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A Danguy

Publications and source records attributed to A Danguy.

At least 91 records · Page 5Linked to original sources

Histological staining by tritiated actinomycin D: a useful tool to study neoplastic cell heterogeneity and estrogen sensitivity of mammary tumors.

The MXT mouse transplantable mammary cancer is characterized by significant amounts of steroid hormone receptors. Moreover this model, as other solid tumors, contains diverse subpopulations of neoplastic cells. In the present study we have examined this pattern as well as the influence of exogenous physiologic doses of estradiol on tumor cell subpopulations. Their identification was undertaken at the morphological level employing incubation of tritiated actinomycin D with fixed material followed by autoradiography. This semiquantitative cytochemical method has proved itself to be a useful tool in order to assess the cellular heterogeneity of carcinoma cells.

Animals↗

Tritiated actinomycin-D staining method: a valuable tool to study oestrogen receptor-induced modifications of transcriptional activity in normal and neoplastic cells.

Exposure at 4 degrees C of purified cell nuclei from uterus and hormone-sensitive mammary cancer to their own cytosol preincubated with oestradiol produced a significant increase in their ability to bind [3H] actinomycin D (3H-AMD). This increase did not occur under conditions preventing the transfer of the oestrogen-receptor into the cell nucleus, nor in cancer cell nuclei devoid of oestrogen-receptors. Uterine cytosol preincubated with the strong antioestrogen 4-hydroxytamoxifen did not modify the 3H-AMD binding capacity of the uterine nuclei but significantly suppressed the increase induced by oestradiol. Moreover, ultrastructural study of tumour nuclei revealed that the oestradiol receptor-induced increase was associated with a marked chromatin dispersion. These results strongly suggest that the 3H-AMD staining method is a valuable tool for the assessment of oestrogen receptor-induced modifications of transcriptional activity in normal and pathological tissue as well.

Animals↗

Preclinical studies on toxicity, antitumour activity and pharmacokinetics of cisplatin and three recently developed derivatives.

Preclinical studies were performed in mice, rats and dogs of cis-diamminedichloroplatinum(II) (CDDP) and its derivatives cis-1,1-di(aminomethyl) cyclohexane platinum(II) sulphate (TNO-6), cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) (CBDCA) and cis-dichloro, trans-dihydroxybis-isopropylamine platinum(IV) (CHIP). In mice toxicity and antitumour activity were determined. All three derivatives were at least as toxic as CDDP for haemopoietic stem cells and were less active than CDDP against the mouse tumours leukaemia L1210 and osteosarcoma C22LR. Toxicology studies in rats revealed no renal toxicity after a single dose of TNO-6. Fractionated doses of TNO-6 and CBDCA did cause renal toxicity but less than CDDP. CHIP produced little or no kidney damage. In dogs, TNO-6 (1.5 mg/kg) produced more severe kidney damage--although this was reversible--than CDDP (2 mg/kg). Half-lives of distribution were 4.0-5.1 min for TNO-6 and 9.7 min for CDDP, while half-lives of elimination were 3.6-6.6 days and 5.9 days respectively. Plasma levels, normalized for the dose, were at least two times higher after TNO-6 than after CDDP. Twelve weeks after drug administration, plasma levels were undetectable, while tissue concentrations could still be measured. The platinum concentration in kidney cortex was higher after CDDP than after TNO-6.

Animals↗

[Histofluorescence localization of cellular sites binding steroid hormones in human breast cancers].

Cytochemical steroids binding activity of human mammary cancer cells is demonstrated in cryostat frozen sections using hydrophilic fluorescent steroid hormone ligands. The cytochemical results indicate that mammary carcinomas are composed of heterogeneous populations of positive and negative cancer cells in varying proportions. A comparison with biochemical data was made. There exists no correlation between the results obtained with the histochemical and the biochemical techniques. The specificity of this new tool of investigation is discussed.

Adenocarcinoma↗

Effects of anterior hypothalamic implantation of gonadal steroids on serum and pituitary gonadotrophins (follicle-stimulating hormone and luteinizing hormone) in the castrated male rat.

Castrated rats were stereotaxically implanted with 1 microng oestradiol benzoate, 5 microng testosterone isobutyrate or, as a control, 10 microng cholesterol, in the hypothalamus. The effects of the steroids on plasma and pituitary gonadotrophins (FSH and LH) were assessed by radioimmunoassay. Our results indicate that, in the male rat, in addition to the arcuate nucleus-median eminence complex, the preoptic suprachiasmatic area is able to control synthesis and secretion of both gonadotrophins, and that it is sensitive to oestradiol and testosterone.

Animals↗

Sensitivity of anterior hypothalamic areas to gonadal steroid implantation in androgenized female rats.

A single injection of 1 mg of a complex of testosterone esters on day 5 of life was used to prepare constantly oestrous rats. Such androgenized female rats were then ovariectomized and submitted to stereotaxical implantation of 1 microgram oestradiol benzoate, 5 microgram testosterone isobutyrate or, as a control, 10 microgram cholesterol in the anterior hypothalamic areas. The effects of the steroids on plasma and pituitary FSH and LH were assessed by radioimmunoassay. As reported previously by us in normal female and male rats, the preoptic-suprachiasmatic area (POA) was able to control synthesis and secretion of both gonadotrophins and did not lose its sensitivity to oestradiol and testosterone in andorgenized rats. Evidence for enhanced prolactin secretion in androgenized rats was derived from immunofluorescence studies of the pituitary gland and from histology of the mammary glands. In this respect the condition of the androgenized females was opposite to that of the males. The present work demonstrated that stimulation of prolactin secretion in androgenized female rats resulted from oestrogen action due to permanent oestrus rather than from impairment of hypothalamo-hypophysial relationships. Indeed, prolactin stimulation was suppressed when the androgenized rats were ovariectomized and restored when they were subsequently implanted with oestradiol in the POA.

Animals↗

Sialic acid residues in the labial salivary glands from Sjögren's syndrome patients.

OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

Diagnosis, Differential↗

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↗