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)

This study evaluates the sleep-related erections in 5 patients with locally advanced prostate cancer (T3NOMO) during 6 months treatment with Casodex by multinight continuous monitoring of penile tumescence and rigidity. Mean serum LH, Testosterone and Estradiol levels shown a no statistically significant increase at the six months control. We found no significant modifications in the number of NPT episodes, maximum penile circumference and rigidity time before and after therapy. Penile arterial flow and neurologic examination were also unmodified. All patients had a stable disease and unchanged performance status after 6 months. This pure antiandrogen in a men with prostate cancer does not seem to interfere with self reported libido and erectile capability.
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PMID:[Monitoring of erection function in patients with prostatic carcinoma treated with Casodex]. 183 Apr 8

Human prostatic cancer (HONDA) serially transplanted in nude mice grew well in male mice but not at all in untreated female mice or in castrated male mice. Progressive growth in female mice was obtained by i.m. administration of 1 mg of testosterone twice a week. Estradiol inhibited the growth of the tumor in male mice to some extent; however, some growth was observed. The tumor in untreated male mice retained the histological features of poorly differentiated adenocarcinoma. Tumors in castrated male mice showed reduction in size of tumor cell nests with relative overgrowth of stroma. The tumor in androgenized female mice consisted of columnar epithelial cells with large nuclei and more abundant cytoplasms and a large glandular lumen, showing histology of moderately differentiated adenocarcinoma. High levels of human prostatic acid phosphatase (PAP) were detected in sera from untreated male mice. Testosterone markedly increased the content of serum PAP of androgenized female mice. Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight. High-affinity androgen receptors were present in cytosol and in nuclear extract of the tumor in untreated male mice. No measurable amount of progesterone or estrogen receptors was present in cytosol from untreated male mice.
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PMID:Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice. 402 85

A review of the epidemiological evidence indicates that dietary fat very likely has an etiologic role in the development of prostatic carcinoma. While this effect may be mediated by way of altered hormonal action on the prostate, there is little supporting evidence from assays of plasma or urinary hormones in case-control studies or the investigation of high-risk and low-risk groups. The application of metabolic epidemiology to this problem is most likely to succeed by direct studies of the prostate gland, and the performance of relevant assays on prostatic fluid. Estradiol and estrone levels were found to be higher in prostatic fluid than in serum, whereas for prolactin the reverse was true. Testosterone concentrations were very low in prostatic fluid, perhaps because of the high degree of plasma protein binding. Preliminary data indicated that prostatic fluid estradiol and prolactin levels are elevated in some prostate cancer patients; estrone levels appear to be normal.
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PMID:Metabolic epidemiology of prostatic cancer. 636 75

We have established organ cultures of human prostate for in vitro analysis of the hormone responsiveness of prostatic carcinoma. Tissue samples were obtained from total prostatectomies for localized cancer. Normal prostate tissues with age-related hyperplastic changes were obtained from cystoprostatectomies of bladder cancer patients representing the same age group, and they wer cultivated as controls. The explants of prostates were cultured for 7 days in basal medium containing 5% dextran charcoal-treated fetal calf serum, insulin (0.08 IU/ml), and dexamethasone (10(-7) M) with or without dihydrotestosterone (DHT) (10(-7) M) or estradiol (10(-9) M). Control prostates showed involutive changes of morphology when cultured in basal medium. These changes were prevented by DHT, which also maintained a strong epithelial immunostaining for PSA (prostate specific antigen), which was used as a marker for tissue-specific functions. The concentration of PSA in the medium was high. The rate of [3H]thymidine incorporation into DNA was stimulated by DHT in some cultures of control prostates, but no increase was seen in the others. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the antihormone cyproterone acetate. The main morphological response of cultured control prostates to estradiol was induction of squamous metaplasia. This was associated with increased incorporation of [3H]thymidine, which was radioautographically localized to the basal layer of epithelium. Estradiol effects were counteracted by the antihormone toremifene. The expression of androgen receptor mRNA and protein in cultured control prostate was demonstrated by Northern blotting and immunohistochemistry, respectively. Also, the expression of estrogen receptor was demonstrated by the polymerase chain reaction analysis of total mRNA from cultured control and cancer prostate. The cultured explants of prostate cancer maintained the overall morphology of the original carcinoma. However, the presence of DHT improved the morphology of cancerous acini in all better differentiated carcinomas (3 grade I and 5 grade II), and corresponding responses to DHT were observed in the rate of DNA labeling with [3H]thymidine. In 2 of 3 grade I carcinomas, DHT increased DNA synthesis, but in grade II cancers the patterns of hormone responses were more variable. The poorly differentiated grade III prostatic carcinomas did not respond to either hormone as measured by [3H]thymidine uptake, and no hormone effects could be seen in morphology. Immunostaining for PSA differed from that in control prostates: besides cancerous acini, the surrounding stroma was also intensively stained, which suggests unpolarized and impaired secretion of PSA by the cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone regulation of human prostate in organ culture. 769 34

Previous studies have suggested that the clinical efficacy of PC-SPES, a dietary supplement used frequently by men diagnosed with androgen-dependent (AD) or androgen-independent (AI) prostate cancer (CaP), is mechanistically attributed to estrogenic components present in the herbal mixture. To test this hypothesis, we compared estradiol (1 nM), potentially an active principle in PC-SPES, with PC-SPES (using an amount equivalent to 1 nM estradiol) on cell proliferation, induction of apoptosis, and regulation of prostate specific genes, PSA and AR, in androgen-responsive LNCaP cells. Cells cultured in steroid-proficient (FBS) or-deficient (CS-FBS) media to simulate hormonal status pre- and post-castration in vivo, were incubated with estradiol or PC-SPES. Proliferation was reduced in PC-SPES treated cells cultured in media supplemented with FBS or CS-FBS; in contrast, addition of estradiol had no effect on proliferation in FBS cultures, and elicited a 45% growth increase in CS-PBS-supplemented cultures. The differential proliferative response of LNCaP cells to PC-SPES vs. estradiol was also supported by changes in PCNA expression, cell viability, cell cycle phase distribution, and induction of apoptosis. Estradiol elicited time-dependent increases in secreted PSA, whereas PC-SPES suppressed PSA secretion, in both culture conditions. In FBS cultures, PC-SPES lowered intracellular AR and PSA by 61% and 17%, respectively, while estradiol increased intracellular PSA, in parallel with a 42% decrease in AR expression. In comparison with cells maintained with CS-FBS, estradiol induced substantial increases in both intracellular PSA and AR, whereas PC-SPES resulted in a smaller increase in intracellular PSA without affecting the expression of AR. These studies show that the antiproliferative and gene modulatory effects of PC-SPES in androgen-dependent human prostate cancer cells are mechanistically and functionally distinct from effects attributable to estradiol.
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PMID:Effects of PC-SPES on proliferation and expression of AR/PSA in androgen-responsive LNCaP cells are independent of estradiol. 1217 83

Estradiol rapidly activates Src as well as the Src-dependent pathway in human mammary cancer-derived MCF-7 cells, in human prostate cancer-derived LNCaP cells and in Cos cells transiently expressing hERs [EMBO J. 15 (1996) 1292; EMBO J. 17 (1998) 2008]. In addition, estradiol immediately stimulates, yes, an ubiquitous member of the Src kinase family, in human colon carcinoma-derived Caco-2 cells [Cancer Res. 56 (1996) 4516]. Progestins and androgens activate the same pathway in human mammary and prostate cancer-derived cells [EMBO J. 17 (1998) 2008; EMBO J. 19 (2000) 5406]. We observed that estradiol also stimulates the phosphatidylinositol-3-kinase (PI3K)/AKT pathway in MCF-7 cells [EMBO J. 20 (2001) 6050]. In these cells, activation of the Src- and the PI3 K-dependent pathways is simultaneous and mediated by direct interactions of the two kinases with ERalpha. The signalling pathway activation by sex-steroid hormones leads to DNA synthesis and cell growth in human mammary and prostate cancer-derived cells [EMBO J. 19 (2000) 5406; EMBO J. 20 (2001) 6050; EMBO J. 18 (1999) 2500]. Furthermore, androgen stimulation of NIH3T3 fibroblasts activates the same pathways triggered by this hormone in LNCaP cells and promotes the S-phase entry or cytoskeleton changes in these cells [J. Cell Biol. 161 (2003) 547]. All the described effects are rapid and require classic steroid receptors, but, surprisingly, not their transcriptional activity. Indeed, a transcriptionally inactive mutant of hER mediates the estrogen-stimulated DNA synthesis of NIH3T3 fibroblasts [EMBO J. 18 (1999) 2500]. Furthermore, AR in NIH3T3 cells does not enter nuclei and is unable to respond to the hormone with transcription stimulation, whereas it activates signaling pathways and triggers important biological responses. Signaling pathway activation by steroids has also been described by other groups under different experimental conditions and/or in different cell types. In these cells, steroid stimulation triggers various effects, such as neuroprotection, vasorelaxation or bone protection [J. Neurosci. Res. 60 (2000) 321; Nature 407 (2000) 538; J. Cell Biochem. 76 (1999) 206]. Analysis of the mechanisms responsible for the hormone-dependent and steroid receptor-mediated pathway activation in epithelial as well as stromal cells reveals immediate association of steroid receptors with extranuclear signaling effectors [EMBO J. 17 (1998) 2008; Cancer Res. 56 (1996) 4516; EMBO J. 19 (2000) 5406; EMBO J. 20 (2001) 6050; J. Cell Biol. 161 (2003) 547]. These results further highlight the central role of the hormone-regulated protein-protein interactions in the steroid action. They also offer the possibility of interfering with important activities of hormones, such as proliferation or survival, cytoskeleton changes as well as invasiveness and vasorelaxation, without affecting the steroid effects that depend on receptor transcriptional activity.
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PMID:Rapid signalling pathway activation by androgens in epithelial and stromal cells. 1528 63

Malignant cells are known to have accelerated metabolism, high glucose requirements, and increased glucose uptake. Transport of glucose across the plasma membrane of mammalian cells is the first rate-limiting step for glucose metabolism and is mediated by facilitative glucose transporter (GLUT) proteins. Increased glucose transport in malignant cells has been associated with increased and deregulated expression of glucose transporter proteins, with overexpression of GLUT1 and/or GLUT3 a characteristic feature. Oncogenic transformation of cultured mammalian cells causes a rapid increase of glucose transport and GLUT1 expression via interaction with GLUT1 promoter enhancer elements. In human studies, high levels of GLUT1 expression in tumors have been associated with poor survival. Studies indicate that glucose transport in breast cancer is not fully explained by GLUT1 or GLUT3 expression, suggesting involvement of another glucose transporter. Recently, a novel glucose transporter protein, GLUT12, has been found in breast and prostate cancers. In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface. Trafficking of GLUT12 to the plasma membrane could therefore contribute to glucose uptake. Several factors have been implicated in the regulation of glucose transporter expression in breast cancer. Hypoxia can increase GLUT1 levels and glucose uptake. Estradiol and epidermal growth factor, both of which can play a role in breast cancer cell growth, increase glucose consumption. Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells. Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer.
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PMID:Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. 1538 72

Racial differences in disease risk (eg, osteoporosis, metabolic cardiovascular syndrome, and prostate cancer) may arise partly on a hormonal basis. While reports of racial differences in gonadal steroid hormone levels in middle-aged men have produced conflicting results, there is evidence that high sex hormone-binding globulin (SHBG) and estradiol levels are more common among young adult African American men than white men. To determine whether this difference relates to pituitary-testicular functioning or to other factors, we conducted a cross-sectional study of 47 healthy prepubertal African American and white boys aged 5 to 9 years at the time of their annual school physical examination. Height, weight, blood pressure, waist and hip circumference, and Tanner staging were determined, and a fasting blood sample was obtained. The African Americans studied were slightly older than the whites (mean +/- SD, 82.4 +/- 15.0 vs 70.5 +/- 10.3 months, P = .003). African Americans were also slightly taller and heavier and had a lower waist-to-hip ratio, but these differences could be explained by the difference in age. Mean SHBG levels were 25% higher (P = .15) in African Americans than in whites (197 +/- 104 vs 157 +/- 79 nmol/L), and when adjusted for age, values were 46 nmol/L higher among African Americans. The fifth quintile for SHBG (values > 245 nmol/L) included 1 (4.2%) of 24 whites and 8 (35%) of 23 African Americans studied (P = .003). There was no significant correlation between age, body mass index, waist circumference, or fasting insulin and SHBG. Total testosterone, the free androgen index, and dehydroepiandrosterone increased with age in both groups, but after adjusting for age, no racial differences were found. Estradiol, estrone, and inhibin B levels, as well as systolic and diastolic blood pressures, were also comparable in both groups. We conclude that high levels of SHBG are more common among African American than in white boys and hypothesize that this difference and its effect on the ratio between bound and free steroid hormones may contribute to racial differences in disease risk in adult men.
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PMID:Racial difference in circulating sex hormone-binding globulin levels in prepubertal boys. 1556 86

During the progression of prostate cancer from androgen-dependence or sensitivity to androgen-independence, the overall expression of prostate specific membrane antigen (PSMA) increases with its appearance in plasma membrane. However, surprisingly some androgen-independent metastatic prostate cancer cell lines do not express this protein. Estradiol (E2) and basic fibroblast growth factor (bFGF) due to their recognized and strong involvement in prostate growth, development, and pathology were selected with the aim of restoring the expression of PSMA in markedly dedifferentiated prostate cancer PC-3 cells and in Du 145. E2 (10(-7)-10(-11)M) and bFGF (10ng/ml) stimulated the expression of mRNAs for PSMA (2- to 4-fold increase) that apparently were further translated and processed to its membrane form in LNCaP, PC-3, and Du 145 cells. The values of interaction force between the same anti-PSMA antibodies and all studied cells were almost identical (45-64pN), indicating antigenic similarity of the membrane form of PSMA expressed in LNCaP, PC-3, and Du 145 cells.
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PMID:Expression of prostate specific membrane antigen in androgen-independent prostate cancer cell line PC-3. 1568 Sep 1

Estradiol (E2) is traditionally recognised as the female sex hormone. Since discovery of estrogens in the early forties of XX century it has been believed, that these hormones caused impairment of the gonadal function in men or didn't exert any influence. New studies are contradictory, but indicate also a possible involvement of estrogens in the pathogenesis of some systemic diseases of men. The main source of E2 in men is adipose tissue and the brain. E2 is also produced in adrenals, liver, mammary glands, hair and in male gonads. Daily production and blood level of E2 in men are higher than those in postmenopausal women. In 1988 we were the first to demonstrate that E2 is an important hormonal signal for initiation of spermatogenesis. The traditional view about unimportant or inhibitory role of E2 in male physiology was finally refuted thanks to discovery of the estrogen receptors in males. In the middle 90ties transgenic mice with the lack of estrogen receptor (ER knockout) or enzyme aromatase, that enable the conversion of testosterone into E2, were produced. Observations of men with inherited mutations of these genes, considerably extended our knowledge about stimulatory role of E2 in men in the formation of bone stroma, inhibition of their linear growth, lipids metabolism and sexual maturation, the effects that were attributed to testosterone action until today. New data indicate role of estrogens and ER in the function of the cardio-vascular system. Their link with development of arteriosclerosis seems, however, to be bipolar. In single reported cases of men with the inactivating mutations of ERalpha or aromatase genes, a precocious arteriosclerosis is noted. From the other site, men homozygous for the most common variant of ERalpha gene (ESR1c.454-397cc) have a significantly increased risk of myocardial infraction. Estrogens are the risk factors in prostatic cancer and their local tissue increase in autoimmune diseases is connected with aggravation of the proliferative complications of these disorders.
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PMID:[Important functions of estrogens in men--breakthrough in contemporary medicine]. 1654 28


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