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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian and endometrial cancer tissues were examined for the presence of human papillomavirus (HPV) and the results were compared with the findings in normal tissues by polymerase chain reaction. Putative DNA of HPV types 16 and 18 that target DNA sequences from paraffin-embedded tissues were amplified with paired oligonucleotide primers that encode the E6 gene of HPV. The amplified DNA sequences were then detected with Southern blot hybridization analysis. The HPV DNA sequences were detected in both benign (50% ovarian, 70% endometrial) and malignant ovarian (27.2%) and endometrial (37.5%) tissue samples. Interestingly, eight hepatoma samples were also analyzed as tissue controls. The results were negative in seven, but positive in one with repeated tests. The results suggest that the spread of HPV in the upper genital tract may not be uncommon. The explanation of a positive liver tissue study result will have to await further study.
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PMID:Human papillomavirus in benign and malignant ovarian and endometrial tissues. 132 79

Well over 100,000,000 women have used the combined oral contraceptive (OC) pill. As a result of the population explosion in the 1970s and 1980s, there will be almost one third more women in fertile age in the year 2000 than in 1991. In the developing world outside China, the total number of contraceptive users could double in roughly 10 years. China, the total number of contraceptive users could double in roughly 10 years. The pill has a low failure rate, but one study in Egypt found that 90% of women made errors in moving from one packet to the next. Similarly, a 60% error rate was found among users in Colombia. The vaginal ring delivers combined progestogen and estrogen through a silastic wall. The device can be left in place for 21 days out of 28, and such delivery would virtually eliminate the low risk of hepatocellular carcinoma among OC users. A vaginal progestogen ring is being tested. Over 700,000 women have used Norplant, the subdermal implant method with an effectiveness rate of 99%. Depo-provera and norethindrone enanthate injections last 2 to 3 months. The Progestasert IUD, containing 38 mg progesterone released at a rate of 65 mcg per day, is effective. Progesterone-releasing IUDs lasting from 3 to 5 years could complement subdermal implants. Ethinyl estradiol (205 mg) and diethylstilbestrol (25-50 mg) have both been used as postcoital agents taken within 36 hours for 5 consecutive days after unprotected intercourse. In more than 3000 cases there were 17 pregnancies (.05%). These regimens are replaced by giving combined oral contraceptive tables (e.g., .25 mg d-norgestrel and 50 mg ethinyl estradiol), taken 2 at a time and repeated 12 hours later, within 72 hours of unprotected intercourse. Epidemiological studies have confirmed that the use of the combined oral contraceptive for 3 to 5 years halves a woman's risk of ovarian or endometrial cancer, and the protection persists for 10 to 18 years after cessation of use.
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PMID:The future of hormonal contraception. 168 5

A reassessment of the risks of using oral contraceptives regarding cancer of the cervix, endometrium, ovary, breast and biliary system was commissioned in the form of a series of reviews, published in the journal Contraception, June 1991: this is the introduction to the reports. Since 1977, the risks of developing epithelial ovarian cancer and endometrial cancer have been clearly shown to be reduced and that protection persists for years even in ex-pill users. The chance of getting hepatocellular carcinoma is slightly higher in developed countries, still extremely rare; while not noticeably increased in those developing countries that have high liver cancer rates. The likelihood of getting cervical cancer is increased in some studies but not in others, reflecting the difficult problem of controlling of patterns of sexual behavior in this area. Even though broad analyses of breast cancer risks are reassuring, some detailed studies that focus on certain age groups of women do find increased breast cancer. A special multi-center, hospital-based, case-control study in developing countries, sponsored by WHO, concluded that the results of studies on cancer from developing countries are applicable to developing countries as well. So the overall benefits of using oral contraceptives outweigh the risks, both for women in areas where maternal morbidity and mortality are high, because of the effectiveness of the pill in preventing pregnancy; and in industrialized areas, where the benefits of preventing ovarian cancer alone is enough to make pill use safer than other methods, such as the condom. There appears to be no way to predict cancer risks for any subgroup of women who should avoid taking the pill.
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PMID:Oral contraceptives and neoplasia: an introduction. 186 31

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

From the extensive research conducted over the past 28 years, there is a clear picture that the noncontraceptive benefits of steroidal contraceptives are considerable and the benefits outweigh the risks. The risks associated with the increased incidence of thromboembolic disease have reduced with lower doses of both estrogen and progesterone. Also, the increased risk of hepatocellular carcinoma is very low, compared with the benefits. One benefit is the reduction in primary dysmenorrhea which was discovered in 1940. This occurs due to the suppression of ovulation and decrease in endometrial growth. Ovarian cysts resolve spontaneously; 3500 fewer hospitalizations due to ovarian cysts are reported for 1982. 11,000 fewer cases of ectopic pregnancy/year are a result of oral contraceptive (OC) use. Retrospective case studies have found that pelvic inflammatory disease (PID) is prevented by use of OCs. This happens because the cervical mucus remains thick throughout the menstrual cycle with OC use, and thus prevents transportation of bacteria by sperm from the lower to the upper genital tract. Another reason is the decreased amount of blood flow at the time of withdrawal provides a less conducive environment for bacteria growth. 15,000 annual hospitalizations for PID are estimated to have been prevented by OC use. The data on breast cancer are conflicting, but most do not show a link between OCs and breast cancer. In fact, benign breast disease may be reduced by 23,000 annual hospitalizations due to OC use. Another benefit of OC use is the decreased incidence of endometrial and ovarian cancer. The relative risk among OC users in 1987 was estimated at P = 0.6 for primary endometrial cancer. This beneficial effect continues after OC use is discontinued. There is a 40% reduction in the incidence of ovarian cancer among OC users compared with nonusers, and is related to duration of use, but the protective effect continues after OC use discontinuation. Bone mass is increased in women who use OCs, although further study is required to determine whether the increased bone mass protects from osteoporosis after menopause.
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PMID:Noncontraceptive health benefits and risks of steroidal contraception. 257 66

This review on the risks and benefits of oral contraceptives clarifies the risks and misperceptions, and discusses 10 potential health benefits. In the U.S. where maternal mortality is about 20.6/100,000, the risk of death from pills ranges from 1.8 for nonsmokers to 6.5 for smokers. It is likely that most of the small existing mortality risk of pill use is due to thromboembolism. Atherosclerosis, the major cause of death for U.S. women, may be reduced by the pill. It is still controversial whether pills increase risk of hepatocellular carcinoma and malignant melanoma; they protect against endometrial cancer (the 3rd greatest cancer killer) and ovarian (the 4th) cancer; they may increase risk slightly in some subgroups for breast and cervical cancer, although data are conflicting. Pills also protect against ectopic pregnancy, benign breast disease, pelvic inflammatory disease, ovarian cysts, iron deficiency anemia and possibly uterine fibroids and osteoporosis. It is no longer held that orals protect against toxic shock syndrome or rheumatoid arthritis. It is estimated that oral contraceptives avert 50,000 hospital admissions per year in the U.S.
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PMID:The health effects of oral contraceptives: misperceptions, controversies, and continuing good news. 266 76

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.
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PMID:Fine needle aspiration cytology of neoplasms metastatic to the breast. 347 62

This article reviews the research evidence on the relationship between oral contraceptives (OCs) and neoplasia. More recent epidemiologic studies in this area are considered to have greater validity than earlier studies, largely because of improved assessment of confounding factors. Encouraging has been the finding of a protective effect of OCs on endometrial and ovarian neoplasia: about 2000 cases of endometrial cancer and 1700 cases of ovarian cancer are averted in the US each year as a result of OC use. No consistent association, either adverse or beneficial, has emerged between OCs and breast cancer; however, high-dose combined OCs exert a protective effect on the development of benign breast disease after 2 years of use. Longterm combined OC use appears to be related to the development of benign liver lesions, but the research evidence on the association between OCs and hepatocellular carcinoma remains inconclusive. Of concern is the finding that longterm OC use is associated with an increased risk of cervical neoplasia. The mechanisms by which OCs might exert adverse effects on cervical epithelium are unclear.
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PMID:Oral contraceptives and neoplasia: 1987 update. 355 51

Tamoxifen is the major therapeutic agent for the treatment of hormone-dependent breast cancer. Tamoxifen treatment appears to be associated with an increased incidence of endometrial carcinoma in humans and hepatocellular carcinoma in rats. These carcinogenic effects of tamoxifen might be induced by the formation of a tamoxifen reactive intermediate that binds covalently to macromolecules. Liver microsomal cytochrome P450s (CYPs) catalyze the metabolism of tamoxifen, forming a reactive intermediate that binds irreversibly to microsomal proteins, primarily to a 54 kDa protein (Mani, C. and Kupfer, D., Cancer Res., 51, 6052-6058, 1991). The current study identifies the P450 enzymes that catalyze the activation of tamoxifen to a reactive intermediate in rats and humans. Among the species examined, rats, chickens and humans demonstrate low tamoxifen binding activity, ranging from 0.1 to 0.4 nmol bound/mg protein/h. In contrast, hamsters and mice exhibit high binding, 1.2 and 1.6 nmol/mg protein/h respectively. Treatment of male rats with phenobarbital or pregnenolone-16 alpha-carbonitrile (PCN) markedly elevated the binding of tamoxifen to liver microsomal proteins. Methylcholanthrene treatment had no effect on binding. These findings suggested the involvement of CYP3A in catalysis of the covalent binding. Alternate substrates of CYP3A, cortisol and erythromycin, inhibited tamoxifen binding in liver microsomes from PCN- and phenobarbital-treated rats. Treatment of rats with troleandomycin (TAO), an inducer of CYP3A, followed by the dissociation of the TAO-CYP3A complex, elevated the covalent binding to liver microsomes approximately 3-fold. Antibodies against rat CYP3A1 strongly inhibited tamoxifen binding to liver microsomes from PCN- and phenobarbital-treated rats, whereas the antibodies anti-CYP2B1/2B2 did not inhibit binding. In humans, tamoxifen binding was inhibited by the anti-rat CYP3A1 IgG and also by alternate substrates of CYP3A. These results indicate that the activation of tamoxifen to a reactive intermediate by rat and human liver microsomes is principally catalyzed by CYP3A enzymes.
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PMID:Involvement of cytochrome P4503A in catalysis of tamoxifen activation and covalent binding to rat and human liver microsomes. 800 Dec 26

The evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.
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PMID:Combined oral contraceptives: risks and benefits. 832 3


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