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)

A retrospective study has been made on the interrelationship of serum bone alkaline phosphatase (BAP), measured by the Ostase-RIA, and prostate-specific antigen (PSA) in 156 patients with M0 and M1 prostate cancer. BAP is a more sensitive and more specific method of determining osteoblast activity than total alkaline phosphatase (TAP). The main difference between these two assays is seen when the TAP is in the range of normal to twice-normal. BAP shows a low intraindividual variation in M0 disease, and was within normal limits in 18 patients following radical prostatectomy with a PSA < 0.1 ng/ml. A raised BAP was observed in 86.4% of M1 disease at diagnosis before treatment. The change of BAP was concordant with PSA in 69% of 49 cases of M1 disease, although there are marked differences in the rates of change of the two markers. A nadir of PSA < or = 10 ng/ml after androgen blockade in M1 disease was associated with a high probability of a normal BAP.
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PMID:Bone alkaline phosphatase and prostate-specific antigen in the monitoring of prostate cancer. 752 52

One hundred and twenty-four localized prostate cancer patients operated on at Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized for evaluation of prostate cancer progression. Based upon accurate clinical histories, these radical prostatectomy patients included 50 progressors and 74 non-progressors using appearance of serum PSA as an indication of recurrence (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in the study had no involvement of their seminal vesicles or lymph nodes at the time of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8 years. Using paraffin-embedded specimens, several five micron sections were cut and placed on Probe-On slides; one slide was H&E-stained and the other was Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2 beta, was used to capture the Feulgen-stained images and to perform the calculations. From the "dotted" areas, 150 cancer cells were selected for measurement of DNA content and 27 nuclear morphometric shape and size factors, including 21 Markovian chromatin texture variables. Additional sections were used for immunochemistry staining with an alkaline phosphatase streptavidin-biotin complex stain to detect and quantitate cancer cells binding monoclonal antibodies directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen. All data were entered into a statistical program (STATA) for further analysis and univariate and multivariate statistical analysis was performed using logistic regression and its stepwise variant. The biomarkers of greatest utility to detect progressors when analyzed univariately included post-operative Gleason score (p = < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008), and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor features were selected using backward stepwise logistic regression estimate analysis which drops variables due to collinearity. Although post-operative Gleason score is a strong univariate predictor of progression, DNA ploidy and HER-2/neu contributed significantly to further stratification of higher risk groups within the low Gleason score subpopulation. The best Markovian features combined with post-operative Gleason score generated sensitivity = 90%, specificity = 96%, positive predictive value = 94%, negative predictive value = 93% and the area under the receiver operator curve was 0.975.
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PMID:Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu immunohistochemistry for prediction of prostate cancer progression. 752 56

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.
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PMID:Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. 753 Jan 99

Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin-1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ectopic endothelin-1 may be a mediator of the osteoblastic response of bone to metastatic prostate cancer.
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PMID:Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. 758 22

Bone scintigraphy with 99mTc-phosphate compounds is the most popular examination in clinical nuclear medicine. This was developed more than 20 years ago and its roles in various skeletal disorders are well established. Furthermore, improvement of imaging apparatus and application of SPECT strengthened its value extensively. From scintigram alone, in many cases, differentiation between bone metastasis and other "benign" disorders is easily capable. Further improvement in resolution of scinticamera should strengthen its value more. Other recent developments in skeletal nuclear medicine are those in bone densitometry and in measurement of metabolic bone markers. Bone densitometry using DXA is applied on diagnosis and monitoring of therapeutic effects in various metabolic bone diseases, especially, in osteoporosis. Bone mass measurement combined with assessments of specific bone markers such as bone specific alkaline phosphatase and collagen cross-link metabolites might replace the bone biopsy in evaluating bone metabolism. Treatment of bone metastasis in patients with prostate cancer by administering radiolabeled bone seeking substances is another topics in this field and awaits for more extensive clinical evaluation.
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PMID:[Skeletal nuclear medicine]. 759 73

Expression of cancerous isoenzymes in various malignant tumors has been extensively studied using different biochemical techniques. Cancerous alkaline phosphatase (ALP) isoenzymes such as variant ALP and placental ALP are apparently detected in sera or tissues from patients with malignant tumors. Variant ALP is a specific tumor marker for hepatocellular carcinoma (HCC). Placental ALP is found in sera of patients with various malignant diseases. However, the positive rate of each ALP isoenzyme is low except for high positivity of placental ALP in seminoma. Novel gamma-glutamyltranspeptidase (gamma-GTP) isoenzyme is specifically found in about 60% of sera from patients with HCC, but in only 3% of patients with benign liver diseases, suggesting high specificity for HCC. Serum prostatic acid phosphatase (PAT), which increases in activity in parallel with the growth of prostatic tissue, is an useful marker for prostatic cancer. Thus, several cancerous isoenzymes are available for diagnosis of various malignant tumors.
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PMID:[Isoenzyme as tumor marker]. 760 66

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.
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PMID:Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. 767 43

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumour cells. 768 10

Twenty seven patients with endocrine therapy relapsed prostate cancer were studied by measuring their prostatic acid phosphatase (PAP), prostate specific antigen (PSA), gamma-semino-protein (gamma-Sm) and alkaline phosphatase (ALP) serially before change of the treatment, and tumor marker doubling time was calculated. The exponential increase in PAP, PSA and gamma-Sm was observed in all patients and ALP showed a similar pattern in some. The values of PAP doubling time were the same as those of PSA, but gamma-Sm doubling time was slightly longer than the former ones. Tumor marker doubling time correlated with survival after the increase in markers, and also with time between the start of endocrine therapy and the increase in markers. Patients who showed either NC or PR to chemotherapy had a longer tumor marker doubling time than those with PD. In cases showing progression of bone metastasis, patients with exponential increase in ALP showed worse prognosis when compared with those showing other patterns. From these results, it was demonstrated that determination of tumor marker doubling time in patients with endocrine therapy relapsed prostate cancer was a valuable method to measure rate of regrowth, and to assess the prognosis after relapse.
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PMID:[Determination of tumor marker doubling time in the patients with prostate cancer relapsed from endocrine therapy]. 768 40

We developed an ultrasensitive method for measuring prostate-specific antigen (PSA) in serum. The assay includes a capture monoclonal anti-PSA antibody coated to microtiter wells, a biotinylated rabbit polyclonal detection antibody, and alkaline phosphatase (ALP)-labeled streptavidin. The activity of ALP is measured with the substrate diflunisal phosphate; the released diflunisal forms highly fluorescent complexes with Tb(3+)-EDTA that are quantified with microsecond time-resolved fluorometry. The assay is precise and accurate and correlates well with the established Hybritech Tandem-PSA kit. Its distinguishing feature is extreme sensitivity (lowest limit of detection is 0.002 micrograms/L or 2 x 10(6) PSA molecules per assay). This is the most sensitive PSA assay reported thus far; we used it to quantify PSA in patients who had undergone radical prostatectomy. Many patients had < 0.01 micrograms/L PSA in their serum. This method could have important clinical applications in postsurgical early detection of relapse or residual prostate cancer, as recently suggested in the literature (Clin Chem 1992;38:1930-2).
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PMID:Ultrasensitive time-resolved immunofluorometric assay of prostate-specific antigen in serum and preliminary clinical studies. 769 42


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