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)

In a study carried out in Germany between 1985-89 unintended pregnancy was found in 7.9% of girls aged 15-21 in 1985 and in 5.2% in 1989. A study of 2905 young people aged 14-18 in Austria indicated that 75% of girls and 55% of boys had sexual intercourse by age 18 making contraception vital for adolescents. Among oral contraceptives (OCs) micropills with 20 mcg ethinyl estradiol barely affect the follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, but the gestagen component can induce bleeding, spotting, and breast symptoms. Discontinuation quickly restores the normal connection of the hypophysis and ovary without affecting later pregnancy. 5.1 years after the end of high-dose combination OC use for 9-46 months only 3 out of 13 women did not become pregnant. OCs reduce bleeding disorders, anemia, and dysmenorrhea, ovarian cancer, and endometrial cancer. Their effect on breast cancer is not clear. Phenobarbital and rifampicin accelerate OC metabolism, and OCs reduce the effect of anticonvulsives and tolbutamide (for hypoglycemia). Neogynon and Stediril D are postcoital pills used within 48 hours of intercourse. IUDs are not recommended, as adnexal infection is 1.5-2 times higher in girls 14018 using IUDs. The effectiveness of the diaphragm and condom depend on motivation; creams and vaginal sponges are useful but they may cause irritation. The Billings method produced only a 2.9 Pearl-index reliability in 7000 cycles, thus natural methods often fail. Before age 14 girls must have parental consent for prescription of OCs, after 14 the physician is not liable for OC prescription, but induced abortion still requires parental consent until age 18.
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PMID:[Contraception in adolescents]. 174 70

Tamoxifen (TXF), a triphenylethylene antiestrogen, is the major therapeutic agent for breast cancer. In rare cases, TXF treatment appears to increase incidence of endometrial cancer. Also in rats, TXF was found to induce hepatocellular carcinoma. Previous studies suggested that metabolism of TXF may contribute to its antiestrogenic and anticancer activity. The current study demonstrates a novel route of TXF metabolism. TXF is metabolized by rat and human liver microsomes into a reactive intermediate (txf*) which binds irreversibly to microsomal proteins. The binding requires NADPH and O2 and is inhibited by CO, inhibitors of P-450, and antibodies to rat NADPH-P450 reductase, indicating catalysis by P450. Phenobarbital treatment of rats markedly increases binding, suggesting the involvement of induced P450s. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins from incubation of [14C] TXF with phenobarbital-treated microsomes exhibits a major radiolabeled zone which corresponds to a molecular weight of approximately 54,000, suggesting binding to a P-450. Cysteine and glutathione inhibited the binding of TXF without significantly affecting P-450-mediated metabolism of TXF, possibly by reacting with txf* or by competing for the same binding sites. Exposure of phenobarbital-treated microsomes and control-microsomes to 50 degrees C for 90 s, which inactivates the flavin-containing monooxygenase (FMO), diminished binding and pH 8.6 enhanced binding. Also, alternate FMO substrates inhibited binding. These findings indicate that P-450 and possibly FMO catalyze the reactions leading to the formation of txf*. However, incubations with single-labeled and dual-radiolabeled tamoxifen or with [14C]TXF-N-oxide demonstrated that monodesmethyl-TXF and TXF-N-oxide, the principal P-450 and FMO-mediated metabolites, respectively, are not on the major route of txf* formation, indicating that txf* could not be an aldehyde derived from tamoxifen nitrone. Thus, though the structure of txf* was not characterized, certain possibilities were excluded. Speculations on the structure of txf* and on its possible pharmacological and toxicological activity are presented.
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PMID:Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: possible involvement of flavin-containing monooxygenases in tamoxifen activation. 193 68