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

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

Prostate-specific antigen (PSA) is the most commonly used tumour marker for prostate cancer, both in screening and in follow-up. However, there are many false positive increases in the presence of other prostate diseases and, currently, there is no consensus regarding sensitivity and specificity of the PSA test, nor what constitutes the upper limit of normality. We report a case of a 67-year-old patient with metastatic prostate cancer who, with increased level of alkaline phosphatase and normal PSA, showed clinical and radiological evidence of progression of the disease.
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PMID:Metastatic prostate cancer with a normal prostate-specific antigen level. 1623 77

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

Prognostic value of a bone resorption marker, tartrate-resistant acid phosphatase isoform 5b (TRACP 5b), and two matrix metalloproteinases (MMP-2 and MMP-9) was compared with the standard clinical analyses of total alkaline phosphatase (tALP) and prostate-specific antigen (PSA), in prostate cancer (PC) patients with (BM+) or without (BM-) bone metastases. Diagnostic accuracy evaluation showed the highest area under the curve for tALP (AUC=0.98), followed by PSA (AUC=0.87), TRACP 5b (AUC=0.82), MMP-9 (AUC=0.62) and MMP-2 (AUC=0.53). Significantly shorter survival was observed for patients with tALP (p<0.001), TRACP 5b (p=0.002) and PSA (p<0.001) levels, above the determined cut-off values compared with lower marker levels. In multivariate Cox regression analysis, only tALP and PSA, in addition to Gleason score were independent prognostic factors for survival. Of the three novel markers tested, only TRACP 5b proved to be predictive of survival in PC with bone metastases. MMP-2 and -9 are thus not recommended for further studies in this context.
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PMID:Survival markers related to bone metastases in prostate cancer. 1721 55

The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node metastases (N 0, N1) compared with controls and (b) a longitudinal study of 40 hormone refractory prostate cancer patients stratified by skeletal involvement and followed during docetaxel (+/-BM) and zoledronate (+BM) treatment. Presence or absence of bone metastases (BM) was assessed by imaging techniques (magnetic resonance imaging or X-ray) and technetium-99m scintigraphy. The serum or urinary levels of alpha C-telopeptide of collagen type I (alphaalphaCTX), prostate-specific antigen (PSA), and total alkaline phosphatase (tALP) were assessed. PSA was elevated in both N 0 and N1 patients compared with controls, whereas alphaalphaCTX was elevated only in N1 patients. tALP exhibited no difference in any of the groups. In the treatment study, PSA decreased with treatment in both the -BM and +BM groups compared with baseline values, showing similar effect of docetaxel or docetaxel/zoledronate treatment on this marker. On the contrary, alphaalphaCTX and tALP did not decrease with docetaxel treatment in the -BM group compared with baseline, whereas it decreased significantly with docetaxel/zoledronate treatment in the +BM group, already after 1 month of treatment for alphaalphaCTX. Results suggest that alphaalphaCTX is superior to PSA and tALP for identifying patients having a high risk of metastatic disease and for monitoring skeletal progression in +BM prostate cancer patients during treatment.
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PMID:Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers. 1848 50

The purpose of this study was to evaluate the relationship of baseline body mass index (BMI) and serum testosterone level with prostate cancer outcomes in men with castration-resistant metastatic prostate cancer (CRPC). BMI and testosterone levels were evaluated for their ability to predict overall survival (OS) and prostate-specific antigen (PSA) declines in the TAX327 clinical trial, an international phase III randomized trial of one of the two schedules of docetaxel and prednisone compared with mitoxantrone and prednisone. In this study of 1006 men with CRPC, the median serum testosterone level was 14.5 ng per 100 ml (range 0-270), the median BMI was 27 kg m(-2) (range 15.7-46.5), and 26% of men were obese or morbidly obese (BMI>or=30). Obesity was associated with younger age, lower PSA and alkaline phosphatase levels, and higher performance status, primary Gleason sum, testosterone and hemoglobin compared to absence of obesity. In multivariate analysis, neither BMI, presence of obesity, nor baseline testosterone was significantly associated with OS or PSA declines. Higher testosterone levels among obese men suggest incomplete gonadal suppression with current therapies, but these differences may not be clinically relevant in men with CRPC. There was evidence of potential hemodilution of PSA and alkaline phosphatase levels in obese men.
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PMID:The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer. 1857 90

The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer. Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (-)-epigallocatechin-3-gallate (EGCG) and lesser amounts of (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin-3-gallate (a total of 1.3 g of tea polyphenols), until time of radical prostatectomy. Serum was collected before initiation of the drug study and on the day of prostatectomy. Serum biomarkers hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, IGF binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were analyzed by ELISA. Toxicity was monitored primarily through liver function enzymes. Changes in serum components were analyzed statistically using the Wilcoxon signed rank test. Cancer-associated fibroblasts were treated with EGCG, and HGF and VEGF protein and mRNA levels were measured. HGF, VEGF, PSA, IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio decreased significantly during the study. All of the liver function tests also decreased, five of them significantly: total protein, albumin, aspartate aminotransferase, alkaline phosphatase, and amylase. The decrease in HGF and VEGF was confirmed in prostate cancer-associated fibroblasts in vitro. Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.
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PMID:Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. 1954 90

Immunoassays are representative biochemical detection methods. Among them, sandwich-type immunoassays, typified by sandwich ELISA, have used in disease diagnosis or biochemical detection with high target selectivity. Horseradish peroxidase and alkaline phosphatase have been typically used for signal amplification in ELISA. Recently developed sandwich-type immunoassays such as biobarcode immunoassays, immuno-PCR, and immuno-RCA have improved sensitivity by changing mainly the signal amplification method. To develop a novel amplification method in ELISA, an enzyme-cascading system was incorporated into an ELISA, and the new assay is termed a cascading enzyme-linked immunosorbent assay (CELISA). This CELISA includes a trypsinogen-enterokinase combination as the cascading enzyme system, and was used to detect alpha-fetoprotein (AFP), which is a liver cancer marker, and prostate-specific antigen (PSA). Using a colorimetric reagent for signal generation, CELISA had 0.1-10pM limits-of-detection for AFP and PSA in whole human serum and assay buffers, depending on the platform, well plate, or microbead type used. This study represents the first example that incorporated an enzyme cascading step in an ELISA system, resulting in successful signal amplification with sensitive detection of pathogenic antigens in serum.
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PMID:Cascade enzyme-linked immunosorbent assay (CELISA). 1966 63

Recurrent prostate cancer has a complex molecular etiology and a prolonged disease course. Although initially responsive to androgen ablation, many men eventually become castration resistant, develop skeletal metastases, and are palliatively treated with docetaxel-based chemotherapy, radiation therapy, bisphosphonates, and best supportive care. Given the modest success rates of the current standard of care, clinical trial enrollment is encouraged. Castration-resistant prostate cancer (CRPC) is a heterogeneous disease, both in clinical manifestations and outcomes, requiring an individualized approach to both patient care and trial design. Herein, we review surrogate markers of disease progression and treatment efficacy in advanced prostate cancer in light of recently published guidelines that have redefined eligibility, response criteria, and suitable endpoints in prostate cancer drug development. The guidelines have refined outcome measures to potentially better capture clinical benefit and the ability of novel targeted molecular and biologic agents to impact favorably on this disease. We consider prostate-specific antigen changes, circulating tumor cells, bone scan alterations, markers of bone metabolism (urinary N-telopeptide and bone-specific alkaline phosphatase), pain improvements, and progression-free survival. To illustrate the role and challenges of these potential biomarkers and endpoints in drug development, we discuss a class of novel molecularly targeted agents, the src kinase inhibitors. Given that there are currently no validated surrogate markers of overall survival for assessing early clinical benefit from systemic therapy in metastatic CRPC, incorporation of relevant biomarkers into all phases of clinical development is essential to accelerate drug development in this field.
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PMID:Using surrogate biomarkers to predict clinical benefit in men with castration-resistant prostate cancer: an update and review of the literature. 1968 76


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