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)

Unexpected hysterographic findings were encountered in 42 of 105 patients with postmenopausal bleeding or endometrial carcinoma. These included the extent and location of tumor, size and position of the uterus, uterine perforations or fistulas, and undetected myomas, congenital defects, or adnexal pathology. The findings proved of sufficient value in clinical management that hysterography, using water soluble medium, has been adopted as a routine procedure in such cases, especially if radium or cesium packing is employed. There was no statistically significant correlation between the histologic grade of the tumor and the hysterographic appearance of well-circumscribed or diffusely infiltrating lesions. Intravasation of contrast media occurred in 9 patients, lymphatic uptake was observed in 8, and peritoneal spillage of dye in 31 patients. There was no significant morbidity, and results to date show no evidence of tumor spread from the procedure.
 ...
PMID:Routine use of hysterography in endometrial carcinoma and postmenopausal bleeding. 116 21

Aromatase activity and concentrations of cortisol, progesterone and testosterone were measured in samples of breast and abdominal adipose tissue obtained from both pre- and postmenopausal subjects. Enzyme activity was determined by the incorporation of tritium from [1 beta-3H]androstenedione into water and found to be in close agreement to that measured when tritium labelled oestrone (E1) and oestradiol (E2) were isolated. No significant difference in enzyme activity was noted between breast and abdominal adipose tissue. Increased aromatase activity was not observed in adipose tissue taken from a subject with endometrial cancer. Cortisol concentrations were found to be significantly higher (P less than 0.05) in abdominal as compared to breast tissue. Without attaining statistical significance progesterone concentrations were higher in abdominal as compared to breast adipose tissue. Aromatase activity was not related to either cortisol or testosterone tissue concentration, but an inverse relationship between progesterone concentration and aromatase activity was observed (r = 0.542, P less than 0.02). On the basis of results obtained a hypothesis for the increased conversion of androgen to oestrogen as seen after the menopause has been proposed.
 ...
PMID:Aromatase activity and concentrations of cortisol, progesterone and testosterone in breast and abdominal adipose tissue. 372 41

Menopausal disorders coincide with the onset of luteal insufficiency and the resulting relative hyperestrogenism. At this stage the risks to be assessed are mainly related to a worsening of the menstrual syndrome (heaviness of the legs, abdominal distention, water retention, mastodynia, depressive syndrome), cycle changes, or various genital types of hemorrhage requiring investigation for detection of a possible fibroma, hyperplasia, endometriosis, or genital cancer. Once the menopause is settled a reduction in estrogen levels comes with reactive increases in FSM and LM levels, and the principal risk is the development of a cancer. The role of endogenous (obesity, diabetes, Stein-Leventhal, adenomatous hyperplasia) or exogenous (prolonged estrogen therapy alone) estrogens has to be evaluated in endometrial cancer. Cancer of the vulva also appears to be more frequent in menopausal women (natural or artificial), as well as cervical cancer and cancer of the breast. There is an apparent increase in cardiovascular risks in untreated menopausal women, but this is still discussed, as to the benefits of estrogen therapy.
 ...
PMID:[Menopausal risk factors (author's transl)]. 625 25

Adipose tissue is the principal site of extraglandular estrogen formation in nonpregnant women. The importance of adipose tissue as a site of estrogen formation is emphasized by the finding that increased body weight is associated with an increased incidence of endometrial carcinoma. In the present study, the kinetics of estrogen formation from androstenedione by adipocytes and by stromal cells isolated from human adipose tissue as well as by membrane fractions prepared from these cells were investigated. Subcutaneous adipose tissue samples obtained from women were dispersed by collagenase treatment, and aromatase activity was assayed by the incorporation of tritium from [1-3H]androstenedione into [3H]water. As previously reported, aromatase activity was found in intact stromal cells of adipose tissue, whereas little aromatase activity was detected in intact adipocytes. When crude membrane fractions (100,000 X g pellet) of stromal cells and adipocytes were incubated in the presence of [1-3H]androstenedione and an NADPH-generating system, however, aromatase activity was found in membrane fractions of both stromal cells and adipocytes, and estrogen formation increased in a linear manner as a function of time and membrane protein concentration. The apparent Michaelis constant (Km) of aromatase for androstenedione of intact stromal cells was 0.03 microM, whereas intact adipocytes did not convert androstenedione to estrone at substrate concentrations up to 3.0 microM. In membrane fractions of stromal cells, the rate of aromatization as a function of androstenedione concentration did not follow simple Michaelis-Menten kinetics, and both low affinity (Km = 1.03 microM) and high affinity (Km = 0.10 microM) components were observed. The affinity of androstenedione for aromatase of adipocyte membrane fractions was low; the rate of aromatization was not saturable at concentrations of androstenedione up to 3.0 microM. When intact adipocytes were incubated with [1-3H]androstenedione, then homogenized, and the homogenate was treated by differential centrifugation, the radioactivity that was added to the medium was found almost entirely in the lipid fraction of the cells. This finding is indicative that the low aromatase activity in intact adipocytes is the result of sequestration of steroid in lipid droplets in the cells. We suggest that the stromal cells of adipose tissue are a major source of the increased estrogen production in obese persons; a role for adipocytes in the regulation of adipose tissue estrogen formation, however, cannot be excluded at this time.
 ...
PMID:Aromatase activity of membrane fractions of human adipose tissue stromal cells and adipocytes. 664 29

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.
 ...
PMID:Estrogen sulfoconjugation by human endometrial cancer cells (RL95-2) in culture. 669 41

This paper reviews both minor and major adverse reactions caused by estrogenic substances (natural and synthetic, steroidal and nonsteroidal) of which diethylstilbestrol is the prototype of nonsteroidal synthetic estrogen. Minor side effects include nausea, breast tenderness, and excessive cervical secretions (most common), headache, and water and salt retention (less common and often eradicated by lowering estrogen dosage). Vertigo, yeast infections, depression, and photosensitivity are other minor effects. Major side effects are discussed in some detail. Major effects include those on the endocrine system (e.g., feminization in boys and men and precocious puberty in girls); breast tumors; endometrial carcinoma; ovarian tumors; hypertension; thromboembolism; blood clotting excesses; various metabolic effects (including lipid metabolism and carbohydrate metabolism alterations); liver changes (bile alterations and neoplasms); porphyria; melanoma; and effects on a fetus in situ during maternal estrogen administration. In general, lowering doses of estrogen should help eradicate or alleviate most of these effects.
 ...
PMID:Clinical toxicology of estrogens. 741 28

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for the presence of P450arom transcripts in normal endometrium, decidualized endometrium, or endometrial stromal cells in culture. In our hands, assay of aromatase activity using [3H]water release from [3H]androstenedione by endometrial stromal cells in culture treated with MPA and E2, did not reveal any detectable aromatase activity. The same cells responded to MPA plus E2 treatment by a significant increase in PRL secretion into the culture medium. Presently, RT-PCR is the most sensitive method available for the detection of specific mRNA species in low copy numbers. These findings are indicative of the absence of P450arom transcripts in normal human endometrium.
 ...
PMID:Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua. 768 41

Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.
 ...
PMID:[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. 1178 98

Progestin-only injectables are among the most effective and safe of all contraceptives, yet they are not widely used in many countries. This limited use is in part due to a lack of accurate information about health concerns, inadequate counseling for users about managing side effects, and their limited availability. Where they are available, progestin-only injectables rapidly become one of the preferred methods. Depot-medroxyprogesterone acetate (DMPA) and norethindrone enanthate (NET-EN) are the two progestin-only injectables in use worldwide. The former drug is sold under the brand name Depo-Provera, and the latter as Noristerat. DMPA is delivered in a water-based, crystalline suspension and absorbed gradually by the body. The normal injection of 150 mg is intended to be administered every three months, but contraceptive protection continues for an additional two weeks to provide a grace period for women who are late receiving their next injection. NET-EN is an oily solution which requires a larger needle than DMPA for injection. A 200 mg injection of NET-EN is usually administered every two months. Both of these safe, highly effective drugs are injected in either the upper arm or buttocks. DMPA and NET-EN can be distributed easily in nonclinical settings where nonphysicians can provide them to clients. The main disadvantage of the method is the disruption of the menstrual cycle, but that is generally not a serious medical problem. Focusing mainly upon DMPA, this article includes discussion of menstrual irregularity, the reduced risk of endometrial cancer among DMPA users, and method availability.
 ...
PMID:Progestin-only injectables offer many advantages. 1228 28

In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than 30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is .5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not coerced to use it.
 ...
PMID:FDA gives final approval to Depo amid concerns over safety, cost and coercion. 1234 20


1 2 3 4 Next >>