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D Schnorr

Publications and source records attributed to D Schnorr.

At least 73 records · Page 4Linked to original sources
PubMed1998

The percentage of free prostate specific antigen is an age-independent tumour marker for prostate cancer: establishment of reference ranges in a large population of healthy men.

OBJECTIVE: To define the reference range for the ratio of free to total prostate-specific antigen (fPSA%) in a population of healthy men with no clinically evident prostate cancer and to assess the influence of age on this tumour marker, thus determining the utility of fPSA% in enhancing the discriminatory power of PSA to differentiate healthy men and patients with benign prostatic hyperplasia from those with prostate cancer. SUBJECTS AND METHODS: In a prospective cohort study between May and August 1996, 1160 white men aged 20-89 years (957 were 40-69 years old, 82% of all subjects) from nine European and eight non-European countries were assessed. None of the participants who had a history of prostate cancer had undergone prostatectomy. A standard clinical examination including a digital rectal examination was performed to exclude the presence of prostate cancer. Transrectal ultrasonography was not an inclusion criterion, as it was not available in every case. Total PSA (tPSA) and free PSA (fPSA) were determined in 61 laboratories using the appropriate Enzymun-Test for tPSA and fPSA (Boehringer Mannheim Diagnostics, Mannheim, Germany). Serum tPSA, fPSA and fPSA% were then assessed as a function of the subjects' age. RESULTS: The serum tPSA and fPSA were significantly different among age decades 2-8 (P < 0.001), with increasing median values, indicating that both variables depend on age. The recommended upper reference limit (95th percentile) for tPSA is 1.78 ng/mL for men aged 30-39 years, 1.75 ng/mL for 40-49 years, 2.27 ng/mL for 50-59 years, 3.48 ng/mL for 60-69 years and 4.26 ng/mL for 70-79 years. The fPSA% was not significantly different between decades 3-8 (P = 0.06). Those aged 20-29 years had a slightly higher median value (P = 0.03) than the other age groups. The recommended lower reference limit (fifth percentile) for fPSA% is 12.6%. CONCLUSION: The fPSA% for clinically relevant age groups in healthy men was independent of age, which simplifies the use and interpretation of this relatively new tumour marker.

Adult↗
PubMed1998

Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate.

PURPOSE: We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy. RESULTS: The median values of total, free and percentage of free PSA were 4.11 microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84 microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23 microg./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis. CONCLUSIONS: Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.

Aged↗
PubMed1998

p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer.

OBJECTIVES: To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence. MATERIALS AND METHODS: 141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands. RESULTS: TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURP. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH. CONCLUSION: Tp53 mutation in BPH tissue may be a tumour risk factor.

Adenocarcinoma↗
PubMed1998

Relation of free PSA/total PSA in serum for differentiating between patients with prostatic cancer and benign hyperplasia of the prostate: which cutoff should be used?

A review on literature data is given concerning free prostate-specific antigen (f-PSA) and the corresponding cutoffs of f-PSA/t-PSA for differentiating patients with cancer of the prostate from those with benign prostatic hyperplasia. The special importance of the diagnostic criterion (sensitivity, specificity, efficiency) for establishing the cutoff is demonstrated. On the basis of our own data, the application of the f-PSA% is recommended as an additional decision criterion for biopsy.

Biopsy↗
PubMed1998

[Surgical therapy of tumor embolism of the vena cava in renal cell carcinoma].

Radical nephrectomy (Nx) with vena caval thrombectomy represents the only realistic chance of cure for patients with renal cell carcinoma with extension into the vena cava inferior (VCI). For stage III, with tumor extension in the retrohepatic VCI up to the diaphragm, a venous bypass technique is described. From July, 1996 through April, 1998, Nx combined with thrombectomy of the VCI was performed by isolation of the VCI, temporary occlusion of the hepatoduodenal ligament, and temporary extracorporal femoral-axillary veno-venous bypass with the Biomedicus pump. Radical resection of tumor thrombus from the VCI was accomplished under direct vision with minimal blood loss and without cardiopulmonary complications. With a follow-up of 21, 16, 9, 2, and 1 months, respectively, all patients are so far free of complications and without recurrent or metastatic disease.

Carcinoma, Renal Cell↗
PubMed1997

Factors influencing the ratio of free to total prostate-specific antigen in serum.

The ratio of free prostate-specific antigen (f-PSA) to total PSA (t-PSA) in serum, calculated as percent free PSA (f-PSA%), is lower in patients with prostate carcinoma (PCa) than in patients with benign prostate hyperplasia (BPH). This parameter facilitates discrimination between the 2 groups of patients, but there is an overlapping of data. A better understanding of factors influencing this ratio is of practical importance. Therefore, f-PSA% was measured in controls and patients suffering from BPH, PCa and chronic prostatic inflammation with t-PSA concentrations up to 20 microg/l using the IMMULITE assays. The relationships of f-PSA% to clinical situation, age, prostate volume, kind of treatment, and stage and grade of tumor were calculated. Compared with controls or BPH patients, mean f-PSA% values were reduced in PCa patients and in patients with chronic prostatic inflammation. The prostate volume was the most important factor to influence f-PSA%. The difference of f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 was lost if the prostate volumes exceeded 40 cm3. No relationship of f-PSA% to pTNM stage or grade of tumor was observed. In contrast to t-PSA concentrations, the f-PSA% values were not age-dependent and were not influenced by any kind of treatment in BPH and PCa patients either, which simplifies the use of f-PSA% compared with t-PSA. Thus, for using f-PSA% in clinical practice and for interpreting the data correctly, the advantages shown have to be considered along with the potential limitations of f-PSA%.

Adult↗
PubMed1997

Betaine improves the PCR amplification of GC-rich DNA sequences.

Betaine improves the co-amplification of the two alternatively spliced variants of the prostate-specific membrane antigen mRNA as well as the amplification of the coding cDNA region of c-jun. It is suggested that betaine improves the amplification of these genes by reducing the formation of secondary structure caused by GC-rich regions and, therefore, may be generally applicable to ameliorate the amplification of GC-rich DNA sequences.

Alternative Splicing↗
PubMed1997

Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinase-1 and the complex of metalloproteinase-1/tissue inhibitor in plasma of patients with prostate cancer.

We analyzed blood plasma concentrations of matrix metalloproteinase-1 and -3 (MMP-1; MMP-3), the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the complex MMP-1/TIMP-1, and looked for any correlation with prostate cancer stage. These components were measured by ELISA tests specific for these proteins in healthy male controls (n = 35), and in patients with benign prostatic hyperplasia (BPH; n = 29), with prostate cancer (PCa) without metastasis (T2,3pN0M0; n = 29) and with PCa with metastatic disease (T2,3,4pN1,2M1; n = 18). Mean values of MMP-1 and of the complex MMP-1/TIMP-1 were not different among the 4 groups studied. The mean MMP-3 and especially TIMP-1 concentrations were significantly higher in PCa patients with metastases compared with controls, BPH and PCa patients without metastases. Ten of these 18 patients had TIMP-1 concentrations higher than the upper reference limit. TIMP-1 concentrations were correlated with staging but not with grading. Our results point towards plasma TIMP-1 concentration as a potential marker of malignant progression of PCa.

Adult↗
PubMed1997

Increased analytical sensitivity of RT-PCR of PSA mRNA decreases diagnostic specificity of detection of prostatic cells in blood.

The diagnostic specificity of the detection of disseminated prostatic cells by reverse-transcriptase polymerase chain reaction (RT-PCR) of PSA mRNA was investigated. A sensitive nested PCR was developed. In blood samples from 10 healthy female and 10 healthy male persons examined by RT-PCR, mRNA of PSA was detected 3 times in each group. In the groups of patients suffering from benign prostate hyperplasia and prostate cancer, 6 of 11 and 5 of 12, respectively, gave positive RT-PCR results. With increasing analytical sensitivity of the RT-PCR of PSA mRNA, the diagnostic specificity of the assay is decreased. Further development of this diagnostic method requires the introduction of the quantitative PCR which may make possible discrimination between prostatic and non-prostatic source of PSA mRNA by quantification.

Female↗
PubMed1997

The influence of prostate volume on the ratio of free to total prostate specific antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia.

BACKGROUND: Determining the ratio of free to total prostate specific antigen (f-PSA to t-PSA, calculated as the percentage of f-PSA [f-PSA%]) in serum allow for a clearer distinction between patients with prostate carcinoma (PCa) and patients with benign prostate hyperplasia (BPH) than determining the level of t-PSA alone. To find influencing factors on f-PSA%, the authors investigated prostate volume, TNM classification, and tumor stage. METHODS: The authors measured f-PSA and t-PSA in 36 men with untreated PCa (tumor classification: T1, 2, 3pNO, MO), 44 patients with BPH, and 54 healthy controls. Prostate volume was determined by transrectal ultrasound. RESULTS: The median values of t-PSA and f-PSA% were 7.8 micrograms/L and 10.5% in PCa patients, 4.3 micrograms/L and 20.8% in patients with BPH, and 1.4 micrograms/L and 23.6% in the control group. Patients with PCa had a significantly lower proportion of f-PSA than BPH patients and healthy men. There was no correlation of f-PSA% to TNM stage or tumor grade. In PCa patients a significant positive correlation (correlation coefficient [r] = 0.51, P < 0.001) was found between f-PSA% and prostate volume, whereas there was no significant correlation in BPH patients (r = -0.27, P > 0.05). There was a significant difference in f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 (9.0% vs. 21.6%, P < 0.01) but not between patients in these 2 groups with prostate volumes exceeding 40 cm3 (15.1% vs. 18.2%, P = 0.11). CONCLUSIONS: Determining the ratio of f-PSA to t-PSA to discriminate between PCa and BPH patients yields significant results only in men with a prostate volume of less than 40 cm3.

Aged↗
PubMed1997

Analytical aspects regarding the measurement of metalloproteinases and their inhibitors in blood.

OBJECTIVE: Both in vitro and in vivo investigations have shown that the balance between matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) seems to be important in physiological and pathological processes which involve tissue remodeling and repair. DESIGN AND METHODS: In order to investigate the analytical reliability of new commercial ELISA tests. BIOTRAK test kits (Amersham Int.) were used for the determination of metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the MMP-1/TIMP-1 complex in blood. RESULTS: The detection limits and the precision data were in the usual ranges of ELISA tests so that concentrations found in blood could be determined reliably. Since all three analytes were lower in heparin plasma than in serum or EDTA plasma, heparin plasma was selected as the specimen of choice. Measurement of diluted samples gave higher values than those of undiluted native plasma samples because the inhibitory effects of specific/unspecific inhibitors or other matrix components were apparently reduced. To obtain comparable data from different laboratories, the predilution of samples must be defined. We recommend to use diluted plasma samples of 1:5, 1:21, and 1:11 for the determination of MMP-1, TIMP-1, and the complex MMP-1/TIMP1, respectively. The preliminary upper 95% reference limits measured under these conditions in healthy subjects (40 females: 40 males) were 14.4 micrograms/L for MMP-1 in females, 20 micrograms/L for MMP-1 in males. 1668 micrograms/L for TIMP-1 and 116 micrograms/L for the complex MMP-1/TIMP-1. CONCLUSION: The study has shown that the BIOTRAK test combinations for MMP-1, TIMP-1, and MMP-1/TIMP-1 complex allow a reliable measurement of the analyte concentrations in heparin plasma. In order to avoid preanalytical misinterpretations only heparin plasma samples in defined dilutions should be used.

Adult↗
PubMed1997

Antioxidant enzymes in malignant prostate cell lines and in primary cultured prostatic cells.

The antioxidant enzymes catalase, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined in the androgen-response LNCaP and androgen-nonresponsive PC-3 and DU 145 cells as well as in prostatic epithelial cell cultures of benign and malignant human prostatic tissue. There were no differences between the enzyme activities of the human primary cell cultures from cancerous tissue and their normal counterparts. The enzyme activities of the three permanent cell lines were either higher (SOD, catalase, GR) or lower (GST, GPx) than in the primary cell cultures. In LNCaP cells catalase and GR were significantly higher, GST, in contrast, was significantly lower than in PC-3 and DU 145 cells. GST in PC-3 and DU 145 cells, and SOD in all the three cell lines showed no significant differences. Catalase, GPx and GR values were significantly different in the three permanent cell lines. The different enzymatic equipment of the prostate cancer cell lines provides the basis for experimental testing of new concepts of cancer treatment with the help of systematic modulations of the antioxidant defence systems in prostate cancer.

Antioxidants↗
PubMed1997

Elimination of serum free and total prostate-specific antigen after radical retropubic prostatectomy.

Elimination kinetics of serum total and free prostate-specific antigen were studied for a ten days course after radical retropubic prostatectomy on 11 patients suffering from organ confined prostate cancer. Samples were taken before operation, immediately after finishing the operation and 1, 2, 3, 4, 5, 6 h after prostatectomy and then once a day for the following ten days. The measurements were performed with AxSym assays from Abbott Laboratories. The elimination of both total and free prostate-specific antigen followed a biphasic kinetics. In the fast phase, the average of the individual elimination half-lives of total and free prostate-specific antigen amounted to 6.3 h (SD = 6.1 h; range: 0.55 to 37.1 h) and 0.57 h (SD = 0.18 h; range: 0.22 to 0.89 h), respectively. In the slow phase, total prostate-specific antigen disappeared with an average half-life of 85.6 h (SD = 11 h; range: 47.2 to 261.7 h) and free prostate-specific antigen with an average half-life of 14.4 h (SD = 10.4 h; range: 2.4 to 30.3 h). These results might be significant for the use of free and total prostate-specific antigen and its ratio as a diagnostic and prognostic tool.

Aged↗
PubMed1997

Mutation of the tumor suppressor gene p53 in human prostate and bladder cancers--investigation by temperature gradient gel electrophoresis (TGGE).

PURPOSE: To test the value of a recently developed screening method for the detection of p53 mutations in prostate and bladder cancers. MATERIALS AND METHODS: Tumor tissue from 24 prostate cancers and 27 bladder cancers were evaluated. DNA of the critical p53 exons 5-8 were amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done directly from polymerase chain reaction (PCR) products and/or from reamplified mutant and wild type bands excised from the gels. RESULTS: The p53 genotype predicted from the TGGE analysis was always confirmed on the excised DNA fragments, in contrast to only 50% of cases tested by direct sequencing from mixed wild type and mutant DNA present in PCR products. With this screening protocol, 6 of 24 prostate cancers (25.0%) and 11 of 27 bladder cancers (40.7%) showed p53 mutations. At stage T1, none of prostate cancers and 41.2% of bladder cancers contained mutant p53. At higher stages (> or = T2), 30.0% of prostate cancer and 50.0% of bladder cancers were mutated. Histological tumor grading was > G1 in all but two prostate/bladder cancers with mutant p53. It appears that p53 mutations can occur early in bladder carcinogenesis. CONCLUSION: TGGE fulfills the clinical need of a rapid and specific screening method, and, at the molecular level, has the advantage of sorting out the wild type and mutant alleles for consecutive sequencing.

Adolescent↗
PubMed1997

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer.

Development of afterloading techniques in combination with external radiotherapy allows for curative therapy modality for stage C prostate cancer. Between 10/92 and 12/95 128 patients were treated. Stage B and C tumors were found in 36 and 89 cases, respectively. All patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. 9 Gy a week was applied during the first and second weeks of treatment (10/92-12/93: 10 Gy each week) interstitially with high-dose rate iridium192 brachytherapy to the prostate. After this, a four-field box of external beam radiation therapy was given to the prostate to a dose of 45 Gy/25 fractions (10/92-12/93: 40 Gy/20 fractions). Before starting treatment median PSA was 13.8 ng/ml. The median PSA 3, 12, and 24 months after completion of therapy was 1.2, 0.78, and 0.75 ng/ml, respectively. Negative biopsies 12 and 24 months after therapy were observed in 56% (49/87) and 72% (31/43), respectively.

Adenocarcinoma↗