UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkaline phosphatase, prostate-specific antigen and creatinine were made at the time of both bone biopsies and at 1 month. Serum intact parathyroid hormone and vitamin D metabolites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 patients taking E + C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly increased especially in biopsies taken from tumour-involved bone. Treatments with E + C or E both induced a significant decrease in bone resorption, but were associated with the development of hypocalcaemia, secondary hypoparathyroidism, hypophosphataemia and severe impairment of mineralisation of newly formed bone, i.e. osteomalacia. Since the patients were not vitamin D deficient, we conclude that osteomalacia resulted from a relative deficiency of calcium and phosphate. The transiency of pain relief achieved with anti-resorptive agents in the treatment of bone metastases from prostate cancer may be due to the development of osteomalacia.
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PMID:The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study. 791 32

1,25-Dihydroxyvitamin D [1,25(OH)2D3, calcitriol] can inhibit the proliferation of some human prostate cancer cells but its clinical use is limited by hypercalcemia. We therefore explored the bioactivity of less calcemic vitamin D analogs. We studied the effects of calcitriol and 3 synthetic analogs at concentrations of 10(-6) to 10(-12) M on the in vitro proliferation of 3 human prostate carcinoma cell lines: DU 145, PC-3, and LNCaP. Calcitriol and analogs showed significant antiproliferative activity on PC-3 and LNCaP cells. DU 145 cells were inhibited by the analogs only. We conclude that vitamin D analogs warrant further investigation as therapeutic agents in prostate cancer.
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PMID:Human prostate cancer cells: inhibition of proliferation by vitamin D analogs. 807 53

This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25-dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors.
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PMID:Vitamin D and prostate cancer: a prediagnostic study with stored sera. 822 83

Our previous study provided evidence that higher serum levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the progression of subclinical to clinically significant prostate cancer in both black and white men, especially after age 57. This paper extends the prior study by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin D (25-D), in case and control subjects. In addition, the risk of prostate cancer is related to serum levels of vitamin D-binding protein (VDBP) and total dehydroepiandrosterone and to polymorphic variation in VDBP. The expected elevated summer levels of 25-D were seen in case and control subjects and, as expected, 1,25-D did not vary throughout the year in the control subjects. Unexpectedly, lower case levels of 1,25-D were limited largely to the summer months (P = 0.01) in both black and white cases and to cases greater than or equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone and the frequencies of VDBP polymorphisms were similar in case and control subjects, although striking differences were seen in allelic frequencies in black and white men. These observations provide additional evidence that vitamin D metabolism may impact the risk of prostate cancer.
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PMID:Seasonal variation in vitamin D, vitamin D-binding protein, and dehydroepiandrosterone: risk of prostate cancer in black and white men. 854 33

There is increasing evidence that growth and differentiation of prostatic carcinoma cells may be modulated not only by androgens and growth factors but also by vitamin D, retinoids, and phenylacetate (PA). The latter agonists may have a role in the prevention and therapy of prostate cancer but their exact therapeutic potential remains unclear. Since both retinoids and vitamin D act via nuclear receptors, the same way androgens do, we studied the interactions of these compounds with androgen-induced proliferation and differentiation using LNCaP cells as a model of androgen-responsive tumor cells. PA was included because of its suspected different mode of action [H3]-thymidine incorporation was used as a measure of proliferative activity, secretion of prostate-specific antigen (PSA) as a measure of differentiated function. The present data show that 1alpha,25-dihydroxycholecalciferol (VD3), all-trans retinoic acid (atRA), 9-cis retinoic acid (9cRA), and PA stimulated LNCaP cell-differentiated function in the presence or absence of androgens. The effects on cell growth were more complicated. In the absence of androgens growth stimulatory effects were observed for the retinoids and under some conditions for VD3. These effects were limited, however, and tended to be more pronounced at low cell densities. In the presence of androgens nearly exclusively growth inhibitory effects were observed. On a molar basis VD3 was the most effective antiproliferative agonist (ED50 = 10(-9) M). It completely neutralized the stimulatory effects of androgens. Growth inhibition was not due to a decrease in the concentration of androgen receptor: whereas atRA, 9cRA, and PA did not alter androgen receptor levels, VD3 provoked a twofold increase. Neither in the presence nor in the absence of androgens did we observe any cooperativity in the growth stimulatory or inhibitory effects of VD3, atRA, or 9cRA. To test whether treatment with any of the studied agonists resulted in a phenotypic reversion and sustained growth arrest, LNCaP cells were pretreated with VD3, atRA, 9cRA, or PA for 6-12 days and reseeded at equal densities as untreated cells. In all cases tested [3H]-thymidine incorporation was restored within 6 days suggesting that none of these compounds caused irreversible growth inhibition.
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PMID:Control of LNCaP proliferation and differentiation: actions and interactions of androgens, 1alpha,25-dihydroxycholecalciferol, all-trans retinoic acid, 9-cis retinoic acid, and phenylacetate. 862 21

Parathyroid hormone-related protein (PTHrP) has previously been shown to be expressed in human prostatic tissue and in prostatic cancer cell lines. In the present study, PTHrP immunoreactivity was detected in the glandular epithelium of normal prostate and benign prostatic hyperplasia (BPH), as well as in prostatic adenocarcinoma (CaP). Epithelial cell cultures derived from normal, BPH, and CaP tissues were also stained by antibodies against PTHrP, and northern analysis revealed multiple transcripts of PTHrP in the cellular RNA. PTHrP (1-34) was measurable by radioimmunoassay (RIA) in media conditioned by the prostatic epithelial cell cultures, and PTHrP accumulated in conditioned media during a 72 hr time course. Addition of complete growth medium to starved cells resulted in increased PTHrP mRNA levels by 1 hr, with maximal stimulation at 8-24 hr. Several individual factors contained in the complete growth medium were tested for their ability to regulate PTHrP expression. Epidermal growth factor (EGF) was the major inducer of PTHrP expression, while cholera toxin, bovine pituitary extract, hydrocortisone, and insulin had minimal or no effect on PTHrP transcript levels. Since each of these factors is growth stimulatory, the unique ability of EGF to induce PTHrP is apparently unrelated to mitogenicity. 1,25-Dihydroxyvitamin D3[1,25(OH)2D3], an inhibitor of PTHrP expression in several other cell types, had no effect on steady-state levels of PTHrP mRNA expressed by epithelial cells in complete growth medium, although prostate cells have vitamin D receptors and are responsive to 1,25(OH)2D3 in other ways. Our results indicate that PTHrP expression is not confined to the neuroendocrine cells of the human prostate and that our culture system can be used as a model to investigate the role of PTHrP in the prostate.
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PMID:Parathyroid hormone--related protein (PTHrP) is an epidermal growth factor-regulated secretory product of human prostatic epithelial cells. 868 51

A man's risk of developing prostate cancer is influenced by both genetic and nongenetic factors. Genetic factors are particularly important at younger ages, and the attributable risk of strong genetic factors could be as high as 43% among men less than 55 years of age; however, only about 9% of all cases may be directly attributable to a family history of prostate cancer. Race appears to be an important determinant of risk; African-American men are at high risk, whereas men of oriental ancestry are at lower risk. The bases of these racial differences remain obscure but may be related to hormonal differences. Modifiable risk factors are most important from a public health perspective. Diet or closely related factors appear to hold the most promise for prevention, although the precise factors are unknown. The strongest evidence indicates that some component of animal fat intake appears to act as a promoter of prostate cancer. Other dietary factors, including vitamin D, vitamin E, and beta-carotene and lycopene, may confer protection, but these require more study. Many but not all studies that have examined long-term effects of vasectomy suggest that this procedure may increase risk of prostate cancer, but whether this association is causal is not established. Occupational factors, smoking, and physical activity level do not appear to be major determinants of prostate cancer risk.
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PMID:How is individual risk for prostate cancer assessed? 877 95

The incidence of prostate cancer in the United States is second only to skin cancers, and the disease kills almost the same number of men as breast cancer does women. Relatively few risk factors are known for prostate cancer, although several lines of evidence suggest that vitamin D may be an important determinant of prostate cancer risk. A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284-287, 1994). These genetic variants have been correlated with both circulating levels of active vitamin D hormone and in vitro measures of gene expression (Morrison et al., Nature (Lond.), 367: 284-287, 1994). We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate cancer risk using a case-control study of 108 men undergoing radical prostatectomy and 170 male urology clinic controls with no history of cancer. Among the white control group, 22% were homozygous for the presence of a TaqI RFLP at codon 352 (genotype tt), but only 8% of cases had this genotype (P < 0.01). A similar trend was seen among the small number of blacks in this study (13% for controls, 8% for cases), although the difference was not statistically significant. Race-adjusted combined analysis suggests that men who are homozygous for the t allele (shown to correlate with higher serum levels of the active form of vitamin D) have one-third the risk of developing prostate cancer requiring prostatectomy compared to men who are heterozygotes or homozygous for the T allele (odds ratioMH = 0.34; 95% confidence interval, 0.16-0.76; P < 0.01). These results support recent ecological, population, and in vitro studies suggesting that vitamin D is an important determinant of prostate cancer risk and, if confirmed, suggest strategies for chemoprevention of this common cancer.
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PMID:Association of prostate cancer with vitamin D receptor gene polymorphism. 879 74

Epidemiological data suggest that vitamin D3, obtained from dietary sources and sunlight exposure, protects against mortality from prostate cancer (PC). In agreement with this, the most active vitamin D metabolite 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2 D3] regulates the growth and differentiation of several human PC cell lines. Both genomic and non-genomic signalling pathways for 1,25(OH)2 D3 have been reported, although the mechanism of action in PC cells has not been defined. We now provide data supporting an active role for the nuclear vitamin D receptor (VDR) in mediating the growth-inhibitory effects of 1,25(OH)2 D3 on these cells. In the VDR-rich cell line ALVA-31, the observed changes in growth by 1,25(OH)2 D3 are preceded by significant changes in VDR mRNA expression. In contrast, the cell line JCA-1, containing few VDRs, fails to show both early changes in VDR gene expression and later changes in growth with 1,25(OH)2 D3. To assess the role of the VDR more directly, transfection studies were pursued. ALVA-31 cells were stably transfected with an antisense VDR cDNA construct in an attempt to reduce VDR expression. Antisense mRNA expression among clones was associated with: (a) reduced or abolished sensitivity to the effects of 1,25(OH)2 D3 on growth; (b) decreased numbers of VDRs per cell, as measured by radiolabelled-ligand binding; and (c) a lack of induction of the VDR-regulated enzyme 24-hydroxylase in response to 1,25(OH)2 D3. From these studies we conclude that the antiproliferative effects of 1,25(OH)2 D3 require expression of the nuclear VDR in this system.
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PMID:Vitamin D receptor expression is required for growth modulation by 1 alpha,25-dihydroxyvitamin D3 in the human prostatic carcinoma cell line ALVA-31. 883 63

An emerging hypothesis suggests that vitamin D metabolites suppress the development of prostate cancer. In a recent epidemiological study, elevated levels of 1,25-dihydroxyvitamin D (1,25-D) in blood were associated with a greatly reduced risk, particularly in older men. We conducted a nested case-control study to evaluate the relationship between plasma levels of the two major vitamin D metabolites, 1,25-D and 25-hydroxyvitamin D (25-D), and subsequent diagnosis of prostate cancer. We also measured vitamin D-binding protein to investigate the influence of free metabolite levels on risk. Plasma samples from 14,916 participants in the Physicians' Health Study were collected and frozen in 1982-1983. This analysis included 232 cases diagnosed up to 1992 and 414 age-matched control participants. Vitamin D metabolite and vitamin D-binding protein assays were conducted without knowledge of case-control status. Median levels of 25-D, 1,25-D, and vitamin D-binding protein were indistinguishable between cases and controls. Analysis of risk for increasing quartiles of total or free metabolites did not reveal a pattern of decreasing risk. For 1,25-D, men in the highest quartile had an odds ratio of 0.88 (95% confidence interval = 0.53-1.45) compared to those in the lowest quartile. Significant reductions in risk were not seen in analyses restricted to older men, to cases occurring > 3 years from blood collection, or to cases presenting as aggressive prostate cancer. Nonsignificant inverse associations for 1,25-D appeared for some groups according to 25-D level, particularly when the cutoff for defining low 25-D was reduced. These results do not support the hypothesis that high circulating levels of vitamin D metabolites reduce prostate cancer risk, although small to moderate effects cannot be excluded.
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PMID:Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. 885 Feb 73

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