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)

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

To study immunorecognition of free type and complex type prostate-specific antigen (PSA) by current commercial PSA assays, sera from 3 patients with stage D2 prostate cancer were separated by Sephacryl S-200 chromatography and determined by Delfia PSA, ACS-PSA and Eiken PA kits. Two antibodies used in the 3 kits are 2 monoclonal, 1 monoclonal and 1 polyclonal and 2 polyclonal antibodies, respectively. Following chromatography, two PSA peaks were obtained in all patients. One was about 100 kDa and the other about 30 kDa. The former was considered to be the complex type PSA (complex with alpha-1 antichymotrypsin) and the latter to be free type PSA. As to free type PSA, the ACS-PSA kit and Eiken PA kit quantitated PSA values approximately 5.1 and 2.5 times higher than the Delfia PSA kit. For complex type PSA, the quantity determined by ACS-PSA kit was approximately 1.3 times higher than that determined by the Delfia PSA kit, while the quantity determined by the Eiken PA kit was about one third of that determined by Delfia PSA kit. The ratio of complex type PSA to total PSA (free type PSA + complex type PSA) was 74.8 +/- 14.9% (mean +/- SD) when determined by Delfia PSA kit, 59.3 +/- 18.4% by ACS-PSA kit and 52.9 +/- 13.8% by Eiken PA kit. The range of this ratio determined by ACS-PSA kit was from 47.3% to 80.5% in the 3 patients. These findings suggest that there are qualitative differences in immunorecognition of free type PSA and complex type PSA among current commercial PSA assays and that there are quantitative differences in the ratio of the 2 forms of PSA in serum among prostatic cancer patients. The measurement and follow-up of both free type and complex type PSA might be important for diagnosis and monitoring of prostate cancer.
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PMID:[Determination of free type and complex type prostate-specific antigen (PSA): differences in immunorecognition by Delfia PSA, ACS-PSA and Eiken PA kits]. 869 60

Prostate-specific antigen (PSA), produced by prostate cells, provides an excellent serum marker for prostate cancer. It belongs to the human kallikrein family of enzymes, a second prostate-derived member of which is human glandular kallikrein-1 (hK2). Active PSA and hK2 are both 237-residue kallikrein-like proteases, based on sequence homology. An hK2 model structure based on the serine protease fold is presented and compared to PSA and six other serine proteases in order to analyze in depth the role of the surface-accessible loops surrounding the active site. The results show that PSA and hK2 share extensive structural similarity and that most amino acid replacements are centered on the loops surrounding the active site. Furthermore, the electrostatic potential surfaces are very similar for PSA and hK2. PSA interacts with at least two serine protease inhibitors (serpins): alpha-1-antichymotrypsin (ACT) and protein C inhibitor (PCI). Three-dimensional model structures of the uncleaved ACT molecule were developed based upon the recent X-ray structure of uncleaved antithrombin. The serpin was docked both to PSA and hK2. Amino acid replacements and electrostatic complementarities indicate that the overall orientation of the proteins in these complexes is reasonable. In order to investigate PSA's heparin interaction sites, electrostatic computations were carried out on PSA, hK2, protein C, ACT, and PCI. Two heparin binding sites are suggested on the PSA surface and could explain the enhanced complex formation between PSA and PCI, while inhibiting the formation of the ACT-PSA complex, PSA, hK2, and their preliminary complexes with ACT should facilitate the understanding and prediction of structural and functional properties for these important proteins also with respect to prostate diseases.
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PMID:Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building. 873 55

Accurate determination of prostate specific antigen is important because of the increasing use of prostate specific antigen for diagnosis, follow-up and screening of prostate cancer. Standardization of this assay is complicated by the occurrence in serum of two major molecular forms of prostate specific antigen, free prostate specific antigen and a complex between prostate specific antigen and alpha 1-antichymotrypsin. These two forms of prostate specific antigen are recognized differently by many but not all antibodies. Thus, it is possible and desirable to develop methods that measure each form equally. To achieve better comparability, it is also necessary to prepare international standards for prostate specific antigen and its complex with alpha 1-antichymotrypsin. Furthermore, reference methods should be established which use these standards and carefully selected reference antibodies.
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PMID:Problems in the determination of prostate specific antigen. 889 26

Prostate-specific antigen (PSA) is a widely used marker for screening and monitoring prostate cancer. We identified and characterized the epitopes of two anti-PSA monoclonal antibodies (mAbs) designated B80 and B87. The epitopes were initially mapped as nonoverlapping by developing a sandwich immunoassay to measure PSA with the two anti-PSA mAbs. The two antibodies do not cross-react with homologous pancreatic kallikrein, but recognize epitopes unique to PSA. B80 and B87 can recognize both free and complexed PSA and hence measure total PSA. Epitope scanning and bacteriophage peptide library affinity selection procedures were used to identify and locate an epitope on PSA. A possible epitope for B80 was identified as being located on or near PSA amino acid residues 50-58 (-GRH-SLFHP-). The epitope for B87 was likely on an exposed nonlinear conformational determinant, unique to PSA, and not masked by the binding of B80 or alpha 1-antichymotrypsin.
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PMID:Epitope mapping of prostate-specific antigen with monoclonal antibodies. 896 33

Prostate-specific antigen (PSA) is a protease able to bind to serum antiproteases as alpha 1 antichymotrypsin (ACT). Free PSA (FPSA) corresponds to the fraction of total PSA (TPSA) which is unbound to ACT. Specific detection of the FPSA seems to be a valuable tool in the distinction between prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). Our aim was to evaluate retrospectively the FPSA/TPSA ratio in comparison to TPSA or FPSA determination, using two new immunoradiometric assays (PSA-RIACT and FPSA-RIACT, CIS bio international, Gif Sur Yvette, France) in the early diagnosis of PCa. 256 men, with TPSA levels between 0.7 and 44.7 ng/ml (median age = 69 years), including 164 sera obtained from patients with BPH and 92 sera from patients with untreated PCa were assayed. All diagnoses were histologically confirmed and patients tested before any adjuvant treatment. The evaluation of the median FPSA/TPSA ratio in the two groups showed significantly different values (BPH group: 24.2%, PCa group: 12.1%, P < 0.0001). By R.O.C. (Receiver-Operating-Characteristics) analysis, we show that the FPSA/TPSA ratio is the method of choice for discriminating BPH and PCa, since the area under curve is the greatest for the FPSA/TPSA ratio curve, as compared to the TPSA or FPSA curves (P < 0.0001). The best accuracy (number of true positive + true negative/total = 82.4%) was obtained with a FPSA/TPSA ratio < or = 15% with high odds ratio (20.5; confidence interval (CI): 11.2; 37.7). Of interest, similar results were also confirmed even in the subpopulation with serum TPSA levels between 2.5 and 10 ng/ml (161 patients including 99 BPH and 62 PCa). We thus confirm that combined serum measurement of FPSA and TPSA is of particular interest in the early diagnosis of PCa for patients with non-suspicious digital rectal examination and a TPSA value between 2.5 and 10 ng/ml. In those patients, biopsy should be reserved to the cases with FPSA/TPSA below 15%, which allows significant odds ratio (12.8; CI: 5.2; 31.4). Otherwise, to avoid the risk of missing any PCa, usual follow-up with combined TPSA and FPSA determination would be required with the same criteria of biopsy (i.e. FPSA/TPSA ratio < or = 15% when TPSA value is between 2.5 and 10 ng/ml; or TPSA > 10 ng/ml).
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PMID:Percentage of free serum prostate-specific antigen: a new tool in the early diagnosis of prostatic cancer. 901 50

Prostate-specific antigen (PSA) is a kallikrein-like serine protease mainly expressed in the human prostate. It is responsible for the proteolysis of the gel-forming proteins in human semen. Two major extracellular protease inhibitors, alpha-1-antichymotrypsin (ACT) and alpha-2-macroglobulin (AMG) may inactivate PSA escaping from the prostate. The predominant immunodetected form of PSA in serum is complexed to ACT but PSA exists also in a free non-complexed form despite the large excess of inhibitors. The concentrations of PSA in serum are normally less than 4 micrograms/l. but elevated concentrations are found in a majority of patients with prostate cancer (CAP) and the analysis of PSA in serum has become invaluable in the detection and monitoring of patients with CAP. However, it is not an ideal tumor marker in the sense that there are CAP patients with normal PSA concentrations in serum and patients with benign hyperplasia of the prostate (BPH) with elevated PSA concentrations. Analysis of the various PSA forms in serum attracts much interest as there is a higher proportion of PSA in complex with ACT in patients with CAP than in those with BPH. Optimal combinations of monoclonal antibodies have been used to design sensitive noncross-reacting immunoassays for the detection of free PSA, PSA-ACT complexes and the detection of both free PSA and PSA complexes in an equimolar fashion (i.e. total PSA). Several studies have demonstrated that the analysis of the proportions of the free-to-total PSA in serum may increase the diagnostic specificity by 15-20% without significant loss in the sensitivity for detection of CAP.
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PMID:Individual prostate-specific antigen (PSA) forms as prostate tumor markers. 902 29

The introduction of prostate-specific antigen (PSA) testing into clinical medicine in 1986 revolutionized the management of patients with prostate cancer. The major limitation of this tumor marker stems from its inability to provide a clear distinction between benign prostate disease and prostate cancer, especially in patients with upper limit of normal or slightly increased PSA values. Recent research has established that PSA exists in the serum in several molecular forms. Patients with benign prostatic hyperplasia have more of the free form, whereas those with prostate cancer have more of a complexed form (PSA covalently bound to alpha 1-antichymotrypsin). Several investigations have now confirmed that determining percent free PSA (proportion of free PSA to total PSA) enhances the ability of PSA testing to distinguish between prostate cancer and benign prostatic hyperplasia. In addition, percent free PSA seems to have the greatest clinical significance in patients whose total PSA values range from 2.5 or 3.0 ng/mL (lower limit) to 10.0 ng/mL (upper limit). When the total PSA value is in the normal range (2.5 or 3.0 to 4.0 ng/mL), percent free PSA makes PSA a more sensitive test (increases cancer detection). When the total PSA level is minimally increased (4.1 to 10.0 ng/mL), percent free PSA makes PSA a more specific test (eliminates performance of unnecessary prostate biopsies). Although further work remains, it seems that percent free PSA can substantially improve the clinical utility of the PSA test for detecting early, curable prostate cancer.
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PMID:Percent free prostate-specific antigen: entering a new era in the detection of prostate cancer. 912 Nov 81

Prostate-specific antigen (PSA) forms in serum two stable complexes with alpha 1-antichymotrypsin and alpha 2-macroglobulin. PSA complexed to alpha 1-antichymotrypsin is the predominant fraction of PSA. A minor fraction of serum PSA is not associated with proteinase inhibitors. These molecular differences explain the possibility to distinguish free from total PSA (F/T ratio). Free and complexed PSA have different clearances and significant differences between clearance of free PSA after radical prostatectomy (RP) and after open surgery for benign prostatic hyperplasia (BPH) are observed. These differences are explained by the entire removal of prostatic cells responsible for PSA synthesis and storage during RP, i.e. the source of free PSA present in the intravascular pool. The proportion of free PSA is significantly lower in patients with prostate cancer than in patients with BPH. Thus, the mean F/T ratio in prostate cancer is lower than that in BPH and may be helpful to distinguish cancer from BPH especially in the gray zone of total PSA (4-10 ng/ml). The reason why complexed PSA increases in patients with prostate cancer remains unknown but could be explained by the requirement of an enzymatically active PSA released by the malignant prostate tissue to bind to alpha 1-antichymotrypsin. However, a consensual threshold value for L/T ratio is yet to be found to be of widespread clinical use in the differential diagnosis between cancer and BPH.
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PMID:Free/total prostate-specific antigen ratio--hope and controversies. 918 94

We have established a procedure for the production of milligrams of free PSA (fPSA) from LNCaP cells derived from a human carcinoma of the prostate. By growing LNCaP cells in a serum-free medium in the presence of a synthetic androgen (R1881) and taking advantage of the special design of the Micro-mouse Hollow Fiber Bioreactor, relatively pure fPSA could be obtained. We found that columns containing either Sephacryl S-100 or S-200 could be used to remove the small amount of bovine serum albumin (BSA) and PSA-alpha 1-antichymotrypsin complex (PSA-ACT) from the preparation. More than 90% of the PSA from LNCaP cell cultures are fPSA. Like fPSA from seminal plasma, two fractions of fPSA differing in protease activity can be separated by DEAE-Sepharose chromatography. Based on the band pattern exhibited on the Western blot following sodium dodecyl sulfate-polyacrylamide electrophoresis separation, fPSA from LNCaP contains more inactive PSA isoforms. This was confirmed by chromatofocusing: the isoelectric point (pl) of the major PSA isoforms from the LNCaP cell culture were higher (6.8 and 6.6) than that (6.4 and 6.1) of fPSA from seminal fluid. We conclude that the LNCaP cell culture is a reliable source for obtaining large quantities of pure fPSA both for the preparation of assay calibrators and controls and for studying the difference in fPSA between benign prostate disease and prostate cancer.
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PMID:Production of milligram concentrations of free prostate specific antigen (fPSA) from LNCaP cell culture: difference between fPSA from LNCaP cell and seminal plasma. 948 63


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