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)

19-Nor-1alpha,25-dihydroxyvitamin D2 (paricalcitol) is an analogue of 1,25(OH)2D3 with reduced calcemic effects that is approved in the United States for the suppression of parathyroid hormone in chronic renal failure. Paricalcitol has anticancer activity in prostate cancer cells. We tested the effects of paricalcitol on the HL-60 leukemia cells, studying cellular differentiation, cell cycle changes, apoptosis and cellular proliferation. Paricalcitol at 10(-8)M concentration induced the maturation of HL-60 cells in a time-dependent manner, as shown by increased expression of CD11b differentiation surface antigen. The ability of HL-60 cells to reduce nitroblue tetrazolium (NBT) was markedly increased after exposure to paricalcitol at 10(-8)M for 72 h. Paricalcitol inhibited colony formation of HL-60 cells in a soft agar semisolid media after 10-day incubation (estimated IC50 of 5 x 10(-9) M. Exposure to 10(-8)M paricalcitol for 72 h increased the number of cells in G0/G1 phase, and decreased the number of cells in S phase, and significantly increased the number of HL-60 cells undergoing apoptosis. The concentration required to achieve inhibition of growth of HL-60 cells is comparable to clinically achievable levels. These findings support the clinical evaluation of paricalcitol as an antileukemia agent.
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PMID:19-Nor-1alpha,25-dihydroxyvitamin D2 (paricalcitol) exerts anticancer activity against HL-60 cells in vitro at clinically achievable concentrations. 1522 34

Hypercalcemia is a common complication of malignant diseases with or without bone metastasis. Hypercalcemia in prostate cancer is rarely seen. The exact mechanism of prostate cancer-related hypercalcemia is still uncertain. Secretion of parathyroid hormone-related peptides (PTH-rP) is thought to be one of the possible mechanisms. We reported a rare case of prostate cancer with hypercalcemia (13 mg/dL). Bone marrow biopsy showed metastatic adenocarcinoma. The cells were also positive for neuron-specific enolase, which is the specific marker for neuroendocrine cell. The finding suggested that the prostate cancer cell derived from the neuroendocrine cell, which might synthesize PTH-rP and be responsible for the observed hypercalcemia.
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PMID:Hypercalcemia in prostate cancer with positive neuron-specific enolase stain. 1535 84

Measuring the free:total ratio of prostate-specific antigen (f/t-PSA) can improve the specificity of single-serum PSA values, distinguishing between benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCa) in men over the age of 50. Additionally, clinical trials have shown that dihydroxyvitamin D3 can slow the rate of PSA rise in PCa patients. However, little is known regarding the applicability of those findings in men undergoing chronic peritoneal dialysis (CPD). In the present study, we investigated the prevalence of increased serum PSA levels among CPD patients and correlated those values with serum levels of vitamin D [25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3]. We undertook a cross-sectional study of 71 male CPD patients without a known history of prostate cancer from 24 centers in Canada, Greece, and Turkey. All of the patients were more than 50 years of age. In these patients, we measured serum concentrations of PSA, free PSA (f-PSA), total PSA (t-PSA), prostate alkaline phosphatase (PAP), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH). We recorded serum PSA levels < 4 ng/mL in 62 patients (87.3%, group A) and levels > 4 ng/mL in 9 patients (12.7%, group B). The f/t-PSA ratio was < 0.25 in 16 patients (22.5%). Group B patients were older than those in group A (median: 73 years vs. 65 years, p < 0.01) and had a lower body weight (median: 66.5 kg vs. 76.7 kg, p < 0.05). We observed no statistically significant difference between the two groups for serum 1,25-dihydroxyvitamin D3 (median: 9.8 ng/mL vs. 10.1 ng/mL) or 25-hydroxyvitamin D3 (8 ng/mL vs. 8.2 ng/mL) levels. Also, we observed no correlation between vitamin D levels and f/t-PSA, but iPTH levels were significantly higher in group A (200.5 pg/mL vs. 61.2 pg/mL, p < 0.04). Also, serum PAP levels correlated significantly with PSA (r = 0.49, p = 0.01) and with f-PSA (r = 0.56, p = 0.000). Our results showed no clear relationship between vitamin D and serum levels of PSA or-of f/t-PSA in PD patients. However, further studies are needed to better define the uses of these PSA markers in PD patients because, in such patients, other relevant factors might be implicated in their predictive value.
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PMID:Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients. 1538 27

Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.
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PMID:Serum interleukin-8 is elevated in men with prostate cancer and bone metastases. 1545 5

Bone metastasis are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. The consequences of bone metastasis are often devastating. Osteolytic metastasis can cause different kinds of skeletal related events including severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. These skeletal-related events are the result of the resorption of mineralized bone by osteoclasts. Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate compounds that inhibit bone resorption. Potent bisphosphonates, pamidronate and, more importantly zoledronic acid may cause hypocalcemia, but mostly asymptomatic, mild, transient in most cases. Sufficient calcium and vitamin D intake needs to be ensured in patients with malignancy who have borderline or low levels of calcium when commencing treatment with bisphosphonates. Vitamin D itself induce the formation of osteoclasts by increasing the expression of RANKL on marrow stromal cells. Local calcium also promotes tumor growth and the production of parathyroid hormone-related peptide which in turn stimulates bone resorption. Vitamin D and calcium supplementation during bisphosphonate administration for the purpose of elimination of the side effects related to hypocalcemia in patients with bone metastasis may increase the bone resorption and decrease the efficacy of bisphosphonates. Therefore, vitamin D and calcium supplementation must not be routinely recommended during bisphosphonate administration.
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PMID:Calcium and vitamin D supplementation during bisphosphonate administration may increase osteoclastic activity in patients with bone metastasis. 1569 11

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.
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PMID:The management of secondary osteoporosis. 1630 Nov 95

Neuroendocrine (NE) cells are the minor cell populations in normal prostate epithelial compartments. During prostate carcinogenesis, the number of NE cells in malignant lesions increases, correlating with its tumorigenicity and hormone-refractory growth. It is thus proposed that cancerous NE cells promote prostate cancer (PCa) cell progression and its androgen-independent proliferation, although the origin of the cancerous NE cells is not clear. To investigate the role of cancerous NE cells in prostate carcinogenesis, we characterized three NE subclone cell lines-NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated from androgen-sensitive human PCa LNCaP cells by culturing in an androgen-depleted environment, resembling clinical androgen-ablation therapy. These subclone cells acquire many features of NE cells seen in clinical prostate carcinomas, for example exhibiting a neuronal morphology and expressing multiple NE markers, including neuron-specific enolase, chromogranin B, neurotensin, parathyroid hormone-related peptide, and to a lesser degree for chromogranin A, while lacking androgen receptor (AR) or prostate specific antigen (PSA) expression. These cells represent terminally differentiated stable cells because after 3 months of re-culturing in a medium containing androgenic activity, they still retained the NE phenotype and expressed NE markers. Despite these NE cells having a slow growth rate, they readily developed xenograft tumors. Furthermore, media conditioned by these NE cells exhibited a stimulatory effect on proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions. Additionally, we found that receptor protein tyrosine phosphatase alpha plays a role in upregulating multiple NE markers and acquiring the NE phenotype. These NE cells thus represent cancerous NE cells and could serve as a useful cell model system for investigating the role of cancerous NE cells in hormone-refractory proliferation of PCa cells.
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PMID:Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. 1660 Dec 85

Several factors are known to be involved in the regulation of vitamin D and sunlight and diet are the two sources in humans, but the relative importance of each of them is not well defined. Vitamin D, parathyroid hormone and serum insulin-like growth factor-I (IGF-I) were found to be independent predictors of total bone density. Thus, the growth hormone (GH)/IGF-I is thought to play an important role in the regulation of bone mineral density and the skeleton is second only to the liver as a source of circulating levels of IGF-I. The mechanisms by which IGF-I may influence bone metabolism is not fully understood but they are a predictor of bone mass density and are positively associated with vitamin D concentrations. There is a physiological decline of the GH/IGF axis with ageing. The high affinity IGF-binding proteins (IGFBP-I to 6) have also been involved in IGF-I regulation, and it is important to include the IGF-independent properties, particularly those of IGFBP3 that may be involved in the osteoblastic differentiation observed in human bone marrow stromal cell cultures. These hormones have been shown to up regulate each other. 1,25-(OH) D(3) has been shown to promote the action of IGF-I by increasing IGF-I receptors and IGF-I can also elevate 1,25-(OH) D(3) concentrations by stimulating the hydroxylation of 25-(OH) D(3) in the active 1,25-(OH) D(3) hormone. Both GH and IGF-I significantly increased renal 1alpha-hydroxylase expression and serum 1, 25-(OH) D(3) concentrations. In prostate cells, 1,25-(OH) D(3) is growth inhibitory for many established cell lines and the role of IGFBPs, especially IGFBP-3, can be growth inhibitory or stimulatory and IGFBP-3 expression increases in response to 1,25-(OH) D(3), or its analogs, in established prostate cancer cell lines. Body fat is inversely associated with 25-(OH) D(3) in relation to with anthropometric measures, indicating a specific role of adipose tissue. IGF-I may be involved in both normal and abnormal fetal growth and stimulation of IGF-I synthesis during normal pregnancy may be associated with an increase in GH production by the placenta. Thus, maternal and umbilical cord serum IGF-I and 1,25-(OH) D(3) concentrations are lower in preeclampsia and umbilical cord serum IGF-I, IGFBP-1 and IGFBP-3 concentrations are associated with low newborn birth weights.
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PMID:The role of insulin-like growth factor I components in the regulation of vitamin D. 1672 47

Neuroendocrine (NE)-like cells are hypothesized to contribute to the progression of prostate cancer by producing factors that enhance the growth, survival or metastatic capabilities of surrounding tumor cells. Many of the factors known to be secreted by NE-like cells, such as neurotensin (NT), parathyroid hormone-related peptide, serotonin, bombesin, etc., are agonists for G-protein-coupled receptors, but the signaling pathways activated by these agonists in prostate tumor cells are not fully defined. Identification of such pathways could provide insights into novel methods of treating late-stage disease. Using conditioned culture medium (CM) from LNCaP-derived NE-like cells (as a source of these agonists) or NT (a prototypical component of CM) to treat PC3 cells, we found that the epidermal growth factor (EGF) receptor (EGFR) was transactivated and that such activation was required for maximal PC3 cell mitogenesis, as measured by 5-bromo-2'-deoxy-uridine incorporation or cell number. NT also induced a time-dependent increase in EGFR Tyr(845) phosphorylation and phosphorylation of c-Src and signal transducer and activator of transcription 5b (Stat5b) (a downstream effector of Tyr(845)), events that were blocked by specific inhibition of c-Src (which mediates Tyr(845) phosphorylation of EGFR) or of EGFR. Introduction of mutant forms of EGFR (Tyr(845)) or Stat5b in PC3 cells, or treatment with selective, catalytic inhibitors of EGFR, c-Src and matrix metalloproteinases (MMPs) resulted in the loss of NT-induced stimulation of DNA synthesis, relative to wild-type controls. These data indicate that the mitogenic effect of NT on prostate cancer cells requires transactivation of the EGFR by MMPs and a novel downstream pathway involving c-Src, phosphorylation of EGFR Tyr(845) and activation of Stat5b.
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PMID:Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src/Stat5b pathway. 1686 79

Bony metastases from prostate cancer are a significant cause of morbidity and mortality. These metastases are predominantly blastic (bone-forming) and commonly cause increased serum levels of parathyroid hormone (PTH) as calcium ions are transferred from serum into blastic bone. The epidemiologic and clinical significance of secondary hyperparathyroidism in advanced prostate cancer have not been widely appreciated. Prostate cancer bony metastases show increased expression of the PTH receptor (PTH-IR) and PTH promotes the growth and invasiveness of prostate cancer cells in bone. Thus, blastic metastases appear to induce a "vicious cycle" in which PTH resorbs normal bone to support the growth of blastic bone. Recognition of the potential role of PTH in the progression of skeletal metastases suggests novel opportunities for prostate cancer secondary prevention. In particular, we propose that suppressing serum PTH in advanced prostate cancer may reduce morbidity by decreasing fractures and pain caused by bone resorption and may reduce mortality by retarding the progression of metastatic disease.
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PMID:Prostate cancer, serum parathyroid hormone, and the progression of skeletal metastases. 1834 65


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