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)

We present a patient with prostate cancer who developed symptomatic hypocalcemia while taking oral clodronate for painful bony metastases. He had a past history of a bowel resection for Crohn's disease, and, although he was normocalcemic prior to taking clodronate, it is likely that the surgery had caused mild hyperparathyroidism. The addition of clodronate prevented the chronic osteolysis of bony metastases, which would have helped maintain normocalcemia. The case was complicated by hypomagnesemia and hypokalemia resulting from diarrhea. Hypomagnesemia is a cause of refractory hypocalcemia and hypokalemia. This case illustrates two important points. First, care must be taken with bisphosphonates in patients with a previous bowel resection. Second, magnesium plays a key role in the metabolism of both calcium and potassium, and must be considered in the evaluation of the hypocalcemic patient.
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PMID:Symptomatic hypocalcemia with oral clodronate. 949 15

PTH and ionized calcium levels were measured in 131 patients with advanced prostate cancer, all of whom had received at least first-line hormone therapy. Patients were classified into those in remission, those with stable disease, or those with progressive disease according to their prostate-specific antigen response and their clinical status. Thirty-four percent of all patients had PTH levels above the upper level of normal for controls of similar age (7.0 pmol/liter), and in 44% of these patients this was associated with a normal ionized calcium. Patients with proven bone metastases had significantly higher PTH levels than those without. (7.3 +/- 0.5 vs. 4.3 +/- 0.4 pmol/liter, P < 0.0005). There was evidence for a difference in the PTH levels between the three response groups. The PTH levels tended to be higher in patients with progressive disease. Thirty-seven of 65 patients (57%) with both progressive disease and proven bone metastases had elevated PTH levels. Mean levels of urinary deoxypyridinoline and cAMP were significantly greater in patients with high PTH than in those with a normal PTH. Treatment with oral calcium supplements in 32 patients with a high PTH seemed to have only a transient effect on elevated PTH or low ionized calcium levels. These data show that secondary hyperparathyroidism occurs frequently in patients with advanced prostate cancer, particularly in those with both progressive disease and bone metastases. The increased PTH levels are associated with an increase in bone resorption markers. These findings raise important questions about the role of PTH in progression of prostatic cancer in bone and the potential limitations of the use of bisphosphonates in patients with a raised PTH or low serum calcium.
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PMID:Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. 1193 46

The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors that controls mineral ion homeostatis and has potential tumor-suppressive functions for various cancer types, specifically prostate cancer. A VDR ablated transgenic animal model (VDDRII, vitamin D-dependent rickets type II) has been developed and the animals typically have various diseases including, hypocalcemia, hyperparathyroidism, rickets, osteomalacia, and alopecia. This transgenic mouse system provides us with a model to decipher the influences of the VDR on prostatic growth and function. VDRs are abundant both in prostatic epithelial and stromal cells, and vitamin D signaling can be studied in this model. Although, there were no gross differences between the prostate tissue of the experimental and control groups, VDR null mice showed fat necrosis and individual cell apoptosis in the periprostatic adipose tissue. This indicates a possible role of VDR in the signaling pathways resulting the prostate. This may be particularly attractive for VDR targets for the inhibition of cancer progression using VD(3) and its analogs as potential chemo-preventive agents.
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PMID:Increased apoptosis of periprostatic adipose tissue in VDR null mice. 1535 70

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

Vitamin D functions to regulate calcium homeostasis in intestine, kidney, and bone. Vitamin D deficiency during bone development causes rickets and in adults vitamin D deficiency, which has been shown to be common in the elderly population, can cause secondary hyperparathyroidism that can result in osteomalacia and increased risk of fracture. Recent evidence has suggested that vitamin D can have numerous other physiological functions including protection against certain autoimmune diseases, such as diabetes and multiple sclerosis and inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells. Exactly how vitamin D affects numerous different systems is a subject of continuing investigation. This article will review new developments related to the function and regulation of vitamin D target proteins in classic vitamin D target tissues that have provided novel insight into the mechanism of vitamin D action.
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PMID:New insights into the mechanisms involved in the pleiotropic actions of 1,25dihydroxyvitamin D3. 1683 19

The active form of vitamin D, 1,25-dihydroxyvitamin D3, is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the superfamily of nuclear receptors, and exerts a number of diverse biological functions. The natural hormone and synthetic VDR agonists are well known for their capacity to control calcium and bone metabolism, but they also regulate proliferation and differentiation of many cell types, and possess exquisite immunoregulatory properties, mostly by targeting dendritic cells (DC) and T cells. These properties have been clinically exploited in the treatment of different diseases, from secondary hyperparathyroidism to osteoporosis to psoriasis. The VDR is expressed by most cell types, including cells of the urogenital system such as prostate and bladder cells. In particular, the prostate has been recognized as a target organ of VDR agonists and represents an extra-renal synthesis site of 1,25-dihydroxyvitamin D3, but its capacity to respond to VDR agonists has, so far, been probed only for the treatment of prostate cancer. We have taken a different approach, and have analysed the capacity of VDR agonists to treat benign prostatic hyperplasia (BPH), a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary irritative symptoms, and a possible inflammatory component. Pre-clinical data reviewed here demonstrate that VDR agonists, and notably BXL-628 (Elocalcitol), reduce the static component of BPH by inhibiting the activity of intra-prostatic growth factors downstream of the androgen receptor, and the dynamic component by targeting bladder cells. These data have led to a proof-of-concept clinical study that has successfully shown arrest of prostate growth in BPH patients treated with BXL-628. Ongoing clinical studies will assess the capacity of this VDR agonist to reduce symptoms and ameliorate flow parameters in BPH-affected individuals. The pronounced effects of BXL-628 on bladder smooth muscle cells and its anti-inflammatory properties indeed anticipate beneficial effects also on BPH-related lower urinary tract symptoms.
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PMID:Pre-clinical evidence and clinical translation of benign prostatic hyperplasia treatment by the vitamin D receptor agonist BXL-628 (Elocalcitol). 1695 18

Zoledronic acid is a highly potent bisphosphonate that has been shown to reduce skeletal-related events in patients with androgen-independent prostate cancer metastatic to bone. We report a patient with androgen-independent prostate cancer and extensive bone metastases. After receiving a single dose of zoledronic acid, the patient developed hypocalcemia that persisted for approximately 60 days despite intravenous and oral calcium supplementation, likely because of excess unopposed osteoblastic activity. This case underscores the need for calcium and vitamin D monitoring and supplementation to avoid bisphosphonate-induced secondary hyperparathyroidism and highlights the possibility that extensive osteoblastic metastasis alone might lead to hypocalcemia.
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PMID:Persistent hypocalcemia induced by zoledronic acid in a patient with androgen-independent prostate cancer and extensive bone metastases. 1795 15

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

Mutations of the HRPT2 gene, which are responsible for hyperparathyroidism-jaw tumor (HPT-JT) syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. The aim of this study was to investigate differences in expression of the most important genes connected with parathyroid carcinoma between HPT-JT syndrome due to an HRPT2 splicing mutation, normal parathyroid tissue and sporadic parathyroid adenoma. Total RNAs were extracted from parathyroid carcinoma in HPT-JT syndrome harbouring HRPT2 splicing mutation or sporadic parathyroid adenoma and normal parathyroid gland, and subjected to Illumina DASL-based gene expression assay. Unsupervised hierarchical clustering analysis was used to compare gene expression in HPT-JT syndrome, sporadic parathyroid adenoma and normal parathyroid glands. We identified differentially regulated genes in HPT-JT syndrome and sporadic parathyroid adenoma relative to normal parathyroid glands using a combination of Welch's t-test and fold-change analysis. Quantitative PCR, RT-PCR and IHC were used for validation. Sixteen genes differentially regulated in the parathyroid carcinoma were associated with signal pathways, MAPK, regulation of actin cytoskeleton, prostate cancer and apoptosis. FGFR1 expression was confirmed to be significantly upregulated by validation experiments. Our gene expression profiling experiments suggest that upregulated FGFR1 expression appears to be associated with parathyroid carcinoma in HPT-JT syndrome due to an HRPT2 splicing mutation.
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PMID:Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation. 2488 87

Tc-MIBI has long been used to localize hyperfunctioning parathyroid tissue in patients with hyperparathyroidism. This tracer can also concentrate in various neoplastic tissues including prostate adenocarcinoma. We herein report a case with parathyroid hormone-secreting metastatic prostate cancer mimicking an ectopic parathyroid adenoma on the Tc-MIBI scan. We conclude that metastatic prostate cancer should be included as one of the differential diagnoses when interpreting Tc-MIBI scan.
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PMID:Metastatic Parathyroid Hormone-Secreting Prostate Adenocarcinoma Mimicking Ectopic Parathyroid Adenoma Demonstrated on 99mTc-MIBI Image. 3245 86


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