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

Estradiol and progesterone receptor concentrations have been measured and their hormonal regulation extensively studied in normal human endometrium. However, in endometrial cancer, the biochemical assays presently used face the complex problem of tumor and tissue heterogeneity. This problem may be circumvented by immunocytochemistry on tissue sections proven to be histologically malignant. The in vivo experimental model developed in our laboratory is an ideal source of tissue necessary for purification of the progesterone receptor and antibody production. Hopefully, the physiology of the receptor may be studied under ideal conditions in this experimental system.
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PMID:Sex steroid receptors in normal and malignant endometrium. 352 89

A discrepancy has been found between the progestogen level necessary for treatment of endometrial cancer and the steroid receptor level detected for the response indicator. Therefore the relationships between the steroid binding quantity detected biochemically and the steroid reactivity determined immunofluorescently was evaluated subcellularly in the endometrial cancers. Estradiol-17 beta and progesterone fluorescences were not always related to the classical steroid receptor binding quantities. These two steroids bound to the nuclear components directly, but heterogeneously. In the biochemical method using fractionated dispersed cancer cells, cellular heterogeneity of the steroid receptor mechanism in a given endometrial cancer tissue was proved. Steroid fluorescence was not related to the steroid-receptor complex quantity in the normal endometrial nucleus. This suggests that the binding of steroid antibody to the steroid-receptor bound already to the nucleus seems to be inhibited due to steric hindrance. Therefore the nuclear steroid fluorescence did not always give the nuclear steroid-receptor complex quantity. These results indicate heterogeneity in the estrogen and progestogen receptor mechanism in endometrial cancer, when studied by the biochemical and immunofluorescent techniques, and that these steroids bind to the nucleus directly and may influence the nuclear mechanism. Therefore, in endometrial cancer progestogen does not always have a therapeutic effect through the progestogen receptor and does not affect the therapeutic effect on any of the cells.
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PMID:Implications of subcellular steroid binding sites in endometrial cancer, determined by an immunofluorescent steroid-antibody technique and biochemical assay. 636 89

Estrogen metabolism was studied in a newly established cell line (RL95-2) derived from a human endometrial carcinoma. Estradiol and estrone were metabolized to water-soluble derivatives by cells under in vitro culture conditions. Between 80-90% of the added steroids were metabolized, with nearly quantitative recovery of the products from the incubation medium. Arylsulfatase treatment converted the metabolites to ether-soluble forms, whereas beta-glucuronidase had no effect on the aqueous solubility of these compounds. Butanol extracts of the water-soluble estradiol metabolites cochromatographed on high performance liquid chromatography with 17 beta-estradiol-3-sulfate (93.6%) or estrone-3-sulfate (3.5%). No more than 6% of the estradiol added to the incubation medium was recovered in the form of estrone, either as estrone or estrone sulfate. After arylsulfatase treatment of the estradiol conjugates, 92% of the ether-soluble radioactivity cochromatographed with estradiol, and 3.8% cochromatographed with estrone. Estrogen-sulfurylating activity was localized in the cytosol of subcellular fractions of RL95-2 cells. The sulfoconjugation of estrogens by RL95-2 cells may prove useful as a model for the investigation of estrogen metabolism in endometrial carcinoma cells.
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PMID:Estrogen sulfoconjugation by human endometrial cancer cells (RL95-2) in culture. 669 41

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

The Authors report the results of study carried out on ten post-menopausal patients affected with endometrial carcinoma (FIGO stage I & II) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). Estradiol, Testosterone and Prolactin plasma levels were assayed before surgery and in the 2nd, 10th and 30th post-operative day. The evaluation of the data supports the opinion that in postmenopause Estradiol origin is mainly extraglandular and the ovaries produce Testosterone; the evaluation of Prolactin levels before and after surgery, at last, cannot rule out the hypothesis of an hypothalamo-pituitary disfunction in post-menopausal patients affected with endometrial cancer.
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PMID:Hormonal profile following total abdominal hysterectomy and bilateral salpingo-oophorectomy in post-menopausal endometrial carcinoma. 716 98

Various aspects of climacteric treatment with natural human estrogens are discussed. Estradiol, estradiol valerate, estron sulfate, or estriol are used separately or together in various preparations to treat the symptoms of approaching menopause. Estrogen treatment causes proliferation of the endometrium and causes a decrease in LHRH, FSH, and LH secretion. Treatment can take the form of continuous or cyclic treatment with estrogens alone, or sequential estrogne/gestagen preparations can be used. Ovarian function decreases as menopause approaches and results in the cessation of ovulation. Then the hypolutein phase begins, during which the secretion of progesterone is reduced and menstrual bleeding irregularities begin to occur. Eventually, estrogen production decreases so much that menstruation ceases completely, and symptoms such as heat flashes are experienced. Women who want treatment for climacteric symptoms but who want no regular menstrual bleeding can be administered low doses of pure estrogen. Regular abrasio control of endometrial development should be performed, however. Pure estrogen treatment can also be used in the case of hysterectomized women. Otherwise, a sequential treatment is generally indicated. Possible side effects of estrogen substitution therapy are changes in the genitalia, breasts, menstrual bleeding, blood pressure, and weight. There is also an indication that estrogen use can induce endometrial cancer. Besides the definite contraindication of endometrial cancer, relative contraindications of estrogen therapy include breast cancer, reduced liver function, thromboembolic disease, and serious hypertension. Estrogen therapy is to be used to solve acute climacteric symptoms; women should be well informed about possible side effects and that the therapy is no panacea for all menopausal problems.
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PMID:[Peroral treatment with natural human estrogens in the climacteric]. 744 54

Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [125I]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [125I]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [125I]des-(1-3)IGF-I as the ligand. Des-(1-3) IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [125I]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [125I]IGF-I and [125I]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels.
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PMID:Modulation of insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol. 775 Apr 75

Since postmenopause unopposed oestrogen replacement therapy (ERT) increases the incidence of endometrial carcinoma, the addition of a progestin in non-hysterectomised women is mandatory for hormonal substitution. On the other hand, progestins have a negative influence on serum lipids and may thus put in question the benefits of the ERT with regard to the cardiovascular risk. Progestins lower HDL and increase LDL in a dose-dependent way according to their chemical structure. In the present non-randomised study, the influence of a cyclic combined oestrogen progestin substitution on the serum lipids has been measured. From a total of 90 apparently healthy postmenopausal patients, 59 received a transdermal ERT with 17 beta-Estradiol (Estraderm TTS 50), whereas 31 women obtained a daily dose of 0.625 mg conjugated equine oestrogens (CE) perorally. Additionally all patients were given 10 mg medroxyprogesterone-acetate (MPA) daily during the first 10 days of each month. After 6 months of therapy, the following changes of serum lipids, expressed as percentage of initial values, were measured: total cholesterol in the transdermal group -2.3% (n.s.), in the peroral group -11.8% (p < 0.00001); triglycerides -3.7% (n.s.) resp. +8.6% (n.s.); HDL cholesterol + 0.2% (n.s.) resp. -1.8% (n.s.); LDL cholesterol +1.3% (n.s.) resp. -14.8% (p < 0.00001). The calculated atherogenic indices showed a decrease in the peroral substituted group of -6.5% (n.s.) for the HDL/total cholesterol ratio and -14.8% (p < 0.002) for the LDL/HDL ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cyclical gestagen (MPA) supplement for continuous transdermal or oral estrogen substitution in postmenopause: modification of serum lipids]. 827 Jan 55

Type II nuclear-estrogen binding sites (type II EBS) have been postulated to play a crucial regulatory role in estrogen-stimulated uterine growth. The pathogenesis of endometrial cancer is known to be connected to estrogens. However, there are no data on type II EBS in human endometrial cancer. Therefore, we investigated the presence of nuclear type II EBS and nuclear type I estrogen receptors (ER) by radioligand-binding assays in endometrial tumorous tissues (n = 135). Determination of cytoplasmic ER and progesterone receptor (PR) concentrations were also included in the study. Estradiol (E2) and progesterone (P) hormone levels in sera of patients were determined by RIAs. In addition, all data were analyzed on 5-year survival rates. Saturation analyses of 3H-E2 binding in crude nuclear pellets (n = 5) showed two types of estradiol binding: type I ER having high affinity and low capacity and type II EBS binding estradiol with lower affinity and high capacity in a positive cooperative fashion. The nuclear type II EBS and type I ER concentrations were significantly higher in cancers of increasing grade. In contrast, a significant decrease of cytoplasmic 3H-E2 binding was detected. Cytoplasmic PR binding capacities were high in G1 and G2, but low in G3 tumors. The 5-year survival data showed nuclear type I ER to have the best correlation for prognostic value (cut-off, 0.5 pmol/mg DNA), while type II EBS had no significant impact on it. Serum E2 concentrations decreased with tumors of higher grade, but were generally still higher than the control values. The serum P levels did not alter. None of the parameters investigated here differed from control values in adenoacanthoma (n = 6), suggesting a separate pathomechanism. As type II EBS are known to be stimulated by E2 under conditions that cause uterine hyperplasia, we concluded that the higher "runaway" nuclear type II EBS levels, in contrast with the lower serum estradiol concentrations, might be connected with the strong proliferative and invasive character of higher grade endometrial adenocarcinomas. This is the first demonstration of the presence of nuclear type II EBS and their possible pathological role in human endometrial cancer, and of the high prognostic significance of nuclear type I ER to identify a subgroup having a fatal form of the disease in a 5-year survival study.
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PMID:Nuclear type II estradiol binding sites and type I estrogen receptors in human endometrial cancer: a 5-year follow-up study. 842 28

Repair of human endometrium after menstruation and preparation of the endometrium for implantation involves profound angiogenic changes. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. Four species of mRNA encoding VEGFs were identified in human endometrium and myometrium. All species were present throughout the menstrual cycle. Two species, VEGF165 and VEGF121, were present in peripheral leukocytes, indicating tissue-specific splicing of the two other VEGF transcripts. In situ hybridization of mRNA encoding VEGF was not restricted to vascular smooth muscle but was present in epithelial and stromal cells of endometrium throughout the cycle, and the distribution changed during the course of the cycle. All four species of VEGF were expressed by the endometrial carcinoma cell lines Ishikawa, HEC 1-A, and HEC 1-B. Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells. Conditioned medium from these cells possessed angiogenic activity that was depleted by passage through a heparin affinity column. None of the cell lines demonstrated mRNA for acidic or basic fibroblast growth factor (FGF), despite previous reports of the identification of immunoreactive basic FGF in HEC 1-A and HEC 1-B cells. These findings show that VEGFs, not FGFs, are the principal angiogenic growth factors secreted by these cells and that human endometrium expresses a secreted angiogenic growth factor whose site of expression changes during the menstrual cycle.
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PMID:Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. 848 75


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