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Biomedical subjects

G Sica

Publications and source records attributed to G Sica.

At least 73 records · Page 4Linked to original sources

Antiproliferative effect of interferons on human prostate carcinoma cell lines.

The effect of purified human fibroblast beta-interferon (B-IFN) and recombinant alpha-2b-interferon (A-IFN) on cell proliferation was investigated in two human prostate carcinoma cell lines, named PC-3 and DU-145. Both cell lines respond to the antiproliferative action of interferon, B-IFN being more effective than A-IFN. PC-3 is more sensitive than DU-145 cell line, showing 95% inhibition of cell proliferation at the highest concentration of B-IFN. As interferons, besides reducing cell growth, are able to modify steroid receptor content in different hormone-sensitive human tumours, our results may be of some relevance as these drugs might be used to regulate both cell proliferation and hormone-sensitivity in prostate cancer.

Cell Division↗

Hormonal modulation of brain tumour growth: a cell culture study.

Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.

Aged↗

Morphometry of in vitro systems. An image analysis of two human prostate cancer cell lines (PC3 and DU-145).

Morphometric analysis on two human prostate cancer cell lines (PC3 and DU-145) was carried out to better characterize these cells and to approach some problems concerning their polymorphism. In our hands, these cells appear to differ either in their ability to oxidize testosterone or in their androgen receptor content. Morphometric evaluation was performed by means of an Interactive Image Analysis System (IBAS 1), which computes several parameters related to the whole cell and to the nucleus. Our results clearly indicate that nuclear parameters alone may discriminate PC3 from DU-145 cells. Particularly, the Nuclear Roundness Factor appeared important, since it quantifies changes in nuclear shape. Nevertheless, the value of this parameter for "in vitro" morphometry may be overshadowed by the polymorphism common to the cultured cells. However, morphometric evaluation of PC3 and DU-145 cells is relevant to a better understanding and definition of the biologic nature of these cells, even if polymorphism, heterogeneity and genetic instability, specially of PC3, require further investigations.

Cell Nucleus↗

In vitro effects of beta-interferon on steroid receptors and prostaglandin output in human endometrial adenocarcinoma.

The effect of natural beta-interferon (beta-IFN) on steroid receptor levels and output of prostaglandins (PGs) was investigated in human endometrial cancer. beta-IFN determines in endometrial adenocarcinoma explants an increase of cytosolic estradiol (ER) and progesterone (PR) receptors at concentrations ranging from 10 to 1000 IU/ml of culture medium. Only cases in which there was an enhancement of at least 50% with respect to control values were considered. Low concentrations of beta-IFN (10 IU/ml of culture medium) produce an enhancement of ER in 60% and of PR in 42% of cases, while higher concentrations of beta-IFN (1000 IU/ml of culture medium) produce an enhancement of ER in 32%, and of PR in 82% of cases. Since PGs are involved in proliferation control in a large variety of tumors, we evaluated the ratio between PGF2-alpha and PGE2 levels in culture medium. This ratio increased, in our experimental model, after treatment with 10 and 1000 IU/ml of beta-IFN in 38% and 58% of cases respectively. Our data suggest that beta-IFN could affect cellular hormone sensitivity through a modification of ER and PR and it can also determine a variation of PG output in human endometrial cancer.

Adenocarcinoma↗

Effect of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells.

The effect of natural beta-interferon (beta-IFN) on cell proliferation and steroid receptor level was investigated in CG-5 human breast cancer cell line. beta-interferon determines an appreciable diminution of cell growth, at concentrations ranging from 100 to 1000 IU/ml, which is enhanced when serum content of the culture medium is lowered. Low concentrations of beta-IFN (10-100 IU/ml) produce, after a 5-day treatment, an increase in estrogen receptors (ER) and progesterone receptors (PR). No variation of ER and PR levels is observed when beta-IFN is added directly to the cell homogenate before the assay. Our data suggest that beta-IFN could affect hormone sensitivity through a modification of ER and PR in neoplastic mammary cells.

Breast Neoplasms↗

Estrogen responsive creatine kinase in human breast cancer cells.

The brain type (BB) isoenzyme of creatine kinase (CK) is a very sensitive marker of estrogen action in rat uterus and in experimental mammary tumors. In order to detect useful markers for estrogen dependent human breast cancer cell proliferation we measured CK levels and isoenzyme composition in the CG5 cells, an estrogen supersensitive variant of the MCF-7 human breast cancer cell line. Under basal conditions, CK-BB accounted for 10%-15% of total enzymatic activity, while the MM isoenzyme represented the overwhelming component. In cells cultured in the presence of 5% charcoal-treated fetal calf serum, physiological concentrations (0.1-1 nM) of estradiol increased CK-BB levels in a dose- and time-related fashion. The effect was specific for estrogens and was prevented by antiestrogens. Our results show that CK-BB is estrogen regulated in the CG5 cells and suggest a possible role for this enzyme as an additional marker of the hormonal responsiveness of breast cancer.

Breast Neoplasms↗

Malignant fibrous histiocytoma. Report of a case and review of the literature.

Malignant Fibrous Histiocytoma is a sarcoma characterized by two different principal cell types, which has its origin in mesenchymal undifferentiated clones. So it must be included in the differential diagnosis of the very rare primary breast tumors with stromal origin. The review of available literature allows us to define the histopathological and biological peculiarities of this kind of tumor and it confirms the extreme malignity and rarity of the case we observed.

Breast Neoplasms↗

Estrogen stimulates cell proliferation and the increase of a 52,000 dalton glycoprotein in human breast cancer cells.

In an estrogen supersensitive variant of the MCF-7 cell line, CG-5, estrogen was found to stimulate the labelling of a glycoprotein released into the culture medium which has the same electrophoretic migration pattern as that previously reported in MCF-7 cells (Biochem. Biophys. Res. Commun., 90: 410-416, 1979). To test the possibility that the 52 K is a marker of estrogen-dependent breast cancer cell proliferation, we have correlated the effect of estrogen and antiestrogen on protein labelling and cell proliferation under different experimental conditions. In cells cultured in the presence of 5% charcoal-treated fetal calf serum, physiological concentrations (0.1-1 nM) of estradiol stimulated in a dose- and time-related fashion both 52 K labelling and cell proliferation. However at high concentrations (10-100 nM) estrogen decreased 52 K labelling while it still stimulated cell proliferation. Concentrations of the tamoxifen derivative, 4-hydroxytamoxifen, which effectively prevented estrogen-stimulated cell proliferation also blocked estrogen-stimulated increase of 52 K labelling. Time-course experiments suggest that the estrogen-stimulated increase of 52 K labelling (detectable after 22 h of hormone exposure) precedes the effect of cell proliferation (detectable after 3 days of hormone exposure). In cells cultured under serum-free conditions there was no effect of estradiol at any of the concentrations and times used on either 52 K labelling or cell proliferation.

Breast Neoplasms↗

Tamoxifen induced membrane alterations in human breast cancer cells.

It was previously shown that proliferation of CG-5 cells, an estrogen supersensitive variant of the MCF-7 cell line, is inhibited by tamoxifen starting three days after addition to culture medium. In this paper we report here on the effect of tamoxifen on CG-5 cell membrane morphology using scanning electron microscope. The addition of the antiestrogen to CG-5 cells causes marked alterations of cell surface, consisting of reduction in the length and the number of microvilli. Moreover, cells appear flattened and of reduced thickness. These modifications are more pronounced in cells plated at low density, but they are observed also in nearly confluent monolayers. In this case alterations are more evident in the center of cell islands, while at the periphery there is a certain mobility as reflected by the persistence of few microvilli and philopodia. These early effects of tamoxifen on cell membrane raise the possibility that parallel modifications in membrane function may occur which are responsible for alterations impairing transport mechanisms.

Breast Neoplasms↗

Two new estrogen-supersensitive variants of the MCF-7 human breast cancer cell line.

Two new estrogen-sensitive variants of MCF-7 human breast cancer cells, CG-4 and CG-5, are described in this report. These cells were derived from a casual contamination by MCF-7 cells of primary cultures from a human adenocarcinoma of the breast and a pleural effusion of a patient with advanced breast cancer, respectively. Careful characterization of these variants revealed chromosomal properties highly similar to and alloenzyme phenotypes identical to those of MCF-7 cells which were simultaneously cultured in the laboratory. MCF-7, CG-4 and CG-5 cells were tested for estrogen responsiveness under identical growth conditions, that is in the presence of culture medium supplemented with 5% charcoal-treated serum. While the number of MCF-7 cells increases by about 40% over the controls in the presence of physiological concentrations of estradiol, the number of CG-4 cells doubles and the number of CG-5 cells triples. All these cell lines have approximately the same number of estrogen, androgen, glucocorticoid, and progesterone receptor sites/cell. Since several difficulties arise in demonstrating the estrogen responsive growth stimulation of currently available human breast cancer cells, these two new variants, characterized by a high and reproducible estrogen responsiveness, afford a new model for studying the mechanisms by which estrogen regulates cell proliferation. The problems related to the careful characterization of every established cell line are discussed.

Adenocarcinoma↗

Presence and steroid inducibility of glutamine synthetase in human leukemic cells.

Glutamine synthetase (EC 6.3.1.2; GS) is present in lymphoblasts from patients with acute lymphoblastic leukemia (ALL) as well as in normal peripheral blood lymphocytes. In 16 out of 20 ALL patients studied exposure of the cells to physiological concentrations of dexamethasone in vitro increased enzyme activity above the control levels. The increase was specific for glucocorticoid receptor ligands. A direct correlation was found between the magnitude of glucocorticoid-mediated increase of GS activity and the cellular levels of specific glucocorticoid receptors assayed in the same cell specimen. Moreover, the basal levels of the enzyme measured in cells prior to exposure to dexamethasone correlated negatively with receptor density. It is suggested that the presence of steroid-inducible GS in ALL cells may prove to be a marker for functional receptor sites.

Enzyme Induction↗

Binding of (3H)R5020 to progesterone receptor and serum contaminants in human endometrium.

The binding of [3H]R5020 to cytosol from human endometrium was utilized to evaluate the concentration of progesterone receptor by means of agar gel electrophoresis, using D-norgestrel as cold competitor. It was observed that radioligand binds predominantly to the receptor, and that serum contaminants such as albumin and corticosteroid-binding globulin do not interfere in the assay procedure.

Binding, Competitive↗