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

Addition of cGMP to cytosol of human endometrium or to cells of the endometrial cancer line HEC-1 produced severalfold increases in specific estrogen binding (EB) levels. This effect was maximal with 1 microM cGMP in the presence of 0.1 mM isobutylmethylxanthine (a phosphodiesterase inhibitor) during incubations with [3H]estradiol. In contrast, cAMP decreased EB levels under similar conditions. The effects of cyclic nucleotides on EB levels were complete in less than 15 min in the presence of Mg2+, Mn2+, or Ca2+. The EB sites generated by the addition of cGMP during labeling of cytosol with 10 nM [3H]estradiol were found to sediment in the 8S and 4S regions of low-salt glycerol gradients. No changes in EB levels were observed when cyclic nucleotides were added to cytosol depleted of ATP by preincubation at 4 degrees C for 3 hr, but responsiveness was restored by addition of exogenous ATP. The ATP requirement and the pattern of dependence of cyclic nucleotide actions on divalent cation concentrations suggest that cGMP and cAMP effects may be mediated by kinases and may involve phosphorylations. Another possibility is that the cyclic nucleotides interact allosterically with the binder in the presence of ATP. Addition of sodium molybdate, ATP, and GTP to homogenates of endometrial tissue or HEC-1 cells produces increases in EB levels similar to those obtained by the addition of cGMP. However, these compounds are much less active when added to cytoplasm or cytosol. On the basis of these and other observations, it is hypothesized that molybdate, ATP, and GTP affect EB levels primarily by increasing cGMP concentrations through processes involving a plasma membrane-bound guanylate cyclase.
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PMID:Rapid changes in specific estrogen binding elicited by cGMP or cAMP in cytosol from human endometrial cells. 630 87

The use of estrogen replacement therapy in postmenopausal women is under close scrutiny. The indications and side effects of replacement therapy are reviewed, and recommendations regarding its use are made. Hot flashes, atrophy of the vaginal epithelium, and prevention of osteoporosis have been established as indications for estrogen replacement therapy. Prevention of cardiovascular disease, aging changes of skin, and the occurrence of mental illness have also been suggested as indications, but beneficial effects of estrogen replacement therapy for these problems have not been clearly established. Studies have shown that side effects of estrogen replacement therapy include endometrial cancer, hypertension, gallbladder disease, and angina pectoris. Breast cancer may also be a risk factor, but a consensus of opinion has not been established. Pulmonary embolism, cerebral vascular accident, or myocardial infarction has not been associated with estrogen replacement therapy. The use of progesterone with estrogen replacement therapy has been shown to reduce the occurrence rate of endometrial carcinoma, but it does not prevent all the actions of estrogen. Oral administration of estrogen is the preferred route despite misgivings about portal absorption and liver metabolism. Further studies must examine this question. Various agents have been shown to be effective in treating some climacteric symptoms. These include progesterone for hot flashes and calcium for the prevention of osteoporosis. Other agents may also be effective but have not been tested critically.
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PMID:Estrogen replacement therapy. 702 79

Entry into menopause is associated with a severe diminution of ovarian estrogen and progesterone secretion and a reduction of circulating androgens, although, in the presence of ovaries, a degree of testosterone secretion persists. Menopause is associated to a varying degree and severity, with hot flashes--a disorder of central thermoregulation--progressive sex tissue atrophy, and accelerated bone mineral loss that eventually leads to a substantial prevalence of osteoporosis, with spine, hip, and radial fractures, particularly in thin, inactive smokers with low calcium intake. Treatment with estrogens eliminates hot flashes and sex tissue atrophy and prevents osteoporosis. Unfortunately, oral estrogen therapy results in overstimulation of the liver, producing secreted proteins and an increased risk of endometrial carcinoma and gallbladder disease. The addition of a progestogen will diminish the risk of endometrial carcinoma, presumably by reducing estrogen-receptor concentration and increasing estradiol dehydrogenase activity but will usually result in vaginal bleeding in women with uteri. The use of estrogen therapy with or without a progestin should be an informed joint decision of physician and patient that must be reevaluated regularly as new information becomes available.
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PMID:Menopausal endocrinology and management. 704 70

Fasting calcium excretion, renal phosphorus threshold, plasma 1,25 dihydroxyvitamin D, immunoreactive PTH, nephrogenous cyclic AMP excretion, and tumor burden were assessed in nine patients with gynecologic neoplasms and hypercalcemia. Gynecologic neoplasms were responsible for hypercalcemia in seven of 34 (20.5%) consecutive patients with malignancy-associated hypercalcemia. The tumor burden in each patient was large. Three of four endometrial carcinomas contained squamous elements. All patients displayed biochemical evidence of nonparathyroid humorally mediated hypercalcemia (bone resorption). Treatment of hypercalcemia did not appear to diminish production of the humoral calcemic factor but eradication of tumor eliminated biochemical evidence of the humoral syndrome. It can be concluded that (1) gynecologic neoplasms are a frequent cause of malignancy-associated hypercalcemia, (2) humoral mechanisms appeared to be responsible for the hypercalcemia in 100% of the patients in this series, (3) squamous features occur with unexpected frequency in hypercalcemic endometrial carcinoma, (4) the presence of hypercalcemia connotes a large tumor burden, and (5) treatment directed at the neoplasm (but not treatment directed at hypercalcemia) may eliminate evidence of ectopic calcemic hormone production.
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PMID:Hypercalcemia associated with gynecologic malignancies: biochemical characterization. 707 51

We investigated the synthesis and biological effects of platelet-activating factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC-1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded cells, PAF stimulates [Ca2+]i increase with a median effective concentration of 5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the nuclear protooncogene c-fos with a median effective concentration of 130 nM and stimulates DNA synthesis (median effective concentration, 700 nM). All of these effects are inhibited by the PAF receptor antagonist L659,989. Radioligand binding studies indicated the presence of two populations of PAF receptors with affinity constants in the nanomolar and micromolar range. Since the PAF antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA synthesis. Our results provide evidence for the existence of an autocrine proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.
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PMID:Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A. 752 Mar 61

A comparative study was carried out in 350 women using VCu200 intrauterine devices (IUD) and 350 women using stainless steel ring (SSR) IUD for 5-18 years. The endometrial changes and shapes of IUD were studied. The results showed that the pregnancy rate was significantly lower in VCu200 group after 5 years of insertion. In spite of the oxidation, erosion or breakage of the copper wire, calcium deposit of even deformation of the IUD, they were not associated with an increased incidence of endometrial carcinoma and pelvic inflammatory disease. It is suggested that VCu200 IUD need not to be removed if the IUD keeps normal shape and the copper wire remains intact by X ray examination.
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PMID:[Long-term clinical observation on VCu200 intrauterine devices]. 783 33

An adequate calcium intake is important to attain peak bone mass and to oppose that component of age-related bone loss due to insufficient intestinal calcium absorption. Calcium and appropriate vitamin D supplements are particularly important for preventing cortical bone loss and associated hip fractures in the elderly (Type II osteoporosis). Within the initial 5 years following menopause, there is an accelerated loss of trabecular bone from the spine and distal radius (Type I osteoporosis). At that time, estrogen replacement is most effective for preventing the rapid trabecular bone loss that could otherwise result in vertebral or Colles' fractures. During this early period of estrogen deficiency when excessive bone turnover is releasing large amounts of calcium into the circulation, supplemental calcium is ineffective. Progesterone, often given with estrogen to prevent endometrial carcinoma, may itself have a trophic influence on bone.
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PMID:Calcium, estrogen, and progestin in the treatment of osteoporosis. 798 85

Osteoporosis is a major health problem in postmenopausal women. Although estrogen replacement in adequate dosage can slow or even prevent bone loss, only a small percentage of postmenopausal women receive such therapy; many who do fail to comply with the prescribed regimen because of the fear of cancer and the occurrence of withdrawal bleeding, irregular bleeding, or both, and other side effects. Use of lower estrogen dosages has been suggested as a means of improving compliance and enhancing safety without compromising efficacy. Compared with standard therapy, low-dosage estrogen may minimize the increased risk of both endometrial hyperplasia and endometrial cancer. Most women find low-dosage estrogen more acceptable than higher dosages because they experience less bleeding and are more likely to become amenorrheic. Low-dosage estrogen along with sufficient calcium intake effectively maintains bone density in postmenopausal women. In the recent study of unopposed estrogen therapy described here, micronized 17 beta-estradiol in the range of 0.5 to 2.0 mg, given with dietary and supplemental calcium to ensure a minimum of 1500 mg/day, effectively maintained spinal trabecular bone density. None of the women who received the lowest dosage of 0.5 mg/day micronized 17 beta-estradiol experienced vaginal bleeding, and after 18 months the incidence of endometrial hyperplasia in this dosage group (17%) tended to be lower than those in the 1.0-mg and 2.0-mg dosage groups (29% and 22%, respectively). There was a trend toward fewer vasomotor symptoms among women who received the 0.5-mg and 1.0-mg dosages of micronized 17 beta-estradiol compared with those who received placebo. The 2.0-mg dosage group had a significantly lower incidence of vasomotor symptoms (P = 0.02) than the placebo group. Micronized 17 beta-estradiol (0.5 mg/day) with an adequate intake of dietary or supplementary calcium (1500 mg/day) is an appropriate choice for postmenopausal women in whom low-dosage estrogen therapy is indicated. This regimen, while proving efficacious in the prevention of bone loss, may be especially helpful for women who wish to minimize the bleeding that accompanies usual-dosage hormone-replacement regimens and should enhance compliance with the prescribed therapy.
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PMID:Use of low-dosage 17 beta-estradiol for the prevention of osteoporosis. 811 15

The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy. This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin. Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus, but the contribution of progestins for about 10 days every month excludes this risk. Breast cancer in relation to estrogen-progestogen therapy has been given much concern, and the problem is still not fully solved. If there is a risk, it is small, and only after prolonged use of estrogen (15-20 years). The decision whether or not to use hormone replacement therapy should, of course, be taken by the individual woman in question, but her decision should be based on the available scientific information. It is the opinion of the authors that the advantages of hormone replacement therapy far exceed the disadvantages. We suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular diseases.
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PMID:Postmenopausal hormone replacement therapy--clinical implications. 819 55

Cancers of the breast and endometrium, although hormonally-dependent, are not complete contraindications to hormonal replacement therapy. About 70% of women with endometrial cancer will be completely cured of their disease using appropriate surgical techniques and therefore can be given oestrogen without in any way compromising their long-term survival. In fact oestrogen will probably allow such women to survive longer with a higher quality of life. Most postmenopausal women with cancer of the breast should be offered an impeded oestrogen such as tamoxifen as their first line of hormonal treatment. There may be improvement in the vagina and bone calcium content following the use of this 'anti-oestrogen' but some women will continue to suffer from vasovagal symptoms. Women with breast cancer which is small, node-free and relatively non-aggressive may also do well on HRT. Because of the influence of progestogens in reducing oestrogen receptor production, in reducing the expression of various growth factors and in inducing apoptosis, it is wise to administer high-dose progestogens to these women as well as oestrogen. There is no clinical evidence that HRT administered to such women will induce any increase in tumour growth or recurrence. Women with a disease-free survival of 10 or more years can also be regarded as 'cured' and can also be offered oestrogen in conjunction with high-dose progestogens. Finally, those women with known secondary spread but who are severely disadvantaged by their oestrogen deficiency symptoms should be offered high-dose progestogens first and if their symptoms persist, then have oestrogen added to the regimen till the symptoms subside.
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PMID:Hormone therapy following breast and uterine cancer. 843 54


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