Search PubMed⌕ Search

Biomedical subjects

D Schnorr

Publications and source records attributed to D Schnorr.

At least 55 records · Page 3Linked to original sources

Elimination of serum complexed prostate-specific antigen after radical retropubic prostatectomy.

Total prostate-specific antigen (PSA) and complexed PSA were determined in venous blood from 12 patients with prostate cancer before and after radical prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed PSA were compared with that of total PSA. Nearly constant concentrations of complexed PSA were found during the first six hours after surgery, in contrast to the rapid elimination of free PSA and the significant decrease of total PSA. From day one to ten there was a continuous and nearly identical decrease of complexed PSA compared to total PSA. Our findings suggest that the initial rapid decrease of free PSA immediately after operation could be caused by formation of new PSA-complex.

Humans↗

Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions.

The effect of sample collection, storage conditions (time and temperature), and freeze-thaw cycles on the stability of free prostate-specific antigen (fPSA), PSA complexed with alpha1-antichymotrypsin (ACT-PSA), and total PSA (tPSA) in serum was studied. The analytes were quantified using immunoassays for tPSA and fPSA on the Elecsys system 2010 and a research assay for ACT-PSA on the ES system (Roche Diagnostics). The stability of the analytes was calculated as percentages of the values measured in samples 1 h after blood collection. When the samples were stored at 37 degrees C, at room temperature or at 4 degrees C, the stability of ACT-PSA was less impaired than that of fPSA. To avoid erroneous results in the determination of PSA isoforms and their corresponding ratios, serum samples should be preserved at 4 degrees C when the analysis is performed within 8 h after blood collection, or they should be stored at -80 degrees C if the analysis is not feasible during that period.

Blood Chemical Analysis↗

Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications.

BACKGROUND: Patients with prostate cancer (PCa) show a lower ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in serum than patients with benign prostatic hyperplasia (BPH). The patterns of the intracellular PSA isoforms in malignant and benign prostatic tissue have been studied as potential molecular reasons for this phenomenon. METHODS: Prostatic tissue samples were obtained after cystoprostatectomy from patients with bladder cancer (n = 10), from BPH patients (transurethral resection of the prostate, n = 10; adenomectomy, n = 10), and from the cancerous and noncancerous parts of the same prostates removed surgically by prostatectomy because of PCa (n = 20). PSA pattern was characterized by gel filtration, immunoblotting, and immunoassays for tPSA, fPSA, alpha(1)-antichymotrypsin-PSA (ACT-PSA), and complexed PSA (Bayer Immuno 1 assay). Comparisons were made with the PSA concentrations in serum. RESULTS: The major portion of tPSA in all tissue samples was fPSA; complexed PSA forms were <2%. Samples from cystoprostatectomy patients had the lowest and those from adenomectomy patients the highest values of tPSA and fPSA. PSA concentrations were lower in cancerous than in the noncancerous parts of the prostate. No significant correlations were found between tumor stage or grade and the amounts of tPSA, fPSA, and ACT-PSA in tissue. Tissue PSA values were not correlated with the serum PSA concentrations nor with the ratios fPSA/tPSA and ACT-PSA/tPSA in sera. CONCLUSIONS: The amounts of tPSA and the PSA isoforms in prostatic tissue explain neither the concentrations of tPSA and PSA isoforms in serum nor the behavior of the ratio fPSA/tPSA in patients with BPH and PCa.

Adult↗

Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer?

BACKGROUND: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except alpha(2)-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. RESULTS: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 microg/L (areas under the curve, 0.851 vs 0.838). CONCLUSIONS: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.

Adult↗

Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer.

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and for the monitoring of patients with this diagnosis. Molecular forms of PSA and also human kallikrein 2 have been used to discriminate between benign prostatic hyperplasia and prostate cancer as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha1-antichymotrypsin (ACT-PSA), and complexed PSA is given together with our results. The ratio of fPSA:tPSA has been shown to improve the specificity of prostate cancer diagnosis on the basis of tPSA measurements. Unnecessary biopsies can be reduced by about 19-64% in the total PSA range of 4-10 microg/liter while only missing 5-10% of cancers. Furthermore, carcinomas in patients with PSA values <4 microg/liter can be detected, indicating an improved sensitivity because of the percent fPSA at low PSA values. ACT-PSA or complexed PSA alone and the calculated derivatives are not superior in their discriminatory power compared with the percent fPSA. The diagnostic significance of the other molecular PSA forms and human kallikrein 2 needs to be evaluated in more extensive clinical trials.

Biomarkers, Tumor↗

Rapid detection of elevated prostate-specific antigen levels in blood: performance of various membrane strip tests compared.

OBJECTIVES: To compare the ability of four commercially available membrane strip tests to detect increased (4 microg/L or more) concentrations of prostate-specific antigen (PSA) in blood. METHODS: Serum samples with PSA concentrations less than 4 microg/L (n = 67) and from greater than 4 microg/L to 20 microg/L (n = 32) were independently examined by two observers using the PSA membrane strip tests from Chembio, Medpro, Seratec, and Syntron. The positive and negative results of each membrane strip test were classified as either true positive or negative and false negative or positive by comparing them with the quantitative PSA assay of Immulite DPC using the conventional threshold value of 4 microg/L. RESULTS: The interobserver variations of the tests were between 93% and 97%. The color stability of the Seratec and Chembio tests did not show significant differences between test results read within 10 to 20 minutes of the reaction time; however, the results of the other two tests were especially affected by variations in the reading time. The sensitivity and specificity of the tests in relation to the threshold of 4 microg/L were 67% to 93% and 87% to 97%, respectively. CONCLUSIONS: The Syntron test and, within certain limitations, the Seratec test fulfill the concept of a rapid and convenient PSA determination to detect PSA concentrations greater than 4 microg/L. Methodologic optimization of the tests by a grading of the PSA measuring ranges (eg, between 0 and 2, 3 and 4, 4 and 6, and 7 and 10 microg/L) should be taken into account for future development.

Aged↗

Determination of alpha1-antichymotrypsin-PSA complex in serum does not improve the differentiation between benign prostatic hyperplasia and prostate cancer compared with total PSA and percent free PSA.

OBJECTIVES: To evaluate the analytical performance and diagnostic utility of alpha1-antichymotrypsin (ACT)-prostate-specific antigen (PSA) complex in serum to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: Serum concentrations of total PSA (tPSA), free PSA (fPSA), and ACT-PSA were measured in 112 untreated patients with PCa (median age 65 years), 34 patients with BPH (median age 66 years) with histologic confirmation, and 33 men without prostate disease and with a normal digital rectal examination considered as controls (median age 54 years). Sera were frozen at -80 degrees C within 2 hours after collection and then analyzed during a 12-week period. Determinations were made with the Enzymun-Test for tPSA and fPSA and with a prototype assay for ACT-PSA on the ES system (Roche Diagnostics, Boehringer Mannheim). RESULTS: The new ACT-PSA assay showed reliable data of analytical performance. The lower detection limit amounted to 0.068 microg/L. The assay was linear to 50 microg/L. Spiking experiments showed a mean recovery rate of 98.2%. No interferences of the assay were observed in patients with acute inflammation and highly increased ACT concentrations. The values of intra- and interassay imprecision ranged from 1.51% to 3.48% and 2.1% to 6.3%, respectively. The median value of ACT-PSA concentrations were significantly different (P <0.001) between controls and patients with BPH and PCa (0.40, 3.86, 5.26 microg/L, respectively). The median fPSA/tPSA and fPSA/ACT-PSA ratios were significantly different between BPH and PCa (24.3% versus 12.2%, P <0.001 and 32.9% versus 15.0%, P <0.001, respectively), but no difference of the ACT-PSA/tPSA ratio was observed (78.2% versus 78.7%, P = 0.696). Receiver operating characteristics of ACT-PSA (area under the curve = 0.630) and all the derivative ratios of fPSA/ACT-PSA (area = 0.737) and ACT-PSA/tPSA (area = 0.528) were not different from that of tPSA (area = 0.619), but showed a lower discrimination power between BPH and PCa than the fPSA/tPSA ratio (area = 0.790). CONCLUSIONS: Using this prototype assay to quantify ACT-PSA in serum, we have demonstrated that ACT-PSA and the calculated derivatives are not superior in the differentiation between BPH and PCa compared with tPSA and the ratio of fPSA to tPSA.

Adult↗

Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue.

Elevated activities of cysteine proteinases, the cathepsins B, H, L (CB, CH, CL) and diminished cysteine protease inhibitors (CPI) have been demonstrated in a variety of tumours and have been suggested to contribute to invasion and metastasis. The situation for prostate cancer is still unknown. In this study, using fluorimetric assays, the catalytic activities of CB, CH, CL were measured in prostatic tissue samples after radical prostatectomy, adenomectomy, transurethral resection of the prostate, in cell cultures grown from cancerous and non-cancerous parts of human prostate after prostatectomy and in the cell lines LNCaP, DU 145 and PC 3. CPIs were determined using heat activation before testing their inhibitory activity against purified CB. Comparing matched pairs of normal and cancerous tissue samples from the prostate, significantly decreased levels of CB, CL in malignant parts of the prostate were found. In contrast, primary cell cultures from cancerous samples showed elevated levels of CB, CH, CL and increased ratios of cathepsins to CPI compared with cell cultures from normal prostate. Established cell lines showed a similar distribution pattern of each cathepsin, DU 145 containing the highest levels, followed by LNCaP and PC 3. Our results suggest that elevated cathepsin levels and consequently increased ratios of cathepsins to CPI in primary cell cultures from cancerous versus non-cancerous parts of the prostate may be indicative of a cellular proteolytic imbalance in prostatic cancer cells. In this respect, primary cell culture experiments should be preferred to determinations in tissue samples.

Adult↗

Quantification of matrix metalloproteinases and tissue inhibitors of metalloproteinase in prostatic tissue: analytical aspects.

BACKGROUND: The balance between matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) has been seen as important during tumor invasion and progression. The determination of these components needs a special strategy of tissue preparation. This analytical problem has not been considered for prostatic tissue. METHODS: We adapted an extraction method consisting of two extraction steps with 0.25% Triton X-100/CaCl2 solution and two heat extraction steps at 60 degrees C for 4 min. This combination allowed a complete extraction of MMP (measured as enzyme activity) and TIMP-1 (measured with an ELISA test) from cancerous and normal prostatic tissue samples. RESULTS: The median values for cancerous vs. normal MMPs (50.8 mU/g wet tissue and 1,580 mU/g protein vs. 88.8 and 2,497) and TIMP-1 (4.49 micrograms/g wet tissue and 96.7 micrograms/g protein vs. 12.4 and 237.8) were significantly lower, whereas the respective ratios for MMP/ TIMP-1 (11.1 vs. 4.0 on wet weight and 15.5 vs. 5.3 on protein basis) were significantly higher. CONCLUSIONS: An optimized extraction procedure was elaborated for determining MMPs and TIMP-1 in prostatic tissue samples. The increased ratio of MMP/TIMP-1 can be interpreted as an indicator of the imbalance between MMP and TIMP, characteristic of prostate carcinoma tissue.

Enzyme-Linked Immunosorbent Assay↗

[Metalloproteinases (MMP-1, MMP-3) and their inhibitors (TIMP) in blood plasma of patients with prostate carcinoma].

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in important processes of tumor invasion and metastasis. In the study presented, matrix metalloproteinase 1 (MMP1) and 3 (MMP3), the tissue inhibitor of metalloproteinase 1 (TIMP1) and the complex MMP1/TIMP1 were measured by ELISA tests specific for these proteins in blood plasma. These components have been investigated in prostate cancer patients (PCa) with metastases (n = 18; T2, 3, 4 pN1, 2M1), prostate cancer patients without metastases (n = 29; T2, 3 pNOMO), patients with benign prostate hyperplasia (BPH; n = 29) and in healthy men (n = 35). Mean values of MMP1 and of the complex MMP1/TIMP1 were not different among the four groups. The mean values of MMP3 and especially TIMP1 were significantly higher in prostate cancer patients with metastases compared with controls, BPH patients and prostate cancer patients without metastases. Ten of these 18 patients had TIMP1 levels higher than the upper reference limit. TIMP1 concentrations correlate to the tumor stage but not to the tumor grade. These results indicate, that TIMP1 could be an potential marker for metastases in prostate cancer patients.

Aged↗

High-dose rate interstitial with external beam irradiation for localized prostate cancer--results of a prospective trial.

PURPOSE: A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. MATERIALS AND METHODS: Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). RESULTS: Before starting treatment, a PSA value of > or =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of > 1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. CONCLUSION: The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

Adenocarcinoma↗