scholarly journals Quantification of a Proteotypic Peptide from Protein C Inhibitor by Liquid Chromatography–Free SISCAPA-MALDI Mass Spectrometry: Application to Identification of Recurrence of Prostate Cancer

2013 ◽  
Vol 59 (10) ◽  
pp. 1514-1522 ◽  
Author(s):  
Morteza Razavi ◽  
Lisa DS Johnson ◽  
Julian J Lum ◽  
Gary Kruppa ◽  
N Leigh Anderson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Liquid Chromatography ◽  
High Throughput ◽  
Protein C ◽  
Specific Antigen ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Biomarker Validation ◽  
Protein C Inhibitor ◽  
Proteotypic Peptide

BACKGROUND Biomarker validation remains one of the most challenging constraints to the development of new diagnostic assays. To facilitate biomarker validation, we previously developed a chromatography-free stable isotope standards and capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high-throughput quantification of protein analytes in large sample sets. Here we applied this assay to the measurement of a surrogate proteotypic peptide from protein C inhibitor (PCI) in sera from patients with prostate cancer. METHODS A 2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI and soluble transferrin receptor (sTfR) was used to measure these peptides in 159 trypsin-digested sera collected from 51 patients with prostate cancer. These patients had been treated with radiation with or without neoadjuvant androgen deprivation. RESULTS Patients who experienced biochemical recurrence of prostate cancer showed decreased serum concentrations of the PCI peptide analyte within 18 months of treatment. The PCI peptide concentrations remained increased in the sera of patients who did not experience cancer recurrence. Prostate-specific antigen concentrations had no predictive value during the same time period. CONCLUSIONS The high-throughput, liquid chromatography–free SISCAPA-MALDI assay is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes in complex serum samples. Decreased serum concentrations of the PCI peptide were found to be related to recurrence of prostate cancer in patients treated with radiation with or without hormone therapy. However, a larger cohort of patients will be required for unequivocal validation of the PCI peptide as a biomarker for clinical use.

scholarly journals Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2

2004 ◽  
Vol 50 (9) ◽  
pp. 1607-1617 ◽  
Author(s):  
Ville Väisänen ◽  
Susann Eriksson ◽  
Kaisa K Ivaska ◽  
Hans Lilja ◽  
Martti Nurmi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Detection Limit ◽  
Solid Phase ◽  
Specific Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Human Kallikrein 2 ◽  
Kallikrein 2 ◽  
Capture Antibody ◽  
Total Psa

Abstract Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 μg/L. The median total hK2 concentration was 0.022 μg/L (range, 0.0015–0.37 μg/L). hK2 concentrations were 0.1–58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41–50 and 51–60 years of age. The ratio of hK2 to PSA steadily decreased from 5–30% at PSA <1 μg/L to 1–2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 μg/L (range, 0.0015–16.2 μg/L). The median free hK2 concentration was 0.070 (range, 0.005–12.2) μg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.

scholarly journals Serum Omentin Levels in Patients with Prostate Cancer and Associations with Sex Steroids and Metabolic Syndrome

2020 ◽  
Vol 9 (4) ◽  
pp. 1179
Author(s):  
Artur Borowski ◽  
Lucyna Siemińska
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Sex Steroids ◽  
Specific Antigen ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Serum Concentrations ◽  
Prostate Hyperplasia ◽  
Metabolic Characteristics ◽  
Persistent Inflammation

Mechanisms linking obesity and prostate cancer (PC) include increased insulin signaling, persistent inflammation, and altered adipocytokines secretion. Previous studies indicated that omentin may play a potential role in cancerogenesis of different sites, including the prostate. In this study, we focused on the hormonal and metabolic characteristics of men recruited for prostate biopsy. We evaluated serum concentrations of adipocytokines and sex steroids where concentrations are related to the adiposity: omentin, leptin, testosterone, estradiol, and sex hormone-binding globulin (SHBG). Aim: The aim of the study was to assess the concentration of serum omentin in men with PC. We also investigated relationships between omentin, leptin, sex steroids, SHBG, age, and metabolic syndrome (MS). Methods: Our study was conducted on 72 patients with PC and 65 men with benign prostate hyperplasia (BPH). Both groups were compared for body mass index. Results: Comparing men with PC to subjects with BPH there were significantly higher serum concentrations of omentin, estradiol, and prostate specific antigen (PSA) in the former. Estradiol/testosterone ratio, which is a marker of testosterone to estradiol conversion, was also significantly higher in the PC group. MS was diagnosed in 47 men with PC and in 30 men with BPH, the prevalence was significantly higher in the PC group. When the subjects with PC were subdivided into two subgroups, the serum omentin did not differ between those with MS and without MS. In the overall sample serum, omentin was positively associated with age, SHBG, and leptin. A positive correlation was also found between omentin and estradiol/testosterone ratio, and negatively with testosterone/SHBG ratio. Positive correlations were noted between age and SHBG, PSA and estradiol/testosterone ratio. In our study, a drop of total testosterone and testosterone/SHBG ratio, due to age, was also demonstrated. Conclusions: In patients with prostate cancer, serum omentin may be a diagnostic indicator. Omentin levels do not correlate with estradiol or testosterone concentrations but they are related to the testosterone/SHBG ratio. Omentin is not associated with an increased likelihood of having metabolic syndrome in men with prostate cancer.

scholarly journals Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System

2002 ◽  
Vol 48 (8) ◽  
pp. 1272-1278 ◽  
Author(s):  
Barbara R Grzeda ◽  
Tuan Le Bui ◽  
Cheryl N Warner ◽  
Tracy L Pirucki ◽  
Lisa M Dewey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Whole Blood ◽  
Prostate Cancer Screening ◽  
Specific Antigen ◽  
Blood Collection ◽  
Serum Samples ◽  
Stabilizing Solution ◽  
Professional Assistance ◽  
Comparison Of The Results

Abstract Background: Prostate-specific antigen (PSA) is widely used in the detection and monitoring of prostate cancer. We developed a system for the self-collection and transport of capillary whole blood for PSA analysis, with the goal of reducing phlebotomy visits and, thus, increasing the access and utilization of PSA in prostate cancer screening and monitoring. Methods: The blood collection device [BIOSAFE Blood Transport System (BTSTM)] collects 70 μL of blood through a heparin-coated material into 200 μL of stabilizing solution. The diluted whole blood is used for measurement of PSA by a modified version of the Hybritech® Tandem-MP PSA Assay. Results were compared for matched samples of professionally and self-collected BTS blood and for matched BTS samples sera from blood collected by venipuncture. Imprecision for the whole-blood PSA measurement was estimated from analysis of whole-blood controls in duplicate, twice per day, over 20 days. Results: BTS samples (n = 140) collected by a qualified healthcare professional compared with serum samples yielded the regression equation: y =1.02x + 0.04 (Sy|x = 0.35; r = 0.99). Comparison of the results for samples (n = 128) collected by the patient without professional assistance with serum samples yielded: y = 1.08x + 0.02 (Sy|x = 0.31; r = 0.99). The between-run CVs at 0.069, 0.53, 2.9, and 10.7 μg/L were 21%, 6.0%, 3.5%, and 3.8%, respectively. PSA was stable in BTS samples stored for 21 days at 18–24 °C and for 7 days at 37 °C. Conclusion: The BIOSAFE BTS system allows accurate and convenient measurement of circulating PSA by a precise method for diluted whole blood.

Discordant prostate specific antigen test results despite WHO assay standardization

2018 ◽  
Vol 33 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Martin Boegemann ◽  
Christian Arsov ◽  
Boris Hadaschik ◽  
Kathleen Herkommer ◽  
Florian Imkamp ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Specific Antigen ◽  
Test Results ◽  
Serum Samples ◽  
Prostate Specific Antigen Test ◽  
Free Psa ◽  
Prostate Biopsies ◽  
Cancer Early Detection ◽  
Total Psa

Introduction: Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Methods: Within the scope of the Prostate Cancer Early Detection Study Based on a ‘‘Baseline’’ PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing–Bablok regression method. Results: Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%–20%, and +17%–23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%–31%, and +22%, respectively. Discussion: Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.

The Interaction among Protein C Inhibitor, Prostate-Specific Antigen, and the Semenogelin System

2007 ◽  
Vol 33 (1) ◽  
pp. 046-052 ◽  
Author(s):  
Koji Suzuki ◽  
Hideaki Kise ◽  
Junji Nishioka ◽  
Tatsuya Hayashi
Keyword(s):  
Prostate Specific Antigen ◽  
Protein C ◽  
Specific Antigen ◽  
Protein C Inhibitor

Serum concentrations of prostate specific antigen and its complex with α1-antichymotrypsin before diagnosis of prostate cancer

The Lancet ◽  
1994 ◽  
Vol 344 (8937) ◽  
pp. 1594-1598 ◽  
Author(s):  
U-H Stenman ◽  
J Leinonen ◽  
M Hakama ◽  
P Knekt ◽  
A Aromaa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Concentrations

scholarly journals Use of sertraline, paroxetine and fluvoxamine by nursing women

2001 ◽  
Vol 179 (2) ◽  
pp. 163-166 ◽  
Author(s):  
Victoria Hendrick ◽  
Alan Fukuchi ◽  
Lori Altshuler ◽  
Mel Widawski ◽  
Amy Wertheimer ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Significant Negative Correlation ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Treatment Of Depression ◽  
Daily Dose ◽  
Nursing Mothers ◽  
Medication Exposure

BackgroundThe pharmacological treatment of depression in nursing women requires information on the magnitude of medication exposure to the infant that may occur through breast milk.AimsTo examine serum concentrations of antidepressants in infants exposed to these medications through breast-feeding.MethodMaternal and infant serum concentrations of sertraline, paroxetine and fluvoxamine were determined with high-performance liquid chromatography (limit of detections=1 ng/ml).ResultsNo detectable medication was present in any infant exposed to paroxetine (n=16) or fluvoxamine (n=4). Among infants exposed to sertraline (n=30), detectable medication was present in 24% of serum samples. A significant negative correlation was found between infant age and infant serum concentration. Sertraline was significantly more likely to be detected in an infant if the mother's daily dose was 100 mg or higher. No adverse sequelae occurred in any infant.ConclusionsThis study shows that paroxetine, fluvoxamine and sertraline produce minimal exposure to infants when taken by nursing mothers.

Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 10-10
Author(s):  
Mahmood Moshiri ◽  
Kiarash Moshiri ◽  
Arsha Moshiri ◽  
Hassan Monhemi ◽  
Mohammad Hadi Sekhavati
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Sandwich Elisa ◽  
Specific Antigen ◽  
High Serum ◽  
Cancer Tissue ◽  
Serum Samples ◽  
Psa Testing ◽  
Detect Prostate Cancer

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n > 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.

scholarly journals Prostate Cancer Risk-Associated Single-Nucleotide Polymorphism Affects Prostate-Specific Antigen Glycosylation and Its Function

2019 ◽  
Vol 65 (1) ◽  
pp. e1-e9 ◽  
Author(s):  
Srilakshmi Srinivasan ◽  
Carson Stephens ◽  
Emily Wilson ◽  
Janaththani Panchadsaram ◽  
Kerry DeVoss ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Association Studies ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Genetic Association Studies ◽  
Glycosylation Site ◽  
Nucleotide Polymorphisms ◽  
Serum Samples ◽  
Single Nucleotide

Abstract BACKGROUND Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of the kallikrein-related peptidase 3 (KLK3) gene encoding prostate-specific antigen (PSA) was reported to be strongly associated with PCa risk (P = 2.3 × 10−8). However, the biological contribution of the rs61752561 SNP to PCa risk has not been elucidated. METHODS Recombinant PSA protein variants were generated to assess the SNP-mediated biochemical changes by stability and substrate activity assays. PC3 cell–PSA overexpression models were established to evaluate the effect of the SNP on PCa pathogenesis. Genotype-specific correlation of the SNP with total PSA (tPSA) concentrations and free/total (F/T) PSA ratio were determined from serum samples. RESULTS Functional analysis showed that the rs61752561 SNP affects PSA stability and structural conformation and creates an extra glycosylation site. This PSA variant had reduced enzymatic activity and the ability to stimulate proliferation and migration of PCa cells. Interestingly, the minor allele is associated with lower tPSA concentrations and high F/T PSA ratio in serum samples, indicating that the amino acid substitution may affect PSA immunoreactivity to the antibodies used in the clinical immunoassays. CONCLUSIONS The rs61752561 SNP appears to have a potential role in PCa pathogenesis by changing the glycosylation, protein stability, and PSA activity and may also affect the clinically measured F/T PSA ratio. Accounting for these effects on tPSA concentration and F/T PSA ratio may help to improve the accuracy of the current PSA test.

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