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Biomedical subjects

G Feriotto

Publications and source records attributed to G Feriotto.

At least 55 records · Page 3Linked to original sources
PubMed1992

New isoxazole derivatives of retinoids: synthesis and activity on growth and differentiation of tumor cells.

The effects of several newly synthesized isoxazole analogues of retinoids on differentiation and proliferation of 'in vitro' cultured tumor cell lines are reported. Some of the tested compounds exhibit significative differentiating action, inducing adipogenic conversion of the Chinese hamster FH06T1-1 cell line in a range of 2-10 times the activity of retinoic acid and retinol. In addition, most of the compound tested display antiproliferative activity comparable to that of natural retinoids. The reported data could be of interest for experimental anticancer therapy.

Adipose Tissue↗
PubMed1991

Transgenic mice mimic the methylation pattern of the human HLA-DR alpha gene.

The methylation pattern of the human HLA-DR alpha gene has been studied in different tissues of transgenic mice. Offspring from two transgenic lines was selected for this analysis, carrying the integrated HLA-DR alpha gene in either single or multiple (8-10) copies per diploid genome. In transgenic animals two distinct methylation patterns of the HLA-DR alpha gene are generated, due to a complete methylation of all the GCGC and CCGG sites the former, and to unmethylation restricted to one or both the GCGC sites located in the 5' portion of the HLA-DR alpha gene, the latter. Unmethylation restricted to the 5' portion of the HLA-DR alpha gene is a highly conserved feature in human tissues and in vitro cultured cell lines; therefore, it is concluded that the methylation pattern of the human HLA-DR alpha transgene may be faithfully reconstituted in transgenic animals. Northern blotting analysis of the RNA isolated from tissues of the transgenic mouse carrying single-copy HLA-DR alpha transgene demonstrates its tissue specific expression, suggesting that transgenic mice may represent an "in vivo" experimental system to study the relationship between methylation state and transcriptional activation.

Animals↗
PubMed1991

Distamycin inhibits the binding of a nuclear factor to the -278/-256 upstream sequence of the human HLA-DR alpha gene.

In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for nuclear protein binding and is likely to interact with distamycin. The present results, by showing that distamycin inhibits the interaction between nuclear factors and the GTATA/IFN-gamma oligonucleotide, suggest that distamycin might alter the binding of transacting factors to cis-elements containing AT/TA sequences. Alterations of nuclear protein binding to specific target sequences could be one of the molecular mechanism(s) by which distamycin exerts its antiproliferative activity on living cells.

Antineoplastic Agents↗
PubMed1991

Tissue-specific expression of the HLA-DRA gene in transgenic mice.

Transgenic mice were produced containing a 33 kilobase (kb) DNA fragment encompassing the five exons and all the known regulatory regions of the class II HLA-DRA gene. The transgene displayed regulated expression [constitutive and interferon-gamma (IFN)-gamma induced] of the human products in most mouse tissues. The tissue distribution of the DRA transgene products more closely resembled that of their mouse homologues, the endogenous H-2 Ea products, than the wider distribution of DRA products in humans. This was evident in several tissues (endothelia of small vessels, especially those of glomerular capillaries, Kupffer cells, and epithelial cells lining the gastrointestinal tract), known to differentially express class II molecules in the two species. Thus, the wider human specific pattern of expression requires an exact cis/trans complementation which is incompletely reconstituted in transgenic mice, suggesting that human-specific cis-acting elements may have arisen during evolution to direct the expression of class II genes to those anatomical regions which usually lack them in the mouse. The only example of aberrant expression of the DRA gene in the present series of transgenic mice was in the dendritic and/or epithelial cells of the thymic cortex, which displayed greatly reduced DR alpha levels in spite of a normal expression of the endogenous E alpha molecules.

Animals↗
PubMed1991

N1-substituted benzamidines: synthesis, antiproteinase activity and inhibition of tumor cell growth.

We have synthesized N1-substituted benzamidines and poly-benzamidines with the aim to produce antitumor drugs retaining differential biological properties with respect to unsubstituted compounds. Antiproliferative activity on in vitro cultured human leukemic cells was exhibited by N1-substituted poly-benzamidines, while N1-substituted benzamidines were found to retain very low antitumor effects. Furthermore, our results suggest that N1-substituted benzamidines and some of poly-benzamidines exhibit low activity on trypsin and kallikrein. Taken together these data indicate that some N1-substituted poly-benzamidines could be of interest for experimental antitumor therapy, since are likely to retain low side effects due to alteration of proteinase activity.

Animals↗
PubMed1991

Effects of aromatic polyamidines on the electrophoretic mobility of HIV-1 genomic regions amplified by polymerase-chain reaction.

In this paper we describe the use of polymerase chain reaction (PCR) to amplify DNA sequences suitable for studies on the activity of DNA-binding drugs of possible interest in anti-tumor as well as anti-viral therapy. To this aim (a) we amplified by PCR two regions of the HIV-1 genome (one localized within the LTR, the other within the env gene), known to bind nuclear factors and (b) we determined whether different aromatic polyamidines are able to differentially affect the electrophoretic mobility of these HIV-1 PCR fragments. We found that aromatic polyamidines differentially affect the electrophoretic migration of PCR-amplified HIV-1 genomic regions. This differential effect, related to a differential DNA-binding activity, could lead to a differential inhibition of protein-DNA interactions.

Base Sequence↗
PubMed1990

Establishment and characterization of a leukemic murine cell line derived from MCF 247 MuLV-induced T-cell lymphoma.

Understanding of the leukemic evolution of human non-Hodgkin's lymphomas is hindered by the lack of appropriate animal models. For this purpose, a highly leukemic cell line NQ22, derived from a MCF 247 murine leukemia virus (MuLV)-induced murine T-cell lymphoma, was established, and its preliminary characterization is described. The NQ22 cell line is easily transplantable subcutaneously (s.c.) into syngeneic AKR mice exhibiting early peripheral blood invasion and widespread dissemination with a leukemic pattern of infiltration. Such peculiar in vivo behavior is a stable phenotypic feature, probably determined genetically. Biological and differentiation characteristics of the NQ22 cell line were analyzed and compared to those of other non-leukemic T-lymphoma lines. In addition, no evidence of possible involvement of plasminogen activator (PA) enzymes and of their inhibitors (PAI) in the spreading ability of NQ22 cells was observed.

Animals↗
PubMed1990

A coordinated proto-oncogene expression characterizes MCF 247 murine leukemia virus-induced T-cell lymphomas irrespectively of proviral insertion affecting myc loci.

Proto-oncogene transcriptional activation was analyzed in a group of MCF 247 MuLv-induced T-cell lymphomas to identify transformation-specific gene activations and determine whether the proviral insertion near a myc gene could promote a peculiar mechanism of transformation through a differential proto-oncogene expression pattern. Of the six lymphomas analyzed, three showed the MCF 247 provirus integrated within the N-myc locus, one carried the provirus integrated near c-myc, whereas for the remaining two, no evidence of proviral integrations in any of the known myc loci was obtained. Independently of the integrative events, the pattern of proto-oncogene expression was almost identical in all six lymphomas. These findings seem to rule out the existence of a peculiar pathway of transformation associated with the proviral insertion near a myc locus. Moreover, the transcription pattern observed was qualitatively identical to that displayed by normal thymocytes; only quantitative differences in c- or N-myc, c-myb and Ha-ras were observed. These results suggest that the T-cell proto-oncogene activation program is not qualitatively affected by the transforming event(s).

Animals↗
PubMed1989

Induction of murine erythroleukemia cell differentiation by proteinases is inhibited by aromatic poly-amidines.

The effects of the tetra benzamidine serine-proteinase inhibitor 1,3-di-(p-amidinophenoxy) -2,2- bis- (p-amidinophenoxymethyl)propane (TAPP-H) and related compounds, including halo-derivatives, were determined on the erythroid differentiation of murine erythroleukemic cells induced by trypsin and kallikrein. These aromatic poly-amidines and their halo derivatives were found to be strong inhibitors of both trypsin and kallikrein mediated induction of commitment of MEL cells to erythroid differentiation, hemoglobin synthesis and accumulation, globin mRNA production. No inhibitory effects were detected by treating proteinase-induced MEL cells with benzamidine. Only slight inhibitory activity was found after treatment of trypsin-induced MEL cells with other antiproteinase compounds widely used in the control of proteinase-dependent functions, including leupeptin, antipain and Bowman-Birk proteinase inhibitor. MEL cells induced to erythroid differentiation by proteinases could be proposed as an experimental system to test the biological activity of proteinase inhibitors.

Amidines↗
PubMed1989

N-myc activation by proviral insertion in MCF 247-induced murine T-cell lymphomas.

N-myc proto-oncogene rearrangement was found in three out of six AKR murine T-cell lymphomas induced by the highly oncogenic MCF 247 MuLV. Molecular analyses showed that structural modification of the proto-oncogene in all three lymphomas was in the consequence of MCF 247 proviral integration within the gene III exon. All integrated proviruses have the same transcriptional orientation as the N-myc gene. As a consequence of proviral insertion, the N-myc gene becomes transcriptionally active, producing an abnormal mRNA. These findings suggest a possible causative role of such an integrative event in murine T-cell lymphomagenesis.

Amino Acid Sequence↗
PubMed1988

Induction to erythroid differentiation of K562 cells by 1-beta-D-arabinofuranosylcytosine is inhibited by iron chelators: reversion by treatment with hemin.

Erythroid differentiation of human leukemic K 562 cells is inhibited by the iron chelator desferrioxamine (DF). In addition, desferrioxamine induces an increase of uptake of hemin. When hemin is added to the culture medium, the DF-mediated inhibitory effects on erythroid induction are reversed. Briefly, hemin allows hemoglobin synthesis by K 562 cells induced to erythroid differentiation by 1-beta-D-arabinofuranosylcytosine (ara-C) and treated with 12.5 micrograms/ml DF. In addition, it was found that hemin treatment leads to a reversion of inhibition of K 562 cell proliferation mediated by 50-75 micrograms/ml DF. This effect of hemin was also detected in other cultured human tumor cell lines (B-lymphoid, erythroleukemic and from breast carcinomas, melanomas and kidney carcinomas).

Cell Differentiation↗
PubMed1988

Differential effects of benzamidine derivatives on the expression of c-myc and HLA-DR alpha genes in a human B-lymphoid tumor cell line.

In this paper, we report the effects of aromatic tetra amidines (TAPP-H) on cell growth and gene expression of a B-lymphoid human tumor cell line, WI-L2. The results obtained give evidence (a) for inhibition of cell proliferation by TAPP-H; (b) for stronger antiproliferative activity of TAPP-halo derivatives; (c) for TAPP-mediated inhibition of accumulation of c-myc RNA sequences but not of HLA-DR alpha mRNA and DR antigens. These results suggest that this class of antiproliferative compounds exhibit differential effects on cell-cycle specific and differentiation specific genes. In addition, also TAPP-related compounds containing 2 (DAPP) or 3 (TAPB) benzamidine residues retain inhibitory activity on the proliferation of WI-L2 cells. These latter compounds might be proposed as useful substrate in the synthesis of drug-conjugated monoclonal antibodies or growth factors.

Amidines↗
PubMedDate not supplied

Inhibition of 'in vitro' tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity.

Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene. After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA. We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects on in vitro cultured cells.

Amidines↗