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G Prodi

Publications and source records attributed to G Prodi.

106 records · Page 6Linked to original sources

Interferon-mediated enhancement of metastasis. Are MHC antigens involved?

The relationship between major histocompatibility complex (MHC) antigens and metastasis was investigated on B16 melanoma variants. B16 cell lines express low amounts of murine MHC (H-2) antigens. A high expression can be induced in line B16-A by in vitro treatment with immune interferon (IFN-gamma) or by in vivo transplant in allogeneic mice. The increase of H-2 antigens correlated with an enhancement of lung colonization in young syngeneic mice. The higher metastatic capacity of B16-A cells with induced high levels of H-2 antigens was observed also in adult mice and in young mice pretreated with cyclophosphamide. These results were confirmed investigating the behaviour of a mutant B16 clone (B78H1) which was selectively resistant to the H-2-inducing action of IFN-gamma: lung colonization ability was not increased by IFN pretreatment. The study of variants derived from individual B16-A lung colonies revealed a wide range of H-2 levels. Variants with a low expression had a low colonization ability; one out of two variants with a high H-2 expression also was poorly colonizing. IFN-gamma-mediated H-2 expression appeared to act as an enhancer, rather than a determinant of B16 metastatic capacity.

Animals↗

TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma.

A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 +/- 1 days; it did not show significant transplant immunogenicity in syngeneic animals; it was able to give rise to both spontaneous lung metastases and artificial lung colonies; it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (10(6) cells killed 100 per cent DBA/2 mice in 58 +/- 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia.

Animals↗

High-metastatic clones selected in vitro from a recent spontaneous BALB/c mammary adenocarcinoma cell line.

The metastatic TS/A line has been recently derived from a spontaneous BALB/c mammary tumor. When TS/A cells were cultured in 0.33 per cent agar, two morphologically distinct types of colonies were observed from which two sets of clones were obtained. E clones were derived from small, transparent colonies, whereas F clones were from large, thick, actively growing colonies. All the clones were tumorigenic in syngeneic BALB/c females. However, E clones showed higher ability than F clones to metastasize spontaneously to the lung. Comparison between E and F clones shows that the high level of spontaneous metastasization to the lung is associated with epithelial-like in vitro growth pattern, spontaneous dome formation and growth pattern in 0.33 per cent agar cultures. The ability to give rise to lung colonies following intravenous inoculation is not a predictive parameter for the spontaneous metastatic potential.

Adenocarcinoma↗

Lymphocyte functions in the rat spleen at various times after urethan administration.

The effect of urethan on various spleen-lymphocyte functions was studied in the rat for 45 days after administration of the carcinogen. For 3 days following the last injection of urethan, the total cell number and LPS reactivity were greatly reduced. Certain reactivities, probably T-cell dependent functions, such as responsiveness to the in vitro mitogenic effect of PHA, Con A, and primary stimulation by histocompatibility alloantigens in the one-way reaction, were selectively enriched during the first 2 days. Thereafter several dissociations of these lymphocyte functions can be observed: i.e., various intervals succeed during which one function may be enriched and other(s) diminished. It seems that the kinetics of enrichment, decay and recovery of the T-cell subsets involved in the reactions investigated follow a distinctive profile for each one of them. It is suggested, as a working hypothesis, that the unbalanced situations derived from the time-course discordance of the quantitative changes in the various lymphocyte functions may allow, or even enhance, tumor development.

Animals↗

Are colony-stimulating factor-producing cells facilitated in the metastatic process?

The relationship between production of Colony-Stimulating Factor (CSF) and metastasis has been investigated in the TS/A murine model. CSF production was determined in TS/A cell variants isolated through serial in vivo selection of lung metastatic nodules induced by intravenous or subcutaneous injection of tumor cells (artificial and spontaneous metastases, respectively). All the cell variants selected for high artificial metastatic ability produced higher amounts of GM-CSF in vitro and stronger haematological alterations in vivo than cells obtained by serial selection of spontaneous metastases. Our data suggest that the late, rather than the early, steps of the metastatic process could be enhanced by GM-CSF production.

Animals↗

Epirubicin-induced differentiation of human neuroblastoma cells in vitro.

On the basis that inhibition of cell proliferation may play a role in the differentiation process, we have studied the effect of the antineoplastic drug epirubicin, an antibiotic of the anthracycline group, on human neuroblastoma cell lines SK-N-MC, SK-N-SH, SJ-N-KP, TS12 and AF8. Epirubicin induced morphological and biochemical differentiation in these cultured cell lines; treatment with it stimulated the outgrowth of neurites and increased acetylcholinesterase activity.

Acetylcholinesterase↗

The in vitro effect of epirubicin on human normal and leukemic hemopoietic cells.

Epirubicin, at concentrations ranging between 10(-7) and 10(-13) M, was assayed in semisolid cultures of human normal hemopoietic cells and in liquid cultures of 5 different human leukemic cell lines. The growth of all normal hemopoietic progenitor cells was inhibited by the higher drug concentrations; at the lowest concentration, only CFU-E and 7th-day CFU-GM were not inhibited. On the other hand, leukemic cells were sensible only to the higher concentration of epirubicin, which, nevertheless, was not fully inhibitory. Leukemic cell differentiation was not promoted by the drug, as evidenced by a panel of monoclonal antibodies, by cytochemistry and by functional tests. These results suggest a marked in vitro myelotoxicity of epirubicin, that does not appear to be compensated by a powerful control of leukemic cell proliferation.

Antibodies, Monoclonal↗

Inhibition and potentiation of T lymphocyte response to mitogens. Studies using two mitogenic stimuli simultaneously.

Rat thymocytes were stimulated with phytohaemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS) or with mixtures of two of these mitogens, added simultaneously to in vitro cultures. Four-five concentrations of first mitogen were matched with four-five concentrations of second mitogen, in all possible combinations. Synergistic effects were observed with LPS plus PHA and LPS plus PWM and inhibitory effects with PHA plus Con A and LPS plus Con A. The hypothesis is discussed that an inhibitory effects occurs when two mitogens react with identical or very similar receptors on the lymphocyte surface, while a synergistic effect is produced by two mitogens reacting with different receptors.

Animals↗

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↗

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↗