Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, various analytical aspects of the determination of serum prostate-specific antigen are described as applied to the Abbott IMx PSA and the Hybritech Tandem-E PSA assays. We used mainly specimens from a prostate cancer screening study in progress. A very good comparability between the assays proved to exist in our hands. The long-run variation (16 months) was also rated as acceptable, both for the IMx and the Tandem-E method. The method of choice, Tandem-E, showed good reagent stability over this period. We found, however, a difference in accuracy (Tandem-E +/- 8% higher values) that could not be explained by comparison with Tandem-R.
 ...
PMID:Some analytical considerations on the measurement of prostate-specific antigen. 893 5

We have recently demonstrated in liquefied human seminal plasma the presence of the novel kallikrein hK2 in association with protein C inhibitor (PCI) as a 75-kDa complex. In the present study, we showed that hK2, immediately after ejaculation, was recovered only in its free form but complex formation with PCI occurred rapidly thereafter and was completed within 10 minutes. That reaction required an enzymatically active kallikrein. In order to determine the patterns of hydrolysis of major seminal vesicle proteins, semenogelins and fibronectin were exposed to hK2 and to hK3 (prostate-specific antigen or PSA) and cleavage sequences were identified by N-terminal sequencing. Free hK2 was able to hydrolyze semenogelins and fibronectin in vitro. Most of cleavage sites were at the carboxyl-side of arginyl residues. Semenogelins were hydrolyzed to a similar extent by catalytic (and similar) concentration of either hK2 or PSA though no common cleavage sites was identified for both proteinases. Unlike semenogelins, fibronectin was hydrolyzed much more efficiently by hK2 than by PSA. These results show that hK2 is enzymatically active during a short period of time after ejaculation, that major seminal vesicle proteins can be the target of this proteolytic activity, and that hK2 and PSA have different substrate specificities.
 ...
PMID:Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. 901 96

In this communication a limited analytical study is described on the new Prostatus PSA Free/Total assay. The study is considered as a side study of the European Randomized Study of Screening for Prostate Cancer. The between-day imprecision with 8 control samples for free prostate-specific antigen ranged from 10.3% at 0.17 microg/l to 3.7% at a concentration of 35.5 microg/l, while for total prostate-specific antigen we found 7.3% at 0.69 microg/l and 4.3% at 70.7 microg/l. For total prostate-specific antigen we found excellent agreement between the new assay and well-established assays like Abbott IMx and Hybritech Tandem-E, both for prostate cancer and benign prostate hyperplasia specimens. The age-specific reference ranges proved to be well-comparable with the literature data both for free and total prostate-specific antigen.
 ...
PMID:Analytical evaluation of the new Prostatus PSA Free/Total assay for prostate-specific antigen as part of a screening study for prostate cancer. 905 53

A calibrator composed of 90% prostate-specific antigen-alpha 1-antichymotrypsin (PSA-ACT) and 10% free PSA reduces the variation in control serums with widely divergent amounts of free PSA, from a mean of 28% among nine different assays to 9% after recalibration. The lyophilized form of the Stanford 90:10 calibrator is stable and therefore an excellent candidate for international standardization of PSA assays.
 ...
PMID:Progress in standardization of immunoassays for prostate-specific antigen. 912 23

The name prostate-specific antigen has been given to a protein that now is known not to be prostate-specific; however, prostatic tissue does produces extremely high levels of PSA and secrets it into the seminal plasma. Seminal plasma contains about 1 million micrograms/L of PSA and is the richest source of PSA reported. The biologic fluid with the second highest PSA concentration, however, is nipple aspirate fluid from the female breast (up to about 5000 micrograms/L), and the third is milk from lactating women (up to 300 micrograms/L). Male serum PSA is usually less than 4 micrograms/L. In nonprostatic tissues, PSA exists mainly in its free molecular form, but PSA-ACT complex is also present in most of the fluids that contain PSA, such as breast secretions and amniotic fluid. The gene expression and protein production of PSA in nonprostatic tissues are under the regulation of steroid hormones via their receptors. Androgens, glucocorticoids, and progestins up-regulate the PSA gene expression, resulting in an increase of protein production. Estrogen by itself seems to have no effect on PSA regulation, but it can impair PSA production induced by androgen. It remains unknown whether PSA is enzymatically active and what is the physiologic role of PSA in nonprostatic tissues. It is speculated that PSA may be involved in the regulation of growth factors. Measuring PSA in breast cancer cytosol, breast-nipple aspirate fluid, and female serum may have potential clinical utilities, including breast cancer prognosis, breast cancer risk assessment, and evaluation of androgen excess. Further studies are needed to identify the exact function and regulation of PSA in nonprostatic tissues and to explore the clinical application of this protein.
 ...
PMID:Nonprostatic sources of prostate-specific antigen. 912 24

Our work was undertaken to compare the relative efficiency of 2 purified prostatic kallikreins, namely, hK2 and prostate-specific antigen (PSA or hK3), in the activation of single-chain urokinase (scuPA). We found that hK2 converts scuPA into an active enzyme with an efficiency equal to approximately 1/50 that of plasmin. During the activation of scuPA by hK2, two fragments of 33 and 22 kDa were generated. The NH2-terminal amino acid sequence of the 33 kDa fragment showed that hK2 cleaved scuPA between Lys158 and Ile159. In contrast to a previous report by another group, our purified hK3 preparation containing no trypsin-like contaminants was totally unable to activate scuPA. Our results show that kallikrein hK2 has plasmin-like activity and suggest that it could be the initiator of a proteolytic cascade leading to prostatic cancer invasion.
 ...
PMID:Prostatic kallikrein hK2, but not prostate-specific antigen (hK3), activates single-chain urokinase-type plasminogen activator. 918 Jan 62

The precursor or zymogen form of prostate-specific antigen (pro-PSA) is composed of 244 amino acid residues including an amino-terminal propiece of 7 amino acids. Recombinant pro-PSA was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified. The zymogen was readily activated by trypsin at a weight ratio of 50:1 to generate PSA, a serine protease that cleaves the chromogenic chymotrypsin substrate 3-carbomethoxypropionyl-L-arginyl-L-prolyl-L-tyrosine-p-nitroanili ne- HCl (S-2586). In this activation, the amino-terminal propiece Ala-Pro-Leu-Ile-Leu-Ser-Arg was released by cleavage at the Arg-Ile peptide bond. The recombinant pro-PSA was also activated by recombinant human glandular kallikrein, another prostate-specific serine protease, as well as by a partially purified protease(s) from seminal plasma. The recombinant PSA was inhibited by alpha1-antichymotrypsin, forming an equimolar complex with a molecular mass of approximately 100 kDa. The recombinant PSA failed to activate single chain urokinase-type plasminogen activator, in contrast to the recombinant hK2, which readily activated single chain urokinase-type plasminogen activator. These results indicate that pro-PSA is converted to an active serine protease by minor proteolysis analogous to the activation of many of the proteases present in blood, pancreas, and other tissues. Furthermore, PSA is probably generated by a cascade system involving a series of precursor proteins. These proteins may interact in a stepwise manner similar to the generation of plasmin during fibrinolysis or thrombin during blood coagulation.
 ...
PMID:Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein. 926 Nov 79

The present study addressed the question as to whether prostate-specific antigen reverse transcriptase-polymerase chain reaction (PSA RT-PCR) could be used to identify prospectively men who have prostate cancer and to help determine which patients with an initially negative biopsy would benefit from rebiopsy. PSA RT-PCR was performed prospectively on 90 patients who were to have a prostate biopsy because of an elevated PSA level, an abnormal digital rectal examination, or both. PSA RT-PCR was performed, and the sensitivity of the test was enhanced by hybridization of the PCR with a 32P-labeled PSA cDNA probe (exons 3-5). Of the 90 men, 36 (40%) had prostate cancer on biopsy. Of these 36 men, 5 (13.9%) had a positive PSA RT-PCR finding, whereas 31 (84.1%) tested negative. Of 54 men with negative biopsies, 8 (14.8%) had a positive PSA RT-PCR result. The sensitivity of PSA RT-PCR for the detection of biopsy-proven prostate cancer was 13.9% and the specificity was 85.2%. Only 3 of 12 (25%) patients with advanced disease had a positive test result. The sensitivity of PSA RT-PCR for the detection of biopsy-proven prostate adenocarcinoma in men suspected of having prostate cancer is poor. Indeed, men without biopsy-proven prostate cancer are just as likely to have a positive result in the PSA RT-PCR as are men with cancer. Whether these men with negative prostate biopsies and positive PSA RT-PCR findings may eventually develop prostate cancer remains to be determined. At this time, PSA RT-PCR for the prospective detection of prostate cancer should be considered investigational.
 ...
PMID:Can prostate-specific antigen reverse transcriptase-polymerase chain reaction be used as a prospective test to diagnose prostate cancer? 928 55

The ratio of free prostate-specific antigen (f-PSA) to total PSA (t-PSA) in serum, calculated as percent free PSA (f-PSA%), is lower in patients with prostate carcinoma (PCa) than in patients with benign prostate hyperplasia (BPH). This parameter facilitates discrimination between the 2 groups of patients, but there is an overlapping of data. A better understanding of factors influencing this ratio is of practical importance. Therefore, f-PSA% was measured in controls and patients suffering from BPH, PCa and chronic prostatic inflammation with t-PSA concentrations up to 20 microg/l using the IMMULITE assays. The relationships of f-PSA% to clinical situation, age, prostate volume, kind of treatment, and stage and grade of tumor were calculated. Compared with controls or BPH patients, mean f-PSA% values were reduced in PCa patients and in patients with chronic prostatic inflammation. The prostate volume was the most important factor to influence f-PSA%. The difference of f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 was lost if the prostate volumes exceeded 40 cm3. No relationship of f-PSA% to pTNM stage or grade of tumor was observed. In contrast to t-PSA concentrations, the f-PSA% values were not age-dependent and were not influenced by any kind of treatment in BPH and PCa patients either, which simplifies the use of f-PSA% compared with t-PSA. Thus, for using f-PSA% in clinical practice and for interpreting the data correctly, the advantages shown have to be considered along with the potential limitations of f-PSA%.
 ...
PMID:Factors influencing the ratio of free to total prostate-specific antigen in serum. 942 61

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
 ...
PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>