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S Grilli

Publications and source records attributed to S Grilli.

103 records · Page 6Linked to original sources
PubMedDate not supplied

Dexamethasone modulation of in vitro growth pattern and of lung colonization ability in clones of a metastatic BALB/c mammary carcinoma cell line.

The expression of steroid receptors and the in vitro responsiveness to steroids were used to investigate the cell heterogeneity of a BALB/c mammary carcinoma cell line (TS/A) by means of its high- and low-metastatic clones previously selected in vitro. All the clones studied contained appreciable levels of receptors for oestrogens and for glucocorticoids. The in vitro responses of clones to 17 beta-oestradiol were very poor and comparable; conversely, a heterogeneous pattern of responsiveness to glucocorticoids was observed. In the presence of dexamethasone, the in vitro growth of high-metastatic clones was either unaffected or stimulated and dome formation was significantly increased. Dexamethasone treatment of low-metastatic clones caused inhibition of in vitro proliferation and a morphological shift from a fibroblast-like growth pattern towards the epithelial phenotype. One out of the three low-metastatic clones tested acquired the ability to form domes in the presence of dexamethasone, albeit sporadically. The in vitro treatment with dexamethasone significantly increased the lung colonization ability of the two low-metastatic clones studied, whereas no significant effect was observed with high-metastatic clones. Data presented here suggest that TS/A cell line consists of heterogeneous populations with peculiar proliferative and differentiative responses to glucocorticoids.

Animals↗
PubMedDate not supplied

Effects of the protease inhibitor antipain on cell malignant transformation.

BACKGROUND: Several natural products have been found to exhibit a chemopreventive activity both in in vivo and in vitro experimental systems. Among them, protease inhibitors seem to play a key role in the regulation of growth and phenotypic expression of transformed cells as well as in the regulation of the late events of carcinogenesis. We evaluated the effect of antipain (AP), a natural protease inhibitor, on chemically induced BALB/c 3T3 cell transformation, on invasion and chemotactic motility of transformed cells and on their gelatinase expression. METHODS: BALB/c 3T3 cells were plated and exposed to 2.5 micrograms/ml 3-MCA or 50 micrograms/ml, 1,2-DBE. The effect of a non-cytotoxic dosage of AP (10 microM) was studied by: a) pretreating cells with AP for 48 hours before the carcinogen exposure; b) adding AP simultaneously to the carcinogen treatment; c) chronic addition of AP at each medium change throughout the experimental duration. The effectiveness of the treatment was analysed as the ability to reduce or inhibit the occurrence of transformed foci. Modulation of the invasive phenotype by anti-transforming dosages of AP was evaluated by in vitro Matrigel invasion assay. Gelatin zymography was performed in order to assess AP regulation of proteolytic enzymes, such as metalloproteases, involved in invasion and metastasis. RESULTS: AP treatment can reduce the transformation rate both in 3-MCA- and 1,2-DBE-initiated cells. Its effectiveness depends on the administration schedule, and chronic addition seems to be the most effective treatment. The concentration of AP, which is effective in the antitransformation assay, is not able to significantly affect the migration and invasion of chemically transformed cells or their gelatinase activity. CONCLUSIONS: AP can suppress chemically induced BALB/c 3T3 cell transformation through mechanisms which do not involve modulation of the invasive phenotype.

3T3 Cells↗
PubMedDate not supplied

In vitro effects of fenretinide on cell-matrix interactions.

BACKGROUND: Understanding the molecular basis of the metastatic spread of cancer and the underlying mechanisms is crucial for the development and appropriate clinical use of novel therapeutic agents directed at prevention of metastasis. Retinoids have been reported to inhibit cell proliferation, modulate cell differentiation, enhance apoptosis and to prevent the conversion of in situ cancer to locally invasive malignancy by suppressing the invasive process as well as by inhibiting angiogenesis. Fenretinide (4-HPR), a synthetic derivative of retinoic acid, is less toxic than natural retinoids and is active in the prevention and treatment of a variety of tumours in animal models. Its efficacy in cancer chemoprevention and therapy has been investigated in clinical trials. MATERIALS AND METHODS: In order to evaluate the effects of 4-HPR on the late stages of tumour progression, chemically transformed BALB/c 3T3 cells, showing a fully malignant phenotype, were exposed to 4-HPR (0.25-10 microM; 72 hours pre-treatment) and then analysed for in vitro invasive ability. The possible mechanisms of action responsible for the anti-invasive activity of 4-HPR were investigated, analysing cellular adhesion, motility, and proteolytic capability. RESULTS: Data showed that 4-HPR significantly inhibited the invasive phenotype of chemically transformed cells; the reduction in Matrigel invasion was dose-dependent and seemed not to be related to cytotoxic effects or reduction in cell proliferation rates induced by 4-HPR assayed doses. The 4-HPR-induced decrease in chemotactic motility of transformed cells correlated well with the invasion inhibition. 4-HPR, at active concentrations, differently affected cell adhesion to the extracellular matrix, depending on the coating substrate used (laminin, collagen IV, fibronectin and vitronectin). 4-HPR treatment significantly enhanced cell adhesion to laminin, while reducing cell-vitronectin attachment. It did not modify the attachment of the cells to fibronectin and collagen IV. Zymographic analysis failed to demonstrate 4-HPR involvement in the modulation of the activity and expression of gelatine degrading enzymes. CONCLUSION: These data suggest that 4-HPR inhibits tumour cell invasion through a basement-like matrix, by suppressing chemotactic motility and by altering cell-matrix interactions.

3T3 Cells↗
PubMedDate not supplied

[Specific cytoplasmic receptors for steroid homones in benign and malignant breast diseases, in normal glandular tissue and pectoral muscle].

An improvement to the DCC (destran-coated charcoal) method for determining receptors for 17-beta-oestradiol, 5-alpha-dihydrotestosterone and progesterone in benign and malignant breast conditions, normal glandular tissue and muscular tissue is reported. Preliminary results on 16 malignant cancers and 4 fibrocystic mastopathies are discussed together with a critical review of the technique employed and the results obtained in hormone competition.

Adult↗
PubMedDate not supplied

Major discrepancies between results obtained with two different methods for evaluating DNA damage: alkaline elution and alkaline unwinding. Possible explanations.

The fluorometric assay of DNA alkaline unwinding, developed by Birnboim and Jevcak (Cancer Res 41: 1889-1892, 1981) was applied to rat liver DNA, after treatment in vivo. N-nitrosodimethylamine, for which DNA damage in rat liver has been extensively investigated, was tested as a standard compound. The results were in complete agreement (both in terms of damage and repair) with data from the literature and with our own results obtained with other methods of detecting DNA alkaline fragmentation. Sensitivity was also of the same order of that of usual methods, with the effect of 0.3 mg/Kg of N-nitrosodimethylamine being detectable. Other DNA damaging carcinogens such as 1,2-dimethylhydrazine, 2-naphthylamine and dacarbazine were also correctly detected. Compounds like nitrofurantoin, benzoin and caprolactam, which appeared clearly positive with the alkaline elution technique, but for which genotoxicity and carcinogenicity are doubtful (nitrofurantoin) or most likely negative (benzoin and caprolactam), gave negative results with this method. This is also in agreement with previous results, observed using a different approach to measuring DNA unwinding. On the basis of these and other observations, we suggest that, under certain conditions, the alkaline elution technique is perhaps not only sensitive to DNA breaks but also to changes in chromatin conformation. Unwinding methods could be more specific in the detection of DNA fragmentations.

Animals↗
PubMedDate not supplied

DNA repair after UV and gamma irradiation. I. Rat spleen cells.

An in vitro microculture was set up to standardize DNA enzymatic repair in rat spleen lymphocytes after exposure to ultraviolet or gamma rays by measuring the tritiated thymidine uptake. A relation between irradiation dose and DNA repair is always observable when cell viability and scheduled DNA synthesis are taken into account. This micromethod utilizing rat spleen cells appears to be a suitable system for such a study since it permits a satisfactory evaluation of DNA repair.

Animals↗
PubMedDate not supplied

DNA repair after UV and gamma irradiation. II. Human lymphocytes.

A technique of an in vitro microculture system has been set up in order to standardize DNA repair in adult human lymphocytes after ultraviolet and gamma irradiation measuring tritiated thymidine uptake. The results obtained in DNA unscheduled synthesis were different if ultraviolet or gamma rays were employed.

Cells, Cultured↗