Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, the mRNA for prostate-specific antigen (PSA) has been investigated as a potential marker for molecular staging of prostate cancer. We report a simple, rapid, and sensitive assay protocol for the quantification of PSA mRNA in peripheral blood by using reverse transcriptase polymerase chain reaction (RT-PCR) and a chemiluminometric hybridization assay. A recombinant RNA internal standard (IS) that has the same size and primer binding sites as the PSA mRNA is included in the RT-PCR mixture. Total RNA from the sample is coextracted with a constant amount of IS RNA and subjected to RT-PCR. Amplified sequences are labeled with biotin during PCR by using a biotinylated upstream primer. The products are heat-denatured and hybridized with oligonucleotide-specific probes (for PSA and IS) that are immobilized in microtiter wells. Immobilization of oligonucleotide probes is achieved by adsorption of their conjugates with bovine serum albumin. The hybrids are measured using alkaline phosphatase-labeled streptavidin and a dioxetane chemiluminogenic substrate. The ratio of the luminescence values obtained for the PSA mRNA and the RNA IS is a linear function of the initial amount of PSA mRNA present in the sample prior to RT-PCR amplification. The linear range extended from 50 to 500,000 PSA mRNA copies, and the overall reproducibility of the assay, including RT-PCR and hybridization, ranged from 11.5 to 14.2%. Samples containing total RNA from PSA-expressing LNCaP cells give luminescence ratios that are linearly related to the number of cells in the range of 0.04-400 cells. The method was applied to PSA mRNA determination in peripheral blood of healthy individuals, patients with benign prostate hyperplasia, patients with prostate cancer, and patients with other types of localized cancer.
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PMID:Determination of prostate specific antigen mRNA in peripheral blood by reverse transcriptase polymerase chain reaction and a simple chemiluminometric hybridization assay in a high-throughput format. 1257 64

A 66-year-old male patient with advanced prostate cancer presented with bony metastases, including pathologic fractures and hepatosplenomegaly. The patient responded to luteinizing hormone-releasing hormone agonists for more than 1 year. A clear progression while taking luteinizing hormone-releasing hormone agonists manifested as a progressive rise in prostate-specific antigen, alkaline phosphatase, hepatosplenomegaly, and myelophthisic pancytopenia. We administered capecitabine for 5 months with a complete clinical response. At last follow-up, the patient's liver function tests and prostate-specific antigen level have normalized. Liver size by computed tomography and blood counts both improved. To our knowledge, no previous case reports of capecitabine in the treatment of prostate cancer have been published.
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PMID:Hormone-refractory prostate cancer responding to capecitabine. 1259 73

Epidemiological and clinical studies suggesting a significant inverse relationship between intake of dietary selenium and overall cancer risk have led to initiation of a randomized, placebo-controlled, phase III clinical trial testing the safety and efficacy of selenized yeast as a chemopreventive agent for prostate cancer. Participants eligible for the 'Negative Biopsy Study', which was initiated in August 1999, are men considered to be at high risk for prostate cancer because of at least one negative sextant prostate biopsy, which was clinically indicated within 1 year of enrollment to the study. After a 30-day run-in period to ensure protocol compliance, participants are randomized to receive either 200 or 400 microg selenized yeast or matched placebo once daily. Primary study endpoints include development of prostate cancer and prostate-specific antigen (PSA) velocity. Secondary biochemical endpoints include change in chromagranin A and alkaline phosphatase. As of 1 June 2003, 514 eligible participants had been enrolled. Randomization schema was effective for selected parameters including age, body mass index, smoking status, baseline PSA and baseline plasma selenium level. Various data, including medical history, family history, and urological symptoms and specimens (including blood and subsequent prostate biopsy samples) had been collected at baseline, and throughout both the intervention and follow-up stages of the protocol. The goal for accrual is 700 evaluable participants.
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PMID:Selenium and prevention of prostate cancer in high-risk men: the Negative Biopsy Study. 1450 80

Impediment of the promotion and progression stages of carcinogenesis of the prostate could have a profound impact on treatment choice and prognosis for prostate cancer. Efficacious chemopreventive agents that elicit their activity by slowing the processes of progression could make watchful waiting a viable alternative for a large population of men or could delay the necessity for surgery, radiation or other more invasive treatment modalities associated with frequent side effects. Reports from the Nutritional Prevention of Cancer (NPC) study reported that dietary supplementation with selenium significantly reduced the risk of developing prostate cancer. These data led to initiation of the Watchful Waiting Study, a phase II, multi-center, randomized, double-blind, placebo-controlled clinical intervention study testing the effects of two doses of selenized yeast on progression of prostate cancer. Participants are men with biopsy-proven prostate cancer who have elected to forgo therapy and be closely followed by 'watchful waiting' that includes quarterly prostate-specific antigen (PSA) screening. Subjects are randomized to receive 200 or 800 microg of selenized yeast or matched placebo daily. Endpoints include time to disease progression and PSA velocity. Secondary endpoints include time to initiation of therapy as well as biochemical markers of disease progression including chromagranin A and alkaline phosphatase. Immunohistochemical analyses for indicators of apoptosis, proliferation and differentiation will be performed on baseline and subsequent prostate biopsy specimens. This report summarizes the primary objectives, research methods and the randomized subjects in this important clinical trial.
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PMID:Selenium and inhibition of disease progression in men diagnosed with prostate carcinoma: study design and baseline characteristics of the 'Watchful Waiting' Study. 1450 81

Prostate cancer (CaP) develops metastatic bone lesions that consist of a mixture of osteosclerosis and osteolysis. We have previously demonstrated that targeting receptor activator of nuclear factor kappaB ligand (RANKL) with osteoprotegerin (OPG) prevents the osteolytic activity of CaP and its ability to establish tumor in bone. However, OPG can block tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis, suggesting that the clinical use of OPG may prevent apoptosis of tumors mediated by TRAIL. Thus, methods to block RANKL activity, other than OPG, may be important. Accordingly, we evaluated the ability of soluble murine RANK-Fc (sRANK-Fc) to prevent progression of established CaP in a severe combined immunodeficient mouse implanted with fetal human bone. We first confirmed that sRANK did not block TRAIL-mediated apoptosis of LuCaP cells in vitro and that it did block LuCaP-conditioned media-induced osteoclastogenesis in vitro. Then, LuCaP 35 CaP cells were injected into the marrow space of the bone implanted in the severe combined immunodeficient mice implanted with fetal human bone and allowed to develop into tumors for 6 weeks. Either vehicle or sRANK-Fc was then administered for 6 weeks. sRANK-Fc diminished tumor-induced osteoblastic lesions as demonstrated by radiograph, bone mineral density measurement, and bone histomorphometry. sRANK-Fc also reduced systemic bone remodeling markers, including serum osteocalcin and bone-specific alkaline phosphatase and urine N-telopeptide of collagen. Finally, sRANK-Fc decreased serum prostate-specific antigen levels and tumor volume in the bone, which indicates decreased tumor burden. In contrast, sRANK-Fc had no effect on s.c. implanted LuCaP cells. We conclude that sRANK-Fc is an effective inhibitor of RANKL that diminishes progression of CaP growth in bone through inhibition of bone remodeling.
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PMID:Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. 1463 17

In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer.
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PMID:Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer. 1572 25

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

Back pain, especially in the lumbar region is a frequent symptom in ambulatory medicine. The differential diagnosis is wide and ranges from rather harmless muscular distortions to systematic disease, such as chronic infections or cancer. Our case shows, that sometimes the diagnosis is not quite simple to determine. A atypically picture may lead to unnecessary further evaluations and in some case even invasive diagnostic tests. However, the benefit should overweight the harm and costs. Not every back pain needs to be examined in every case and with every diagnostic possibility. Recent guidelines recommend a conservative approach to patients with back pain if they are younger than 50 years of age and if cancer or chronic infection is not suspected from their clinical evaluation and past medical history. For patients older than 50 years of age and suspicion for systematic disease, a radiograph of the spine and a routine laboratory measurement, including markers of inflammation (e.g. C-reactive protein), alkaline phosphatase, PSA (prostate-specific antigen) and immune-electrophoresis is mandatory. More detailed diagnostic steps, e.g. CT or MRT, should be performed if symptoms persist for longer than 6 weeks. In addition, if symptoms do not resolve with analgesia and physiotherapy more invasive therapeutically options may be considered.
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PMID:[Chronic thoracic vertebral syndrome by roundabout diagnosis]. 1584 54

The detection of prostate-specific antigen (PSA) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in the bloodstream of prostate cancer patients has been hypothesized as a prognostic marker, however little data are available concerning the association between this molecular marker and other laboratory values of potential importance. In this study, in patients with hormone-refractory prostate cancer (HRPC), relationships were determined between PSA RT-PCR positivity, survival, and various relevant markers including serum PSA, LDH, albumin, alkaline phosphatase and hemoglobin. A total of 19/30 HRPC patients were positive for PSA by RT-PCR. Positivity was significantly linked to serum PSA (P=0.004) and serum alkaline phosphatase (P=0.026) but not to the other laboratory variables. Median survival time for RT-PCR-positive patients was 9 months, compared to 19 months for RT-PCR-negative patients (P=0.035). Median survival time for patients with a hemoglobin>or=11 g/dL was 12 months, compared to 9 months for patients with <11 g/dL (P=0.005). Dichotomized (>or=or<median) serum PSA, LDH, alkaline phosphatase, and albumin were not significantly associated with survival in univariate analyses. In multivariate analysis, only dichotomized hemoglobin (<11 g/dL vs. >or=11 g/dL) remained statistically significant (P=0.019), indicating that RT-PCR had no independent association with survival after controlling for hemoglobin status in this study.
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PMID:Relationships between reverse transcriptase-polymerase chain reaction for prostate specific antigen, survival, and various prognostic laboratory factors in patients with hormone refractory prostate cancer. 1590 15

A 73-year-old man with localized prostate cancer was treated with androgen deprivation and radiation therapy. Staging evaluation showed no evidence of metastatic disease. After initiation of androgen deprivation therapy, the patient developed a marked increase in serum alkaline phosphatase (ALP). Despite continuation of hormonal ablation and completion of radiation therapy, ALP and prostate-specific antigen levels continued to increase. Bone metastases were documented 6 months after diagnosis. In this report, we explore the role of serum ALP as an indicator for patients who develop early metastases and thus might benefit from early initiation of aggressive secondary treatments such as chemotherapy.
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PMID:Alkaline phosphatase level increase with initiation of hormone therapy for prostate cancer portends poor prognosis with rapid progression to bone metastases: a case report and review of the literature. 1672 14


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