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)

Gonadotropin-releasing-hormone (GnRH) analogues are synthetic compounds derived from decapeptide neurohormones (LHRH; LH/FSH-RH). They have a key role in hormone dependent cancer, particularly breast and prostate cancer. GnRH analogues produce an efficient inhibition of gonadotropins and sex steroid hormones. Their use in cancer therapy result in a, pharmacological castration (i.e. ovariectomy and orchiectomy), providing an androgen and estrogen ablation. GnRH exert an inhibitory action on the growth of hormone-dependent human and canine mammary tumor. Mammary tumors can produce growth factor that potentially could modulate their own proliferation in an autocrine fashion (i.e. TGF-alpha and TGF-beta or with a paracrine mechanism (i.e. EGF, IGF, FGF). The expression of EGF receptors is related in mammary tissues to the action of oestrogen and progesteron and to the presence of functional receptors for oestrogen (ER) and progesteron (PR). The present review elucidate the role of GnRH receptors in cancer and their connection with steroid hormones. Besides we showed the link between GnRH and signal transductions pathways: Estrogen-receptors, GnRH-receptors, EGF-receptors signal transduction pathways. A very tight link exists between steroid hormones and GnRH analogues both on central pituitary gonadal axis and on tumor receptors peripherically. This last mechanism could be explained either locally activating GnRH receptors or locally interacting with EGF receptor-Intracellular NitricOxide system.
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PMID:GnRH and steroids in cancer. 1204 4

Prostate cancer is the second leading cause of cancer mortality in men in the USA. For the past six decades, hormonal therapy has been the main treatment of advanced prostate cancer. Hormonal therapy has developed from a surgical procedure to a complex pharmacological treatment. Trials comparing the efficacy of different monotherapies have demonstrated the equivalence of DES, LHRH agonists and orchiectomy. Combined androgen blockade has been compared with monotherapy. However, the results of the different trials have been conflicting. Novel hormonal therapy schedules involving intermittent treatment and peripheral androgen blockade are currently in clinical trials. The role of hormonal therapy in locally advanced disease as part of a multimodality therapy is a new and rapidly developing aspect of hormonal therapy. The mechanism of hormone refractoriness in prostate cancer is an active area of basic science and translational research.
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PMID:Hormonal therapy for prostate cancer: past, present and future. 1211 64

Phytoestrogens are plant substances that are similar to 17-beta-estradiol and produce estrogenic effects. A protective role in the development of breast and prostate cancer has been hypothesized. Estrogen receptors and their variant forms play a significant role in the pathogenesis of hepatocellular carcinoma (HCC); therefore weak estrogenic substances in the diet may play a role in its development. To investigate the role of phytoestrogens in HCC an investigation of dietary intake of these substances has been performed. Cases, patients at first diagnosis of cirrhosis or HCC were chosen. Questionnaire was built up using indications from previously published papers, extending the registration of details of the diet to reconstruct intake of nutrients for the last year. Interviews were always performed by the same dietician. Quantities determined with the help of photos of servings. Data were analyzed with Winfood database completed with data regarding content in phytoestrogens of food, beverages and seasonings. So far 92 cirrhotic patients and 32 HCCs have been interviewed. No significant difference was registered among the two groups regarding total caloric intake or single nutrients (lipids, carbohydrates, proteins). A significant lower intake of genistein was evidenced in patients at first diagnosis of HCC in comparison with cirrhotics; no significant difference was found in daidzein intake. Lignans intake was strictly related with wine intake; intake was significantly lower in cases only when wine was taken into account otherwise it was similar. Results can be summarized as follows: (1) there are no clear-cut differences (both qualitative or quantitative) between cirrhotics and HCC patients in the overall daily caloric intake while; (2) definite differences exist in the intake of some of the phytoestrogens (genistein, SEC, MAT); (3) differences between cases and controls in SEC and MAT are mainly attributable to lower alcohol intake in cases while; (4) significantly lower genistein intake in HCC only seems due to personal preferences of patients. In conclusion, these differences that we have evidenced in the diet in regard to estrogen-like substances may be relevant in modulating the risk of developing HCC in cirrhotic patients.
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PMID:Phytoestrogens and liver disease. 1216 Oct 5

In the 60 years since Huggins first demonstrated the hormone dependency of prostate cancer, the introduction of various means of hormonal manipulation has resulted in modest achievements. Orchiectomy reduced testosterone but was irreversible and associated with reduced quality of life. Diethylstilbestrol (DES) represented the first alternative to surgical castration. However, cardiovascular adverse events severely limited its use. The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but suffered from problems of testosterone surge and tumor flare. The introduction of antiandrogens in combination with LHRH agonists appears on meta-analysis not to have improved survival and has implications for the cost and convenience of therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH) antagonists offer for the first time a truly rapid medical means of reducing testosterone and also suppress follicle-stimulating hormone (FSH). However, the clinical benefit of this new class of drugs remains to be evaluated.
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PMID:Hormonal therapy of prostate cancer. 1219 32

Estrogen, which acts through estrogen receptors (ERs) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERalpha and ERbeta in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERalpha expression was restricted to stromal cells of PZ. In contrast, ERbeta was expressed in the stromal cells of PZ as well as TZ. ERbeta-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERbeta.
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PMID:Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia. 1262 27

Prostate cancer is second only to lung and bronchial cancer as the leading cause of cancer death in men. Local treatment, surgery, and radiation remain the mainstay of treatment for early-stage disease. However, in locally advanced and advanced disease, there has been considerable evolution in the hormonal therapies. Suppression of testosterone production, the primary goal of hormonal therapy, may be accomplished with the use of estrogens, antiandrogens, and agonists and antagonists of luteinizing hormone-releasing hormone (LHRH). This article provides an overview of the primary hormonal therapies currently used in prostate cancer. Estrogen therapy was initially the predominant medical form of hormone manipulation and an alternative to orchiectomy. However, serious thrombogenic side effects were associated with its use, which decreased after the introduction of LHRH agonists in the 1980s. Many of the side effects occurring with oral estrogen therapy may be modulated by parenteral administration, and thus estrogen use is being revisited. LHRH agonists effectively reduce testosterone levels to castration levels (<50 ng/mL) within 2 to 4 weeks, although their use is associated with tumor flare. Antiandrogen monotherapy may offer quality-of-life benefits over treatment with androgen deprivation. The additive benefit of combined androgen blockade is yet to be determined. Recent evidence suggests that hormonal therapy may offer a survival benefit when initiated in earlier stages of prostate cancer. Future investigations will be directed to determining the most efficacious regimens.
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PMID:Hormonal therapy: historical perspective to future directions. 1266 81

Isoflavones, including genistein, contribute to the health benefits of a soy diet. However, the estrogenic activity of genistein suggests that there may be adverse effects on reproductive tract development. We investigated the potential of exposure to genistein (250 and 1000 mg/kg diet) and the synthetic estrogen and known male reproductive toxicant, diethylstilbestrol (DES, 75 micro g/kg diet) from d 21 to d 35 to alter rat testicular development. These dietary genistein concentrations resulted in serum concentrations that approximate or exceed concentrations in Asian men on a soy-containing diet. DES exposure reduced testicular weights, altered morphology and increased apoptosis in the seminiferous tubules. The effects of DES were accompanied by a reduction in androgen receptor (AR) protein concentrations, predominantly localized to Sertoli cells. Increased expression and immunostaining for the epidermal growth factor receptor (EGFR) and its downstream extracellular signal-regulated kinases (ERK) 1 and 2 in spermatagonia and spermatocytes were also observed. Immunohistochemical analysis of serial sections demonstrated that greater EGFR expression correlated with increased cellular proliferation, rather than apoptosis, and reflected impaired testicular development in DES-treated rats. Genistein in the diet did not significantly alter testicular weights, morphology, AR, EGFR and ERK expression or apoptosis. However, the higher concentration significantly reduced testicular aromatase activity, an effect that may contribute to reduced estrogen concentrations and suppression of prostate cancer development. These data suggest that exposure to genistein in the diet at concentrations that result in serum concentrations at the upper limit of humans consuming soy products does not adversely affect testicular development, but may provide health benefits.
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PMID:Dietary diethylstilbestrol but not genistein adversely affects rat testicular development. 1284 Jan 95

Studies to elucidate the cause of prostate cancer have met with little success to date. Epidemiological studies suggested that milk consumption is probably as one of the risk factors for prostate cancer. The studies thus focused on the fat and calcium in milk, but reached no definitive conclusion. According to the measurements of estrogen levels in milk by different studies, it was suggested that estrogen in milk was a possible risk to cause prostate cancer. One reason supporting this hypothesis is that Western diet (characterized by milk/dairy products and meat) causes a trend of increasing levels of estrogens, and Western males show a higher incidence rate of prostate cancer than Asia males. Estrogen levels in prostate fluid are also correlated very well with the prostate cancer. During several decades, estrogens, together with testosterone, was commonly used to induce the rodent model of prostate cancer. Our hypothesis also was supported by the presence of estrogen receptors in the prostate gland and the genotoxic role of estrogens on the prostate gland, as possible mechanisms. Therefore, if modern milk consumption does expose consumers to high levels of estrogen and plays an adverse role in prostate cancer, action should be taken to produce the noncontaminant milk.
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PMID:Estrogen: one of the risk factors in milk for prostate cancer. 1560 82

Following Huggins' original observation of the dependence of the prostate on androgens, testosterone suppression by either orchiectomy or oestrogen compounds (e.g., diethylstilbesterol [DES]) became the standard palliative treatment for advanced prostate cancer. Early studies showed testosterone suppression improved symptoms and patient survival by several months but was not curative. In addition, DES treatment resulted in significant cardiovascular morbidity and mortality from increased thrombotic events. Thus, both orchiectomy and DES were indicated for palliation in late stage disease, but were considered too extreme for earlier stage disease. The discovery of the hypothalamic peptide, luteinising hormone releasing hormone (LHRH), and its stimulatory release of luteinising hormone (LH) from the pituitary gland led to the synthesis of LHRH analogues (i.e., hormone therapy). LHRH analogues (e.g., leuprolide acetate) desensitise and downregulate pituitary LHRH receptors, thus reducing LH synthesis and release. The reduced release, in turn, decreases testosterone levels to those observed in DES-treated and orchiectomised patients. In contrast, LHRH analogues do not increase cardiovascular events. Therefore, leuprolide acetate therapy has been adopted as a safer alternative to DES and is considered to be generally reversible. This increased safety has allowed LHRH therapy to be applied in earlier stage prostate cancer. Recent studies have shown decreased rates of biochemical failure and a potential for increased patient survival with hormone therapy in conjunction with radical prostatectomy or radiation therapy. This article will focus on the literature supporting early, adjuvant LHRH therapy and Eligard 7.5 mg, a new depot formulation of leuprolide acetate that uses the Atrigel drug delivery system, causing an increase in bioavailability and optimising testosterone suppression - two key features of depot hormone suppression.
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PMID:A subcutaneous delivery system for the extended release of leuprolide acetate for the treatment of prostate cancer. 1499 40

Diethylstilbestrol is a synthetic nonsteroidal estrogen that was used to prevent miscarriage and other pregnancy complications between 1938 and 1971 in the United States. In 1971, the U.S. Food and Drug Administration issued a warning about the use of diethylstilbestrol during pregnancy after a relationship between exposure to this synthetic estrogen and the development of clear cell adenocarcinoma of the vagina and cervix was found in young women whose mothers had taken diethylstilbestrol while they were pregnant. Although diethylstilbestrol has not been given to pregnant women in the United States for more than 30 years, its effects continue to be seen. Women who took diethylstilbestrol during pregnancy have a slightly higher risk of breast cancer than the general population and therefore should be encouraged to have regular mammography. Women who were exposed to diethylstilbestrol in utero may have structural reproductive tract anomalies, an increased infertility rate, and poor pregnancy outcomes. However, the majority of these women have been able to deliver successfully. Recommendations for gynecologic examinations include vaginal and cervical digital palpation, which may provide the only evidence of clear cell adenocarcinoma. Initial colposcopic examination should be considered; if the findings are abnormal, colposcopy should be repeated annually. If the initial colposcopic examination is normal, annual cervical and vaginal cytology is recommended. Because of the higher risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, obstetric consultation may be required for pregnant women who had in utero diethylstilbestrol exposure. The male offspring of women who took diethylstilbestrol during pregnancy have an increased incidence of genital abnormalities and a possibly increased risk of prostate and testicular cancer. Routine prostate cancer screening and testicular self-examination should be encouraged.
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PMID:Diethylstilbestrol exposure. 1516 59


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