antigenic fractions to interfere with the immune system has been investigated on human mononuclear cells from peripheral blood. Exposure of purified monocytes to the drug at concentrations from 1 to 1000 micrograms/ml, for different periods from 0 to 18 h, significantly increased cell-mediated cytotoxicity against TU5 target cells. Moreover, monocytes exposed for 1 to 18 h to drug concentrations from 0.1 to 1000 micrograms/ml released significant amounts of tumor necrosis factor alpha in a dose-dependent manner in the culture supernatants. The drug was also tested on natural killer (NK) cell activity; mononuclear cells exposed to antigenic fractions for different periods showed a significant increase of NK cytotoxic activity against K562 target cells after 3 and 6, but not 0 and 18 h. Active concentrations were from 1 to 100 micrograms/ml, higher and lower doses being ineffective. Bacterial purified antigenic fractions thus have some ability to interfere in vitro with mechanisms of cytolysis mediated by cells and soluble factors.

Antigens, Bacterial↗
PubMedDate not supplied

Progressive approach to the cytologic diagnosis of retroperitoneal spindle cell tumors.

OBJECTIVE: To assess the utility of fine needle aspiration biopsy (FNAB) in retroperitoneal spindle cell tumors with difficult tumor typing. STUDY DESIGN: Thirty-six cases of spindle cell tumors of the retroperitoneum were studied. Cytological diagnoses were set progressively: first exclusively by morphologic criteria on routinely stained slides, and then with the aid of immunocytochemistry (ICC), electron microscopy (EM) and clinical data. RESULTS: The morphologic diagnosis of benignity or malignancy was first made in double blind fashion by two researchers; it permitted an exact diagnosis in 31 cases (86%) by one examiner and 27 cases (75%) by the second. Using a progressive approach, benignity or malignancy was definitively determined in 35 cases (97%). As far as cytologic tumor typing is concerned, first it proved to be possible in 27 cases (75%) and then in 30 cases (83%) with the progressive approach. CONCLUSION: FNAB proved to be a useful tool in the diagnosis of retroperitoneal spindle cell tumors. A progressive approach to cytopathologic diagnosis, correlating morphology with ICC and EM results and matching them with clinical data, permitted a better differential diagnosis between benign and malignant spindle cell tumors and increased the possibility of correct tumor typing.

Adolescent↗
PubMedDate not supplied

Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.

The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.

Animals↗
PubMedDate not supplied

Bcl-2 oncoprotein expression in acute myeloid leukemia.

BACKGROUND: In lymphoproliferative diseases the expression of Bcl-2, a mitochondrial oncoprotein capable of blocking apoptosis, is well-documented, while little research has been carried out on its distribution in myeloproliferative conditions. METHODS: Using immunocytochemical methods, 63 cases of acute myeloid leukemia (AML) at onset and 10 relapses were studied to investigate Bcl-2 expression and any possible correlations with subtypes of the FAB classification, sex, age or white cell peripheral blood count at onset. RESULTS: Bcl-2 is present in 87.3% of AML cases at onset and in 100% of relapses. In 68.3% of cases at onset and in 90% of relapses the protein is present in more than 20% of the blasts. Relapses always show higher percentages of positive expression than those seen at onset. Our results demonstrate no statistical correlations between the expression of the oncoprotein Bcl-2 and FAB subtypes, sex, age, or white cell peripheral blood count. CONCLUSIONS: The majority of blasts from AML patients express the oncoprotein Bcl-2, which is able to protect leukemic cells from apoptosis. Since numerous chemotherapies are cytotoxic in that they induce apoptosis, we feel that in vitro studies of cells from AML patients are necessary in order to broaden our knowledge about the effects of the most common therapeutic drugs and of those substances which, alone or in association, can modulate Bcl-2 expression.

Acute Disease↗