| 1. |
- Végvári, Ákos, et al.
(författare)
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Bioinformatic strategies for unambiguous identification of prostate specific antigen in clinical samples
- 2011
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 75:1, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- Prostate specific antigen (PSA), as a widely used clinical biomarker in prostate cancer diagnostics, exists in multiple molecular forms. However, all of these forms might not be recognized in a given sample by the standard immunoassays. Therefore, we have investigated PSA isoforms separated by size using mass spectrometric analyses. The objective of these developments was to identify and specify the various forms of PSA. To optimize successful identification of different PSA forms, we have developed a bioinformatic strategy, consisting of high resolution MALDI-MS PMF and sequencing MS/MS data searches. To improve sequence-based identification, the recently introduced Proteios software environment was employed, allowing the combination of multiple database search engines in an automated manner. We could unambiguously identify PSA in clinical samples by all detectable tryptic peptides, which were found to be common in several isoforms.
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| 2. |
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| 3. |
- AHLGREN, GÖRAN, et al.
(författare)
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Impaired Secretory Function of the Prostate in Men With Oligo‐Asthenozoospermia
- 1995
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Ingår i: Journal of Andrology. - 0196-3635. ; 16:6, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: The secretory function of the human prostate and the seminal vesicles is a prerequisite for gel formation and liquefaction of semen, but the relation to poor sperm motility and low sperm count in infertile men remains to be clarifyed. Our aim was to evaluate the secretory function of the prostate and the seminal vesicles in normozoospermic men (n=35) and in asthenozoospermic men, who were all also oligozoospermic (n=27). All 62 subjects belonged to couples undergoing routine infertility evaluation. In liquefied seminal fluid we measured the concentrations of fructose and protein C inhibitor (PCI) contributed by the seminal vesicles, PCI complexed to prostate‐specific antigen (PSA), and the prostatic contribution of zinc, PSA, acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Znα2‐glycoprotein (Znα2‐GP). The concentration of each prostatic secretory protein correlated significantly with that of zinc (P < 0.01) in both the normozoospermic (NZS) and oligo‐astheno‐zoospermic (OAZS) subgroups, but the PCI concentration did not correlate significantly with that of fructose. There was no significant difference between the NZS and OAZS subgroups in ejaculate volume or secretory contribution from the seminal vesicles, whereas the OAZS subgroup was characterized by significantly lower secretory contributions of Znα2‐GP (P = 0.001), Zn, PSA, PAP (P < 0.01), and β‐MSP (P < 0.05). The two subgroups did not differ significantly in the serum concentration of luteinizing hormone (LH), testosterone, or sex hormone‐binding globulin (SHBG). The results thus suggest the secretory contribution of major prostatic proteins and zinc per ejaculate to be significantly decreased in oligo‐asthenozoospermic men. The importance of this finding in relation to poor sperm count and motility as indicators of impaired gonadal function requires further investigation. 1995 American Society of Andrology
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| 4. |
- Ahmad Tajudin, Asilah, et al.
(författare)
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Integrated acoustic immunoaffinity-capture (IAI) platform for detection of PSA from whole blood samples.
- 2013
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 13:9, s. 1790-1796
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Tidskriftsartikel (refereegranskat)abstract
- On-chip detection of low abundant protein biomarkers is of interest to enable point-of-care diagnostics. Using a simple form of integration, we have realized an integrated microfluidic platform for the detection of prostate specific antigen (PSA), directly in anti-coagulated whole blood. We combine acoustophoresis-based separation of plasma from undiluted whole blood with a miniaturized immunoassay system in a polymer manifold, demonstrating improved assay speed on our Integrated Acoustic Immunoaffinity-capture (IAI) platform. The IAI platform separates plasma from undiluted whole blood by means of acoustophoresis and provides cell free plasma of clinical quality at a rate of 10 uL/min for an online immunoaffinity-capture of PSA on a porous silicon antibody microarray. The whole blood input (hematocrit 38-40%) rate was 50 μl min(-1) giving a plasma volume fraction yield of ≈33%. PSA was immunoaffinity-captured directly from spiked female whole blood samples at clinically significant levels of 1.7-100 ng ml(-1) within 15 min and was subsequently detected via fluorescence readout, showing a linear response over the entire range with a coefficient of variation of 13%.
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| 5. |
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| 6. |
- Angelopoulou, Katerina, et al.
(författare)
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Characterization of the BRCA1-like immunoreactivity of human seminal plasma
- 1999
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Ingår i: Urology. - 0090-4295. ; 54:4, s. 753-762
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The subcellular localization of the breast cancer susceptibility gene product BRCA1 has been controversial. Discrepant results have been reported during the past 3 years, partially because of the unavailability of highly specific reagents for BRCA1 protein. Our objective was to characterize the BRCA1-like immunoreactivity that is detected in human seminal plasma by using monoclonal and polyclonal antibodies that are supposedly specific for BRCA1 protein. Methods. We used immunologic, chromatographic, and protein sequencing techniques to detect the immunoreactivity of BRCA1 in seminal plasma and to purify and partially identify the immunoreactive species. Results. We present data indicating that two BRCA1 antibodies, SG-11 and D-20, which were thought to be free of cross- reactivities, strongly interact with proteins present in human seminal plasma. This crossreactivity is detectable even at seminal plasma dilutions as high as 106-fold, and it is effectively blocked by peptides that capture the binding site of either SG-11 or D-20 antibodies. Purification and characterization of the immunoreactive compound revealed that this consists of a macromolecular complex that contains semenogelins. The D-20 polyclonal antibody was found to cross-react with purified semenogelins I and II; the SG-11 monoclonal antibody appeared to recognize a component of the macromolecular complex that was not semenogelin. Conclusions. Our data demonstrate that the BRCA1 antibodies SG-11 and D-20 strongly interact with seminal plasma proteins and are not highly specific for BRCA1 protein. It is thus suggested that BRCA1 antibodies should be used with caution until reagents free of interference are developed and evaluated. In light of the very high cross-reactivity of the two antibodies with seminal plasma proteins, we recommend that new BRCA1 antibodies should be examined for cross-reactivity with seminal plasma proteins to verify specificity.
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| 7. |
- Antfolk, Maria, et al.
(författare)
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A single inlet two-stage acoustophoresis chip enabling tumor cell enrichment from white blood cells
- 2015
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Ingår i: Lab on a Chip. - 1473-0189. ; 15:9, s. 2102-2109
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic disease is responsible for most cancer deaths, and hematogenous spread through circulating tumor cells (CTC) is a prerequisite for tumor dissemination. CTCs may undergo epithelial–mesenchymal transition where many epithelial cell characteristics are lost. Therefore, CTC isolation systems relying on epithelial cell markers are at risk of losing important subpopulations of cells. Here, a simple acoustophoresis-based cell separation instrument is presented. Cells are uniquely separated while maintained in their initial suspending medium, thus eliminating the need for a secondary cell-free medium to hydrodynamically pre-position them before the separation. When characterizing the system using polystyrene particles, 99.6 ± 0.2% of 7 μm diameter particles were collected through one outlet while 98.8 ± 0.5% of 5 μm particles were recovered through a second outlet. Prostate cancer cells (DU145) spiked into blood were enriched from white blood cells at a sample flow rate of 100 μL min−1 providing 86.5 ± 6.7% recovery of the cancer cells with 1.1 ± 0.2% contamination of white blood cells. By increasing the acoustic intensity a recovery of 94.8 ± 2.8% of cancer cells was achieved with 2.2 ± 0.6% contamination of white blood cells. The single inlet approach makes this instrument insensitive to acoustic impedance mismatch; a phenomenon reported to importantly affect accuracy in multi-laminar flow stream acoustophoresis. It also offers a possibility of concentrating the recovered cells in the chip, as opposed to systems relying on hydrodynamic pre-positioning which commonly dilute the target cells.
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| 8. |
- Aus, G, et al.
(författare)
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Free-to-total prostate-specific antigen ratio as a predictor of non-organ-confined prostate cancer (stage pT3)
- 2003
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 37:6, s. 466-470
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate whether the free-to-total prostate-specific antigen (F/T-PSA) ratio can be used to differentiate between stage pT2 and pT3 prostate cancer. Material and Methods: A total of 176 consecutive patients from the Goteborg Screening Study (median T-PSA 4.2 ng/ml) who underwent radical prostatectomy (without neoadjuvant hormonal therapy) were included in the study. The pT stage was correlated with classical risk factors such as T-PSA and Gleason sum and the impact of the F/T-PSA ratio was evaluated. Results: A total of 42/176 patients (23.9%) had stage pT3 prostate cancer. Patients with an F/T-PSA ratio in the lowest quartile (<10.7%) had extracapsular tumor growth in 46.5% of cases, compared to 16.7% for those with an F/T-PSA ratio >10.7% ( p = 0.0002). Patients with high-risk features (T-PSA >10 ng/ml or Gleason sum greater than or equal to7) had a high risk (54-60%) for stage pT3 prostate cancer. In low-risk patients, the subgroup with an F/T-PSA ratio <10.7% had a risk of 37.0%, compared to only 13.3% for those with a ratio of >10.7% (p = 0.0092). Conclusions: In patients with low-risk early-stage prostate cancer, the F/T-PSA ratio provides statistically significant, independent and clinically relevant preoperative information about the risk of extracapsular tumor growth.
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| 9. |
- Aus, G, et al.
(författare)
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Individualized screening interval for prostate cancer based on prostate-specific antigen level - Results of a prospective, randomized, population-based study
- 2005
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Ingår i: Archives of Internal Medicine. - 0003-9926. ; 165:16, s. 1857-1861
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. Methods: The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. Results: Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/ mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/ 1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. Conclusions: Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.
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| 10. |
- Becker, Charlotte, et al.
(författare)
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The role of molecular forms of prostate-specific antigen (PSA or hK3) and of human glandular kallikrein 2 (hK2) in the diagnosis and monitoring of prostate cancer and in extra-prostatic disease
- 2001
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Ingår i: Critical Reviews in Clinical Laboratory Sciences. - : Informa UK Limited. - 1549-781X .- 1040-8363. ; 38:5, s. 357-399
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA or hK3) is a glandular kallikrein with abundant expression in the prostate that is widely used to detect and monitor prostate cancer (PCa), although the serum level is frequently elevated also in benign and inflammatory prostatic diseases. PSA testing is useful for early detection of localized PCa and for the detection of disease recurrence after treatment. However, PSA has failed to accurately estimate cancer volume and preoperative staging. There is no PSA level in serum that definitively distinguishes men with benign conditions from those with prostate cancer, although PCa is rare in men with PSA levels in serum < 2.0 ng/ml. This prompted searches for enhancing parameters to combine with PSA testing, such as PSA density, PSA velocity, and age-specific reference ranges. Due to the protease structure, PSA occurs in different molecular forms in serum and their concentrations vary according to the type of prostatic disease. Human glandular kallikrein 2 (hK2) is very similar to PSA, but expressed at higher levels in prostate adenocarcinoma than in normal prostate epithelium. Blood testing for hK2 combined with different PSA forms improves discrimination of men with benign prostatic disease from those with prostate cancer. Many data have also been reported on the extra-prostatic expression of both PSA and hK2, and it is now believed that they may both have functions in tissues outside the prostate.
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