[Apropos of a statistical series of 26 diving or thoracic goiters].
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Biomedical subjects
Publications and source records attributed to R Plagne.
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Hormonal modulation of Class II histocompatibility antigen expression was studied in female Sprague-Dawley rats with N-nitroso-N-methylurea-induced mammary tumors. The effects of ovarian hormones, pregnancy and lactation were examined when cancers appeared. At this time, rats with tumors were divided into several groups. Different groups received respectively 17 beta-estradiol alone, 17 beta-estradiol in association with progesterone, and tamoxifen alone. Other groups were selected to undergo pregnancy. The control group received carcinogenic treatment only. For all removed tumors, Class II histocompatibility antigens were radiolabeled, specifically immunoprecipitated with monoclonal antibody and quantified by chromatofocusing. The amount of Class II histocompatibility antigens measured in NMU-induced rat mammary tumors without any hormonal treatment decreased significantly after treatment with estrogen alone or in association with antiestrogen and during the pregnancy. Nevertheless, Class II histocompatibility antigen expression was not changed in mammary carcinoma from rats receiving progesterone, but increased significantly during the lactation. These results demonstrated clearly that ovarian hormones change the Class II histocompatibility antigen expression of NMU-induced mammary tumors in female Sprague-Dawley rats.
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In this study, the presence of reverse transcriptase in breast tumours was examined with immunoperoxidase staining using antibodies raised in rabbit against reverse transcriptase of Moloney murine leukemia virus and against reverse transcriptase of avian myeloblastosis virus. The specificity of such antibodies was investigated with ELISA and Western blotting techniques. Five cases of infiltrating ductal carcinomas were found positive with the immune serum anti-reverse transcriptase of Moloney murine leukemia virus on 28 studied infiltrating ductal carcinomas, 2 infiltrating lobular carcinomas and 2 fibroadenomas.
Cyclosporine A (an immunosuppressive cyclic undercapeptide) acts as an antagonist to prolactin receptors on a breast tumour cell line (MCF7) which is known to express specific prolactin receptors. The competition between cyclosporine A and prolactin to prolactin receptors was demonstrated by measuring the decreased specific 125I-labeled prolactin-binding to prolactin receptors in the presence of increasing concentrations of cyclosporine A. Moreover, cyclosporine A inhibiting effects on the cell growth were investigated in this mammary cancer (MCF) by measuring the cell DNA content with flow cytometry. Our results should prove very useful in understanding the mechanisms of prolactin regulation of DNA synthesis in tumorigenesis of the mammary gland.
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The function of reverse transcriptase (RT) in retroviruses is to copy their RNA genomes in DNA to be integrated into the host genome. We report a high purity preparation of this enzyme by adsorption onto poly(U)-sepharose. We analyzed RT activity with poly(rA)--oligo (dT)12-18, poly(dA)--oligo (dT)12-18, poly(rC)--oligo (dG)12-18 and poly(rCm)--oligo (dG)12-18 to obtain a more accurate pattern of RT. 8 out of 16 malignant breast samples were positive for RT activity, more specifically with poly(rC)--oligo (dG)12-18 and poly(rCm)--oligo (dG)12-18. The 5 non-malignant mammary samples tested were negative for RT activity. Assays with poly(rC)--oligo (dG)12-18 and poly(rCm)--oligo (dG)12-18. The 5 non- malignant mammary samples tested were negative for RT activity. Assays with N--nitroso--N--methylurea--induced rat mammary carcinomas were negative for RT activity.
The disposition and the metabolism of 2-chloroethyl nitrosocarbamoylcystamine (CNCC), a new antitumor agent, has been studied in rats. For this purpose, three separate labeled species of CNCC have been used. The tissue distribution and the elimination of the radioactivity were determined in animals after gavage with a single dose of each labeled species of CNCC (35 mumol/kg). It was observed, after analysis of plasma taken at timed intervals after administration, that little radioactivity co-chromatographed with the parent compound. These data suggest that CNCC undergoes an important first-pass metabolism, but chromatographic analysis provided evidence for the formation of four main metabolites. These biotransformation products were isolated from pooled plasma extracts of rats treated with 200 mumol/kg of unlabeled CNCC. They were identified by the combined use of mass spectrometry and chromatographic properties. These metabolites are sulfinyl and sulfonyl derivatives arising from the bioreduction of the disulfur bridge of CNCC with subsequent methylation and oxidation. These compounds are potentially active cytostatic agents. The evaluation of their antitumor activity is currently under investigation.
Previously we have shown that a new nitrosourea, 2-chloroethyl nitrosocarbamoylcystamine (CNCC), undergoes an extensive metabolism in the rat. Two pairs of plasma metabolites have been identified. This suggested our hypothesis that the metabolic pathway involves the reduction of the disulfur bridge followed by the methylation and the oxidation of the thiol groups. The two first intermediates, i.e. the unoxidized metabolites, could not be detected in vivo. Hence, to better understand and to confirm the proposed mechanism of biotransformation of CNCC, its in vitro metabolism has been studied. Incubation of CNCC with a rat liver homogenate or a 10,000g supernatant fraction leads to the formation of four pairs of metabolites. Among them we have identified the two first intermediates not found in vivo and the oxidized metabolites. These findings, together with the kinetics data, suggest that reduction, methylation, and oxidation are very rapid enzymatic reactions. We also show that, for completion of the reaction, the incubation mixture had to contain a cytosolic thioreductase, a microsomal and cytosolic S-methyltransferase, a microsomal oxidase, and an NADPH generating system. The sum of the amounts of metabolites found in the organic extratable material is less than the amount of CNCC metabolized. We conclude that the biotransformation of CNCC proceeds from two fast competitive mechanisms operative on both the disulfur and the nitroso groups.
Female Sprague-Dawley rats aged 50 days received 3 intravenous injections of N-nitroso-N-methylurea, 5 mg/100 g of body weight at 4 weekly intervals. When the first palpable mammary tumours appeared, with an incidence of 50 to 60% after the third injection, rats were randomized into 8 groups: group 1 was treated with 17 beta-estradiol; group 2 received progesterone; group 3 received in association 17 beta-estradiol + progesterone; group 4 was treated with tamoxifen. In group 5, rats received ovine prolactin. In groups 6 and 7, female rats were bred. Group 8, as a control group, received no hormonal treatment. Other control groups of 8 rats aged 140 days were made up of rats receiving 17 beta-estradiol alone (group 9) and rats receiving only ovine prolactin (group 10). The last group was kept without any treatment (group 11). The incidence of mammary tumours was followed in groups 1 to 8. All pituitary glands and mammary tumours were removed and weighed when rats were sacrificed after the last hormonal injection in each group. Light microscopy allowed the anatomopathologist to classify all removed mammary tumours in each group as adenocarcinoma. Light and electron microscopies with all pituitary glands in groups 1 to 11 showed no abnormality. The distribution of the pituitary weights was between 4.0 to 6.8 mg per 100 g of body weight. No adenomas were detected in the pituitary glands of the 5-month-old Sprague-Dawley rats receiving N-nitroso-N-methylurea.
Effects of prolactin on Class II HLA Ag expression have been identified for the first time in a human breast cancer cell line maintained in long-term tissue culture (MCF7) and were reported in this work as follows. Quantification methods for assaying Class II HLA Ag expression modulated by prolactin were established. Class II HLA Ags were internally labelled with [35S] methionine, extracted with Nonidet P-40, immunoprecipitated specifically with anti-Class II HLA MoAbs, isolated on protein A-Sepharose and quantified by chromatofocusing. For low doses of prolactin added to a final concentration (0.015 to 0.350 micrograms/ml culture medium), no change in Class II HLA Ags expressed by MCF7 cells was observed, when compared with controls, the percent of Class II HLA Ags assayed by chromatofocusing was then 4.03 +/- 0.57. For high doses of prolactin added to the final concentration (1.50 micrograms to 3.00 micrograms/ml medium), the percent of Class II HLA Ags increased to 6.05 +/- 0.72. When prolactin was added to the culture medium of MCF7 human breast cancer cell line, increased Class II HLA Ag expression by membrane cells was noted. Prolactin induction of Class II HLA Ag expression by human breast cancer cell lines should prove very useful to study the biology of prolactin in the tumorogenesis of the human breast.
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