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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responsiveness and action mechanisms of steroid hormones and epidermal growth factor on human endometrial carcinoma cells are analyzed by using in vitro culture system. 1) The Ishikawa cells, derived from a well differentiated endometrial adenocarcinoma and possess ER and PR, are shown to respond to estrogens by increasing a variety of parameters, viz cell proliferation, PR levels, ALP and DNA polymerase activities. 2) ER and PR of those cells are localized in the nuclei by immunocytochemical staining using the monoclonal antibodies against to ER and PR, confirming the correctness of Gorski and Greene's one step theory involving the action mechanisms of steroid hormones. 3) Progestins reduced the ER level and stimulate E2DH activities and glycogen content, which are completely abolished by anti-progestin (RU486), suggesting that PR of those cells should be functional. 4) These responses to steroid hormones of Ishikawa cells are synergistically enhanced or appeared earlier by addition of EGF. 5) The main metabolite of E2 incubated with Ishikawa cells is E2-3-sulfate instead of E1, indicate that the higher estrogenic status may be persisted in endometrial cancer tissues.
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PMID:[Responsiveness and mechanisms of action of steroid hormones in human endometrial adenocarcinoma cells]. 251 14

The mechanism of action of sex steroid hormones on endometrial carcinoma was analyzed by a cell culture system. 1) Estrogenic actions such as enhancement of ALP activity, PR level and cellular growth were confirmed in Ishikawa endometrial carcinoma cells which possess ER. 2) ER and PR are both localized immunocytochemically in the nuclei of Ishikawa cells, confirming the correctness of Gorsky and Greene's theory in endometrial carcinoma. 3) In Ishikawa cells with PR, progestins stimulated E2DH activity and glycogen synthesis and reduced ER level, thus proving the existence of their hormonal action. We cannot, however, rule out the pharmaceutical action of progestin, because a decrease in nucleic acid syntheses and ALP activity, alteration in electron microscopic observation and finally cellular death were observed in endometrial cancer cells without PR. 4) Conversely, Tamoxifen, anti-estrogen, stimulated the cellular growth in serum-free environment of culture. We must therefore be careful in using it clinically.
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PMID:[Mechanism of action of endocrine therapy of endometrial carcinoma]. 273 78

Kinetics of estradiol dehydrogenase (E2DH) activity and the in vitro effects of progesterone (P) and synthetic steroids on E2DH activity were investigated in human normal endometrium and endometrial carcinoma. In proliferative and secretory endometrium and endometrial carcinoma, E2DH activities were 1.5 +/- 0.2, 10.1 +/- 1.1 and 1.2 +/- 0.1 nmol/mg protein/h (mean +/- SEM), Km was 2.3 microM, and Vmax were 0.20, 1.7 and 0.14 nmol/mg protein/10 min, respectively. Culturing proliferative endometria with progestogens resulted in a time- and dose-dependent stimulation of E2DH activity up to 72 h and 10(-6) M, respectively. Medroxyprogesterone acetate had the highest effect to stimulate E2DH activity among the steroids investigated. Chlormadinone acetate, norethindrone, P and R2323 were also effective. However, danazol, lynestrenol and E2 had negligible effect. Histological examination showed that progestogens caused early secretory change in the proliferative endometrium. These results indicate that the progestational activity is responsible for the elevation of E2DH activity in proliferative endometrium and that the extent to which each steroid increases E2DH activity may correlate with its local progestational activity. In the endometrial carcinoma, progestogens also stimulated E2DH activity in seven cases out of nine during culture for 48 h, but the elevation was lower than that in the proliferative endometrium.
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PMID:[Studies on estradiol dehydrogenase activity in the human uterine endometrium]. 296 May 69

Estradiol dehydrogenase (E2DH) is a well-known progesterone-dependent enzyme in human endometrium, and its induction has been proposed as a means to test hormonal sensitivity of endometrial carcinoma. While administration of progestins to some patients with endometrial carcinoma resulted in increased endometrial E2DH activity, efforts to induce this enzyme, in vitro, in these tumors have been unsuccessful. The reasons for such failure were investigated in the present study. Progesterone receptor (PR) concentrations and E2DH activities were simultaneously measured in proliferative and malignant endometria under organ culture conditions. Cytoplasmic PR concentrations were determined by Scatchard plot analysis of [3H]progesterone binding in fresh samples and in tissue explants incubated in nutrient medium at 37 degrees in a humidified 5% CO2 atmosphere for various periods of time. Parallel incubations of explants with and without 500 ng medroxyprogesterone acetate per ml were carried out for monitoring E2DH induction. In proliferative endometrium, the progesterone-specific binding sites remained stable during the culture periods, and the E2DH activities were stimulated severalfold by medroxyprogesterone acetate. In contrast, the PR concentrations in carcinoma explants were undetectable after a 24-hr period, and this was associated with a lack of increase in E2DH activity. These findings provide evidence that progestin-induced endometrial E2DH activity is a receptor-mediated phenomenon. In addition, these results demonstrate clearly that the ineffectiveness of progestin to induce E2DH in endometrial cancer specimens, in vitro, is related to the instability of PR under culture conditions. It is suggested that any experiment designed to follow effects of steroids on target tissues must take into account the stability of steroid receptors under in vitro conditions.
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PMID:Failure of progestins to induce estradiol dehydrogenase activity in endometrial carcinoma, in vitro. 694 38