Search PubMed⌕ Search

Biomedical subjects

D Schnorr

Publications and source records attributed to D Schnorr.

At least 37 records · Page 2Linked to original sources
PubMed2001

Molecular forms of prostate-specific antigen in serum with concentrations of total prostate-specific antigen <4 microg/L: are they useful tools for early detection and screening of prostate cancer?

Molecular forms of prostate-specific antigen (PSA) improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) in men with total PSA concentrations between 4 and 10 microg/l. To evaluate the diagnostic utility of free PSA (fPSA) and complexed PSA forms for identification of men with PCa in the low PSA range of <4 microg/l, total PSA (tPSA), alpha(1)-antichymotrypsin complexed PSA (PSA-ACT) and fPSA (Roche Elecsys [ES] system) as well as tPSA and complexed PSA (cPSA) (Bayer Immuno 1 system) were measured in archival serum samples from 31 untreated patients with PCa, 66 patients with BPH, and 90 men without prostatic disease. The median ratios of fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were significantly different between patients with BPH and PCa (27.2 vs. 19.4%, 64 vs. 88%, 77.2 vs. 88.2%, p < 0.05). No associations between PSA forms and tumor stage and grade were found. Analysis of the receiver operating characteristic curves showed that these ratios could discriminate better between BPH and PCa patients than determination of the analytes tPSA, fPSA, cPSA and PSA-ACT alone. The use of one of the ratios would have eliminated roughly half of the unnecessary biopsies in this study. The ratios should be considered as potential tools to increase the selectivity of PCa detection at low PSA concentration. The ratios fPSA/tPSA and cPSA/tPSA can be determined using commercially available assays so that one of these ratios could be preferred instead of PSA-ACT determination. The ratios could be useful in assessing the risk of PCa in the individual and therefore in deciding on prostate biopsy for final diagnosis.

Aged↗
PubMed2001

A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate-specific antigen in prostate cancer diagnosis.

BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43 microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio.

Adult↗
PubMed2001

Receiver-operating characteristic as a tool for evaluating the diagnostic performance of prostate-specific antigen and its molecular forms--What has to be considered?

BACKGROUND: Receiver-operating characteristic (ROC) analysis is often applied as evaluation tool to compare the diagnostic validity of laboratory tests. The aim of this study was to draw attention to preconditions which should be taken into account when ROC analysis is used to assess the diagnostic performance of total prostate-specific antigen (tPSA) and its molecular forms in differential diagnosis between prostate cancer and benign prostatic hyperplasia (BPH). METHODS: Using a standard software (GraphROC for Windows), ROC analyses were performed and the areas under the curves were calculated for four hypothetical pairs of groups. Every group included 40 patients with prostate cancer and with BPH showing different tPSA concentrations (range of 2-10 microg, but similar free-to-total PSA ratios (fPSA%). RESULTS: The area under the fPSA% ROC curve showed the highest value, whereas the areas under the tPSA ROC curves were dependent on the distributions of tPSA concentrations in the patients. The ability of fPSA% to improve the differential diagnosis between prostate cancer and BPH in comparison to tPSA was not furthermore evident, if the prostate cancer group included more patients with higher tPSA concentrations than the BPH group. CONCLUSIONS: When the diagnostic performance of tPSA and its derivatives like molecular forms in patients with prostate cancer and BPH should be compared by ROC analysis, a matching procedure is recommended prior to ROC analysis to compensate the effect of possible unequal tPSA distributions in both groups. Each BPH (or PCa) patient should be matched with a PCa (or BPH) patient with nearest tPSA concentration so that an optimum of overlapping tPSA concentrations in both groups can be achieved.

Diagnosis, Differential↗
PubMed2001

Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma.

OBJECTIVES: To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9 in the urine of patients with bladder cancer according to the stage and grade of tumor and to evaluate their diagnostic clinical validity. In numerous carcinomas, increased expression of MMPs is associated with a higher grade of malignancy and poor prognosis. METHODS: The study population included 44 controls without evidence of malignancy, 14 patients with cystitis, and 43 patients with Stage Ta-T1, 18 patients with Stage T2, and 10 patients with Stage T3-T4 bladder cancer. MMP-2 and MMP-9 excretion in urine samples was measured with gelatin zymography and related to the urine creatinine concentration. The evaluation of data was performed by univariate statistical analysis, logistic regression analysis, and receiver operating characteristic analysis. RESULTS: The upper cutoff limit for MMP-2 and MMP-9 excretion was 277 microg/g creatinine and 648 microg/g creatinine, respectively. Levels of MMP-2 and MMP-9 correlated with each other and with tumor stage and grade. Elevated excretions were mainly observed in patients with invasive tumors (Stage T2-T4). In the receiver operating characteristic analysis, the areas under the curves for MMP-2 and MMP-9 were significantly higher in patients with muscle-invasive than in patients with noninvasive tumors. Related to the cutoff limits, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. In logistic regression analysis, MMP-2 showed the best results. CONCLUSIONS: Urinary excretion of MMP-2 and MMP-9 is associated with a high stage and grade of bladder cancer, and they may serve as indicators of tumor progression and recurrence in the future.

Adult↗
PubMed2001

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). RESULTS: For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different. CONCLUSION: The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Aged↗
PubMed2000

Synthetic inhibitor of matrix metalloproteinases (batimastat) reduces prostate cancer growth in an orthotopic rat model.

BACKGROUND: Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats. METHODS: In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation. RESULTS: Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat. CONCLUSIONS: Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed.

Animals↗
PubMed2000

Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma.

Matrix-metalloproteinases (MMPs) are associated with invasive and metastatic behavior of several human malignant tumors. We have determined MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) in blood plasma and in renal tissue samples of patients with renal cell carcinoma (RCC) from cancerous and non-cancerous parts of the same kidney. In tumor tissue, MMP-9 and TIMP-1 were significantly higher than in normal counterparts. MMP-2 was not different between tumor tissue and normal counterparts. TIMP-2 values could not be measured. In plasma, MMP-9 concentrations were significantly higher in RCC patients than in healthy controls, MMP-2 and TIMP-2 concentrations were higher in healthy controls and TIMP-1 concentrations were not different.

Adult↗
PubMed2000

[Molecular forms of prostate-specific antigen and human kallikrein 2 as possible indicators in prostatic carcinoma diagnosis].

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) 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 alpha 1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results. The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA measurements. The number of biopsies can be reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research and their diagnostic significance needs to be evaluated in more extensive clinical trials.

Biomarkers, Tumor↗
PubMed2000

[Tumor M2 pyruvate kinase in renal cell carcinoma. Studies of plasma in patients].

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.

Biomarkers, Tumor↗
PubMed2000

Urinary markers of malignancy.

Transitional cell carcinoma (TCC) is the second most common malignancy in the genitourinary tract. The majority of urothelial tumors are superficial when the patient first presents, but despite adequate resection of the primary lesion the recurrence rate is particularly high. In a small but significant group of patients the tumor is primary invasive or subsequently can progress and leads to death. Voided urine can be easily obtained and therefore diagnostic urine tests would be ideal for screening or follow up of TCC. Although many urinary markers have been described, none of them is used routinely in clinical practice. Promising tumor markers still need to be evaluated in multi-center clinical studies. Larger prospective trials are necessary in order to identify prognostic indicators that would help to predict disease progression or response to different treatment modalities (BCG, chemo-, radiotherapy, etc.). Hopefully, new diagnostic urine tests will allow to identify patients who will most benefit from early cystectomy with or without adjuvant treatment, bladder sparing protocols or systemic treatment. In this paper we have reviewed the literature and discuss, from the clinician's point of view, the current status of various diagnostic tests for urinary markers. [Lee SJ, Lee WE, Chang SG, Lee CH, Kim JI. A comparative study of telomerase, Lewis X, BTA, NMP22 and urinary cytology in bladder tumor. J Urol 1999;161(suppl):152.]

Antigens, Neoplasm↗
PubMed2000

ACT-PSA and complexed PSA elimination kinetics in serum after radical retropubic prostatectomy: proof of new complex forming of PSA after release into circulation.

OBJECTIVES: To study the elimination kinetics of alpha(1)-antichymotrypsin (ACT)-prostate-specific antigen (PSA) and complexed PSA (cPSA) in comparison to the biexponential decrease of total PSA and free PSA after radical prostatectomy. METHODS: Serum total PSA, free PSA, ACT-PSA, and cPSA values and the corresponding ratios were determined in venous blood from 12 patients with prostate cancer. The samples were taken before surgery, immediately after surgery, 1, 2, 3, 4, 5, and 6 hours after surgery, and then once daily for the next 10 days. Total PSA and cPSA were analyzed by using Immuno 1 PSA assays (Bayer Corporation); free PSA was measured using the AxSym test kit (Abbott Diagnostics). For ACT-PSA, the ES analyzer system was used (Roche Diagnostics). Statistical calculations were performed with the analysis of variance and Wilcoxon tests. RESULTS: During the first 6 hours after radical retropubic prostatectomy, we found nearly constant levels of ACT-PSA and cPSA, in contrast to the rapid elimination of free PSA and significant decrease in total PSA. From days 1 to 10, a continuous and nearly identical decrease of ACT-PSA and cPSA occurred compared with total PSA; free PSA was eliminated more rapidly. CONCLUSIONS: In addition to the opinion that the first PSA decrease might be an effect of the operation itself or caused by renal elimination alone, our findings indicate that the initial rapid decrease of free PSA immediately after surgery could be caused by new complex forming of PSA with ACT and other serum protease inhibitors.

Aged↗
PubMed2000

[The staging of bladder tumors in MRT: the value of the intravesical application of an iron oxide-containing contrast medium in combination with high-resolution T2-weighted imaging].

AIM: To investigate superparamagnetic iron oxide (SPIO) particles as intravesically applied contrast material in combination with high-resolution T2-weighted MR imaging for the diagnostic assessment of urinary bladder tumors. METHODS: A prospective study was performed in 40 patients with suspected urinary bladder tumors who underwent MR imaging with a body phased-array coil at 1.5 T. Prior to imaging, a SPIO-containing solution (179.2 mg Fe/l) was instilled into the bladder. All patients were examined with T2-weighted, half-fourier acquired single shot turbo spin echo sequences and T1-weighted fast low angle shot sequences in 3 planes as well as a T2-weighted turbo spin echo sequence (TSE) using a 512 matrix. An additional gadolinium-enhanced dynamic study was performed in 33 patients. All patients underwent transurethral resection of the bladder or cystectomy. RESULTS: The combination of intravesically applied SPIO particles and a high-resolution T2-weighted TSE sequence depicted intravesical tumors as small as 4 mm. A reliable identification of the different layers of the bladder wall was possible in 5 cases only. The T2-weighted TSE sequence allowed the correct determination of the depth of infiltration in 29 of 36 patients with urothelial cancer by assessing the inner and outer boundary of the urinary bladder wall. This sequence had a diagnostic accuracy of 81% compared to 84% for the dynamic study (26/31). CONCLUSION: Even small tumors could be identified with the T2-weighted TSE sequence after intravesical administration of SPIO particles but it was not possible to reliably differentiate the layers of the bladder wall. The results suggest that a dynamic MR imaging study cannot be dispensed with in patients with urinary bladder cancer.

Administration, Intravesical↗
PubMed2000

[MRI of the prostate after combined radiotherapy (afterloading and percutaneous): histopathologic correlation].

AIM: To identify the MRI changes of the prostate after combined (high-dose rate interstitial with external beam) radiotherapy for, localized prostate cancer and to correlate the findings with histology in order to determine the value of MR imaging in the follow-up of these patients. MATERIAL AND METHODS: Twenty-three patients underwent MR imaging at 1.5 T between 6 and 24 months after completion of combined radiotherapy. The prostate was imaged with axial and coronal T2-weighted sequences and axial T1-weighted sequences before and after intravenous administration of Gd-DTPA. Quadrant or sextant biopsy was performed in all cases and three patients with proven persistence of the tumor underwent salvage prostatectomy. The MRI findings were compared with the biopsy results or the large-area sections. RESULTS: On T2-weighted images the fibrotically changed peripheral zone was hypointense while persistent tumor tissue showed hyperintensity. Solid tumors were depicted when they had a diameter of 1 cm or more. Persistent tumors of the diffuse multifocal type escaped detection. Contrast-enhanced T1-weighted imaging yielded no additional information. The accuracy in detecting persistent tumor was 74%. CONCLUSIONS: Histopathologic changes seen after combined radiotherapy correlate with the findings on T2-weighted MR images. MR imaging cannot replace follow-up by routine biopsy. Its only role is assessing local operability in cases found to have increasing PSA levels during follow-up. Further studies are needed to determine the role of MR imaging in this patient population.

Adult↗
PubMed2000

Genetic analysis of Tp53 from urine sediment as a tool for diagnosing recurrence and residual of bladder carcinoma.

OBJECTIVES: Longitudinal study of Tp53 mutation in urine sediments of 26 patients with mutated primary transitional cell carcinoma (TCC) of the urinary bladder at different time periods after transurethral resection of the bladder (TURB), i.e. before and after the first TURB, prior to the control resection and before treatment of a recurrence. METHODS: DNA of the critical Tp53 exons 5-8 was anaylzed by temperature gradients (TGGE) and sequence. RESULTS: (1) In 11 of 12 patients (91.7%) mutation reoccurred with the detection of recurrence of the disease. The mutation frequency in patients without any recurrence was 1 in 8 (12.5%) after a follow-up period of 4-16 months. (2) In 7 of 10 patients, the mutation was no longer detectable in the urine sediment after TURB. (3) The mutation frequency at the control resection 6 weeks after the first TURB was 5 in 7 (71.4%) in patients found to have residual and 1 in 7 (14.2%) in the tumor-free patients. (4) In 9 of 10 samples identical mutations were found by sequence in the recurrent tumor. These results show a significant correlation between the detection of a Tp53 mutation in the urine sediments and tumor recurrence or residual. CONCLUSIONS: (1) Tp53 mutations in the urine sediment could be a useful indicator of tumor recurrence or tumor residual in patients ( approximately 40%) with primary mutated bladder cancer tissue. (2) These results support the monoclonal seeding theory. (3) The finding of identical mutations at different times indicate that the tumor was never totally removed.

Adult↗