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

The effects of estradiol on DNA polymerase alpha activity were investigated in an estrogen-responsive human endometrial cancer cell line (Ishikawa) derived from a well differentiated endometrial adenocarcinoma. These cells are known to respond to estradiol by increasing progesterone receptor levels, alkaline phosphatase activity, and cell density. Four- to 5-fold increases in DNA polymerase alpha activity occurred when estradiol was added to cultures of Ishikawa cells in medium containing charcoal-treated fetal bovine serum. Maximal stimulation was achieved at 18 h during incubations with 10(-8) M estradiol, but significant effects also were found with 10(-9) and 10(-6) M. These effects were almost completely counteracted by a 100-fold excess of 4-hydroxytamoxifen. At 10(-6) M, the antiestrogen had no influence on the basal levels of DNA polymerase alpha. Medroxyprogesterone acetate (10(-6) M) was ineffective as either an enhancer of enzymatic activity or an antiestrogen when tested in combination with 10(-8) M estradiol, even in the presence of appreciable levels of specific progesterone binders. The responsiveness of the Ishikawa cells to estrogen contrasts with the lack of effects of estradiol on DNA polymerase alpha activity in another human endometrial adenocarcinoma cell line (HEC-50).
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PMID:Effects of estradiol on deoxyribonucleic acid polymerase alpha activity in the Ishikawa human endometrial adenocarcinoma cell line. 294 47

The anti-tumor activities of steroid compounds on endometrical cancer (Ishikawa cell line) were examined in vitro by human tumor clonogenic assay (HT CA). Clinically effective progestational compounds including medroxyprogesterone acetate (MAP), and 17 alpha hydroxy-progesterone caproate were effective. Norethindrone (ENT), which is also a potent progestational compound, and RU486, which is known to be a progesterone antagonist were ineffective in this in vitro system, neither having any influence on the effect of MAP. These results indicated that the anti-tumor activity of MAP did not proceed via the so-called progesterone receptor system. Morphological changes induced by MAP in undifferentiated endometrial cancer, the effectiveness of tamoxifen, hormonochemotherapy, and the use of MAP for adjuvant therapy and prophylaxis were also discussed.
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PMID:[Hormone dependency and progestogen therapy in the treatment of endometrial cancer]. 295 4

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

The morphological effect of a high-dose progestogen (Depo-Provera) on highly differentiated endometrial carcinoma was studied. Thirteen patients were treated by progestogen only, given at the beginning of the treatment in a weekly dose of 1,000 mg for 3 month. Then, progestogen 500 mg was administered for 12 months. Nine patients were operated after the treatment; in 7 of them, a total histological regression was observed. Histological tests of the intraoperatively gained preparations showed 'disappearance' of the original carcinomatous process; only a serious atrophy of the endometrium could be detected.
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PMID:Continuous, high-dose progestogen treatment of endometrial cancer. 296 10

Forty-six eligible women with metastatic endometrial cancer were randomly allocated to receive monthly cycles of either CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or CAF plus Provera 200 mg daily for 3 weeks followed cyclically by Tamoxifen 20 mg daily for 3 weeks. Overall response rates of 15 and 43% were seen with CAF and CAF plus hormonal therapy. Using a multivariate analysis of the results, this difference is significant (P value 0.05). In 8 patients with operable endometrial cancer, negative estrogen receptor concentration (ER less than 15 fmole/mg protein) and Grade 3 disease, the clinical course was aggressive in 4 patients with systemic and local relapse. In 10 other similar patients (negative ER and Grade 3) who received adjuvant cyclical hormonal therapy only 1 relapsed and the other 9 are disease-free for an average of more than 31 months. Sequential cyclical hormonal therapy with ER and progesterone receptor analysis has a place in the management of endometrial carcinoma.
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PMID:Efficacy of sequential cyclical hormonal therapy in endometrial cancer and its correlation with steroid hormone receptor status. 297 97

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.
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PMID:[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen]. 297 92

Medroxyprogesterone acetate (MPA) is used as an adjuvant hormonal medication in patients with different kinds of carcinomas. Since adequate serum levels are thought to be essential we determined the individual, postoperative MPA levels in 36 patients with endometrial carcinoma over a period of 12 weeks. The patients received either an oral dose of 3 X 100 mg MPA or a weekly changing scheme with 2 X 10 mg Tamoxifen and 3 X 100 mg MPA. An additional small group of 4 patients with ovarian carcinoma was enrolled receiving an oral dose of 1000 mg MPA daily. The peripheral serum levels of MPA exhibit enormous inter- and intraindividuell variations and only the high dosage schemes yield levels above 90 ng/ml which are claimed necessary by some authors. The cortisol concentration measured at the same time were within the normal range and did not correlate with the MPA values.
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PMID:[The medroxyprogesterone acetate serum level following various medroxyprogesterone acetate dose schedules in gynecologic oncology]. 297 43

The interactions of an antiestrogen (tamoxifen) and a progestin (medroxyprogesterone acetate) on endometrial 17 beta-hydroxysteroid dehydrogenase activities were studied in short-term experiments (four to 96 hours) in normally menstruating women at the follicular phase and were related to simultaneously measured concentrations of cytosol and nuclear estrogen and progestin receptors. Tamoxifen effected a decrease in the activity of 17 beta-hydroxysteroid dehydrogenase. This was associated with an apparent translocation to and retention of estrogen receptor in the nucleus without any significant changes in cellular progestin receptor. Medroxyprogesterone acetate administration led to a rapid increase in endometrial 17 beta-hydroxysteroid dehydrogenase activity, and depletion of cytosol and total cellular progestin receptor. Combination of the drugs led to effects that could be addressed to the individual drugs separately, and under the experimental conditions the effects of medroxyprogesterone acetate were uninfluenced by simultaneous tamoxifen administration. Put together with the authors' previous findings on the same parameters during long-term (three-week) medroxyprogesterone acetate administration, it seems possible that potentiation of progestin effects on endometrial carcinoma is not to be expected during long-term simultaneous antiestrogen-progestin treatment. It is therefore likely that the favorable effects of combining these two drugs in long-term treatment are due to their different endocrine action mechanisms.
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PMID:Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium. 299 80

We measured concentrations of cytosol and nuclear estrogen, as well as progestin receptors and activities of 17 beta-hydroxysteroid dehydrogenase (17-HSD), and examined histopathology and ultrastructure of endometrial carcinoma specimens taken before and after one-week danazol (200 mg, 3 times daily) or medroxyprogesterone acetate (MPA, 100 mg daily) treatments in 14 and 16 patients, respectively. A typical progestin effect, a significant increase in the activity of 17-HSD, was observed after both treatments. The post-therapy 17-HSD activities correlated significantly with the pretreatment cytosol progestin receptor concentrations in both treatment groups. Both MPA and danazol decreased the proliferative activity and increased the secretory activity of the malignant epithelial endometrial cells. These biochemical and morphological results support the concept that danazol has progestin-like actions on the human endometrium, and might therefore be an alternative for hormonal treatment of endometrial carcinoma.
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PMID:Short-term effects of danazol and medroxyprogesterone acetate on cytosol and nuclear estrogen and progestin receptors, 17 beta-hydroxysteroid dehydrogenase activity, histopathology, and ultrastructure of human endometrial adenocarcinoma. 315 97

Adverse and beneficial effects, especially with regard to mortality rates, of oral contraceptives (OC) are reviewed. In 1980 approximately 80 million women used OCs worldwide. OCs were first marketed in the United States in the 1960's, but by the 1980's low-dose combination pills with less estrogen and progesterone content became widespread along with the minipill, injectable preparations depo- medroxyprogesterone DMPA, and norethindrone containing capsules. Relative disease risk estimates are based on cohort studies and case- control studies. The Royal College of General Practitioners RCGP Oral Contraceptive Study of 1974 involved 46,000 women aged over 15 (50% were OC users, 50% were nonusers) the Oxford Family Planning Association Contraceptive Study of 1976 recruited 17,032 women aged 25-39, 56% of whom used OCs, and the Walnut Creek Contraceptive Drug Study of 1981 studied 16,638 women aged 18-54 of whom 28% were OC users and 33% were former users. A somewhat elevated mortality among ever-users of OCs in the order of 20% seems to be indicated by these studies mostly attributable to diseases of the circulatory system. Current OC use is also a risk factor in thrombotic stroke of the order of 4 or 5, but former use of OCs lowers the risk to 2. The effect of OC dose and formulation, duration of use, and predisposing factors on hemorrhagic and thrombotic stroke appears to be inconclusive with varying data from different studies. There is evidence for some increase in ischemic heart disease among current OC users, and also a 2-fold increase of myocardial infarction (MI) when smoking, serum cholesterol, and hypertension is taken into account, moreover higher estrogen dosage also contributes to a higher incidence of MI. There is also a 5-fold increase of venous thromboembolism among OC users induced by duration of use and estrogen potency, as OCs seem to promote atherogenesis, although the roles of progesterone and estrogen are conflicting. combination pills reduce the rate of endometrial cancer, provided protection against ovarian cancer, and do not seem to increase breast cancer incidence, although the relative risk of cervical cancer is elevated. Mortality risks with older OCs outweigh the benefits.
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PMID:On the epidemiology of oral contraceptives and disease. 331 96


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