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)

Exogenous hormones are widely prescribed in the United States, primarily as oral contraceptives and hormone-replacement therapy. Each of these frequently used categories of drugs has important potential for altering risk of several major human cancers. The efficacy of oral contraceptives in preventing ovarian cancer and endometrial cancer is well established. There remains controversy about the relationship between oral-contraceptive use and breast cancer risk, but most studies show that use in the postmenarcheal and perimenopausal periods is associated with an increased risk of breast cancer in a duration-dependent manner. As with oral contraceptives, the relationship between estrogen-replacement therapy and breast cancer risk is controversial, but several well-designed studies showed a moderate increased risk after long-term use. Estrogen-replacement therapy is a major cause of endometrial cancer. Combination hormone-replacement therapy will probably reduce some of the excess risk of endometrial cancer, but few epidemiological data exist on this relationship. The sparse data suggest that combination therapy may enhance breast cancer risk. As with endometrial and ovarian cancers, hormonal chemoprevention of breast cancer is also feasible. We review two such strategies, ie, gonadotropin-releasing hormone agonists and the antiestrogenic drug tamoxifen.
 ...
PMID:Relationship of hormone use to cancer risk. 161 98

Specific low-affinity high-capacity binding sites for gonadotropin-releasing hormone (GnRH) have recently been discovered in human breast and ovarian carcinomata. We checked whether similar binding sites are present in human endometrial cancer. Plasma membrane preparations were incubated with [125I,D-Ala6-desGly10]-GnRH-ethylamide in the presence or absence of unlabelled GnRH agonists or other peptides. GnRH-binding could be demonstrated in all 12 tumor samples tested. The mathematical analysis of the binding data was consistent with a single class of low affinity (Ka = (0.8-1.4) x 10(5) M-1) and high-capacity (Bmax = (134-142) x 10(-12) M/mg membrane protein) binding sites. Native GnRH had a similar affinity to the binding sites as the GnRH agonist used. Other peptides such as oxytocin, somatostatin and thyrotropin-releasing hormone did not crossreact with the binding sites. A photolabelled derivative of [D-Lys6]-GnRH was prepared with the bifunctional photolabile reagent (4-azidobenzyl)-N-hydroxysuccinimide. Photoaffinity labelling of endometrial carcinoma membranes and subsequent sodium dodecyl sulfate electrophoresis in 10% polyacrylamide gel revealed the presence of a single molecular mass component of 62 +/- 1.9 kDa. The appearance of this photolabelled binding site could be largely suppressed by the addition of unlabelled GnRH-agonist (10(-4) M) and thus represents the specific binding site for GnRH in endometrial cancer.
 ...
PMID:Specific low affinity binding sites for gonadotropin-releasing hormone in human endometrial carcinomata. 165 55

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.
 ...
PMID:[Peroral treatment with natural human estrogens in the climacteric]. 744 54

Women with hyperandrogenic disorders represent a unique group among those with infertility due to anovulation. Although antiestrogens are effective in restoring ovulation in most women, it remains unclear whether these treatments restore fecundability per ovulatory cycle and the ability to maintain pregnancy in these individuals. Moreover, antiestrogens are ineffective in restoring ovulation in some hyperandrogenic anovulatory women, whose condition poses unique and vexing challenges for the infertility therapist. Gonadotropin treatment in antiestrogen-resistant women often leads to ovarian hyperstimulation syndrome, which has been addressed by modification of dosing schedules (e.g., low-dose administration), pretreatment with gonadotropin-releasing hormone (GnRH) analogs, and elimination of luteinizing hormone from the administered gonadotropins. Surgical reduction in ovarian volume has met with some success, although there may be a risk of inducing surgical adhesions of the adnexa. The second major reproductive adversity facing these patients is their elevated risk of endometrial cancer. Unopposed estrogen exposure probably contributes to this risk, but hyperandrogenicity and hyperinsulinism may act independently or in concert with estrogen to amplify the risk in these women. While the risks and strategies for preventive care in these women need to be better defined, reproductive health specialists are urged to continue using presently accepted measures, including education, to maintain these women's reproductive health.
 ...
PMID:Reproductive health and polycystic ovary syndrome. 782 42

In support of a possible clinical use of gonadotropin-releasing hormone (Gn-RH) analogs in the treatment of the endometrial carcinoma, this study was undertaken to establish the presence and characteristics of Gn-RH receptor on endometrial cancer. Materials were human endometrial carcinomas surgically removed and endometrial carcinoma cell lines. Gn-RH receptor was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RH receptor messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (PCR) using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence. Specific Gn-RH binding sites were shown to be present in 16 of 18 well-differentiated and 4 of 7 poorly differentiated adenocarcinoma specimens (Kd = 5.89 +/- 3.59 nM, Bmax = 1.80 +/- 0.95 pmol/mg protein) and cell lines RL95-2 and HHUA with Kd of 2.38 +/- 0.86 nM. The high-affinity binding sites were also detected in six proliferative-phase endometrium (Kd = 4.24 +/- 2.32 nM, Bmax = 2.73 +/- 1.12 pmol/mg protein). Gn-RH receptor mRNA was detected in all endometrial carcinoma and endometrial specimens and cell lines where the specific binding sites were detected, but not in adenomyosis or myometrial samples. The expression of Gn-RH receptor provides a possible point of attack for therapeutic approaches using Gn-RH analogs in this malignancy.
 ...
PMID:Presence of gonadotropin-releasing hormone receptor and its messenger ribonucleic acid in endometrial carcinoma and endometrium. 795 56

The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase III clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50% of breast cancers and 80% of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.
 ...
PMID:The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. 1096 15

Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB.
 ...
PMID:Dysfunctional uterine bleeding (DUB). 797 56

Mitogenesis is a major driving force in neoplastic development. Blocking the effect of breast cell mitogens by reducing the actual exposure of the breast to these mitogens is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. A woman's exposure to ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the synthetic estrogen and progestogen in the COCs effectively replace ovarian estrogens and progesterone, so that breast cell exposure to these hormones is not decreased. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist (GnRHA) to suppress ovarian function and compensate for the resulting hypoestrogenemia with low-dose hormone replacement therapy. Compared to modern COCs, estrogen exposure can be reduced by approximately 60%, and progestogen dose by more than 80%. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years. The possibility that a practical contraceptive could achieve such a major benefit is shown by the dramatic decline in the incidence of both ovarian and endometrial cancer in young women in the U.S. over the last 3 decades--a direct result of COC use.
 ...
PMID:The chemoprevention of breast cancer by reducing sex steroid exposure: perspectives from epidemiology. 800 6

It has been widely accepted that the estrogen is one of the contributing factors to the development of endometrial cancer of the uterus. The objective responsiveness of recurrent endometrial cancer to medroxyprogesterone acetate (MPA) has been substantiated. Many researchers have examined whether the anti-estrogenic agents could be the choice of treatment of endometrial cancer including tamoxifen (TAM), aromatase inhibitors, danazol and luteinizing releasing hormone (LHRH)-agonist as an adjunctive endocrine therapy. In this review, we discussed the pharmacological and clinical aspects of these new agents.
 ...
PMID:[Antiestrogen therapy of patients with uterine cancer]. 816 86

The presence of a direct extra-pituitary action of gonadotropin-releasing hormone (GnRH) via specific receptors in endometrial cancer (EC) has been suggested as an explanation for the therapeutic effect of GnRH analogue (GnRHa) in recurrent disease. We have sought the expression of the GnRH peptide and functional GnRH receptor (GnRH-R) in human tissues and cell lines to investigate the possibility of an autocrine growth regulation mechanism. Using reverse transcription-PCR, differing GnRH mRNA transcripts were detected in two EC cell lines (Ishikawa and HEC-1A), a choriocarcinoma (JEG3) cell line, and tissues from endometrium and placenta. However, secretion of immunoreactive GnRH could be detected by RIA in only 1 of 10 EC tissues in primary culture, and in none of the cell lines. Low levels of GnRH-R mRNA expression were found in the same cells, which were only detectable by reverse transcription-PCR and Southern blotting of the PCR product. In radioligand binding assays using GnRHa goserelin, no pituitary-like, high-affinity GnRH binding sites could be found in either EC cell lines or tissues. Low affinity binding (Kd = 1.0 - 3.1 x 10(-7)M) was detected in three of eight (37%) EC tissues. Furthermore, receptor signal transduction measurements carried out in these cells showed no increases in either total inositol phosphate, cyclic AMP production, or cytosolic Ca2+ in response to either GnRH or GnRHa. Finally, no effect of either GnRH or GnRHa on the growth of EC cell lines was detected in vitro, under estrogen-free conditions, assessed by DNA content. Our data suggest that although there is a potential for autocrine activity for GnRH in EC as judged by the presence of mRNA for peptide and receptor, no functional receptor activity could be detected in vitro. Alternative mechanisms should be studied to explain the in vitro action of GnRHa.
 ...
PMID:The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factor. 861 51


1 2 3 4 5 Next >>