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)

Immunochemical determinations of serum proteinase inhibitors in human semen showed the presence of alpha1-antitrypsin and alpha1,x-antichymotrypsin, whereas inter-alpha-trypsin inhibitor, antithrombin III, alpha2-neuramino-glycoprotein and alpha2-macroglobulin could not be detected. Both serum proteinase inhibitors were determined in the seminal vesicle secretions of two patients with prostatic cancer. Employing the Ouchterlony double immunodiffusion technique pattern of identity was found between alpha1-antitrypsin resp. alpha1,x-antichymotrypsin in seminal plasma, seminal vesicle secretions and serum. Mean alpha1-antitrypsin concentration in seminal plasma of 129 andrological patients was 97.7 mug/ml and that of alpha1,x-antichymotrypsin 32.8 mug/ml. There were no differences in the mean alpha1-antitrypsin concentrations of normozoospermic and oligozoospermic ejaculates and those with seminal plasma fructose deficiency. Azoospermic ejaculates, however, showed a significant decrease of the mean alpha1-antitrypsin concentration (p less than 0.05). Alpha1,x-antichymotrypsin concentrations of normozoospermic ejaculates were significantly higher compared to those of oligozoospermia and azoospermia (p less than 0.05). Alpha1,x-antichymotrypsin levels in semen samples were fructose deficiency were not different from those of the total ejaculate population. The cause and significance of the observed differences in the inhibitor concentrations within the different ejaculate types is not known. However, there are no indications for the involvement of both proteinase inhibitors in male reproductive processes.
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PMID:Quantitative determination of high molecular weight serum proteinase inhibitors in human semen. 108 38

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

Immunologic measurements of the serum concentration of prostate-specific antigen (PSA), an abundant prostatic-secreted serine proteinase, are frequently used to monitor patients with prostate cancer, though it has not been ascertained whether this immunoreactivity represents a PSA zymogen, the active proteinase, or PSA complexed to extracellular proteinase inhibitors. To characterize the PSA immunoreactivity in serum, we used monoclonal antibodies produced against PSA and a polyclonal rabbit IgG against alpha 1-antichymotrypsin in the design of three noncompetitive PSA assays: assay T, which detected PSA both when present as the active proteinase and when complexed to alpha 1-antichymotrypsin; assay F, which recognized the active proteinase but most poorly detected PSA complexed to alpha 1-antichymotrypsin; and assay C, which was specific for PSA complexed to alpha 1-antichymotrypsin. We used the three assays to measure PSA immunoreactivity in 64 patients' sera and in the effluent after gel chromatography of sera from four patients. This identified an 80- to 90-kDa complex between PSA and alpha 1-antichymotrypsin as the predominant fraction of the PSA immunoreactivity in blood plasma; an immunoreactive 25- to 40-kDa compound was the minor fraction.
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PMID:Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. 2094 Mar 31

Prostate specific antigen (PSA) in serum of patients with benign prostatic hyperplasia (BPH) or prostate cancer (P-CA) not bound to alpha-1-antichymotrypsin (ACT) was analyzed by chromatofocusing. The procedure allowed the simultaneous separation of complexed and free PSA and the fractionation of the free PSA fraction into several isoenzymes. The detection of the isoenzymes was strongly dependent on the combination of antibodies introduced in the applied commercially available immunoassays (Cobas Core, Delfia). Isoenzymes in sera of patients with benign prostatic hyperplasia were mainly situated in the pI range of 6.6 to 7.3. Isoenzymes in sera of prostate cancer patients or in PSA from LNCAP cells were mainly situated in the pI range 7.0 to 8.3. Neuraminidase treatment of the sera shifted the isoelectric points of all three sources towards more basic pHs. An irregular glycosylation process in the dysplastic cells of the prostate is suggested to be the cause for the shift of the isoelectric points. The difference of isoenzyme distribution along the pH axis is discussed as a diagnostic tool to differentiate between BPH and P-CA.
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PMID:Serum free prostate specific antigen: isoenzymes in benign hyperplasia and cancer of the prostate. 868 58

Prostate-specific antigen (PSA) in serum is primarily complexed with alpha 1-antichymotrypsin (alpha 1-ACT). However, 12-15% of prostate cancer (PCa) patients present with the predominant form being uncomplexed (free) PSA (Lilja et al., Clin Chem 1991;37:1618-24). We report that commercial immunoassays demonstrate variations in reactivity, especially to the uncomplexed form. We fractionated and analyzed commercial controls, PSA complexes prepared in vitro, and sera from patients with PCa or benign prostatic hyperplasia, using molecular sieve chromatography and Hybritech Tandem-R, Abbott IMx, and Ciba Corning ACS PSA assays. Peak integration of PCa samples demonstrated ACS:Tandem-R ratios of 1-1.3 for PSA/alpha 1-ACT complex. In contrast, ratios of uncomplexed peaks ranged from 2 to 4, suggesting a greater reactivity of the uncomplexed form in the ACS PSA assay. Discrepancies between assays, when PSA was measured in unfractionated sera, correlated directly with the percentage of the uncomplexed form. In controls, fractionation revealed the presence of uncomplexed PSA only, with ratios of ACS:Tandem-R and IMx:Tandem-R of 3:1 and 1.8:1, respectively. Immunoblots of PCa sera detected uncomplexed PSA (approximately 30 kDa) and PSA complexes of approximately 95 kDa (PSA/alpha 1-ACT) and > 200 kDa, indicative of alpha 2-macroglobulin. Maximal recognition of all forms of PSA may be important for early detection of disease progression.
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PMID:Multiple forms of prostate-specific antigen in serum: differences in immunorecognition by monoclonal and polyclonal assays. 752 44

The absolute tissue specificity of prostate specific antigen (PSA) allows the use of PSA test not only for detecting recurrence or metastasis at an early stage after radical prostatectomy but also for screening prostate cancer if combined with digital rectal examination. There is also a need to improve the current PSA test to better differentiate between prostate cancer and benign prostate hyperplasia (BPH). Because of these clinical applications, a much greater demand was placed on PSA test for extra sensitivity, accuracy, and precision even within the normal PSA concentration range. However, the current commercial assay kits for PSA do not provide correct PSA values. Many factors contributing to the problem include the specificity of the anti-PSA antibodies, the composition of the calibrator, the PSA values assigned to the calibrator, the PSA isoform used for anti-PSA antibody preparation, the test design, and the composition of the diluent. Most problems were derived from the failure of realizing earlier that the majority of the PSA exists in serum not as free PSA but as complexes with protease inhibitors. Other problems, such as constantly changing composition of various forms of PSA in serum specimens, and different clearance rates for various forms of PSA make almost impossible to develop an ideal assay for PSA. Therefore, we suggest that test should be designed for measuring PSA-ACT (PSA-alpha 1-antichymotrypsin) complex only. Changing the focus from the measurement of total PSA of various forms to the PSA-ACT complex alone may improve the differentiation between prostate cancer and BPH but may also simplify the selection of anti-PSA antibodies and the preparation of calibrator for the assay.
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PMID:Assay for prostate specific antigen (PSA): problems and possible solutions. 751 21

This paper summarises the results of a comparison of the Serono SR1, Ciba Corning ACS 180, Abbott IMx and Hybritech Tandem-R prostate-specific antigen assays. One hundred serum pools were assayed using the four methods. Linear regression analysis of the data showed that, although overall correlations were good, different assays gave different prostate-specific antigen concentrations. Tandem-R and SR1 assays gave very similar prostate-specific antigen values; in general, the ACS assay gave higher prostate-specific antigen values than the IMx assay gave lower prostate-specific antigen values than the established Tandem-R assay. Following fractionation of serum from prostate cancer patients, all immunoassays detected several immunoreactive prostate-specific antigen forms. The major immunoreactive form (> 88% of immunoreactivity) had an apparent molecular size of M(r) approximately 100,000 and is likely to be a complex of prostate-specific antigen with alpha 1-antichymotrypsin; two minor forms had apparent molecular sizes of M(r) approximately 30,000 (probably free prostate-specific antigen) and 200,000 (probably prostate-specific antigen complexed to high molecular mass anti-proteases). From this study there is no evidence that polyclonal/monoclonal antibody immunoassays are to be preferred to monoclonal/monoclonal antibody immunoassays for the determination of free prostate-specific antigen in serum.
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PMID:Measurement of prostate-specific antigen in serum using four different immunoassays. 751 58

We examined by gel filtration chromatography (Sephacryl 200) sera from 73 untreated patients with peripheral zone prostatic cancer volumes of 1 to 17 cc as well as patients with clinical stages C and D2 cancer. We also examined the sera from 40 patients who had failed radiation or hormonal therapy to determine if clonal cell selection by these 2 therapies altered the binding of prostate specific antigen (PSA) to alpha 1-antichymotrypsin. Finally, we compared sera from 10 patients with benign prostatic hyperplasia (BPH) and 14 with large transition zone-BPH cancer. Without exception, of the total serum PSA recognized by the Hybritech Tandem-R, Yang Pros-Check, Abbott IMx and Ciba Corning ACS assays, 88 to 98% were complexed with alpha 1-antichymotrypsin in all cancer patients. The 10 patients with BPH showed less complexation (73 to 84%). These studies suggest that much of the quantitative differences among assays is determined more by relative differences in recognition of the free and complex forms of PSA than by calibration differences between assays.
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PMID:Serum prostate specific antigen binding alpha 1-antichymotrypsin: influence of cancer volume, location and therapeutic selection of resistant clones. 752 8

Prostate cancer can be detected at an early, potentially curable stage by screening based on digital rectal examination and serum prostate specific antigen (PSA). The value of screening appears doubtful, based on high 10-year survival rates in selected cases of early prostate cancer, but this follow-up time may be insufficient. By linking the information on 21172 men who took part in a screening examination in Finland, 1968-73, with data from the Finnish Cancer Registry, 44 cases of prostate cancer diagnosed up to 1980 were identified. Serum samples from cancer cases and from 74 controls matched for age and time of sampling were assayed for PSA and its complex with alpha 1-antichymotrypsin (PSA-ACT). With a cut-off for PSA of 2.5 micrograms/L giving 92% specificity, 95% of the cancers developing within the first 5 years, and 52% developing in 6-10 years tested positive. As a potential screening test with a 5-year interval for men under 65, the sensitivity would be 92% and specificity 97%. The ratio of PSA-ACT to total PSA was lower in controls than in patients with cancer. Using this ratio, we could eliminate half of the false-positive results in the range 2.5-25 micrograms/L without loss of sensitivity. Cancer was typically diagnosed 5-10 years after PSA exceeded 2.5 micrograms/L, and the median survival after diagnosis was 3.6 years. 10-year survival after drawing the sample was 71% in cancer cases with a PSA concentration less than 4 micrograms/L and 48% in those with higher concentrations. The corresponding figures at 15 years were 53% and 27%, and at 20 years 43% and 18%, respectively. These results suggest it is advisable to confine screening for prostate cancer to men with a life expectancy of clearly more than 10 years--ie, younger men, who have the greatest chance to benefit from early detection.
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PMID:Serum concentrations of prostate specific antigen and its complex with alpha 1-antichymotrypsin before diagnosis of prostate cancer. 1133 Feb 69

This chapter mainly deals with biochemical aspects on prostate specific antigen (PSA) and its clinical value. To a limited extent, also other tumor markers, which might be of importance in the evaluation of patients with prostate cancer are discussed. In serum, PSA exists in a free form or bound to antichymotrypsin. Interestingly, only 10% of PSA secreted from cancer cells seems to exist in a free form, as compared to 30% of PSA secreted from cells in benign prostatic hyperplasia (BPH). PSA seems to be closely, but not absolutely, related to tumor grade and stage. The mean value of PSA in patients with tumors dominated by Gleason grades 3 or below, was 10 ng/ml, compared to 29 ng/ml in those with higher grades. Patients with PSA values of 50 ng/ml or above almost exclusively had tumor of Gleason grades 4 or 5, and this limit usually reflected a generalized disease. Patients with PSA-values below 10 ng/ml almost exclusively had tumors confined to the prostate gland. In countries where screening for prostate cancer is believed in, it is important to understand that normal cut-off values are related to patient's age. The upper normal limit of males below 50 years of age should be set at 2.5 ng/ml, as compared to 6.5 ng/ml for men over 70 years of age. To improve the value of PSA determination and for scientific purposes, the standardization of the assay is urgently needed and under way. Prostate acid phosphatase (PAP) has in most centres been replaced by PSA. An elevated PAP value, as measured by the enzymatic method, invariably indicates a generalized disease and could thus be used as a complementary informative assay to PSA. Other markers have been used mainly to achieve additional prognostic information. In a multivariate analysis, the non-specific tumor marker neopterin, which reflects the host response to tumor antigens, was closely related to short-term prognosis. Neopterin was followed by thymidine kinase, a protein reflecting the cell turn-over and tumor grade. Also PSA at diagnosis seemed to add some prognostic information, whereas other markers did not.
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PMID:Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993. 752 30


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