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)

Although several prognostic factors have been discussed, multivariate analysis that includes tumor marker doubling time has not yet been examined in patients with prostate cancer refractory to endocrine therapy. A number of conventional prognostic factors including doubling times of prostate-specific antigen and/or prostatic acid phosphatase were examined in 56 prostate cancer patients who were refractory to endocrine therapy, using univariate and multivariate analyses. On univariate analysis, 6 parameters (doubling times of prostate-specific antigen and prostatic acid phosphatase at the time of refractory status, performance status, duration from beginning of endocrine therapy to prostate-specific antigen/prostatic acid phosphatase failure, mode of recurrence, the presence or absence of prostate-specific antigen/prostatic acid phosphatase normalization, and alkaline phosphatase) were shown to be significant prognostic factors. On multivariate analysis, only performance status and doubling times of prostate-specific antigen and prostatic acid phosphatase were significant. These observations showed that the doubling times of prostate-specific antigen and prostatic acid phosphatase, calculated at the time of prostate-specific antigen/prostatic acid phosphatase failure by estimating serial prostate-specific antigen or prostatic acid phosphatase, were a valuable prognostic factor in patients with prostate cancer refractory to endocrine therapy.
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PMID:Prognostic factors in patients with prostate cancer refractory to endocrine therapy: univariate and multivariate analyses including doubling times of prostate-specific antigen and prostatic acid phosphatase. 937 15

We report a quantitative analytical methodology for prostate-specific antigen (PSA) mRNA, which is based on the coamplification of the target with a recombinant RNA internal standard (IS) using reverse transcriptase-polymerase chain reaction. PSA mRNA and the RNA IS contain the same primer recognition sites and generate amplification products that have identical sizes but differ in a 24-bp sequence located in the center of the molecule. Amplified sequences are labeled with biotin using a biotinylated upstream primer. The products are captured on streptavidin-coated microtiter wells and hybridized to specific probes labeled with the hapten digoxigenin. The hybrids are determined using alkaline phosphatase-labeled anti-digoxigenin antibody and time-resolved fluorometry. The ratio of the fluorescence values obtained for the PSA mRNA and the RNA IS is a linear function of the amount of PSA mRNA present in the sample. Samples containing total RNA from PSA-expressing cells (LNCaP cells) in addition to 1 microg of RNA from healthy cells give fluorescence ratios related linearly to the number of cells in the range of 4 to 3000 cells.
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PMID:Quantification of prostate-specific antigen mRNA by coamplification with a recombinant RNA internal standard and microtiter well-based hybridization. 962 39

We investigated the usefulness of two biochemical markers of bone formation (PICP, the carboxy-terminal propeptide of type I procollagen, and bone ALP, bone-derived alkaline phosphatase) and a marker of bone resorption (ICTP, the carboxy-terminal telopeptide of type I collagen), to determine whether the presence of bone metastasis in prostate cancer could be evaluated and the extent of bone metastasis could be stratified by the serum levels of these markers, compared to total alkaline phosphatase (T-ALP) and prostate-specific antigen (PSA). The serum levels of PICP, bone ALP, ICTP, T-ALP and PSA were significantly higher in patients with both prostate cancer and bone metastasis (n=49) than in patients with benign prostatic hyperplasia (n=35) and patients with prostate cancer without bone metastasis (n=70). The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic curves. The serum marker levels were compared as a function of metastatic burden in bone (i.e., the extent of disease, EOD grade). We found that bone ALP is the most suitable marker for evaluating bone metastasis, especially for stratifying the degree of bone metastasis. Both PICP and ICTP were useful in this respect, but rather inferior to bone ALP. T-ALP had the lowest ability for detecting bone metastasis, but its correlation with the EOD grade was excellent, second to that of bone ALP. PSA showed limited reliability for stratifying the extent of bone metastasis.
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PMID:Comparison of markers of bone formation and resorption in prostate cancer patients to predict bone metastasis. 962 52

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.
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PMID:Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain. 970 48

Therapeutic options for patients with metastatic prostate cancer relapsing from primary hormonal therapy are limited. On the selective discontinuation of flutamide in patients that have relapsed on combined androgen ablation, a third of the patients will show a significant clinical benefit for 4-6 months. A multivariate model has identified prolonged exposure to combined androgen blockade, high baseline alkaline phosphatase and prolonged flutamide exposure as prognostic factors for patients that have a significant prostate-specific antigen (PSA) decline after the withdrawal of flutamide. This phenomenon has also been described with bicalutamide and other antiandrogens, and thus has been more appropriately renamed the endocrine withdrawal syndrome. The molecular basis for this endocrine withdrawal syndrome is not completely understood but data suggest that mutations in the androgen receptor may be responsible for the paradoxical effect observed. Recognition of this syndrome has introduced a non-toxic therapy for advanced prostate cancer patients and has had a dramatic impact on the interpretation and design of clinical trials in patients with 'hormone refractory disease'.
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PMID:Endocrine withdrawal syndrome and its relevance to the management of hormone refractory prostate cancer. 985 91

In situ DNA fragmentation assays have proved to be particularly useful in the detection of apoptosis in routinely processed, paraffin-embedded tissue sections. In the present study, a triple-antigen labelling technique was performed to demonstrate DNA fragmentation (apoptosis), cell proliferation (MIB-1), and phenotypic markers in the same tissue section. The in situ apoptosis assay was conducted with the TUNEL method developed by a avidin-biotin alkaline phosphatase complex (ABcomplex/AP). The proliferation-associated MIB-1 antigen was demonstrated in the second staining sequence by the avidin-biotin peroxidase method (ABC). The phenotypic markers chromogranin A or prostate-specific antigen (PSA) were visualized by the alkaline phosphatase anti-alkaline phosphatase method (APAAP) in the third staining sequence. The feasibility of this triple-labelling technique was tested in formalin-fixed, paraffin-embedded tissue of prostatic adenocarcinomas from 8 patients with recurrent, hormone-refractory disease. Although these tumours revealed marked neuroendocrine differentiation, cell proliferation and apoptosis were detected exclusively in non-endocrine (chromogranin A-negative) tumour cells that expressed PSA variably. The triple-labelling protocol described here allows the phenotypic characterization of proliferating and apoptotic cell populations in the same tissue section. It may be useful in studies of tissue kinetics in physiological and pathological processes.
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PMID:Simultaneous detection of DNA fragmentation (apoptosis), cell proliferation (MIB-1), and phenotype markers in routinely processed tissue sections. 1007 Dec 38

The aim of this study was to analyse the clinical utility of serum bone alkaline phosphatase (BAP) in addition to prostate-specific antigen (PSA) in the staging of newly diagnosed untreated prostate cancer patients. A prospective study was conducted, analysing serum BAP and PSA concentrations in 295 consecutive newly diagnosed untreated prostate cancer patients (T1-4, N0-1, M0-1b), 93 of whom had bone metastases on bone scan. The relationship of each marker with extent of bone disease, the influence of several clinical variables on both serum marker levels, the efficiency in predicting bone metastasis through receiver operating characteristic curves and, finally, the clinical utility in avoiding unnecessary bone scans were determined. Significant differences were found in the serum levels of both BAP and PSA between patients with and patients without bone metastases. Multiple regression analysis showed the extent of bone disease to be the only variable that influenced both serum levels. However, while serum BAP levels showed a statistical relationship with extent of bone disease, serum PSA levels did not. The best prediction of bone scan findings was obtained with the combination of both markers using a cut-off of 20 ng/ml, with positive and negative predictive values of 46.5% and 100%, respectively. This greater efficiency could permit 32.2% of initial bone scans to be avoided. False-positive and false-negative rates of BAP were 7.5% and 14%, respectively. This study suggests that serum BAP levels could play a complementary role in the diagnosis of bone metastasis in prostate cancer patients. This marker could provide useful clinical information on the degree of skeletal metastasis and constitute an easy way of enhancing the clinical utility of PSA. The addition of this marker to PSA in the initial evaluation could permit staging bone scan to be avoided at a PSA range of 10-20 ng/ml, with significant implications for cost saving.
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PMID:Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients. 1036 48

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.
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PMID:Serum interleukin 6 as a prognostic factor in patients with prostate cancer. 1091 13

We evaluated whether the combination of triptorelin, a LHRH analog (LHRH-A), with dexamethasone and lanreotide, a somatostatin analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IGF-I, T, and dehydroepiandrosterone sulfate levels were assessed at baseline, at response to the combination therapy, and at relapse from it. Ten of 11 stage D3 patients [90.9% of patients; 95% confidence interval (CI), 58.7-99.8%] had durable objective clinical responses (including > or = 50% prostate-specific antigen decline in 8 patients, 72.7%; 95% CI, 39-94%). All patients reported significant and durable improvement of bone pain (for a median duration of 13 months; 95% CI, 12-14 months; range, 6-22 months) and performance status (median duration, 19 months; 95% CI, 13-25 months; range, 7-22 months) without major treatment-related side effects. The median progression-free survival was 7 months (95% CI, 4-10 months; range, 3-17 months), and the median overall survival was 18 months (95% CI, 16-20 months; range, 7-22 months). Five of six total deaths occurred secondary to disease progression. We observed a statistically significant (P = 0.018) reduction in serum IGF-I levels at response to the combination therapy (60% reduction of baseline IGF-I levels). Dehydroepiandrosterone sulfate levels, although already significantly suppressed at baseline, had an additional significant reduction (P < 0.02) at response to therapy. T levels remained suppressed within castration levels (<3 nmol/liter, at baseline and throughout therapy, including relapse). The combination therapy of LHRH-A with dexamethasone plus somatostatin analog produces objective clinical responses and symptomatic improvement in androgen ablation (LHRH-A) refractory prostate cancer patients.
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PMID:A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients. 1173 29

Serum and seminal biologic substances that are produced either by normal or abnormal tissues of the organism and that can be used to diagnose pathological conditions are usually referred as markers. The aim of this article is to briefly review the most relevant clinical features of the main genital markers in the male dog: alkaline phosphatase (AP), carnitine and canine prostate-specific arginine esterase (CPSE). Carnitine and AP are markers for the presence of epididymal fluid in the ejaculate and their measurement in azoospermic dogs has been used as an indicator of tubular patency of the ductal network. Although AP is not present in high concentrations in the testis, this does not preclude the possibility that testicular cells might secrete some AP. If this were true, AP could also reflect, at least in some degree, germ cell function in this species. Prostate-specific arginine esterase, the major secretory product of the canine prostate, is a known marker of gland secretion in the dog. Tumor markers frequently used in human medicine, such as prostatic acid phosphatase and prostate-specific antigen, are is still controversial in the diagnosis of prostatic carcinoma of the dog. Although further research is necessary to define the exact role of CPSE, it seems to be a promising diagnostic tool in nonneoplasic canine prostatic disorders. Future studies should also address the quantitative relationship among serum and prostatic androgen levels, prostatic androgen-dependent problems and how these are affected by anti-androgen treatment. The aim of this article is to briefly review the most relevant clinical features of three main genital markers of the male dog.
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PMID:Serum and seminal markers in the diagnosis of disorders of the genital tract of the dog: a mini-review. 1201 48


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