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Schaefer A.,Free University of Berlin | Stephan C.,University Hospital Charite | Busch J.,University Hospital Charite | Yousef G.M.,University of Toronto | Jung K.,Berlin Institute for Urological Research
Nature Reviews Urology | Year: 2010

MicroRNAs (miRNAs) are small, non-coding RNAs that have an important role in the regulation of carcinogenic pathways. The observations that miRNAs are differentially expressed in tumor versus corresponding normal tissue, and that they regulate important breakpoints during carcinogenesis, are of interest for urologic oncologists. As biomarkers, they might be helpful tools for diagnostic, prognostic and monitoring purposes. Furthermore, miRNAs might be potential targets for novel therapeutic strategies, especially in patients with tumor subtypes that do not respond to currently available therapies. In this Review, we will focus on the current proceedings of miRNA research in urologic tumors. In the past decade, the number of published articles related to miRNAs in urologic oncology has increased, highlighting the ongoing importance of miRNAs in this field. Current studies support the hypothesis that miRNA will gain influence in clinical practice. Here, therefore, we illustrate the current knowledge of miRNA function in urologic tumors and draw the attention of urologists to the future opportunities and challenges of this research field. © 2010 Macmillan Publishers Limited. All rights reserved.

Ecke T.H.,Helios Hospital | Arndt C.,Lukaskrankenhaus Neuss | Stephan C.,Charite University Hospital | Stephan C.,Berlin Institute for Urological Research | And 6 more authors.
Anticancer Research | Year: 2015

Background/Aim: UBC Rapid is a test detecting fragments of cytokeratins 8 and 18 in urine. These are cytokeratins frequently overexpressed in tumor cells. We present the first results of a multi-centre study using UBC Rapid in patients with bladder cancer and healthy controls. Materials and Methods: Clinical urine samples from 92 patients with tumors of the urinary bladder (45 low-grade and 47 high-grade tumors) and from 33 healthy controls were used. Urine samples were analyzed by the UBC Rapid point-of-care (POC) system and evaluated both visually and quantitatively using a concile Omega 100 POC reader. For visual evaluation, different thresholds of band intensity for considering a test as positive were applied. Sensitivities and specificities were calculated by contingency analyses. Results: We found that pathological concentrations by UBC Rapid are detectable in urine of patients with bladder cancer. The calculated diagnostic sensitivity of UBC Rapid in urine was 68.1% for high-grade, but only 46.2% for low-grade tumors. The specificity was 90.9%. The area under the curve (AUC) after receiver-operated curve (ROC) analysis was 0.733. Pathological levels of UBC Rapid in urine are higher in patients with bladder cancer in comparison to the control group (p<0.0001). Conclusion: UBC rapid can differentiate between patients with bladder cancer and controls. Further studies with a greater number of patients will show how valuable these results are.

Ecke T.H.,Helios Hospital | Bartel P.,Helios Hospital | Hallmann S.,Helios Hospital | Koch S.,Institute of Pathology | And 7 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2012

Background: We evaluated the use of the artificial neural network (ANN) program "ProstataClass" of the Department of Urology and the Institute of Medical Informatics at the Charité-Universitätsmedizin Berlin in daily routine to increase prostate cancer (CaP) detection rate and to reduce unnecessary biopsies. Materials and methods: From May 2005 to April 2007, a total of 204 patients were included in the study. The Beckman Access PSA assay was used, and pretreatment prostate specific antigen (PSA) was measured prior to digital rectal examination (DRE) and 12 core systematic transrectal ultrasound (TRUS) guided biopsies. The individual ANN predictions were generated with the use of the ANN application for the Beckman Access PSA and free PSA assays, which relies on age, PSA, percent free prostate specific antigen (%fPSA), prostate volume, and DRE. Diagnostic validity of total prostate specific antigen (tPSA), %fPSA, and the ANN was evaluated by ROC curve analysis. Results: PSA and %fPSA ranged from 4.01 to 9.91 ng/ml (median: 6.65) and 5% to 48% (median: 15%), respectively. Of all men, 46 (22.5%) demonstrated suspicious DRE findings. Total prostate volume ranged from 7.1 to 119.2 cc (median: 35). Overall, 71 (34.8%) CaP were detected. Of men with suspicious DRE, 28 (60.9%) had CaP on initial biopsy. The ANN was 78% accurate in the original report. The AUC of ROC curve analysis was 0.51 for PSA, 0.66 for %PSA, and 0.72 for the ANN-Output, respectively. Conclusions: Our results in this independent cohort show that ANN is a very helpful parameter in daily routine to increase the CaP detection rate and reduce unnecessary biopsies. © 2012 Elsevier Inc..

Lu H.,University Hospital Charite | Lu H.,Berlin Institute for Urological Research | Busch J.,University Hospital Charite | Jung M.,University Hospital Charite | And 10 more authors.
Clinica Chimica Acta | Year: 2016

Background: There is inconsistent information about the clinical usefulness of circulating cell-free DNA (cfDNA) in plasma from clear cell renal cell cancer (RCC) patients. This is attributed to preanalytical, analytical, and clinical factors that were considered as far as possible in this study. Methods: cfDNA was extracted from EDTA plasma of healthy people (n=40), non-metastatic (n=145) and metastatic (n=84) RCC patients using the QIAamp Circulating Nucleic Acid Kit. Genomic and mitochondrial cfDNA concentrations were determined using qPCR of different cfDNA fragments (67-306. bp). Their diagnostic and prognostic potential was estimated using receiver operating characteristics (ROC) and Cox regression analyses. Results: The 67. bp and 180. bp genomic cfDNA fragments did not differ between the three study groups while the 306. bp fragment was lower in RCC patients than in controls. The mitochondrial cfDNA was higher in metastatic than in non-metastatic patients and controls. The cfDNA integrity indices decreased from controls to metastatic patients. Models built by logistic regression and Cox regression resulted in area under the ROC curves > 0.75 and concordance indices of > 0.800 in predicting recurrence-free survival and overall survival. Conclusion: The study suggests that combinations of cfDNA markers have promising diagnostic and prognostic potential in RCC patients and are worth for further validation in future prospective multicenter studies. © 2015 Elsevier B.V.

Jentzmik F.,University Hospital Charite | Stephan C.,University Hospital Charite | Miller K.,University Hospital Charite | Schrader M.,University Hospital Charite | And 6 more authors.
European Urology | Year: 2010

Background: Sarcosine in urine was recently suggested to be a promising tool in prostate cancer (PCa) diagnostics. Objective: To reevaluate sarcosine as a potential biomarker for early PCa detection and for prediction of tumour aggressiveness. Design, setting, and participants: Sarcosine was measured in urine samples from 106 PCa patients and 33 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies, after standardised digital rectal examination, as well as from 12 healthy men and women. The results were related to the clinicopathologic data on prostate volume, tumour stage, Gleason score, and prostate specific antigen (PSA). Measurements: Sarcosine in urine was determined by gas chromatography-mass spectrometry using a commercial amino acid assay and was normalised to urine creatinine. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance. Results and limitations: The median sarcosine-creatinine ratio in urine was 13% lower in PCa than in NEM patients. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs ≥7). ROC analyses proved that the discrimination between PCa and NEM patients was not improved by sarcosine in comparison with total PSA, but it was significantly worse than the percent free PSA. The higher proportion of PCa than NEM patients can be considered a limitation of this study. Conclusions: Sarcosine in urine after rectal digital examination cannot be considered as a suitable marker to differentiate between patients with and without PCa. © 2010 European Association of Urology.

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