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R Barbieri

Publications and source records attributed to R Barbieri.

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

Binding of nuclear factors to the IFN-gamma consensus sequence of the human HLA-DR alpha gene: effects of IFN-gamma on tumor cell lines.

The binding of nuclear proteins from human tumor cells to synthetic double stranded oligonucleotides mimicking upstream regions of the HLA-DR alpha gene was studied. As the HLA-DR alpha gene is inducible by interferon(IFN)-gamma, nuclear extracts were also purified from IFN-gamma treated cells. Our data indicate that a) nuclear binding proteins (named IFN-gamma-B3 and Z-B1/B2) are detectable, specific for the IFN-gamma and Z boxes of the human HLA-DR alpha gene; b) both IFN-gamma-B3 and Z-B1/B2 are present in HLA-D negative cell lines and c) the content of IFN-gamma-B3 and Z-B1/B2 is not modulated by IFN-gamma treatment. These data suggest that the presence in the nuclear compartment of these factors, presumably necessary for the correct regulation of the HLA-DR alpha gene, is not sufficient to explain its differential constitutive and induced expression in a variety of in vitro cultured cell lines of different lineage.

Base Sequence↗
PubMedDate not supplied

Effects of the proteinase inhibitor tetra-p-amidinophenoxyneopentane on in vitro adhesion and invasiveness of tumor cells.

Some of the biological processes which enhance the metastatic capacity of tumor cells are associated with the activation of proteinases. In this paper we examined the effects of aromatic polyamidines on "in vitro" invasiveness of tumor cell lines. In addition to their antiproteinase activity, aromatic polyamidines exhibit antiproliferative activity toward tumor cell lines and inhibit expression of specific oncogenes. The results obtained show that the aromatic polyamidine TAPP-Br does not affect attachment, but inhibits the "in vitro" invasiveness of tumor cells cultured on a reconstituted basement membrane composed by laminin, type IV collagen, entactin, heparan sulphate proteoglycans. Our data suggest that this and related compounds should be further studied as experimental antitumor agents.

Amidines↗
PubMedDate not supplied

Regulation of the antigenic phenotype of human melanoma cells by recombinant interferons.

The ability of interferons to modulate the antigenic phenotype of tumor cells may involve alterations in the transcription, translation, membrane expression and shedding of Major Histocompatibility Complex (MHC) and Tumor Associated Antigens (TAAs). In the present study we have investigated possible mechanisms by which recombinant human interferons, IFN-alpha, -beta and -gamma, alter the antigenic profile of long- and short-term human melanoma cultures. IFN-alpha and -beta induced similar changes in the synthesis, expression and shedding of two TAAs, a HMW-MAA and a Cyt-MAA, in the established melanoma cell line Colo 38, whereas IFN-gamma exerted a differential effect on these melanoma associated antigens. Moreover, IFN-gamma was relatively more effective than IFN-alpha or -beta in upregulating the synthesis, expression and shedding of class I MHC antigens. At the same time a dramatic differential effect of the interferons was observed with class II MHC antigens. IFN-alpha or -beta induced a modest increase in the synthesis and expression of these antigens, whereas IFN-gamma was greater than 3-fold more active in inducing the synthesis and expression of DR/DP antigens and greater than 4- and greater than 10-fold more effective in increasing the synthesis and expression, respectively, of DQ antigens. Analysis of the levels of cytoplasmic mRNA for the DR-alpha and DQ-beta genes indicated no significant difference between IFN-alpha, beta or -gamma treated cells suggesting that IFN-gamma enhancement of the synthesis of DR and DQ antigens may occur at a posttranscriptional level. In the case of a newly established human melanoma cell line (MG-3) IFN-gamma enhanced the synthesis but not the expression of DR antigens and did not alter either the synthesis or expression of DQ antigens. Our studies indicate that the effects of interferons on the antigenic phenotype of melanoma cells will vary depending on the type of interferon employed, the antigen monitored and the target cell studied. In addition, it is also apparent that some of the biosynthetic steps involved in regulating the synthesis, expression and shedding of antigens may be coordinately regulated in some melanoma cells, whereas these processes may be under independent control in other melanoma populations.

Antigens, Neoplasm↗
PubMedDate not supplied

Antitumor activity of the proteinase inhibitor tetra-p-amidinophenoxyneopentane in a nude mouse model of human melanoma.

An aromatic poly-amidine (tetra-p-amidinophenoxyneopentane, TAPP-Br) exhibiting anti-proteinase activity and known to exert antitumor activity in vitro was analysed for its ability to inhibit the in vivo growth of a human melanoma cell line transplanted in nude mice. 5 X 10(6) melanoma cells were injected subcutaneously in groups of nude mice and treatment with TAPP-Br was performed (0.125-1 mg/0.2 ml injections, repeated three times at the beginning of the experiment and after 20 days). After 25 days tumors displaying a volume of 0.9-1.8 cm3 were detectable in control untreated mice. Mice treated with TAPP-Br on the other hand did not develop sizable tumors or consistently developed tumors of significantly smaller sizes. Despite these therapeutic effects, significant chronic toxicity of the compound was observed when administered at higher dosage (500-1000 micrograms). These side effects, which may hamper the therapeutic use of TAPP-Br, are likely to be circumvented by alternative routes of administration or by vehiculation into liposomes. These alternative strategies of treatment are currently investigated.

Animals↗
PubMedDate not supplied

New synthetic retinoids: effects on proliferation and differentiation.

Nine retinoid analogues were synthesized and their effects on cell proliferation and differentiation of tumor cell lines were analysed and compared with those of natural retinoids (retinoic acid, retinol, retinal). Our results demonstrate differential inhibitory effects of the synthetic retinoids on cell growth. This inhibitory activity of the synthetic retinoids was, in some cases, higher than that of retinoic acid and retinol. Natural and synthetic retinoids were found to be able to induce to a different extent erythroid differentiation of murine erythroleukemia cells and adipogenic conversion of Chinese Hamster FHO6N1-1 cells. Our data suggest that studies on the relationship between structure and biological activity could be approached by using the analysed synthetic retinoids.

Animals↗
PubMedDate not supplied

DNA methylation of the Ha-ras-1 oncogene in neoplastic cells.

The DNA methylation pattern of the human Ha-ras-1 oncogene and the levels of specific mRNA have been analysed in established tumor cell lines and in surgical biopsies. In long-term cultures, the Ha-ras-1 gene is hypomethylated at its 5' end and highly methylated at its 3' portion. The GCGC sites at the 5' end have been shown to become methylated only when E. Coli HhaI methylase is added to isolated DNA, while they remain unmethylated when the enzyme is added to chromatin. These data indicate that the 5' portion of this protooncogene is maintained physiologically unmethylated, possibly because it is necessary for gene transcription. Along the same line of evidence, when levels of mRNA and methylation of the gene were comparatively analysed in breast tumors and autologous normal mammary tissue, no appreciable differences in the degree of methylation were found despite significant differences in mRNA content. These findings show that the levels of Ha-ras- mRNA are independent of the DNA methylation state.

Breast Neoplasms↗
PubMedDate not supplied

Effects of benzamidine derivatives on Ha-ras-1 mRNA accumulation in a Chinese hamster cell line transformed with the activated human T24 Ha-ras-1 oncogene.

Tetra benzamidine derivatives were found to inhibit proteinase activity, cell proliferation and accumulation of the Ha-ras-1 mRNA in the FHO6T1-1 Chinese Hamster cell line, transformed with the activated human T24-Ha-ras-1 oncogene. Di- and Tri-benzamidine derivatives were also found to be potent inhibitors of proliferation of FHO6T1-1 cells. These latter compounds could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors.

Amidines↗
PubMedDate not supplied

Cytogenetic, molecular and phenotypic characterization of the newly established renal carcinoma cell line KJ29. Evidence of translocations for chromosomes 1 and 3.

The established non papillary human renal carcinoma cell line (RCC) KJ29 was submitted to a multiparametric characterization to evaluate its potential use for in vitro and in vivo studies. The cell line grows in vitro as monolayer as well as cell suspension. Cytogenetic analysis has shown a modal chromosome number of 50 with some marker chromosomes, including rearrangements of chromosomes 1 and 3. The antigenic phenotype is characterized by co-expression of cytokeratin and vimentin, as well as expression of urothelium differentiation antigens, low levels of class II MHC antigens and no class I antigens. A differential expression of the VLA-3 integrin heterodimer has been detected between the adherent and non adherent cell population. The cell line which is highly tumorigenic in athymic mice displays expression of erb B-2 and c-met oncogenes and high expression of cell-cycle related and Ha-ras 1 genes.

Animals↗