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)

Mortality rates from multiple sclerosis show a well-known north-south gradient, both within the United States and internationally. Mortality rates from prostate cancer show a similar gradient and are significantly correlated with multiple sclerosis (MS) mortality and MS prevalence. This finding adds prostate cancer to the set of diseases whose geographic distributions are significantly correlated with MS and whose members include colon cancer, dental caries, and Parkinson's disease. Review of the literature indicates that these clinically dissimilar diseases may share an aberration in vitamin (hormone) D. Recent evidence demonstrating a multi-faceted role for vitamin D in immunoregulation suggests that a vitamin D aberration may also contribute to the etiology of MS. A vitamin D hypothesis can illuminate several unexplained features of the epidemiology of MS and suggests opportunities for epidemiologic, laboratory, and clinical investigation.
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PMID:Multiple sclerosis and prostate cancer: what do their similar geographies suggest? 129 88

Tubular reabsorption of calcium (Ca) is becoming recognized as a determinant of malignant hypercalcemia. However, its importance as compared to increased bone resorption has not yet been widely investigated. We determined Ca fluxes of bone resorption and tubular reabsorption in 141 rehydrated patients with hypercalcemia of malignant or benign origin, before any specific treatment. Bone resorption (BRI) was evaluated by fasting urinary Ca excretion and Ca tubular reabsorption using an index (TRCaI) calculated from a nomogram relating fasting urinary Ca excretion and calcemia. The relationship between alterations in TRCaI and in the tubular capacity to reabsorb inorganic phosphate (Pi), as judged by TmPi/GFR, was also examined for each cause of hypercalcemia. Among 101 cases with malignancy, 67% had overt bone metastases, but all displayed increased BRI. Calcemia was highest in breast cancer and lowest in prostate carcinoma. BRI was markedly increased in breast cancer, lymphoma, and multiple myeloma, whereas it was slightly elevated in lung squamous cell, renal, and liver carcinomas. TRCaI was increased in 49% of malignant hypercalcemia, particularly in epidermoid (above the upper normal limit in 71% of the cases), renal, and liver carcinomas. It was elevated in 54% of breast cancer and normal in multiple myeloma and prostate cancer. In nonmalignant hypercalcemia, BRI was markedly increased in vitamin D intoxication, sarcoidosis, and immobilization. In primary hyperparathyroidism (PHP), BRI was moderately increased. TRCaI was abnormally elevated in PHP, but normal in vitamin D intoxication, sarcoidosis, and immobilization. In malignant hypercalcemia, TmPi/GFR was low in 77% of patients and in all types of tumors, except in prostate carcinoma. The index ratio [TRCaI/(TmPi/GFR)] gave a better discrimination of PHP from other causes of nonmalignant hypercalcemia than the use of either TRCaI or TmPi/GFR taken alone. Thus, in malignant hypercalcemia, increased bone resorption is associated with an elevation in tubular Ca reabsorption in half the patients surveyed, whereas low tubular Pi reabsorption is observed in more than 75%. Increased TRCaI is restricted to some types of tumor, whereas decreased TmPi/GFR is observed in all types except prostate carcinoma. In nonmalignant hypercalcemia, a significant increase in mean TRCaI was only observed in PHP, of which individual cases can be fully discriminated from other conditions by using a new index taking into account alteration in the renal transport capacity of both Ca and Pi.
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PMID:Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and nonmalignant hypercalcemia. 205 36

For prophylaxis of cancer and treatment of manifest cancer Morerman recommends as the basis of his therapy a lactovegetable diet and, in addition, the '8 essential substances': vitamins A, B, C and E, iodine, sulfur, iron and citric acid. At a later stage he also recommends supplementary vitamin D and selenium. The most important aspect is the change in dietary habits required by the diet prescribed by Moerman and the ingestion of the '8 essential substances' in the form of conventional preparations. The daily cost of treatment of a prostatic cancer, for instance, ranges from about Fr. 3.- to Fr. 6.-. Side effects are not mentioned. The diet and therapy were developed by the Dutch physician Dr Moerman (1893-1988) as long ago as the 1930s. The promoters are the iridiologist J. Landman, the nutritional consultant E. Wannee and the writer R. Jochems. All three have written a book on Moerman. In Switzerland, the Lifecare Association endeavours to disseminate this form of therapy. A chronic deficiency of the '8 essential substances' is said to lead to metabolic disturbances, structural and behavioural anomalies of the regeneration tissue and alkalosis, which is claimed to be a fertile soil for the 'symbionts' that can transform healthy cells into cancer cells. Moerman came to this conclusion on the basis of his observations of pigeons. By means of a lactovegetable diet and substitution of the '8 essential substances', this metabolic disorder is said to be reversible, thus robbing the 'symbionts' of their growth medium. The results of the experiments with pigeons have, as far as we know, never been published.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cancer treatment using Dr. Moerman's diet and therapy. Documentation No. 24]. 218 63

To study the bone turnover in patients with bone metastasis from cancers of the kidney, bladder, prostate and other organs, Ca metabolism, vitamin D related hormones and various markers, such as bone glaprotein (BGP) and hydroxyproline, were investigated. In the group with osteolytic metastasis of non-prostatic cancer patients, BGP which is a measure of bone absorption was significantly increased and urinary excretion of hydroxyproline, Ca and P was elevated. Serum Ca was also higher and 1 alpha 25 (OH)2D and 250HD, measures of the metabolism of vitamin D, were lower. It was shown that bone absorption was promoted with the osteolytic findings by clinical X-ray examination, but osteoblastic changes which did not depend on osteoblast cells, seemed to exist in this group. On the contrary, in the group with osteoblastic metastasis from prostatic cancer, the level of BGP was not increased, but urinary hydroxyproline was moderately increased. Serum and urinary Ca and P levels were increased. In addition, 1 alpha 25 (OH)2D and 24 x 25 (OH)2D were lower than in the control group. These results indicate that urinary hydroxyproline is a useful marker for patients with bone metastasis, but BGP was correlative with neither the clinical findings of bone metastasis nor the bone turn over and metabolisms.
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PMID:[Clinical evaluation of bone turnover in patients with bone metastasis of various cancer of urogenital tract]. 223 10

We report 2 cases of true hypocalcemia (not caused by decreased binding proteins) associated with metastatic prostate cancer and review previously reported cases. Hypocalcemia is a common but frequently unrecognized complication of prostatic cancer. Estrogen therapy often is associated with the hypocalcemia, which may be asymptomatic. The hypocalcemia is always associated with osteoblastic metastases and usually it is associated with increased serum alkaline phosphatase activity, acid phosphatase activity and serum parathyroid hormone concentration. Serum concentrations of magnesium, phosphorus and vitamin D frequently are decreased. Patients are in a positive calcium balance. The osteoblastic metastases seem to act as a calcium sink, creating a "hungry tumor phenomenon". The role of estrogens may be to stop the resorption of normal bone resulting in lower serum calcium concentrations.
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PMID:Hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate. 317 54

In 14 patients with densifying bone metastases of prostatic cancer, the analysis of blood and urine P-Ca parameters, serum 25 OH D3, Ca infusion test, and histomorphometry with measure of calcification rate shows that: - hypocalcemia is common in such patients, sometimes associated to a lack of vitamin D with hypocalciuria and increased Ca retention at the infusion test, and sometimes unexplained; - from a histological point of view, this osteopathy is characterized by a hyperosteoidosis, often an important one, around and only around the metastasis foci, the malignant cells being indispensable to induce the osteoidosis. The entire mineralization of the osteoid matrix may happen but rarely because the hyperosteoidosis is most often increased by a vitamin D deficiency.
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PMID:How and what kind of bone is made by metastatic cells of prostatic cancer. 716 73

Data from epidemiological studies has suggested that vitamin D deficiency may promote prostate cancer, although the mechanism is not understood. We have previously demonstrated the presence of vitamin D receptors (VDR) in three human prostate carcinoma cell lines (LNCaP, PC-3, and DU-145) as well as in primary cultures of stromal and epithelial cells derived from normal and malignant prostate tissues. We have also shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can elicit an antiproliferative action in these cells. In the present study we compared the biological actions of 1,25-(OH)2D3 to those of a series of natural vitamin D3 metabolites and several synthetic analogs of vitamin D3 known to exhibit less hypercalcemic activity in vivo. In ligand binding competition experiments, we demonstrated the following order of potency in displacing [3H]1,25-(OH)2D3 from VDR: EB-1089 > 1,25-(OH)2D3 > MC-903 > 1,24,25-(OH)3D3 > 22-oxacalcitriol (OCT) > 1 alpha,25-dihydroxy-16-enecholecalciferol (Ro24-2637) > 25-hydroxyvitamin D3, with EB-1089 being approximately 2-fold more potent than the native hormone. No competitive activity was found for 25-hydroxy-16,23-diene-cholecalciferol. When compared for ability to inhibit proliferation of LNCaP cells, MC-903, EB-1089, OCT, and Ro24-2637 exhibited 4-, 3-, and 2-fold greater inhibitory activity than 1,25-(OH)2D3. Interestingly, although OCT and Ro24-2637 exhibit, respectively, 10 and 14 times lower affinity for VDR than 1,25-(OH)2D3, both compounds inhibited the proliferation of LNCaP cells with a potency greater than that of the native hormone. The relative potency of vitamin D3 metabolites and analogs to inhibit cell proliferation correlated well with the ability of these compounds to stimulate prostate-specific antigen secretion by LNCaP cells as well as with their potency to induce the 25-hydroxyvitamin D3-24-hydroxylase messenger RNA transcript in PC-3 cells. In conclusion, these results demonstrate that synthetic analogs of vitamin D3, known to exhibit reduced calcemic activity, can elicit antiproliferative effects and other biological actions in LNCaP and PC-3 cell lines. It is noteworthy that although binding to VDR is critical for 1,25-(OH)2D3 action, the analog data indicate that additional factors significantly contribute to the magnitude of the biological response. Finally, the strong antiproliferative effects of several synthetic analogs known to exhibit less calcemic activity than 1,25-(OH)2D3 suggest that these compounds potentially may be useful as an additional therapeutic option for the treatment of prostate cancer.
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PMID:Actions of vitamin D3, analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3. 753 Jan 93

An hypothesis has been forwarded linking prostate cancer to low serum levels of vitamin D metabolites. We sought to test this hypothesis using sera obtained in a large, prospective cohort study. A serum bank in Washington County, Maryland (United States) has stored sera obtained from 20,305 county residents during a blood collection campaign undertaken in August through November 1974. We studied sera obtained from 61 residents who were diagnosed with prostate cancer during the period 1980 through 1992. Each prostate cancer case was matched to two controls on age (+/- 1 yr) and race. Controls had donated blood in the same blood-collection campaign and had not been diagnosed with prostate cancer through 1992. Serum levels of vitamin D metabolites did not differ significantly between cases and controls. Mean 25-hydroxyvitamin D (25-D) levels were 34.3 ng/ml and 33.2 ng/ml, and mean 1,25-dihydroxyvitamin D (1,25-D) levels were 41.0 pg/ml and 40.1 pg/ml, in cases and controls, respectively. No statistically significant trends or differences between cases and controls were found in an analysis by quintile of serum level. We also did not observe the association of vitamin D metabolites with prostate cancer to be strongest among older men with more severe disease, as previously has been reported. In summary, although our study's power was limited, our findings provide little support for the hypothesis that vitamin D metabolite levels are associated strongly with subsequent risk for prostate cancer.
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PMID:Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States) 1018 38

Our findings demonstrate the presence of VDR in various human prostate cancer cell lines and in primary cultures derived from normal, BPH and prostate cancer. In addition, 1,25-D induced several bioresponses in these cells including growth inhibition and PSA stimulation. Based on examples in many different malignant cells as well as our data in prostate cells, that vitamin D is anti-proliferative and promotes cellular maturation, it seem clear that vitamin D must be viewed as an important cellular modulator of growth and differentiation if addition to its classical role as regulator of calcium homeostasis. In this respect, vitamin D has the potential to have beneficial actions on various malignancies including prostate cancer. Its ultimate role in prostate cancer remains to be determined, but 1,25-D may prove useful in chemoprevention and/or differentiation therapy. We believe the data currently available provide the basis for an optimistic view on the possible use of vitamin D to treat prostate cancer in patients and that further investigation is clearly warranted to better define its potential therapeutic utility.
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PMID:Vitamin D and prostate cancer. 764 28

It has been suggested that vitamin D deficiency may promote prostate cancer, although the mechanism is not understood. In this study three human prostate carcinoma cell lines, LNCaP, DU-145, and PC-3, were examined both for the presence of specific 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] receptors (VDRs) and also employed to study the effects of hormone on cell proliferation and differentiation. Ligand binding experiments demonstrated classical VDR in all three cell lines examined with an apparent dissociation constant of 7.5, 5.4, and 6.3 x 10(-11) M for LNCaP, DU-145, and PC-3 cells, respectively. Corresponding binding capacity for the three prostate carcinoma cell lines were 27, 31, and 78 fmol/mg protein, respectively. The presence of VDR in the three cell lines was also confirmed by immunocytochemistry. In addition, one major 4.6-kilobase messenger RNA transcript hybridizing with a specific human VDR complementary DNA probe was identified in all three cell lines. Interestingly, both DU-145 and PC-3 but not LNCaP cell lines exhibited 1,25(OH)2D3-stimulated induction of 24-hydroxylase messenger RNA employed as a marker of 1,25(OH)2D3 action. Physiological levels of 1,25(OH)2D3 dramatically inhibited proliferation of the LNCaP and PC-3 cell lines. However, in spite of the presence of high affinity VDR, proliferation of DU-145 cells was not inhibited by 1,25(OH)2D3 at the doses tested. Treatment with 1,25(OH)2D3 caused a dose-dependent stimulation of prostate-specific antigen secretion by LNCaP cells. In conclusion, these results demonstrate that these three human prostate carcinoma cell lines all possess specific VDR and that 1,25(OH)2D3 treatment can elicit both an antiproliferative and a differentiating action on these cancer cells. The findings lend support to the hypothesis that vitamin D might exert beneficial actions on prostate cancer risk.
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PMID:Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. 768 37


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