Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of medroxyprogesterone acetate (MPA) in therapy of patients with endometrial cancer has been recently examined by the Japan Gynecological Cancer Treatment Group. The response rate of oral MPA was 23.6% (13/55 evaluables) and the average period up to the onset of response was 15.2 weeks (4-28 wks). The response rate was higher in well-differentiated tumors than in poorly differentiated ones. Although it is well known that steroid hormone action is mediated by steroid hormone receptor, the presence of progesterone receptor in cancer tissue seems to be not absolutely necessary for the responsibility to MPA, a potent progestational compound. The reason was studied, in vitro, in our laboratory by using the technique of human tumor clonogenic assay. In this system, MPA showed a marked suppressive effect on the colony formation of endometrial cancer cells. Similar effects were also observed with progesterone, 17 alpha-hydroxyprogesterone caproate and megestrol acetate. Norethindrone and norgestrel, which are both potent progestational compounds, showed almost no anticancer activity on Ishikawa cell in this in vitro system. It became clear that progestational activity was not always associated with anticancer activity, and norethindrone had no influence on the inhibitory effect of MPA, although norethindrone has a strong affinity for progesterone receptor. Similarly, RU 486, which is known as a potent antiprogestogen agent and has a high affinity to progesterone receptor, did not influence the effect of MPA. These results clearly indicated that the anticancer activity of MPA was not mediated by high affinity low capacity progesterone receptor, and a pharmacological effect must be considered for understanding the effect of MPA on endometrial cancer.
 ...
PMID:[Progestogen therapy in the treatment of endometrial cancer--clinical results and mechanism of steroid action]. 296 80

Effects of medroxyprogesterone acetate (MPA) and danazol (1 nM-10 microM) on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were simultaneously investigated. Of twenty-four endometrial adenocarcinomas examined, five tumors were successfully maintained in primary cell culture. The addition of MPA as well as danazol in culture of cells from the five tumors resulted in a significant inhibition of [3H]thymidine incorporation in cancer cells from three tumors having progesterone receptors (PR). The minimum effective concentrations of MPA and danazol for the inhibition of [3H]thymidine incorporation were found to be 10 and 100 nM, respectively. The difference in effective concentration could be explained by a higher affinity of MPA to PR than that of danazol in cancer cells. On the other hand, neither danazol nor MPA affected [3H]thymidine incorporation in cultured cells from the remaining two tumors, in which PR was absent in one but present in the other. These findings, together with our previous findings that danazol inhibited the growth of a human endometrial cancer cell line with PR, suggest that a growth-inhibitory effect of danazol on human endometrial cancer cells is mediated through PR in the cells.
 ...
PMID:Inhibitory effects of danazol and medroxyprogesterone acetate on [3H]thymidine incorporation in human endometrial cancer cells. 296 34

Protein synthesis in cancerous and normal human endometrium was investigated by the incorporation of [35S]methionine and analysis of products by two-dimensional polyacrylamide gel electrophoresis. Comparison of the cellular products from organ cultures of endometrial carcinoma, obtained from each subject before and after in vivo administration of medroxyprogesterone acetate (MPA) for 10-14 days revealed: (i) a decrease in the synthesis of tubulin and of a protein of molecular weight (mol. wt) 68 kDa, isoelectric point (pI) 6.0, and (ii) an increase in the synthesis of creatine kinase (CK) and of protein of mol. wt 36 kDa, pI 4, following MPA therapy. The 68 kDa protein was expressed at relatively reduced levels in organ cultures of normal human endometrium throughout the menstrual cycle. In primary cultures of normal human endometrium throughout the menstrual cycle. In primary cultures from cancerous endometrium endometrium established for several weeks the 68 kDa protein was not expressed but could be induced by heatshock. Primary cultures were also used to investigate the early events following progesterone stimulation which revealed a decrease in synthesis of a protein mol. wt 36 kDa, pI 8 at 8 h following administration.
 ...
PMID:Progestin regulation of protein synthesis in endometrial cancer. 296 99

221 patients with endometrial cancer stage Ia and Ib have been operated on between 1980 and 1986. 99 patients have been irradiated postoperatively. 122 patients got 300 mg medroxyprogesterone acetate per day over one year provided that the carcinoma was limited to the uterine corpus, the invasion into the myometrium was at a maximum of 2/3 of the uterine wall, there was no invasion of the lymphatic vessels and the tumour was histologic uniform. The 5-year-survival rate of the patients operated on without irradiation but with gestagens was 98.1 per cent calculated with actuarial method in contrast to a matched group from the years 1970 to 1979 with operation and irradiation but without gestagens of 93.2 per cent. These results demonstrate that an individualized therapy in stage I is possible in patients with a low risk of recurrence.
 ...
PMID:[Adjuvant gestagen therapy in stage I endometrial cancer]. 297 95

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.
 ...
PMID:[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen]. 297 92

Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. alpha 2-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for alpha 2-PEG before treatment although after MPA therapy all specimens obtained exhibited marked alpha 2-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize alpha 2-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of alpha 2-PEG production after stimulation with an oral progestogen.
 ...
PMID:Immunohistological localization of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate. 297 52

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.
 ...
PMID:Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium. 299 80

The effect of high dose medroxyprogesterone acetate (MPA) on serum lipids, on adipose tissue lipoprotein lipase (LPL) and serum lecithin cholesterol acyltransferase activities were studied in 15 postmenopausal patients with endometrial cancer. After 2 weeks of MPA treatment total cholesterol decreased by 14% (P less than 0.001) and HDL cholesterol by 33% (P less than 0.01) from the respective pretreatment values; correspondingly the ratio of HDL to total cholesterol decreased (P less than 0.05). The decrease of HDL2 cholesterol was 35% (P less than 0.01) and that of HDL3 cholesterol 15% (P less than 0.01). The levels of serum triglycerides decreased significantly (P less than 0.05) during the treatment period. Serum LCAT activity was significantly lower (P less than 0.05) after treatment than before, but adipose tissue LPL activity was not altered. The mean serum testosterone level decreased significantly (P less than 0.001) from the pretreatment values. Significant positive correlations were present between LPL activity and MPA concentrations and between LPL activity and testosterone concentrations after the drug treatment.
 ...
PMID:Effects of high dose progestin on serum lipids and lipid metabolizing enzymes in patients with endometrial cancer. 315 2

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.
 ...
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

The steroid receptor content of the primary endometrial cancer of 22 patients who were treated for recurrent or advanced disease has been measured and correlated with response to medroxyprogesterone acetate. No patient with a progesterone receptor (PR)-negative tumor responded and only 2 patients with PR-positive tumors responded, perhaps related to the low levels of PR in the tumors. It waits to be assessed whether receptor status is as good a guide to response to hormone therapy as tumor differentiation, site of recurrence, or disease-free interval.
 ...
PMID:Endometrial carcinoma: steroid receptors and response to medroxyprogesterone acetate. 315 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>