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Biomedical subjects

G Formisano

Publications and source records attributed to G Formisano.

12 recordsLinked to original sources
PubMed1991

Different effects of sequential combinations of N-methylformamide with 5-fluorouracil on human colon carcinoma cells growing in nude mice.

The effects of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on tumor growth and morphological features of human colon carcinoma cells (HT29) implanted in nude mice were assessed. Both agents were administered i.p. at tolerable doses: 5-FU at 19 mg/kg for 5 days and NMF at 200 mg/kg for 12 days. Four main schedules were tested: 5-FU alone, NMF alone, NMF followed by 5-FU and 5-FU followed by NMF. The last sequence was the most effective, as compared with the other treatment regimens. In particular, the 5-FU----NMF combination induced a tumor inhibition of about 75% at the end of the treatments (17th day) versus an inhibition of 23%-43% in the other schedules. Morphological observations, carried out by light and electron microscopy, indicated a possible relationship between the presence of structural changes and tumor growth inhibition. The results of this study renew interest in the use of NMF in sequential combination confirming sequence as a critical factor for the optimal combination of NMF and 5-FU.

Adenocarcinoma↗
PubMed1989

Morphologic changes induced in vitro by 2,5 hexanedione.

The effects of 2,5 hexanedione (2,5 HD), a metabolite of n-hexane, were investigated in different in vitro systems. A human mammary carcinoma cell line, a human melanoma cell line, and fetal mouse neuronal cells in primary culture were considered. Light and electron microscopic observations demonstrated clearly that changes in cell proliferation can be detected. Furthermore, morphologic differentiative phenomena characterized by a noticeable increase in cell protrusions and dendriticlike processes can occur. Differences in the features of these processes were also detected between the different cell lines. These data can indicate non-neuronal cells as possible further targets of the toxicant. The possibility could be hypothesized that toxic neuropathies are generalized disorders, being neuronal system exceptionally vulnerable to 2,5 HD. Moreover, results obtained suggest that the sensitivity of in vitro systems could represent a useful tool in studying the mechanisms of action of the neurotoxicant 2,5 HD.

Animals↗
PubMed1989

Cytoskeletal changes induced in vitro by 2,5-hexanedione: an immunocytochemical study.

The effects of 2,5-hexanedione, the main metabolite of the solvents hexane and methyl butyl ketone, have been explored in different in vitro epithelial (CG5 and HEp-2) and melanoma (JR8) cells by means of immunochemistry and electron microscopy. The administration of the toxicant to the cell monolayers at noncytolytic concentrations for 24 and 48 hr exerted several effects on the cell lines studied. Most epithelial and melanoma cells detached from the substrate were in the mitotic phase, whereas cells adhering to the substrate showed time-dependent organelle changes. In fact, after treatment with 2,5-hexanedione, mitochondria appeared swollen, with distorted cristae and rarefied matrix; changes in intracytoplasmic vesicles were also detected. Cytoskeletal components were also investigated. A remarkable rearrangement of microfilaments and intermediate filaments (keratin and vimentin) was detected in a time-dependent manner. In particular, actin ruffles and intermediate filament aggregates were observed. Furthermore, the microtubular apparatus seemed to be less affected. The results here reported seem to indicate cytoskeletal components as probable targets of 2,5-hexanedione cytotoxicity in cultured cells.

Actin Cytoskeleton↗
PubMed1988

Modulation of the cytotoxic effect of 5-fluorouracil by N-methylformamide on a human colon carcinoma cell line.

The cytotoxic effect of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on cell survival of the human colon cancer line HT29 was assessed. The differentiating activity of NMF was evidenced by morphological maturation and conversion of cell culture characteristics to those consistent with a more benign phenotype. In combination experiments, the noncytotoxic concentration of 1% NMF was chosen and doses of 5-FU ranging from 5 to 25 micrograms/ml were employed. Two main schedules were tested either on exponentially or stationarily growing cells: (a) 1% NMF for 72 h followed by 12-h exposure to 5-FU; (b) 5-FU for 12 h followed by 72-h exposure to 1% NMF. The results obtained demonstrated that the 5-FU----NMF sequence determined a powerful reduction in the surviving fraction of HT29 cells, while the reverse sequence did not increase the killing effect of 5-FU given alone. Immunocytochemical and scanning electron microscopy studies seemed to confirm that the association in which the differentiating agent followed the 5-FU treatment strongly impaired cellular integrity and function and that cytoskeletal elements, particularly microfilaments, and surface structures could play an essential role in the mechanisms of cytotoxicity. Furthermore, the results of this work indicate that drug sequence is a critical factor for the optimal combination of 5-FU and NMF.

Adenocarcinoma↗
PubMed1988

In vitro effects of styrene on cytoskeletal apparatus: an immunocytochemical study.

Styrene is known as an organic solvent implicated in neurological disorders occurring in exposed workers. Our studies were focused on the effects of styrene on the cytoskeletal apparatus, involved in several toxic neuropathies. The cultured cells were considered as living systems useful to investigate the mechanisms of cytotoxicity. Preliminary results reported here were obtained on two different epithelial cell lines (CG5 and HEp-2) by immunocytochemical methods. Treatment with styrene at 0.04% and 0.08% for 24 and 48 hours, induced changes in cytoskeletal elements. In particular, styrene seemed to induce a decrease in number of cells adhering to the substrate and some alterations in microtubule assembly. Moreover, a rearrangement of the keratin filaments was observed while styrene did not seem to induce noticeable changes in actin filament network. Data obtained seem to confirm in vitro studies as a useful tool in toxicity assessment of xenobiotic compounds at subcellular levels.

Actin Cytoskeleton↗
PubMed1987

Modification of the cell surface expression of histocompatibility antigens induced by the neurotoxin 2,5 hexanedione.

Class I histocompatibility antigens (HLA) are expressed on the surface of almost all nucleated mammalian cells; the expression of this surface antigenic molecule may be changed or abrogated by several factors. In this paper, a modification in HLA expression in a human carcinoma cell line following exposure to the neurotoxicant 2,5 hexanedione is reported. This compound is known to produce a wide spectrum of subcellular pathological events; in this study, we describe an effect on the surface and cytoplasmic distribution of both light and heavy subunits of HLA antigens, demonstrated by immunocytochemical and immunoelectron microscopy techniques. Human carcinoma cells, which under normal growing conditions express the HLA, abrogate the surface expression of this glycoprotein after exposure to 2,5 hexanedione and an intracytoplasmic accumulation seems to occur. Several possibilities are discussed, such as an effect of the toxicant on the transport of the nascent glycoprotein.

Breast Neoplasms↗
PubMed1987

Cell membrane changes induced by lonidamine in human erythrocytes and T lymphocytes, and Ehrlich ascites tumor cells.

Lonidamine, a derivative of indazol carboxylic acid, has been found to exert a powerful inhibitory effect on oxygen consumption and aerobic glycolysis of neoplastic cells through mechanisms yet to be defined. Recent freeze-fracture studies have shown that Lonidamine alters the distribution of intramembranous particles in the plasma membrane, suggesting that the cell membranes, rather than the energy metabolism, are the drug's primary target. The present study was carried out to further evaluate the effects of Lonidamine on cell membranes, using normal human erythrocytes and T lymphocytes and Ehrlich ascites tumor cells as cell models. These studies indicate that plasma and mitochondrial membranes are the primary site of the drug's action, though other cell membranes seem to be affected as well. Thus, Lonidamine inhibition of energy metabolism in nucleated cells reported in previous studies must be considered as a consequence of the structural damage of the inner and outer mitochondrial membranes, which in turn affects respiration and glycolysis and then cell viability.

Animals↗
PubMed1987

In vitro effects of 2,5 hexanedione on a melanoma cell line: a morphological study.

The effect of 2,5 hexanedione (2,5 HD) on a cultured human melanoma cell line (JR8) was explored. The addition of the toxicant at noncytolitic concentrations (0.08-0.16%) to the monolayers for 24 and 48 h, resulted in an irreversible inhibition of cell proliferation. Cessation of melanoma cell proliferation was accompanied by wide changes in morphological features of cells still adhering to the substrate. Incubation with the toxicant seemed to induce a differentiative process characterized mainly by a significant increase in cell protrusions. Melanoma cells, losing their bipolar appearance, often increased cell size and developed long dendritic and axon-like processes sometimes ramified in distal portions. Electron microscopic observations established that a change in the polarized appearance of control cells often occurred with 2,5 HD treatment and that a regular arrangement of organelles and cytoskeletal elements was detectable within these dendritic and axon-like protrusions. Furthermore, immunocytochemical studies confirmed an involvement of microtubules and actin network within cell prolongations. After the differentiative process a necrotizing effect occurred, inducing a progressive loss of viable, dendritic cells after 4 or 5 days. Incubation with cyclic AMP was ineffective in control cells while after 2,5 HD treatment seemed to increase the survival rate of neuronal-like cells. Possible mechanisms for the growth inhibitory and differentiative effects of 2,5 HD were discussed.

Cell Division↗