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)

We have studied the forms of prostate-specific antigen (PSA) in serum of patients with prostatic cancer and benign prostatic hyperplasia. Fractionation of serum by gel filtration and assay of the fractions for PSA showed that a considerable part of the PSA immunoreactivity in serum consisted of complexes that were larger than PSA. The complexes were assayed by time-resolved immunofluorometric assays based on an antibody against PSA on the solid phase and europium-labeled antibodies against various protease inhibitors as indicator antibodies. In addition to its monomeric form, PSA was found to occur in complex with alpha 1-antichymotrypsin. The proportion of the alpha 1-antichymotrypsin complex was a major form of PSA and it increased with increasing PSA concentrations, being over 85% at PSA levels exceeding 1000 micrograms/liter. A complex with alpha 1-protease inhibitor was also observed in serum of patients with prostatic cancer and very high levels of PSA. Complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor were detected, but their concentrations were low and similar in sera of cancer patients, normal men, and normal women, suggesting that they were not prostate derived. Commercial immunoradiometric assays for PSA were found to measure free PSA and its complexes with alpha 1-antichymotrypsin but not the complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor. The proportion of the PSA-alpha 1-antichymotrypsin complex was higher in patients with prostatic cancer than in those with benign hyperplasia. Therefore, assay of the complex had a higher sensitivity for cancer than assay of total PSA immunoreactivity.
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PMID:A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. 170 33

Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial immunodiffusion in normal subjects, pregnant women, and in a wide variety of diseases. The normal concentration (448 (SD 75) mg/l) increased significantly (p less than 0.001) in pregnancy to 575 (89) mg/l, and in prostatic cancer treated by oestrogens to 666 (87) mg/l. Inconsistent changes were observed in inflammatory and malignant disease and in liver disease. A temporary pronounced fall of alpha-TPI was seen after burn injury, and a sustained fall after bone marrow transplantation. Crossed immunoelectrophoresis showed that the serum alpha-TPI occurred in two forms, with alpha 2 and alpha 1 electrophoretic mobilities. A heavy demand on this antiprotease may result in suppression of the alpha 1 form.
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PMID:Serum alpha-thiol protease inhibitor concentrations in health and disease. 381 86

The present status of tumor markers in prostate cancer, especially prostate-specific antigen (PSA), for diagnosis and follow-up of prostate cancer patients was reviewed. Due to tissue-specific protein of PSA as well as PAP, serum PSA levels may increase in patients with benign hyperplasia (BPH) which is the disease necessary for differential diagnosis from prostate cancer. Therefore, it has been believed to be difficult to differentiate early stages of prostate cancer from BPH using only PSA determination. However, with the use of recently developed assay systems, the detection of PSA-protease inhibitor complex, or PSA-density, the detection of early stages of prostate cancer may be possible. In following up prostate cancer patients, serially determined PSA is one of the best tools to evaluate treatment response and early detection of disease progression.
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PMID:[Tumor markers in prostate cancer]. 752 99

Quantitative immunoblotting of prostate cancer patient sera revealed that most prostate specific antigen was in complexes with alpha 1-antichymotrypsin or alpha 2-macroglobulin with little of it being free antigen. Complexes of prostate specific antigen with these protease inhibitors in patient sera comigrated during electrophoresis with the respective purified complexes. Each complex was selectively removed from patient sera by absorption with specific antibodies. When prostate specific antigen was added to normal plasma, complexes with alpha 2-macroglobulin appeared first and after 1 hr, the distribution was approximately 40% free antigen, approximately 40% complexes with alpha 2-macroglobulin, and approximately 20% complexes with alpha 1-antichymotrypsin. These data show that prostate specific antigen reacts more readily with alpha 2-macroglobulin than with any other protease inhibitor in plasma and that the antigen complexes with alpha 2-macroglobulin in vivo in cancer patients.
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PMID:Prostate specific antigen-alpha 2-macroglobulin complexes in prostate cancer patient sera. 862 98

Since the identification of prostate-specific antigen (PSA), continued technological advances have provided highly sensitive assays for its quantification. Given its lack of disease specificity, and its recent detection at low levels in an increasing number of non-prostatic tissues, PSA is far from being the perfect "tumour" marker (biological marker). However, the positive predictive value of PSA for assessing cancer risk makes PSA the most useful "tumour" marker for monitoring progression and response to treatment among patients with prostate cancer. Earlier detection through screening for elevated levels of PSA, while controversial, has been proposed as a way to decrease prostate cancer mortality. Haematogenous identification of PSA mRNA may provide stage-related prognostic information, and the use of ultrasensitive assays for PSA may permit earlier identification of residual or recurrent cancer, following treatment and the initiation of adjuvant therapy. Various PSA-related concepts, including the ratio of "free" PSA and complexes of PSA with the protease inhibitor, alpha1-antichymotrypsin, to total PSA, have been proposed and placed within diagnostic and management algorithms. Elevations of PSA in other irregularities of the prostate, notably in benign prostatic hyperplasia, and the increasing frequency and number of non-prostatic tissues, including those in women, expressing PSA, have implications for future immunoassays for PSA and strategies for immunotherapy using PSA-based monoclonal antibodies or vaccines, as well as for the molecular basis for its anomalous expression and physiological function(s).
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PMID:A retrospective and prospective overview of prostate-specific antigen. 962 Feb 15

Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate that has an 80% sequence identity with prostate-specific antigen. Expression of hK2 is elevated in the tumor epithelium compared to benign prostate tissue. We have purified, sequenced, and identified a novel hK2 complex in prostate tissue consisting of hK2 and a serine protease inhibitor known as protease inhibitor-6 (PI-6). This 64-kDa SDS-PAGE stable complex is elevated in the tumor and is approximately 10% of total hK2. No comparable complex of prostate-specific antigen was detected. PI-6, also known as cytoplasmic antiprotease, has been characterized as an intracellular inhibitor of trypsin and chymotrypsin-like proteases, which has high homology to plasminogen activator inhibitor 1 and 2. The physiological role of PI-6 in the prostate and its relationship to hK2 and prostate cancer are under investigation.
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PMID:Identification of a novel complex between human kallikrein 2 and protease inhibitor-6 in prostate cancer tissue. 1046 85

We previously reported cases of advanced prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were remarkably increased. These cases were not complicated with disseminated intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum protease derived from the prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA-alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patients with untreated PCa. The ready association of alpha2M and PSA was assessed using Western blotting to identify complexes of the two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M levels decreased as the disease progressed. However, only the free/total PSA ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there was a negative correlation between the total PSA and alpha2M values (r = -0.57, p < 0.05). In addition, serum alpha2M levels tended to decrease with progression of PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was useful for differential diagnosis between early cancer and BPH. Levels of serum alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone metastases.
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PMID:Progression of prostate cancer: diagnostic and prognostic utility of prostate-specific antigen, alpha2-macroglobulin, and their complexes. 1129 72

Prostate-specific antigen (PSA) is a tissue-specific serine protease which forms complexes with protease inhibitors such as alpha 1-antichymotrypsin and alpha 2-macroglobulin. We have studied the interaction between PSA and alpha 1-protease inhibitor (API) in vitro and found that 15% of the added PSA binds to API while the majority of API is cleaved between Met358 and Ser359 when PSA is incubated with a 5-fold excess of API at 37 degrees C for 7 days. The complex between PSA and API (PSA-API) formed in vitro displays the same chromatographic behavior, molecular size and immunoreactivity as endogenous PSA-API occurring in serum, indicating that they are identical. PSA-API can be detected in serum by a time-resolved immunofluorometric assay (IFMA), in which a monoclonal antibody to PSA is used as a catcher and a polyclonal antibody to API labeled with a Eu-chelate is used as a tracer. Purified PSA-API formed in vitro is used as a calibrator. PSA-API in serum represents 1.0-7.9% (median 2.4%) of total PSA (tPSA) in prostate cancer (PCa, n = 82) and 1.3-12.2% (median 3.6%, p < 0.01) in patients with benign prostatic hyperplasia (BPH, n = 66). The IFMA for PSA-API in serum is hampered by a variable background, which is caused by non-specific adsorption of the huge excess of API in serum to the solid phase. The background can be determined by an assay using the same tracer as in the IFMA for PSA-API but PSA-unrelated antibody on the solid phase. The background signal is subtracted from the PSA-API signal. The clinical utility of PSA-API in serum has been evaluated in PSA-positive subjects from the Finnish PCa screening trial. After subtraction of the background, the proportion of PSA-API in relation to tPSA is lower in PCa than in controls, 0.9% vs. 1.6%, respectively (p < 0.001). Logistic regression analysis showed that the concentration of PSA-API was independent of the proportion of free PSA as a diagnostic variable among subjects with a tPSA of 4-10 micrograms/l (p = 0.009). The probability of PCa calculated by logistic regression using the concentration of PSA-API and the proportion of free PSA in serum significantly improved cancer specificity at high sensitivity levels (85-95%) as compared to the proportion of free PSA alone.
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PMID:Characterization and determination of the complex between prostate-specific antigen and alpha 1-protease inhibitor in benign and malignant prostatic diseases. 1131 42

Prostate specific antigen (PSA) is a protease which is characteristic of the prostate. It is widely used as a serum marker for the early diagnosis of prostate cancer (PCa). Nevertheless, for concentrations between 4 and 10 ng/mL, PSA does not enable PCa to be distinguished from benign diseases, such as benign prostate hyperplasia (BPH). In sera, the use of a ratio between free PSA (PSA uncomplexed with protease inhibitor) and total PSA (free PSA and PSA bound to alpha-1 anti-chymotrypsin) enables the "gray zone" to be reduced, but an important proportion of patients are still wrongly classed. Using two-dimensional electrophoresis, we demonstrated using 52 PCa and 40 BPH well-documented clinical cases that BPH sera show a significantly greater percentage of low-molecular-weight free PSA elements (IwPSA) than PCa sera. In our study, the use of a ratio between IwPSA and standard free PSA enables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as against when 73.1% and 42.5% respectively were correctly diagnozed using the total PSA and the free/total PSA ratio. This important finding may be related to differences in the mechanism secreting PSA from the prostate into the bloodstream. We have shown how a tissue marker may be turned into a powerful tumor marker by events probably unrelated to its expression.
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PMID:Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis. 1142 43

This article presents the current reports of complexed prostate-specific antigen (PSA) aimed for the enhancement of prostate cancer detection. Further studies are needed to ascertain the variability of complexed PSA. Comparisons of percent free PSA, potential additive value of alpha(1)-antichymotripsin-bound PSA (PSA-ACT) and Bayer complexed PSA (cPSA) remains controversial in men with intermediate elevated total PSA concentration. Volume-referenced complexed PSA (PSA-ACT and cPSA) can enhance prostate cancer detection. Preliminary results show that PSA-alpha(2)-macrobloblin (PSA-a(2)M) and PSA-alpha(1)-protease inhibitor (PSA-API) are promising assays for improving cancer detection.
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PMID:Complexed prostate-specific antigen improvement in detecting prostate cancer. 1208 74


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