Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.
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PMID:Prostatic specific antigen. 753 74

The current assays for serum prostate specific antigen (PSA) have failed to produce the same PSA values on the same specimens because of problems with antibody specificity and calibrator preparation. To eliminate these problems, we proposed to replace the current serum PSA assay with an assay specific for the PSA-ACT (PSA-alpha 1-antichymotrypsin) complex in the serum. An assay specific for the PSA-ACT complex was established using the anti-PSA antibody to coat the microplate for capturing the PSA complex and anti-ACT polyclonal antibodies for quantification. There was an excellent correlation between serum concentrations of PSA-ACT and total PSA, using either the Hybritech calibrator (gamma = 0.996) or a serum calibrator prepared in house (gamma = 0.993), in random as well as in serial specimens from 14 individual patients. Even though we did not find a gradual increase in the percentage of PSA-ACT with the increase of total PSA in cancer patients, a slightly higher percentage of free PSA was measured in pooled normal sera (18%) and in pooled sera containing only 12 ng/ml of total PSA (12%), compared to serum pools containing elevated PSA (> 100 ng/ml) level, in which most PSA was in the complex form (95%). Therefore, using an assay that specifically measures the PSA-ACT complex in the serum not only simplifies the preparation of calibrator but eliminates the difficulty of antibody selection, it also allows various assay kits to produce identical PSA values and also improve the test specificity for prostate cancer.
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PMID:Correlation of serum concentrations of PSA-ACT complex with total PSA in random and serial specimens from patients with BPH and prostate cancer. 753 35

We developed a simple one-step dual-label immunoassay for simultaneous measurement of the free, noncomplexed form of prostate-specific antigen (PSA) and total PSA. The assay is based on time-resolved fluorescence and includes a stable fluorescent chelate of Eu to label a monoclonal antibody (mAb) that detects only free PSA, whereas a second mAb labeled with a fluorescent chelate of Tb provides equimolar detection of both free PSA and PSA complexed to alpha 1-antichymotrypsin. A third mAb on a solid phase captures the free and complexed forms of PSA in an equimolar fashion. The simultaneous measurement of the free-to-total PSA ratio (F/T) with the one-step dual assay is not sensitive to variations in the sample volume. The discrimination between benign prostatic hyperplasia and prostate cancer patients, i.e., the area under the receiver-operating characteristic curve, increased from 0.64 (total PSA assay) to 0.78 and 0.81 when the F/T ratio was measured with single and dual assays, respectively.
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PMID:Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum. 754 33

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to alpha 1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 micrograms/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 micrograms/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 micrograms/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.
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PMID:Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer. 754 78

Standardization of determinations for prostate specific antigen (PSA) has become an important issue due to the widespread use of these determinations for prostate cancer screening. Standardization of this assay is complicated due to the occurrence of two major forms of PSA in serum, the free antigen and a complex between PSA and alpha 1-antichymotrypsin (PSA-ACT). These two forms of PSA are recognized differently by different antibodies, but by careful selection of antibodies, it is possible to design methods that measure each form equally. It is suggested, that standards for PSA and PSA-ACT should be prepared and established as international standards. Furthermore, reference methods should be established on the basis that these standards and carefully selected reference antibodies.
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PMID:Standardization of PSA determinations. 754 84

PSA is a proteolytic enzyme produced in the prostatic epithelium and secreted into the seminal fluid. PSA can also be a constituent of the serum even under apparently normal conditions. In many cases of prostate cancer (PCa), increased serum concentrations are found. Elevated serum levels, however, are also observed in benign prostatic hypertrophy (BPH), thus limiting the specificity of serum PSA as a marker for prostate cancer. Recently, subfractions of PSA ("free PSA"; PSA-antichymotrypsin complex) were analyzed in order to gain a higher specificity of PSA as a tumor marker. The present paper describes biochemical features and clinical significance of the various PSA subfractions, pointing out an improved discrimination of PCa and BPH by evaluating the ratio "free PSA": total PSA.
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PMID:[Molecular forms of prostate-specific antigen and their clinical significance]. 754 41

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.
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PMID:Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. 768 16

Prostate-specific antigen (PSA) is a chymotrypsin-like serine protease exclusively produced by the prostate epithelium, and abundant in seminal fluid. In serum, PSA is predominantly complexed to a liver-derived serine protease inhibitor, alpha-1-antichymotrypsin (ACT). A higher proportion of serum PSA is complexed to ACT in prostate cancer than in benign prostate hyperplasia. Since the molecular basis for this is unclear, we have investigated whether or not ACT may be produced in the prostate gland. Immunocytochemistry, using either monoclonal or polyclonal IgGs, demonstrated specific immunostaining for ACT in normal PSA-containing prostate epithelium. Production of ACT in the normal PSA-producing prostate epithelium was demonstrated by means of nonradioactive in situ hybridization using 30-mer anti-sense DNA probes for ACT and for PSA. The ACT and PSA coding transcripts, as detected by in situ hybridization, were distributed perinuclearly, in contrast to the specific immunostaining for ACT and PSA which was most intense in the apical portion of the secretory cells. The results strongly suggest local production and release of ACT by the normal prostate epithelium that may be important for interaction between PSA and ACT in extracellular compartments.
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PMID:Production of alpha-1-antichymotrypsin by PSA-containing cells of human prostate epithelium. 769 14

Prostate-specific antigen (PSA) is the most important tumor marker for early detection and monitoring of prostate cancer (PCa) patients. PSA is also elevated in many patients with benign prostatic hyperplasia (BPH). The study of the serum PSA forms, free PSA (f-PSA) and PSA complexed with alpha 1-antichymotrypsin (PSA-ACT), may improve the discrimination between PCa and BPH. An immunoassay specific for f-PSA is reported with very low cross-reactivity (0.7%) to PSA-ACT. Serum specimens from BPH and PCa patients (determined by biopsy) with PSA levels from < 1 to > 100 ng/ml were tested. No f-PSA was detected in serum specimens from normal females (N = 50). Low levels (0-0.3 ng/ml) were detected in specimens from healthy males (N = 60). In specimens from PCa and BPH patients, the f-PSA to total PSA ratio (f/t) was found to range from 1% to higher than 60%. While maintaining an 80% sensitivity for cancer, the f/t ratio improved specificity to approximately 80%, as compared to 55% for total PSA alone. The receiver operating characteristics (ROC) curve analysis of the f/t ratio displayed a greater area under the plot (0.84) compared to total PSA alone (0.745). The results demonstrate that the f/t ratio significantly increases specificity for PCa detection compared to total PSA alone, showing the potential clinical value of the f-PSA immunoassay.
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PMID:Dual monoclonal antibody immunoassay for free prostate-specific antigen. 854 76

Gamma-seminoprotein (gamma-Sm) is one of the serine proteinases in seminal plasma, and is well known as a tumor marker of prostate cancer. In the blood, a major portion of gamma-Sm combines with alpha 1 antichymotrypsin (ACT), a serine proteinase inhibitor. We developed a sensitive enzyme immunoassay (EIA) for the gamma-Sm-ACT complex using two different monoclonal antibodies (MoAbs). One MoAb, prepared against gamma-Sm, is used for the capture, and the other, prepared against ACT, is conjugated with horseradish peroxidase and used for detection. The detectable range of this assay in clinical applications was from 0.2 to 50 units/ml. The intra-assay coefficients of variation (CV%) obtained from ten repeated assays of three sera were 3.6 to 5.5%. The mean gamma-Sm-ACT complex concentration in the sera of normal individuals was determined to be 0.86 +/- 0.11 units/ml for males (n = 50) and 0.11 +/- 0.08 units/ml for females (n = 54). There was no significant increase in the level of the complex with increasing age in males. The ratio of the gamma-Sm-ACT complex to free gamma-Sm tended to be significantly higher in patients with prostate cancer than in those with benign prostatic hyperplasia.
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PMID:[Specific quantification of gamma-seminoprotein-alpha 1 antichymotrypsin complex in serum by monoclonal antibody-based enzyme immunoassay]. 855 80


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