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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of synthetic estrogens on the N-nitrosomorpholine (NNM)-induced liver carcinogenesis in ovariectomized young adult female rats was investigated and compared to rats which received only the carcinogen or estrogens. Estrogens when chronically administered after the cessation of carcinogen treatment increased the carcinogenic effect of NNM. In such conditioned animals the number of nodules per number of rats was 23/31, that of hepato-cellular carcinomas 9/31, whereas in animals which received only the hepato-carcinogen the incidence of nodules and carcinomas in liver was respectively 11/31 and 3/31. Higher incidence of benign and malignant tumors in other organs was also observed in these animals. Rats which received a single dose of estrogens simultaneously with NNM developed slightly fewer tumors in liver and in other organs. Since under my experimental conditions the long-term treatment with synthetic estrogens alone did not induce any focus, nodule or hepatocellular carcinoma in the liver. I suggest that the estrogens were acting rather as tumor promotors than true initiators of liver carcinogenesis.
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PMID:The effect of estradiol-17-phenylpropionate and estradiol benzoate on N-nitrosomorpholine-induced liver carcinogenesis in ovariectomized female rats. 20 83

The effects of long-term estrogen replacement therapy upon neoplastic diseases were studied in 301 treated patients and 309 untreated patients. 207 women of each group had uteri in situ. Incidence figures for neoplasia were compared between the 2 groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 (p .05) and 9.3, respectively. The addition of synthetic progestin to estrogen therapy provided significant (p .001) protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. The data did not show an increased incidence of breast cancer among estrogen treated women, even with higher dosages or long-term therapy. It is recommended that estrogen therapy should be instituted whenever appropriate indications are present and no major contraindications exist; estrogen should be administered in the lowest dosage and duration that can adequately treat the indication for its use. Estrogens should probably be administered in cyclic fashion, especially if the uterus is in place, with sequentially added progestin.
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PMID:Effects of long-term estrogen replacement therapy. II. Neoplasia. 22 Aug 75

Some of the available data concerning the suspected association between oral contraceptive (OC) use and the development of cancer is surveyed, and the attempt is made to evaluate possible associations between OCs and human neoplasia in light of pregnancy risk or benefit of oral contraception. The principal investigative methods in humans include various epidemiologic approaches, and the methodologies most often used are case reports (tumor registries), disease rates and trends, case-control studies, and cohort studies. These methods cannot prove a causal relationship between exposure to a possible carcinogen and the occurrence of disease. Consistent positive or negative evidence, confirmed by multiple epidemiologic approaches, can be used to guide physicians and regulatory agencies in formulating policy for the clinical use of OCs. Both the progestogen-only and the combined OCs have been shown to have a protective effect on the development of benign breast disease with this protective effect not appearing until 2 years of use. Long-term combined OC use appears to be related to the development of benign liver neoplasia, and this risk increases with the dose of the steroid and the age of the user. These lesions are quite rare but may be life threatening because of potential spontaneous rupture and hemorrhage. Long-term postmenopausal use of estrogens appears to increase significantly the risk of developing endometrial hyperplasia and adenocarcinoma of the endometrium. Estrogens appear to be related to the growth of pre-existing uterine leiomyomas. Endocervical cells under the influence of progestogens may develop adenomatous changes, and these benign changes have on occasion been misinterpreted as carcinoma.
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PMID:Oral contraceptives and neoplasia. 37 12

This lengthy discussion of possible associations between both endogenous and exogenous estrogens and progestins to occurrence of human cancers begins by discussing endogenous metabolism of the 2 sex steroid types. For example, the endogenous production of estrogen is associated with anovulation and endometrial cancer, although clearly other risk factors are associated with these diseases, and breast cancer, which account for some or all of the sex hormones apparent carcinogenic effect. Also discussed are the modulating effects of estriol on response of the breast and endometrium to estradiol and estrogens, and the modulating effects of androgens on development of breast cancer. The bulk of the monograph concerns summaries of data on the correlations of exogenous sex hormones and human cancers. Attention is also paid to the use of exogenous sex hormones for treatments of human cancers. Estrogens have been used to treat endometrial cancer, breast cancer, and benign breast disease. Side effects of hormonal contraception discussed include gross and microscopic changes in the breast, benign breast disease, and breast cancer; in the uterus, exogenous hormonal contraception is associated with neoplastic changes in the cervix, cervical neoplasia, endometrial cancer, trophoblastic tumors, and uterine fibroids. Ovarian effects include nonneoplastic and benign lesions and ovarian cancers. Oral contraception may also correlate with incidences of pituitary and melanoma malignancies. Liver effects include both benign neoplasms and malignant tumors.
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PMID:Oestrogens and progestins in relation to human cancer. 39 83

Estrogens stimulate prolactin (PRL) synthesis by GH3 cells, a clonal strain of rat pituitary cells grown in culture. At 4 degrees C the binding of [3H]17 beta-estradiol to monolayer cultures of GH3 cells was specific and of limited capacity, with half-maximal and maximal binding after 1--2 h and 12 h, respectively. Scatchard analysis showed one single class of binding sites with Kd = 3.1 X 10(-10) M and n = 309 X 10(-15) mol 17 beta-estradiol/mg cell protein, calculated to give approx. 25,000 binding sites per cell. At 4 degrees C less than 10% of the specifically bound [3H]17 beta-estradiol was found in the nuclear fraction. When the incubation temperature was raised to 37 degrees C, the amount of radioactivity in the nucleus increased to 25% within 30 min with a corresponding reduction in the cytoplasm. The cytosol fractions from monolayer cultures as well as from tumors of GH3 cells contained specific 17 beta-estradiol binding proteins, having a sedimentation constant close to 8S in a salt-free buffer and 4S in the presence of 0.5 M KCl. scatchard analysis showed one single class of binding sites with Kd = 3.6 X 10(-10) M and n = 258 X 10(-15) mol 17 beta-estradiol/mg cytosol protein (GH3 tumor tissue). Thus, GH3 cells grown in culture and in the intact animal have similar binding characteristics as judged from the data for binding affinity, capacity and specificity. After the in vivo administration of [3H]17 beta-estradiol to GH3 tumor-bearing rats, radioactivity could be extracted (0.5 M KCl) from purified nuclei bound to 4.5S macromolecules. We suggest that the action of 17 beta-estradiol on GH3 cells involves an initial binding of the steroid to specific receptors in the cytoplasm, followed by transport of a fraction of the hormone-receptor complexes to the nucleus involving a temperature-sensitive step.
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PMID:Receptors for 17beta-estradiol in prolactin-secreting rat pituitary cells. 56 89

When present at diagnosis or when developing in the course of disease, the presence of bone metastases from prostate cancer is generally considered an indication to begin endocrine therapy, as this is clearly the most effective form of treatment for this problem. Endocrine therapy can stop progression of prostate cancer in 80-85% of cases. Endocrine therapy can relieve pain, prevent pathologic fractures, and prevent neurologic complications from bone metastases from prostate cancer. Rarely, bone scans may become normal after the start of endocrine therapy, but partial improvement or stabilization of bone scans are more commonly seen. While endocrine therapy has been the first line of treatment of metastatic prostate cancer for the past 50 years, the recent development of newer forms of endocrine therapy have increased the options in the past few years. In addition to orchiectomy and estrogens, newer alternatives include inhibitors of androgen synthesis, the class of agents termed "antiandrogens", and luteinizing hormone releasing-hormone (LHRH) analogues either alone or in combination. Orchiectomy causes a prompt fall in serum testosterone and is regarded by many as the "standard" form of endocrine therapy, but there is concern about the psychologic impact of surgery. Estrogens are being used less frequently today because of their real or potential side-effects, including cardiovascular and thromboembolic complications. The development of analogues of LHRH has resulted in another major choice for endocrine therapy, and one which is therapeutically equivalent to orchiectomy or estrogens. Since LHRH analogues may cause an early rise or "flare" in serum testosterone before it drops to castrate level, these agents should not be given alone to patients with severe pain or neurologic problems. The newly available antiandrogen flutamide can block the "flare", and may also improve survival when used with LHRH analogues or orchiectomy, especially when disease is less advanced. Not all studies of "combination therapy" support this conclusion. However, the use of flutamide is increasing significantly in the United States. Both the LHRH analogues and flutamide are fairly safe, but they are very expensive. Their use, in combination, is likely to become a progressively more common form of initial endocrine therapy in the future. The growing application of prostate specific antigen (PSA) as a tumor marker for prostate cancer has made the difficulty in interpreting changes in bone scans a much less critical problem in determining response to endocrine or other forms of therapy for advanced prostate cancer.
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PMID:Hormone therapy of prostatic bone metastases. 149 25

Previous studies from this laboratory have described that LNCaP prostate tumor cells contain an androgen receptor (AR) with a point mutation in the steroid-binding domain (codon 868, Thr to Ala). This defect leads to a change in specificity of the AR. Estrogens, progestagens, and some anti-androgens (e.g., cyproterone acetate, hydroxyflutamide, nilutamide) stimulate LNCaP cell growth rate through the AR. The present studies indicate that not all anti-androgens showed agonistic effects with the mutated receptor. The growth rate of LNCaP cells did not increase with the anti-androgen ICI 176334, nor could this compound increase transcription activation of the reporter gene construct via the mutant receptor in a cotransfection system [HeLa cell cotransfection system with an androgen-regulated reporter gene construct (pG29G-tk-CAT) and the mutant receptor as trans-vector]. Interaction of the AR of LNCaP cells with heat-shock proteins was studied by isolation of the receptor with a specific monoclonal antibody and characterization of associated proteins. Hsp90, hsp70, and hsp56 were found to coprecipitate with the AR. Incubation of the cells at 37 degrees C with androgen (R1881, 10 nM) or the anti-androgen hydroxyflutamide, prior to receptor isolation, resulted in dissociation of the AR-heat-shock protein complex. This dissociation is paralleled by the transformation to a tight nuclear-binding form of the AR. In contrast, ICI 176334 could not induce a release of heat-shock proteins and did not increase nuclear binding, but inhibited the transformation process induced by R1881.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation. 154 May 95

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acts as a potent liver tumor promoter in female but not in male rats. As a basis for studying mechanisms of growth control by liver tumor promoters, the effects of TCDD, of two congeners and ethinylestradiol have been examined in primary cultures of hepatocytes. The agents alone were relatively ineffective but acted as co-mitogens when DNA synthesis was stimulated by epidermal growth factor (EGF). The co-mitogenic effect of TCDD was only observed in adult animals, which are less sensitive to EGF than juvenile animals. Similar effects were seen with two TCDD congeners (1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin and octachlorodibenzo-p-dioxin) in the rank order of their affinity to the Ah receptor. The concentration maximum required for their co-mitogenic action (3 x 10(-12) M for TCDD) was lower than that required for enzyme induction. TCDD was not able to overcome the inhibitory action of TGF-beta (1 ng/ml). Ethinylestradiol additively or even synergistically increased the effect of TCDD. The results suggest: (i) co-mitogenic actions of TCDD and congeners are mediated by the Ah receptor. They are elicited at lower concentrations than those required for the induction of drug-metabolizing enzymes. (ii) Estrogens enhance the co-mitogenic actions of dioxins.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin and ethinylestradiol as co-mitogens in cultured rat hepatocytes. 154 36

This review of the action of estrogens and progestagens, the steroids in oral contraceptives, on cells in the endometrium, breast, ovary, cervix and other tissues, regarding possible causative role in cancer development focuses on the level of steroid receptors and observed actions of these hormones on the cellular level. The steroid hormones are thought to interact with cells by binding to a specific receptor on the cell surface, especially estrogen receptors, while progestagen receptors overlap with glucocorticoids and androgens. Oral contraceptives typically have progestin dosages at the plateau of the dose-response curve, but lower estrogen doses may possible improve the cancer risk. Plasma levels are not reliable estimates of estrogen influence; moreover, estrogens are synthesized locally. Carcinogenesis is a multi-stage process requiring cell proliferation, involving an initiating event, and probably promotion agents, resulting in tumor growth. Estrogens increase cell replication in endometrium, and progestins counter it. Breast cancer evolves in several cell types in the epithelium of the terminal ductal lobular unit, with a 20-year latency. Estrogens stimulate ductal growth and progestins its development, and both are required for full stimulation, as in pregnancy. Estrogens usually stimulate cancer growth, but the precise sensitivity to steroids depends on the timing in the life cycle of the tumor. Ovarian cancer is unique in that neoplasms arise from the epithelium, not the hormone-sensitive tissue. Therefore the suppressive effect of steroids on ovarian neoplasia is thought to be via down- regulation of the gonadotropins, prevention of follicular rupture and consequent cell division of the epithelium, or some effect on growth regulating factors. The effect of steroids on the cervix is unclear, since cervical cancers are hormone-resistant, but there may be a step in transformation by human papilloma virus that involves a glucocorticoid- or progesterone receptor. Steroid receptors are also known to exist in tumors of liver, skin, colon, kidney and anterior pituitary, but their function is neoplasia is unknown.
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PMID:Biology of female sex hormone action in relation to contraceptive agents and neoplasia. 165 Dec 4

Estrogens have been known to induce PRL cell hyperplasia in the anterior pituitary of some species for many decades. Recent studies have shown variable susceptibility to estrogen-induced hyperplasia in different strains of rats. The distinction between hyperplastic pituitaries and adenomas is usually not made by most investigators in this field, although true neoplasms can usually be propagated by serial transplantation. The growth of transplantable tumors is usually inhibited by estrogen in vivo. Estrogens have a biphasic effect on pituitary cell proliferation in vitro with higher concentrations of estradiol inhibit cell growth, and lower concentrations stimulating PRL secretion. Estrogens can regulate PRL gene methylation in vivo thus affecting PRL mRNA expression. Recent studies have suggested that estrogen regulates signal transduction by stimulating protein kinase C. Estrogens also regulate specific proto-oncogenes such as c-myc and c-fos. These observations may help to explain some of the regulatory effects of estrogens on cell proliferation and tumor development.
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PMID:Effects of estrogens on pituitary cell and pituitary tumor growth. 192 54


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