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N Olea

Publications and source records attributed to N Olea.

69 records · Page 4Linked to original sources
PubMed1989

Negative controls of cell proliferation: human prostate cancer cells and androgens.

LNCaP cells represent a useful tool to explore the mechanism of sex hormone action on cell proliferation in an "in culture-in animal" model. Results indicated that: (a) these cells were inhibited from proliferating for extended periods (up to 30 days) when placed in charcoal-dextran-stripped sera; they remained, however, viable because they proliferated when sex hormones were added to this medium; (b) the inhibitory effect of sera was reversed by the addition of 5 alpha-dihydrotestosterone at 3 x 10(-10) M, 17 beta-estradiol at 3 x 10(-8) M and higher concentrations, and progesterone at 3 x 10(-10) M and higher concentrations; (c) while the dose response to androgens was biphasic (i.e., 5 alpha-dihydrotestosterone at concentrations higher than 3 x 10(-10) M resulted in progressively lower cell yields), estrogens and progestagens exhibited a monophasic pattern; (d) these cells were exceedingly sensitive to the nutritional environment in which they grew; (e) while these cells have androgen receptors (68 fmol/mg protein; Kd = 2 x 10(-9) M), estrogen and progestagen receptors could not be detected by biochemical and immunocytochemical techniques; (f) tumors grew at the site of inoculation in castrated nude mice carrying 17 beta-estradiol and progesterone pellets and in intact male nude mice implanted with placebo pellets, while tumors did not grow in castrated nude mice implanted with a 5 alpha-dihydrotestosterone pellet. Taken together the data collected are compatible with the following conclusions: (a) the proliferative response in LNCaP cells seems not to be directly mediated by their intracellular androgen receptors; (b) plasma-borne trypsin-sensitive inhibitors of the proliferation of these cells (androcolyone I) appear to play a significant role in the proliferative event; (c) natural and synthetic androgens, estrogens, and progestagens cancelled the inhibition by charcoal-dextran-stripped human sera; (d) only androgens were able to trigger an inhibition of cell proliferation (shutoff effect) at concentrations higher than those that affected maximal cell yields (direct negative hypothesis); and (e) a faulty shutoff response is probably a crucial event for the tumorigenesis of these human prostate cells.

Adenocarcinoma↗
PubMed1989

[Proliferation and liberation kinetics of the tissue polypeptide antigen of MCF-7 cells. Hormonal influence].

The presence or absence of tissular polypeptide antigen (TPA) in the culture medium of hormone dependent breast cancer tumoral cells, the relationship between TPA concentration and cellular proliferative activity, have been investigated as well as whether TPA levels change in response to steroid preparations or the action of different antiestrogens. Results show that in MCF-7 cell line culture media, proteins antigenically related to TPA can be detected in concentrations which parallel the number of cells in culture. Consequently, TPA can be considered a cell proliferation marker. Hydroxy-tamoxifen at a concentration of 10(-7) M inhibited both cell proliferation and TPA antigen release, while the relative proportion between number of cells (valued by DNA quantification) and TPA concentration remained unchanged.

Cell Division↗
PubMed1987

[Proliferation kinetics of MCF-7 cell cultures. I. Relative influence of estrogens and antiestrogens on the growth of the cell population].

The cellular hormone dependent cell line MCF-7 is a tumoral model of mammary cancer the growth kinetics of which operating under the influence of varied and opposed hormonal factors (estrogens and antiestrogens at precise concentration levels) has provided the means of knowing the action mechanisms of such agents. In this study, carried out with cultured MCF-7 cells under well defined experimental conditions, it has been shown that: 1) antiestrogens (OH-TAM) seem to be opposed to the growing process of the cellular population the elements of which, under the influence of OH-TAM, double the value of the parameter TD (Doubling Time); 2) estrogens (17-beta-E2) cancel out this effect and promote the growth of MCF-7 cells whether OH-TAM is previously or simultaneously added to the culture medium; 3) the observation of this estrogenic action needs accurate experimental conditions without which the effect may not be seen.

Cell Division↗
PubMed1987

[Proliferation kinetics of MCF-7 cell cultures. II. Synchronization and cell recruitment induced by hormones].

The culture of MCF-7 cells in well known experimental conditions and the analysis of the cellular uptake of 3HTdR under the influence of estrogens (17-beta-E2) and antiestrogens (OH-TAM) at precise concentration levels (10(-6)/10(-9) M) have made possible the study of the growing kinetic process of the cellular cultured population and the determination of the action of such hormonal preparations on the same process. The main findings are as follows: the growing rate of the cultured cells appears to slow down in presence of OH-TAM; the reason for this slowing growth seems to be the "blockade" of the cultured cells in the last part of G1 phase, a phenomenon that has proved to be dose-dependent; by the stimulating effect of the 17-beta-E2, the MCF-7 cells, synchronized in G1, progress simultaneously in their vital cycle during, at least, three divisory cycles; and this "recruitment" effect seems to be characteristic of the estrogen since the synchronization process fades or disappears when the 17-beta-E2 is absent from the culture medium.

Cell Division↗
PubMed1985

[Determination of estrogen and progesterone receptors in cancer of the breast. Frequency of presentation and prognostic significance].

The assay of estrogen and progesterone receptors (RE and RP) is used to know the hormone dependency of breast tumors and to predict the response to endocrine therapy. In this study 68 per 100 of the patients were RE(+) within a range of 5 to 180 fmol/mg, and 45 per 200 were RP(+) between 10 and 400 fmol/mg. The frequency and concentration increase with age. Significative variations were not observed in RE(+) for either frequency or concentration between primary and metastatic samples. There is a correlation between phenotypes RE(+) and RE(-) and histopathologic prognostic features.

Breast Neoplasms↗
PubMed1985

[New method for the determination of estrogen and progesterone receptors in human breast cell lines].

A method for the determination of estrogen and progesterone receptor levels in human mammary cell lines (MCF-7, Cama-1, ZR-75-1, Evsa-T and HBL-100) is described. Cells cultured as monolayers were incubated with the tritiated steroids, [3H]-17 beta-Estradiol or [3H] ORG-2058. Binding of steroids to receptors was a function of cellular uptake. Incubation periods of 50 min were sufficient to attain maximum intracellular incorporation. The binding of 17 beta-E2 and ORG-2058 to MCF-7 cells, a phenomenon which is saturable at low concentrations for the radioactive ligand, is a linear function of the number of cells assayed (Interval: 2.5 X 10(4) to 1.5 X 10(6) cells per well). Binding data and their Scatchard plot allowed for the calculation of affinity and capacity values. Thus, for ER, Kd = 2.0 +/- 0.5 X 10(-10) M and n = 3.76 +/- 0.91 Fmol/microgram DNA, and for PgR Kd = 2.0 +/- 0.2 X 10(-10) M and n = 14.02 +/- 2.30 Fmol/microgram DNA (Mean +/- SD). Binding specificity of 17 beta-Estradiol and ORG-2058 to MCF-7 cells was analysed by means of study on the inhibitory effect of increasing concentrations of unlabelled competitors: 17 beta-Estradiol, ORG-2058, Estrone, DES, R-5020, Cortisol, Androsterone and Testosterone. Only pharmacological doses of some of the mentioned molecules produce displacement of the hormonereceptor binding. This phenomenon appears to be related to the affinity of these chemical compounds for the receptor macromolecules to which estrogens and progesterone bind.

Binding, Competitive↗
PubMed1982

[Pharmacokinetics of theophylline in infantile bronchial asthma. Clinical findings].

Authors have studied pharmacokinetic parameters of theophylline in a sample of 21 children with bronchial asthma, through evolution of plasmatic concentrations, evaluated by RIA, in order to appreciate therapeutic response to it depending on the time-variation of such concentrations. They have determined that theophylline's kinetic obeys to a "depending dose" reaction represented by Michaelis-Menten equation. This induce them to refuse those therapeutic methods based on the establishment of maintaining doses depending on drug clearance, as minimal increases in posology can give spectacular decreases of drug clearance. They have also seen that great amplitude of individual variation for pharmacokinetics parameters of theophylline, in intra-patient studies is very short.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

[Perspectives on endocrine disruption].

Two decades ago, reports of alterations in the reproductive function of some wild animal species and clear evidence of human and animal exposure to chemical substances with hormonal activity agonist and antagonist generated what is known now as the hypothesis of endocrine disruption. This is an emerging environmental health problem that has challenged some of the paradigms on which the control and regulation of the use of chemical compounds is based. The need to include in routine toxicology tests new research objectives that specifically refer to the development and growth of species and to the homeostasis and functionality of hormonal systems, has served to complicate both the evaluation of new compounds and the re-evaluation of existing ones. The repercussions on regulation and international trade have not taken long to be felt. On both sides of the Atlantic, screening systems for endocrine disrupters have been designed and established, and research programmes have been launched to characterise and quantify adverse effects on human and animal health and to develop preventive measures.

Animals↗
PubMedDate not supplied

Inadvertent exposure to xenoestrogens in children.

This article reviews previous studies and presents new data on pesticide exposure in order to provide some indications of the extent and significance of childhood exposure to xenoestrogens, including pesticides, epoxy resins, and polycarbonates. After more than four decades of pesticide use, little is known about their adverse effects on health. There is a need to address the potential risks associated with the current contamination of water, soils, and foods in many agricultural areas. In southeastern Spain, along the Mediterranean coast, extensive areas alongside residential zones are devoted to intensive farming in plastic greenhouses, with the use of large amounts of pesticides. Human tissue samples have been investigated for pesticide residues. Samples of fat from children living in farm areas contained a total of 14 pesticides, including lindane, HCH, heptachlor, aldrin, dieldrin, endrin, endosulfan, o,p'-DDE, and o,p'-DDD, among others. Of the 113 samples studied, 43 were positive for one or more pesticides, some of which have estrogenic activity. The number of new substances that mimic the action of endogenous estrogens is increasing rapidly. These endocrine-disrupting chemicals are not restricted to pesticides. Several different compounds used in the food industry, in plasticizers, and in dental restorations are also estrogenic. The few studies that have investigated their effects in humans all indicate that concerns are warranted. If there is indeed an association between zexposure to substances with hormone-disruptive activity and certain disorders of sexual maturation, the incidence of such disorders should be greater in areas where exposure to agents with this activity is high. We used a spatial ecological design to search for variations in orchidopexy rates and to analyze relationships between these differences and geographical variations in exposure to pesticides. Our results are compatible with a hypothetical association between exposure to hormone-disruptive chemicals and the induction of cryptorchidism. Several methodological limitations in the study design make it necessary to evaluate the results with caution. In conclusion, a closer scrutiny is required to determine whether epoxy resins and polycarbonates contribute, together with estrogenic pesticides, to the exposure of human consumers, especially children, to xenoestrogens.

Adipose Tissue↗