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)

The role of phosphorus-32 (32P) was evaluated in patients experiencing pain due to skeletal metastases from prostate cancer and refractory to other modes of treatment. Twenty patients received 185 MBq (5 mCi)32P intravenously; 12 patients received a single dose each, five patients were injected twice and three patients three times at 3-month intervals. A blood count and clinical assessment for bone pain, tender sites, mobility and analgesic intake were performed before and 4, 8 and 12 weeks after the administration of 32P. A bone scan was performed before and 12 weeks after therapy. The results showed a significant decrease in pain at 4 weeks and a palliative response persisted for up to 12 weeks. Analgesic medication intake decreased significantly (F = 13.2213, P < 0.0001) and mobility improved after therapy. Quantitative analysis of the bone scans showed a statistically significant reduction in osteoblastic activity in metastatic lesions after therapy (t = -3.80, P < 0.001). Transient myelosuppression after 4 weeks, which was statistically significant for WBC and platelet counts only (F = 3.0226, P = 0.0358; F = 6.2514, P = 0.0009 respectively), returned within normal limits by 8 weeks. We conclude that 32P is an effective and safe therapy for pain palliation.
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PMID:Effective and economical option for pain palliation in prostate cancer with skeletal metastases: 32P therapy revisited. 1045 77

A survey of UK consultants in clinical oncology was carried out in November 1997. The aim of this was to explore their attitudes towards radionuclide therapy and to determine the proportion of clinical oncologists involved in this modality. Three hundred and twenty-eight questionnaires were sent out and 227 (69.2%) were returned. Approximately one-half of those responding treat thyroid cancer or benign thyroid disease with radioactive iodine ((131)I) or prostate cancer with strontium ((89)Sr). The median number of patients treated per year with (131)I for benign thyroid disease was 12, with evidence of increasing subspecialization. Treatment with radioactive phosphorus ((32)P) for haematological disorders and yttrium ((90)Y) for intra-articular conditions was carried out by 31% (median number treated per year, two) and 6% (median number per year, five) respectively. There was strong support for the continuing involvement of clinical oncologists in radionuclide therapy for thyroid and prostate cancer. There was significant support for patients with benign thyroid disease or requiring intra-articular (90)Y to be treated by a specialist in nuclear medicine. However, this support was less strong amongst those currently involved in treatment compared with those not involved. There was support for the continued involvement of clinical oncologists in the use of (32)P. Attitudes appeared not to vary in different parts of the UK.
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PMID:Survey of attitudes of UK clinical oncologists towards radionuclide therapy. 1047 15

This Phase I study of 1alpha-hydroxyvitamin D(2), an p.o. administered vitamin D analogue, in patients with advanced hormone-refractory prostate cancer was designed to assess the toxicity, pharmacokinetic and biological markers of drug activity, and lastly tumor response data to recommend a dose for Phase II studies. 1alpha-Hydroxyvitamin D(2) was administered daily at doses ranging from 5 to 15 microg/day. Patients were monitored for toxicity and tumor response, and blood and urine samples were collected for pharmacokinetics (1alpha,25-dihydroxyvitamin D(2) levels) and other parameters of biological activity (bone markers, parathyroid hormone, urine calcium, and serum phosphorus levels). Twenty-five patients were enrolled. Main toxicities were hypercalcemia with associated renal insufficiency. No other significant toxicity was seen. Pharmacokinetics showed an increase in the active metabolite 1alpha,25-dihydroxyvitamin D(2) that reached a plateau by week 4 despite continuous drug dosing. Elevation in daily urinary calcium excretion and serum phosphorus levels was seen, whereas a decrease in serum parathyroid hormone was evident. Two patients showed evidence of a partial response, whereas 5 others achieved disease stabilization for > or =6 months. 1alpha-Hydroxyvitamin D(2) was well tolerated with main toxicities being hypercalcemia and renal insufficiency. All of the toxicity was reversible with drug discontinuation. Evidence for drug activity was seen in surrogate markers, and pharmacokinetic analysis showed substantial increases in vitamin D metabolite levels among the various cohorts. Whereas the defined maximum tolerated dose was not reached, the recommended Phase II dose was 12.5 microg/day given continuously.
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PMID:Phase I trial of 1alpha-hydroxyvitamin d(2) in patients with hormone refractory prostate cancer. 1223 22

The combination of magnetic resonance spectroscopy (MRS) and imaging (MRI) has led to mapping metabolites from normal and neoplastic tissue within the time limits of a routine study. MRSI (magnetic resonance spectroscopy imaging) detects metabolites that contain protons, phosphorus, fluorine, or other nuclei. The uniqueness of the information available in vivo and in a non-invasive manner encouraged radiologists and oncologists to apply MRSI in research and clinical practice. Both (1)H- and (31)P-MRS have revealed significant disturbances in amino acids, lipids, and phosphorus-containing metabolites within tumors. Phosphocreatine is often diminished in neoplasms compared to their primary host or surrounding tissues. However, the reduction of the compound does not appear to be closely correlated to the degree of malignancy. Moreover, abnormalities in (31)P spectra from neoplasms are shared by other disorders. Changes in high-energy phosphate levels almost invariably occur with radio- and chemotherapy of tumors. The spectroscopic alterations are often seen before any variations in tumor size and shape can be detected. However, opposite responses can be associated with the same clinical outcome. (1)H-MRS has been successfully used to quantify the extent of neuronal cell loss imposed on the brain during radiotherapy. Recently, MRSI was successfully integrated into radiotherapy planning in prostate cancer patients. (19)F-MRS opens access to artificially induced fluorocompounds such as 5-fluorouracil and its metabolites.
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PMID:Magnetic resonance spectroscopy in clinical oncology. 1524 22

The effects of androgen deprivation therapy (ADT) include not only suppression of tumor growth, but also adverse effects on various bodily functions. The aim of this study was to determine the metabolic effects of ADT in patients with nonmetastatic prostate cancer. Forty-nine men with prostate cancer were treated with ADT before beginning radical therapy for 6 months. Body weight, peripheral red blood cell counts, hemoglobin, hematocrit, fasting blood sugar, serum total cholesterol, blood urea nitrogen, uric acid, compensated calcium, inorganic phosphorus, bone-specific alkaline phosphatase, urinary deoxypyridinoline, and radial bone density determined using dual energy x-ray absorptiometry were examined before and 6 months after ADT treatment. Body weight (P = 0.037) and the levels of fasting blood sugar (P = 0.014), serum total cholesterol (P = 0.017), blood urea nitrogen (P = 0.030), compensated calcium (P < 0.001), inorganic phosphorus (P < 0.001), bone-specific alkaline phosphatase (P < 0.001), and compensated urinary deoxypyridinoline (P < 0.001) increased significantly. Peripheral red blood cell counts (P < 0.001), hemoglobin level (P < 0.001), hematocrit (P < 0.001), uric acid (P < 0.001), and radial bone density (P = 0.023) decreased significantly. These effects of ADT on various bodily functions warrant systematic study in clinical trials. We should be aware of the far-reaching consequences of ADT and incorporate strategies for preventing and managing adverse effects into routine practice.
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PMID:The influence of androgen deprivation therapy on metabolism in patients with prostate cancer. 1556 7

Bone pain associated with advanced prostate and other cancers is a frequent and significant complication, and the effective management of metastatic bone disease and accompanying symptoms continues to be one of the major problems facing patients and their physicians. Treatment is in part dependent on prior treatments; usually a combination of systemic and local modalities is used because no single treatment regimen is effective for an extended period of time. The 3 radionuclides currently approved for treatment of bone pain (phosphorus-32, strontium-89, and samarium-153) are discussed in this review as viable treatment options, with emphasis on the third-generation agent in this category, samarium Sm 153 lexidronam. Clinical trial data are described that support the use of this agent in patients with hormone-refractory prostate cancer with painful metastatic bone disease, and the efficacy of and role for combination therapies are also discussed.
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PMID:Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease. 1698 30

There is evidence that electromagnetic fields (EMF) play some part in the pathogenesis of prostate cancer, but the pathogenic mechanism remains unknown. The normal prostate gland and both benign and malignant prostate lesions contain abundant calcium/phosphorus crystalloids with various morphologies, which seem to be heterogeneously and diffusely distributed within the gland. We hypothesize that an environmental EMF may result in simultaneous, multidirectional and diffuse compression or expansion of these crystalloids (a piezoelectric effect). This would result in a slight mechanical distortion of the prostate, potentially altering cell behavior and enhancing the expression of specific genes, particularly those involved in suppressing apoptosis. A mathematical model of the cell mechanical effect is presented, and the hypothesis is related to current clinical evidence and to potential validation by critical laboratory tests.
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PMID:Piezoelectricity and prostate cancer: proposed interaction between electromagnetic field and prostatic crystalloids. 1829 12

Bone cells, particularly osteoblasts and osteoclasts, exhibit functional responses to calcium (Ca(2+)). The identification of the calcium-sensing receptor (CaR) in parathyroid glands as the master regulator of parathyroid hormone (PTH) secretion proved that cells could specifically respond to changes in divalent cation concentration. Yet, after many years of study, it remains unclear whether this receptor, which has also been identified in bone, has functional import there. Various knockout and transgenic mouse models have been developed, but conclusions about skeletal phenotypes remain elusive. Complex endocrine feedback loops involving calcium, phosphorus, vitamin D, and PTH confound efforts to isolate the effects of a single mineral, hormone, or receptor and most models fail to account for other local factors such as parathyroid hormone related protein (PTHrP). We review the relevant mouse models and discuss the importance of CaR in chondrogenesis and osteogenesis. We present the evidence for a non-redundant role for CaR in skeletal mineralization, including our experience in patients with activating CaR mutations. Additionally, we review emerging research on the importance of the CaR to the regulation of serum calcium homeostasis independent of PTH, the role of the CaR in the hematopoietic stem cell niche with implications for bone marrow transplant, and early evidence that implies a role for the CaR as a factor in skeletal metastasis from breast and prostate cancer. We conclude with a discussion of drugs that target the CaR directly either as agonists (calcimimetics) or antagonists (calcilytics), and the consequences for bone physiology and pathology.
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PMID:The role of the calcium-sensing receptor in bone biology and pathophysiology. 1935 39

Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.
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PMID:Molecular imaging of cancer: MR spectroscopy and beyond. 2055 45

Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo- and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases (Phosphorus-32, Strontium-89, Rhenium-186, Rhenium-188, Samarium-153, and Radium-223) and the combination therapy with biphosphonates and chemotherapy.
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PMID:Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium. 2418 Jun 69


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