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

The sex steroid hormone receptor levels of uterine cytosol were assayed in the course of experimental induction of endometrial carcinoma in rats. Effects of administration of various hormones on the receptor levels were examined with each histological pattern of endometrium. 1) The dissociation constants for E2 and R5020 bindings with uterine cytosol were almost fixed in spite of various histological patterns of endometrium. 2) The influence of administrated hormones on the receptor assay system could be neglected by the preincubation of uterine cytosol with DCC for five times. 3) By the administration of DES for six weeks, estrogen receptor levels were increased significantly in adenocarcinoma, while progesterone receptor levels did not show the tendency of decreasing. 4) By the administration of MPA combined with DES, estrogen receptor levels were not decreased significantly in both atypical adenomatous hyperplasia and adenocarcinoma; progesterone receptor levels were decreased in all groups. 5) By the administration of MPA, estrogen receptor levels were decreased significantly in adenocarcinoma. These data suggest that receptor levels can be controlled by the administration of sex hormones in the course of development of endometrial carcinoma.
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PMID:[Changes of sex steroid hormone receptors in rat uterine cytosol during experimental induction of endometrial carcinoma (author's transl)]. 645 22

Objective response to progestin therapy occurs in 30% to 35% of patients with recurrent or metastatic endometrial carcinoma. Measurement of progesterone receptor (PR) in these tumors has been suggested as a method for distinguishing between responders and nonresponders. However, studies on steroid receptor measurements in endometrial carcinoma may be subject to complexities of tumor, tissue, and cellular heterogeneity. The authors provide evidence for the existence of various types of heterogeneity and address the problem of cellular heterogeneity by determination of PR concentrations in the glandular and stromal cells of the endometrium. It is concluded that until the problem of tumor and tissue heterogeneity is resolved, PR concentrations in endometrial carcinoma must be interpreted with caution.
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PMID:Heterogeneity and progesterone-receptor distribution in endometrial adenocarcinoma. 668 93

In vitro responsiveness of endometrial adenocarcinoma to progestins was evaluated histologically by incubation of tissue fragments in medium containing 10(-6) M medroxyprogesterone acetate. In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response to medroxyprogesterone acetate added to the medium, was observed in well-preserved glandular epithelial cells only when the level of cytosolic progesterone receptor was above 300 fmol/mg protein. Previously, we have reported similar results obtained in in vivo experiments. The present findings suggest that simple organ culture and histological procedures can be used to identify specimens of endometrial cancer that have functional progesterone receptors and are capable of responding to progestins. They also indicate that levels of progesterone receptor required to obtain responses to progestins are considerably higher than those necessary for analytical detection and that therefore the quantity and not merely the detectability of progesterone receptors must be taken into consideration for the prediction of responses to progestins. In addition, in vitro responses to progestins may indicate the presence in endometrial cancer tissue of functional estrogen receptors and potential responsiveness to antiestrogens, since estrogen stimulation appears to be needed for the synthesis of progesterone receptors.
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PMID:Histological evaluation of in vitro responses of endometrial adenocarcinoma to progestins and their relation to progesterone receptor levels. 669 40

The effect of tamoxifen (TAM) on human endometrial carcinoma was investigated in nude mice bearing an estrogen receptor-positive or estrogen receptor-negative tumor. The receptor-negative tumor grew rapidly, and the rates of tumor growth of 17 beta-estradiol or TAM-treated animals were identical to the rate of controls. The estradiol receptor and progesterone receptor (PR) concentrations in the tumor cytosol remained undetectable under all experimental conditions. In contrast, the rate of growth of steroid receptor positive tumor was significantly accelerated in the presence of TAM compared to controls (p less than 0.02). The increased tumor growth rate was, however, significantly lower (p less than 0.01) than that observed in animals receiving 17 beta-estradiol. The PR concentration in these tumors was elevated in response to TAM treatment. That the TAM-induced PR was indeed functional was evident from (a) increased activities of the progestin-sensitive enzyme, 17 beta-estradiol hydroxysteroid dehydrogenase and (b) histological appearance of subnuclear vacuolization in these tumors after progestin administration. These studies indicate that continuous, short-term administration of TAM to nude mice results in an estrogen-like effect on endometrial carcinoma. Based on the finding that TAM induces functional PR, we predict that steroid receptor-positive endometrial carcinoma may show a greater response rate to combined, long-term treatment with TAM and progestin.
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PMID:Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. 674 16

This paper reviews the recent laboratory findings about the nonsteroidal antiestrogen, tamoxifen, and its more potent major metabolite, monohydroxytamoxifen. Both compounds stimulate progesterone receptor synthesis in the rat uterus, and there is an inhibition of cell division in the uterine luminal epithelial cells. The effects of tamoxifen in vivo may be a result of the net effects of the parent compound and monohydroxytamoxifen. In rats with dimethylbenzanthracene (DMBA)-induced rat mammary carcinomata, young tumors that are estrogen receptor- and progesterone receptor-rich respond more favorably to tamoxifen that do older estrogen receptor- and progesterone receptor-poor tumors. However, the antitumor effect of tamoxifen in the DMBA-induced rat mammary carcinoma model is probably a result of the blockade of tumor estrogen receptors, a reduction in circulating gonadotropins, lower circulating estrogen levels, and lower circulating prolactin levels. The 30-days treatment of rats with tamoxifen 30 days after DMBA resulted in a dose-related decrease in the appearance and numbers of mammary tumors; however, only continuous therapy maintained animals in a tumor-free state. Monohydroxytamoxifen was a less-potent antitumor agent, probably because it is cleared from the rat more rapidly than tamoxifen. The present laboratory findings support the clinical use of tamoxifen as a treatment of endometrial carcinoma and the resultant metastases and as an adjuvant therapy after surgery for breast cancer.
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PMID:Pharmacology of tamoxifen in laboratory animals. 677 7

A model for studying the growth of primary tumors of human endometrium and its regulation by 17 beta-estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17 beta-dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.
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PMID:Human endometrial adenocarcinoma transplanted into nude mice: growth regulation by estradiol. 684 15

Receptors for steroid hormones are necessary for hormonal action. All tissues which are targets for hormonal action contain receptors. Estrogens seem to be required to induce progesterone receptor. Progesterone, in turn, has been shown to lower the level of estradiol receptors in the endometria of normal women. This would be likely to prevent the development of endometrial hyperplasia, a known precursor of endometrial cancer. Progesterones are, thus, related to endometrial cancer as both antagonists of estrogens and as therapeutic agents.
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PMID:Sex steroid receptors in endometrial hyperplasia and neoplasia [proceedings]. 693 74

Similarities between endometrial and mammary tissue as targets for ovarian hormones indicate that measurements of estradiol and progesterone receptor (RE and RP) levels may be as useful in endometrial cancer as they are in breast cancer for the prediction of responses to treatment with steroids and antiestrogens. Receptor levels cannot be inferred from the degree of differentiation of the endometrial tumors, although RP values are lower in poorly differentiated adenocarcinoma. Current studies aim to relate RP levels to objective remissions of metastases after progestin therapy, and attempts are being made to increase RP with tamoxifen before treatment with progestins or assaying for RP. In vitro studies aim to elucidate fundamental problems related to the action of steroids on the tumors, e.g., mechanism by which receptors mediate the effects of pharmacologic doses of drugs, factors that regulate receptor levels, and homogeneity in the distribution of receptors in tumor cell populations.
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PMID:Hormone receptors in endometrial cancer. 702 68

Women treated with estrogen exhibit a higher risk of developing endometrial cancer. steroid hormones exert their effects on target tissue through specific cytosol receptor protein. Knowledge of this steroid receptor concentration in endometrial carcinoma might facilitate the treatment of recurrences. We have compared the concentrations of endometrial estrogen and progesterone cytosol receptors with the histologic grade of endometrial carcinoma as well as the rate of 3H-thymidine incorporation. We found a significant difference in receptor concentration between well-moderately differentiated tumours and poorly differentiated ones. No correlation was found between 3H-thymidine incorporation rate and differentiation. A positive correlation between thymidine incorporation rate and progesterone receptor concentration was noticed. The concentration of receptors varies within a wide range of each group of differentiation; thus 23% and 4% of the poorly differentiated tumours had higher concentration of estradiol and progesterone receptors respectively than the median values for well differentiated tumours.
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PMID:Correlation between estradiol-17 beta and progesterone cytosol receptor concentration, histologic differentiation and 3H-thymidine incorporation in endometrial carcinoma. 714 49

Seventy-eight endometrial carcinoma specimens from 74 patients were evaluated for estrogen (E2R) and progesterone (PrR) receptors by multiconcentration saturation and sucrose density gradient analysis. The clinical stage and histologic grade of the tumors and the patients' clinical course were compared to the qualitative and quantitative evaluations of E2R and PrR. Although no correlation was seen between receptor content and extent of disease, tumors with significant levels of E2R and PrR tended to be less aggressive than those in which neither receptor was detected. The histologic grade correlated with a combination of estrogen and progesterone receptor content. In 92% of the patients there was a concordance between the presence or absence of E2R and PrR in the tumor and a clinical response to progestin therapy. The significance of these findings in relationship to the presence of multiple forms of steroid binding is discussed.
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PMID:Clinical correlates of estrogen- and progesterone-binding proteins in human endometrial adenocarcinoma. 718 47


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