Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred and twelve patients treated for prostatic cancer grade I or II were investigated for cardiovascular complications. The patients were part of a multicentre study in the Stockholm area and had been randomized to treatment with either estramustine phosphate (Estracyt) or polyestradiol phosphate and ethinyl estradiol. Cardiovascular complications categorized as impaired arterial circulation including ischemic heart disease, venous thromboembolism, cardiac incompensation and cerebral depression were found to be equally frequent following the two different forms of treatment. Among the patients getting cardiovascular complications, these occurred within two months after the start of treatment in 50% and within one year in 85% of them. There was a statistically significant correlation between the incidence of cardiovascular complications and a history of previous cardiovascular disease. This criterion was however in retrospect found to predict cardiovascular complications in only 67 of the 126 patients getting one or several of these complications.
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PMID:Cardiovascular complications to treatment of prostate cancer with estramustine phosphate (Estracyt) or conventional estrogen. A follow-up of 212 randomized patients. 693 12

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated with estrogens. Changes of the plasma lipoproteins are related to the development of ischaemic cardiovascular disease and can be brought about by hormonal treatment. We have therefore studied plasma lipoproteins during estrogen treatment and after orchidectomy. 16 patients with prostatic carcinoma were treated with ethinyl estradiol daily by mouth and polyestradiol phosphate intramuscularly once a month. 15 other patients were treated by bilateral orchidectomy. Cholesterol (C), triglyceride (TG), and phospholipid (PL) concentrations in plasma and in the very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) fractions were determined before starting treatment and 2 weeks and 8 weeks later. In the estrogen treated group the mean plasma C concentration decreased by 14 and 10%, while the mean HLD-C increased by 23 and 53%, and the mean LDL-C decreased by 24 and 25% at 2 and 8 weeks respectively. The mean PL concentration in HDL increased by 36 and 79% while that in LDL decreased by 12 and 18%. The mean plasma TG concentration was increased by 36 and 46%, mainly reflecting a rise of TG in the HDL-LDL fraction. Orchidectomy created only slight changes of plasma lipids. After 8 weeks the mean C concentration in plasma was raised by 10% and the mean PL concentration by 11%, owing to a 13% rise in the mean HDL-PL level. The changes in plasma lipoprotein pattern created by high doses of estrogens are mainly thought to protect against the development of atherosclerosis. The slight changes that take place after orchidectomy can hardly affect the incidence of cardiovascular disease.
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PMID:Plasma lipoproteins during anti-androgen treatment by estrogens or orchidectomy in men with prostatic carcinoma. 726 28

Estrogens in the male are secreted by the testes and derived extragonadally from the aromatization of certain androgens. In some brain regions critical for the control of gonadotropin secretion and behavior, androgens may be aromatized to estrogens within the cells that are regulated. Estrogen may have other physiological roles on the testes to control testosterone secretion and on accessory sex glands to promote both fibromuscular growth and secretion. High doses of estrogen given for treatment of prostatic cancer or modulation of reproductive function not only reduce testosterone secretion but also interact with the liver, changing the secretion of various plasma proteins and causing several undesirable side effects. The hypothalamus, pituitary, testes, accessory sex glands, and liver all contain an apparently identical protein, the estrogen receptor, which may mediate the actions of estrogen.
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PMID:Estrogen receptors in the male. 730 38

Epidermal growth factor receptor (EGF-R) was studied in Dunning prostatic cancer models using competitive binding assays and solution hybridization assay. EGF-R-binding capacity and mRNA were demonstrated in a hormone-sensitive R3327 prostatic tumor from both control and castrated animals while no such activity was found in the hormone-independent AT-1 tumors. Castration induced no quantitative changes in the EGF-R. Estrogen treatment induced a significant reduction of the binding capacity of EGF-R and its mRNA. It was concluded that EGF-R is present in the androgen-sensitive Dunning prostatic tumor models (R3327), but that the androgen-insensitive, undifferentiated AT-1 tumor lacks EGF-R expression. Endocrine treatment has no significant effect on the EGF-R in these tumor models.
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PMID:Epidermal growth factor receptor content in rat prostatic adenocarcinoma: effects of endocrine treatment. 767 34

The catabolism of lipoprotein(a), Lp(a), remains unclear. Very recently we observed that estrogen, a hormone known to increase low-density lipoprotein (LDL) receptor activity, reduced serum Lp(a) levels in a man with familial hypercholesterolemia (FH) (JAMA 267: 2328, 1992). In the present study, we attempted to further evaluate this Lp(a)-lowering action of estrogen in men without FH. Seven men, aged 61-84 yr, treated with estrogen for prostatic cancer were the subjects and seven men who underwent surgical treatment without estrogen therapy served as controls. Fasting blood was collected before and 1-3 months after estrogen therapy, and serum Lp(a) levels and lipoprotein profiles were determined. Estrogen treatment caused significant changes in serum lipoproteins, i.e., decreases in LDL-cholesterol, and increases in high-density lipoprotein (HDL)-cholesterol. Serum triglyceride levels tended to increase. Serum apo A-1 underwent a two-fold increase, while apo B did not change. Serum Lp(a) levels ranged from 8 to 62 mg/dl. After estrogen treatment serum Lp(a) was reduced markedly, with a mean reduction of 81% (71-95%). Serum lipids, lipoproteins and Lp(a) did not change significantly in the controls. The results demonstrated a regulating effect of estrogen on serum Lp(a) levels, and the findings further suggested that Lp(a) is removed via LDL receptors. However, previous studies have shown that maneuvers causing a decrease in LDL-cholesterol do not always cause a reduction in serum Lp(a). Thus, our findings suggested the possible presence of a receptor which is estrogen-inducible and different from the LDL receptor.
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PMID:Reduction of serum lipoprotein (a) by estrogen in men with prostatic cancer. 795 16

Many of the most common cancers occur in sites that are under hormonal regulation by the steroid sex hormones. These include the breast, ovary, endometrium and possibly the colon for women, and the prostate and testes for men. Much information on chemoprevention of these cancers has accrued indirectly as a result of the use of estrogens and progestagens for contraception or postmenopausal hormone replacement therapy. Estrogen-based contraceptives clearly reduce the risk of ovarian cancer, but without an opposing progestagen they increase the risk of endometrial cancer. Progestagens reduce the risk of endometrial cancer and when used premenopausally appear to be able to more than counteract the carcinogenic effect of exogenous estrogens at this site. The effect of oral contraceptives on breast cancer appears to be quite minimal, but probably increases risk when taken for long periods at a young age. Recent studies suggest that the use of an agonist of leuteinizing hormone releasing hormone as a contraceptive may reduce the risk of breast cancer. Estrogens used in postmenopausal hormone replacement therapy increase the risk of both breast and endometrial cancer, but addition of a progestagen may counteract the increased risk to the endometrium. The agent most intensively under study for breast cancer prevention is tamoxifen, which has proven effectiveness as a therapeutic agent. When taken for more than two years it has been shown to reduce the occurrence of new contralateral tumours by about 50% in women who have had breast cancer. Three large international trials are currently evaluating its role in a preventive setting. For men, interest has centred on the use of 5 alpha-reductase inhibitors to block the prostatic conversion of testosterone to dehydrotestosterone and potentially inhibit the development of prostate cancer. The 5 alpha-reductase inhibitor finasteride is currently under test in a prevention trial.
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PMID:Medicinal drugs with hormonal activity as chemopreventive agents. 892 22

Epidemiological research serves to continue surveillance of fertility regulation agents once phase 3 clinical trials have been completed and the contraceptives have been marketed. Epidemiologic research conducted during the past 20 years has had a major impact on family planning program policies and clarified many concerns about contraceptive side effects that emerged in the early 1970s. Central has been the reassessment of the risk of malignant neoplasms associated with use of hormonal contraception. Data from large-scale studies such as the Cancer and Steroid Hormone Study in the US and the World Health Organization Collaborative Study involving 9 developing and 2 developed countries suggest that combined oral contraceptives (OCs) decrease the risk of ovarian and endometrial cancer, especially in long-term users. Although there is emerging evidence that OC use exceeding 5 years is associated with a modest increase in cervical cancer risk, the causality of the association is questionable given the probable influence of confounding factors such as sexually transmitted diseases. Moreover, epidemiologic studies launched in the 1980s confirmed that the previously noted association between OCs and cardiovascular diseases has been reduced as a result of lower doses of ethinyl estradiol and revised prescribing practices. Other foci of epidemiologic investigations have included possible side effects associated with natural family planning, the impact of modern IUDs on pelvic inflammatory disease and ectopic pregnancy risks, and the association between vasectomy and testicular and prostate cancer. Given the observational nature of epidemiologic research and the potential for bias, findings from several studies addressing the same research question with different methodological approaches are generally assessed.
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PMID:Twenty years of epidemiology in fertility regulation. 900 93

Estrogen receptors (ERs) in the prostate and prostatic urethra were examined in 33 men with benign prostatic hyperplasia (BPH) and in 11 with prostate cancer (PC). The Abbot monoclonal ER-ICA assay was used for immunohistochemical investigation. In the BPH group, ERs were revealed in the prostatic stroma in eight cases and in the glandular epithelium in one. In four cases ERs were seen in the prostatic stroma and in the glandular epithelium. In the prostatic urethra, ERs were found in 19 cases located in the urothelium, lamina propria and/or periurethral glands. In the PC group, ERs were demonstrated in the prostatic stroma and/or prostatic urethra in 6 out of 11 cases. In both BPH and PC patients, immunoreactivity was weak and confined to few cells, indicating low ER content in the prostate as well as in the prostatic urethra. Dextran-coated charcoal (DCC) analysis was used for detection and quanticization of cytosolic and nuclear ERs. In the BPH group, ERs were detected once in the prostate and prostatic urethra in the nuclear and cytosol, and additionally in the prostatic urethra in the cytosol fraction in three cases. In all cases, ER content was low, ranging from 10-15 fmol/mg protein. In the PC group, ERs were detected in the prostatic urethra and/or prostate in the cytosol fraction from two patients. The contents were low, ranging from 10-13 fmol/mg protein. We conclude that in human BPH and PC, ERs can be present in the prostate and prostatic urethra. In the prostate, ERs are mainly located in the stroma, but in BPH specimens they can also be found in the glandular epithelium. Biochemically, the use of the DCC analysis is of limited value, since ER content in the human prostate and prostatic urethra is at the limit of detection with this method.
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PMID:Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. 1051 86

Estrogen exposure represents the major known risk factor for development of breast cancer in women and is implicated in the development of prostate cancer in men. Human breast tissue has been shown to be a site of oxidative metabolism of estrogen due to the presence of specific cytochrome P450 enzymes. The oxidative metabolism of 17beta-estradiol (E2) to E2-3,4-quinone metabolites by an E2-4-hydroxylase in breast tissue provides a rational hypothesis to explain the mammary carcinogenic effects of estrogen in women because this metabolite is directly genotoxic and can undergo redox cycling to form genotoxic reactive oxygen species. In this chapter, evidence in support of this hypothesis and of the role of P4501B1 as the 4-hydroxylase expressed in human breast tissue is reviewed. However, the plausibility of this hypothesis has been questioned on the grounds that insufficient E2 is present in breast tissue to be converted to biologically significant amounts of metabolite. This critique is based on the assumption that plasma and tissue E2 levels are concordant. However, breast cancer tissue E2 levels are 10-fold to 50-fold higher in postmenopausal women than predicted from plasma levels. Consequently, factors must be present to alter breast tissue E2 levels independently of plasma concentrations. One such factor may be the local production of E2 in breast tissue through the enzyme aromatase, and the evidence supporting the expression of aromatase in breast tissue is also reviewed in this chapter. If correct, mutations or environmental factors enhancing aromatase activity might result in high tissue concentrations of E2 that would likely be sufficient to serve as substrates for CYP1B1, given its high affinity for E2. This concept, if verified experimentally, would provide plausibility to the hypothesis that sufficient E2 may be present in tissue for formation of catechol metabolites that are estrogenic and which, upon further oxidative metabolism, form genotoxic species at levels that may contribute to estrogen carcinogenesis.
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PMID:Tissue-specific synthesis and oxidative metabolism of estrogens. 1096 22

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.
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PMID:Low-dose estrogen supplementation improves vascular function in hypogonadal men. 1171 90


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