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Y de Launoit

Publications and source records attributed to Y de Launoit.

81 records · Page 5Linked to original sources
PubMed1988

Prevention of ovarian damage induced by cyclophosphamide in adult female mice by hormonal manipulations.

Doses of 10 or 20 mg cyclophosphamide/kg body weight were administered daily to mice for up to 20 days. This caused significant reductions in the incidence of prenatal (developing) follicles and significant increases in atretic (degenerating) follicles within the ovaries. Attempts to prevent cyclophosphamide-induced damage by simultaneous treatment with oestrogen alone, oestrogen plus progesterone, or danazol (a synthetic androgen) demonstrated that danazol effectively prevented the ovarian damage. The efficacy of danazol was considered to be due to its ability to inhibit LH/FSH secretion and, indirectly, the development of new ovarian follicles.

Animals↗
PubMed1987

Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor.

The MXT tumor is an experimental mammary neoplasm which is maintained by serial transplantation using B6D2F1 mice, and which contains significant amounts of estrogen and progesterone receptors. The aim of the present study is to examine the effects of ovariectomy (OVX) or ovariectomy plus hypophysectomy (OVX-HX) on both the macroscopic growth and the cell proliferation of this tumor. This cell proliferation was evaluated by means of in vivo tritiated thymidine autoradiography. In addition, we investigated the effects of a GnRH analog (Gonadorelin: HRF, 5-oxo-Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-hydrochloride) on MTX tumor cell proliferation on 7 day-OVX and 5 day-HX (OVX-HX) mice. The uterine luminal epithelium was chosen to monitor the methodology. Our data clearly demonstrate that there is a delay in the growth of MXT tumors grafted into hypophysectomized animals and, to a lesser degree, ovariectomized animals. With respect to proliferation, castration induced a dramatic decrease of the thymidine labelling index (TLI) in the tissue used to monitor the methodology (the uterine luminal epithemium); in contrast, no cell proliferation was induced by hypophysectomy or HRF administration. In 4-week-old MXT tumors, ovariectomy also markedly decreased the TLI within a few days of its taking place. However hypophysectomy, performed on castrated animals, induced a significant and transient increase of cell proliferation in this neoplasm, an increase which lasted from the 2nd to the 5th day following the operation. The high basal level of MXT cell proliferation recorded in OVX-HX animals decreased dramatically after the administration of HRF between 12 and 48 h prior to the sacrifice of the animals. It is concluded that the HRF exerts a direct effect on the MXT tumor cells, and this HRF might be essential for their growth.

Animals↗
PubMed1987

Effect of prolactin and estradiol on cell proliferation in the uterus and the MXT mouse mammary neoplasm.

With the use of an in vivo tritiated thymidine [( 3H]dThd) nuclear labeling followed by autoradiography, the effects at different times before sacrifice of prolactin (PRL) and/or 17 beta-estradiol (E2) were studied in C57BL X DBA/2f)F1 mice given transplants of the MXT hormone-sensitive mammary tumor whose growth was previously shown to be influenced by E2 and/or progesterone. Uteri were chosen as controls for the methodology. Experiments were conducted on ovariectomized mice submitted to endocrine manipulation to achieve plasma PRL modifications. In addition to E2, the proliferation of cancer cells, assessed by the measurement of thymidine labeling indices (TLIs), was demonstrated to be enhanced by ovine prolactin (oPRL) and Sulpiride and strongly slowed down by castration and 2-bromo-alpha-ergokryptin treatment, thus emphasizing the great importance of PRL in mammary cancer development. Moreover, a pulse of 1 mg oPRL/animal produced a marked TLI rise in tumors, lasting from the 6th to the 48th hour after its injection and reaching a maximum at 24 hours. PRL had no proliferative effect on the uterine luminal epithelium. When PRL and E2 were injected concomitantly, the profile of stimulation was quite similar to that obtained with E2 alone; i.e., a maximum stimulation was observed at the 24th and 36th hours after hormonal pulse. From these data it is concluded that, in spayed mice, not only E2 but also PRL is of major importance leading to enhanced proliferation of MXT mammary neoplastic cells. Further investigations are needed to throw light on the cellular events presiding over the action of PRL and E2 at the cancer cell level.

Animals↗
PubMedDate not supplied

Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV.

The HSD17B4 gene codes for a 80 kDa multifunctional enzyme containing three distinct functional domains and is localized in peroxisomes. The N-terminal part exhibits 3-hydroxyacyl-CoA dehydrogenase and 17beta-hydroxysteroid dehydrogenase activity whereas the central part shows enoyl-CoA hydratase activity. The carboxy-terminal part of the protein has sterol-carrier-protein activity. The protein is widely expressed, however in several tissues like brain, uterus and lung its expression is limited to specific cells like Purkinje cells or luminal epithelium. The HSD17B4 gene consist of 24 exons and 23 introns with classical intron-exon junctions spanning more than 100 kbp. The importance of the HSD17B4 protein is stressed by the identification of patients with severe clinical abnormalities due to mutations in the HSD17B4 gene. We have now checked the consequences of one frequent mutation, G16 S, which results in inactivation of the enzyme due to loss of interaction with NAD+.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Comparison of biochemical and immunoenzymatic macromethods and a new immunocytochemical micromethod for assaying estrogen receptors in human breast carcinomas.

Estrogen receptors (ERs) were assayed in 23 breast carcinomas by: (1) the conventional biochemical assay with dextran-coated charcoal (DCC); (2) the immunoenzymatic assay using a monoclonal antibody (MAb), ER-EIA (Abbott); and (3) an original cytochemical method using another MAb, ER-ICA (Abbott). The first two techniques were performed on biopsy samples, whereas the last was carried out on fine needle aspiration (FNA) samples. The ER contents in aspirates were evaluated by: (1) scaled proportions of colored neoplastic cells; (2) scaled coloration intensity; (3) total grading (= proportion plus intensity); (4) product grading (= proportion times intensity); and (5) a new index (NI) described in this paper. The ER-EIA assay correlated best, with a high statistical significance, with the NI (P less than .001); NI was also the only index that significantly correlated (P less than .05) with the DCC results. The results show that the ER-ICA assay offers the great advantages of being applicable to FNA specimens and of producing rapidly available results. This new technique enriches the panel of MAbs for the diagnosis of adenocarcinomas and offers a new tool for the therapeutic follow-up of breast cancer patients. Our preliminary results suggest that the anti-ER MAbs might be helpful for measuring the hormone dependence of small lesions not assayable by DCC, even under endocrine therapy, thus avoiding false-negative assays.

Antibodies, Monoclonal↗
PubMedDate not supplied

In vitro influence of estradiol or progesterone on the thymidine labeling indices of human benign breast tumors.

Using an in vitro tritiated thymidine (3H-dThd) nuclear labeling followed by autoradiography, the effects of 17-beta-estradiol (E2) or progesterone (Pg) on cell proliferation were studied in 22 human benign breast tumors, i.e. 7 fibroadenomas 8 fibrocystic dysplasias 4 gynecomastias and 3 phyllodas. Small tumor fragments were incubated in a chemically-defined medium without serum and were hormonally stimulated in vitro. The procedure used allowed discrimination between weak labeling, suggestive of DNA repair mechanism, and strong labelling, suggesting a true DNA synthesis (S phase). Taking this into account, our results have shown that both estradiol and progesterone can induce in vitro cell replication of both ER+PgR+ and ER-PgR- human breast fibroadenoma, without affecting those of fibrocystic dysplasia, gynecomastia and phylloda. Progesterone, but not estradiol, might significantly decrease DNA repair mechanism in fibrocystic dysplasia, according to the Pg-induced decrease of nuclear incorporation of small amounts of 3H-dThd. We have thus characterized a dynamic test of hormone dependence which permits in vitro study of the hormonal sensitivity of human benign breast tumors, as well as that of any other human neoplasm. This test could be of great value to help clinicians to diagnose and treat hormone-dependent neoplasms properly. Its clinical relevance is now under study.

Autoradiography↗
PubMedDate not supplied

Effect of estradiol -17- beta (E2) on cell proliferation in the uterus and the MXT mammary tumor borne by intact, ovariectomized and/or hypophysectomized mice.

The aim of the present work was to study the effects of estradiol (E2) on cell proliferation in well-differentiated mammary MXT tumors borne either by intact (INT), or by castrated (OVX), or by hypophysectomized (HX), or by castrated and hypophysectomized mice) OV-X-HX). Ovariectomy and hypophysectomy were performed, respectively, 6 days and 5 days before the sacrifice of animals bearing tumors during a 28 day period. Cell proliferation was measured by using an in vivo nuclear labeling with tritiated thymidine (3H-TdR) followed by autoradiography. Uteri were used as controls for the methodology. Our data demonstrate that E2 exerts a significant and transient stimulatory effect on cell proliferation in the uterine luminal and glandular epithelia of OVX or OVX-HX adult mice. This mitogenic enhancement is significantly higher in OVX-HX mice than in the other experimental groups. In MXT tumors, a significant increase of cell proliferation is induced by E2 in INT or OVX mice; however, no enhancement occurs after HX performed either in intact or in castrated mice. In the latter situation (HX), a dramatic increase of basal cell proliferation rates is consistently observed in tumors, as compared to those levels observed in INT or in OVX animals. The paradoxical increase in basal proliferation rates of MXT mammary tumors in HX animals was not suppressed by administration of ovine prolactin. This suggests that other hypothalamo-hypophysial factors might be endowed with direct inhibitory influence on growth of the MXT tumors.

Animals↗
PubMedDate not supplied

A new assay to evaluate cell growth and drug sensitivity in culture using a cell image processor.

The use of a cell image processor for the in vitro assessment of drug effects on cell growth, cell kinetics and chromatin organization is described. We have studied the influence of two well documented cytotoxic drugs, i.e. BCNU and vincristine (VIN), on the above mentioned parameters of the P-388 mouse leukemia, MCF-7 human mammary and HBL human melanoma cell lines. The cells were cultured for 1 to 4 days on glass coverslips put in Petri dishes containing or not (control) 10, 1 or 0.1 microgram/ml medium of the drug, after which they were fixed for histology, Feulgen-stained and analyzed through a cell image processor, i.e. the System for Analytical Microscopic Biomedical Applications (SAMBA 200). Our results showed that both BCNU and VIN exerted a well-known antineoplastic effect that was assessed at three different but highly complementary levels on the same sample of cells in a very rapid and simple procedure.

Animals↗