| 1. |
- Aalamian, M, et al.
(author)
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Inhibition of dendropoiesis by tumor derived and purified prostate specific antigen
- 2003
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 170:5, s. 2026-2030
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Journal article (peer-reviewed)abstract
- Purpose: Prostate specific antigen (PSA) is a serine protease produced by the prostate gland at high concentrations. Serum PSA may be significantly elevated in prostate cancer and benign prostatic diseases. It has recently become evident that, in addition to being a tissue and/or serum marker, PSA may also have biological effects. Despite the voluminous literature on this biomarker in the diagnosis of prostatic diseases relatively few reports have addressed the issue of the physiological function, biological role and immune effects of PSA in the context of prostate cancer development and progression. Materials and Methods: Human dendritic cell (DC) cultures were generated from CD34+ hematopoietic precursors in the presence of PSA. The DC phenotype was assessed by flow cytometry and DC ability to induce T-cell proliferation was detected by allogeneic mixed lymphocyte reaction assay. DCs were also generated in co-cultures with LNCaP cells in the presence of antiPSA antibodies. The concentrations of PSA in cultures were determined by the AXSYM System (Abbott Laboratories, Wiesbaden, Germany). Results: We noted that purified and LNCaP derived PSA inhibited the generation and maturation of DC (dendropoiesis) in vitro, which might have a crucial role in the induction and regulation of specific antitumor immune responses. The addition of active PSA to DC cultures significantly inhibited the generation and maturation of DC, as assessed by the levels of expression of CD83, CD80, CD86 and HLA DR. The ability of DC to induce T-cell proliferation, which depends on the expression of co-stimulatory and major histocompatibility complex molecules, was also suppressed in PSA treated DC cultures. Conclusions: The antidendropoietic effect of PSA in vitro suggests a new mechanism of prostate cancer induced immunosuppression and tumor escape, and provides novel evidence of the immunoregulatory properties of PSA.
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| 2. |
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| 3. |
- Aus, G, et al.
(author)
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Cumulative prostate cancer risk assessment with the aid of the free-to-total prostate specific antigen ratio
- 2004
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In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 45:2, s. 160-165
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the cumulative risk of having a prostate cancer diagnosis in a repeated screening situation in relation to the free-to-total prostate specific antigen ratio (F/T-PSA). Patients and Methods: The present study includes 1385 men (aged 50-70 years) who underwent prostate biopsy for the first time in the screening program that started in 1995. In case of a benign finding, the men have been followed biennially and new biopsies performed in case of persistently elevated PSA. The cumulative risk to be diagnosed with prostate cancer until July 1, 2002 was calculated by the Kaplan-Meier method and comparison was made between different levels of T-PSA and F/T-PSA ratios. Results: Of 2129 biopsies 469 showed cancer. The cumulative 5-year risk to be diagnosed with prostate cancer was significantly dependent of the F/T-ratio. The risk for men with a T-PSA of 3-5.99 ng/ml was 16% [6-25%] for those who had a ratio of >30% and 44% [34-60%] for those with a ratio of <10%. The corresponding difference for patients with a T-PSA of 6-9.99 ng/ml was even more pronounced: 21% [0-42%] vs. 80% [64-96%]. Conclusion: By completing the T-PSA measurement with the F/T-PSA ratio it is possible to significantly better assess the cumulative prostate cancer risk within the next five years (without the aid of further urological work-up).
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| 4. |
- Aus, G, et al.
(author)
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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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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 37:6, s. 466-470
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Journal article (peer-reviewed)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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| 5. |
- Becker, Charlotte, et al.
(author)
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Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater
- 2000
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In: Urology. - 1527-9995. ; 55:5, s. 694-699
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the clinical value of human glandular kallikrein 2 (hK2) compared with free (f) and total (t) prostate-specific antigen (PSA) in the early detection of prostate cancer (PCa). METHODS: In PCa screening conducted in 1995 to 1996 in Goteborg, Sweden, 5853 of 9811 randomly selected men (aged 50 to 66 years; median 61) accepted PSA testing; those with tPSA levels of 3. 0 ng/mL or greater were offered digital rectal examination, transrectal ultrasound, and sextant biopsies. Serum from 604 of 611 biopsied men (18% with positive digital rectal examinations, tPSA range 3.0 to 220 ng/mL, 144 men with PCa) was analyzed for hK2 (research assay) and tPSA and fPSA (Prostatus). Sera were stored at -20 degrees C for a maximum of 2 weeks for tPSA and fPSA and 3 years for hK2. RESULTS: hK2 levels and hK2 x tPSA/fPSA values were significantly elevated in men with PCa. Receiver operating characteristic data revealed that the area under the curve for hK2 x tPSA/fPSA was significantly greater than that for tPSA and greater, but not significantly greater, than that for percent fPSA. Also, the cancer-detecting sensitivity was significantly improved (P <0.05) using hK2 x tPSA/fPSA compared with tPSA and percent fPSA at specificity levels of 75% to 90%. At 75% specificity, a sensitivity of 74% was obtained compared with 64% or 54% using percent fPSA or tPSA; at 90% specificity, the corresponding sensitivity level was 55%, 41%, and 36%, respectively. CONCLUSIONS: Discrimination of men with and without PCa in a randomly selected population was improved by measuring hK2 in addition to tPSA and fPSA.
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| 6. |
- Becker, Charlotte, et al.
(author)
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Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum
- 2000
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In: Journal of Urology. - 1527-3792. ; 163:1, s. 311-316
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate the clinical value of measuring human glandular kallikrein 2 (hK2) compared with free and total prostate specific antigen (PSA-F and PSA-T) in serum from patients with prostate disease. MATERIALS AND METHODS: Serum from healthy controls, from men with benign prostate hyperplasia (BPH), clinically localized prostate cancer (PCa), and advanced PCa were analyzed for hK2 (using an in-house-research assay with detection limit of 0.05 ng./mL and <0.1% cross-reaction with PSA) and for PSA-F and PSA-T (using the Dual Prostatus assay from EG&G Wallac). RESULTS: HK2 concentrations were <0.05 ng./mL in 50/50 healthy volunteers but significantly higher (p <0.0001) and > or =0.05 ng./mL in 28/54 (52%) patients with BPH. In comparison to these men, the hK2 levels were significantly higher (p <0.0001, median 0.085 ng./mL) and > or =0.05 ng./mL in 100/136 (74%) men with clinically localized PCa. Compared with localized PCa, the hK2 levels were significantly higher (p <0.0001, median 0.57 ng./mL) and > or =0.05 ng./mL in 55/57 (96%) patients with advanced PCa. The median hK2 levels ranged from 1.3 to 1.6% of those of PSA-T in all three patient groups, whereas percent hK2/PSA-F and hK2 x PSA-T/PSA-F levels were significantly higher in cancer patients compared with those with BPH. In the discrimination of clinically localized PCa from BPH, hK2 x PSA-T/PSA-F gave the largest area under the receiver operating curve (AUC = 0.81) and significantly (p = 0.025) larger AUC than PSA-T alone (0.70). Further, at 95% sensitivity there was significant gain in specificity, and at specificity levels of 90 to 95% there was significant gain in sensitivity using the measurements of PSA-T+PSA-F+hK2 compared with analysis of PSA-T and/or percent free PSA. CONCLUSIONS: Discrimination of patients with benign prostate disease from those with prostate cancer was significantly enhanced using measurements of hK2 in addition to those of PSA-T and PSA-F. Percent hK2/PSA-F was higher in PCa than in BPH, a phenomena not yet understood.
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| 7. |
- Becker, Charlotte, et al.
(author)
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Sensitive and specific immunodetection of human glandular kallikrein 2 in serum
- 2000
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In: Clinical Chemistry. - 0009-9147. ; 46:2, s. 198-206
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human glandular kallikrein 2 (hK2) is expressed in the prostate and is present in serum from men with prostate cancer. Specific detection in serum is difficult mainly because of low concentrations and immunological cross-reactivity with prostate-specific antigen (PSA). Our objectives were to design an assay with improved analytical detection and functional sensitivity and nonsignificant cross-reactivity with PSA, and to characterize different immunoreactive forms of hK2. METHODS: In the assay, critical PSA epitopes were blocked with four monoclonal antibodies (MAbs) specific for PSA. Subsequently, hK2 was captured using a MAb against hK2 (5% cross-reactivity with PSA), and after washing, hK2 was detected by a europium-labeled MAb with identical affinity for hK2 and PSA. RESULTS: The analytical detection limit was <10 ng/L, and functional sensitivity was 30 ng/L. Cross-reaction with PSA was <0.01%. Between-assay imprecision was 3.1% for 1600 ng/L hK2 and 4. 8% for 160 ng/L hK2; corresponding values for within-assay precision were 1.9% and 4.5%, respectively. Complexes of hK2-alpha(1)-antichymotrypsin (ACT) were detected in vitro with -6% bias compared with the free form of hK2. Gel filtration of patient samples showed that hK2 correlated in size mainly with free hK2; only 4-19% corresponded to hK2 possibly complexed with ACT or protein C inhibitor. CONCLUSIONS: Our assay had extremely low cross-reactivity with PSA, provided a very low detection limit, and allowed close to equimolar detection of the free and complexed forms of hK2. Moreover, we found that free hK2 is the predominant immunoreactive form of hK2 in serum.
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| 8. |
- Becker, Charlotte, et al.
(author)
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Testing in serum for human glandular kallikrein 2, and free and total prostate specific antigen in biannual screening for prostate cancer.
- 2003
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 170:4 Pt 1, s. 1169-1174
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Journal article (peer-reviewed)abstract
- Purpose: We investigated the value of serum measurements for glandular kallikrein 2 (hK2), and free (f) and total (t) prostate specific antigen (PSA) in a second round of biannual screening for prostate cancer. Materials and Methods: In 1995 to 1996, 5,853 of 9,811 randomly selected men in Goteborg, Sweden 50 to 66 years old had PSA measurements. Of 660 men 611 with tPSA 3 ng/ml or greater underwent biopsy and 145 had cancer. All were re-invited 2 years later for PSA testing, and 506 of 596 men with tPSA 3 ng/ml or greater underwent biopsy and 113 cancers were detected. We analyzed hK2, tPSA and fPSA in 423 of 453 (93%) men who underwent biopsy in 1997 to 1998 who were also screened in 1995 to 1996. Results: The 99 of 423 (23%) men who underwent biopsy diagnosed with prostate cancer in 1997 to 1998 had significantly different tPSA, percent fPSA and hK2 x tPSA/fPSA compared to the men with negative biopsies from 2 years earlier. The largest area under curve was obtained for hK2 x tPSA/fPSA in serum from 1995 to 1996 and from 1997 to 1998, but the difference was not significant compared to tPSA and percent fPSA. In serum from 1997 to 1998 measurements of hK2 x tPSA/fPSA gave significantly higher specificity than tPSA at 85% sensitivity, and significantly higher specificity than tPSA and percent fPSA at 70% to 75% sensitivity. In addition, levels of hK2 and hK2 x tPSA/fPSA manifested a significantly greater 2-year increase in men with cancer compared to those with benign biopsies. Conclusions: In men with tPSA levels 3.0 ng/ml or greater who were not diagnosed with cancer during a first round of screening, hK2 measurements enhanced specificity compared to tPSA testing at moderately high sensitivity, and manifested a greater 2-year increase in men with cancer.
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| 9. |
- Becker, Charlotte, et al.
(author)
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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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In: Critical Reviews in Clinical Laboratory Sciences. - : Informa UK Limited. - 1549-781X .- 1040-8363. ; 38:5, s. 357-399
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Journal article (peer-reviewed)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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| 10. |
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