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Ruprecht Kuner,
Maria Fälth,
Nicole Chui Pressinotti,
Jan C Brase,
Sabrina Balaguer Puig,
Jennifer Metzger,
Stephan Gade,
Georg Schäfer, Georg Bartsch,
Eberhard Steiner,
Helmut Klocker,
Holger Sültmann
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ABSTRACT: Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle genes has been associated with prognostic parameters such as biochemical relapse and survival. The identification of novel oncogenic and druggable targets in patient subgroups with poor prognosis may help to develop targeted therapy approaches. We analyzed prostate cancer and corresponding benign tissues (n = 98) using microarrays. The comparison of high- and low-grade tumors (Gleason score ≥ 4 + 3 vs. ≤ 3 + 4) revealed 144 differentially expressed genes (p < 0.05). Out of these, 15 genes were involved in the cell cycle process. The gene maternal embryonic leucine zipper kinase (MELK) was identified to be highly correlated with cell cycle genes like UBE2C, TOP2A, CCNB2, and AURKB. Increased MELK gene expression in high-risk prostate cancer was validated by qPCR in an independent patient cohort (p < 0.005, n = 79). Immunohistochemistry analysis using a tissue microarray (n = 94) revealed increased MELK protein expression in prostate cancer tissues of high Gleason scores. RNAi-based inhibition of MELK in PC3 and LNCaP cells suggested putative function in chromatin modification, embryonic development and cell migration. The concerted inhibition of MELK and other cell cycle targets by the antibiotic siomycin A strongly impaired cell viability of prostate cancer cells, and may point to a novel therapy approach for a subset of high-risk prostate cancer patients.
Journal of Molecular Medicine 09/2012; · 4.67 Impact Factor
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Petra Massoner,
Angelika Lueking,
Heike Goehler,
Annabel Höpfner,
Axel Kowald,
Karl G Kugler,
Peter Amersdorfer,
Wolfgang Horninger, Georg Bartsch,
Peter Schulz-Knappe,
Helmut Klocker
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ABSTRACT: The currently used prostate cancer serum marker has a low cancer specificity and improved diagnostics are needed. Here we evaluated whether autoantibodies are present in sera of prostate cancer patients and whether they are useful diagnostic markers for prostate cancer.
Sera from 20 prostate cancer patients and 20 healthy controls were incubated on expression clone arrays containing more than 37,000 recombinant human proteins. Functional annotation clustering of the identified autoantigens was performed using the DAVID database. Autoantigens identified in the prostate cancer group were validated on microarrays using sera of 40 prostate cancer patients, 40 patients with elevated PSA levels but prostate cancer negative biopsies (benign disease), and 40 healthy controls.
We detected autoantibodies against 408 different antigens in sera of prostate cancer patients. One hundred seventy-four of these were exclusively detected in the cancer group compared to the healthy control group. Functional annotation clustering revealed an enrichment of RNA-associated, cytoskeleton, and nuclear proteins. The autoantibody panel was validated in serum samples of independent prostate cancer patients. Autoantibody profiles discriminated between prostate cancer patients and benign disease patients with an ROC curve AUC of 0.71. TTLL12, a protein recently described to be over-expressed in prostate cancer, was the highest ranked discrimination autoantigen.
A variety of autoantibodies were identified in sera of prostate cancer patients and provide a first step towards autoantibody diagnostics. Serum autoantibodies reflect the disease and represent valuable tools not only for prostate cancer, but also for other diseases affecting the immune response.
The Prostate 03/2012; 72(4):427-36. · 3.48 Impact Factor
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Martin Kerick,
Melanie Isau,
Bernd Timmermann,
Holger Sültmann,
Ralf Herwig,
Sylvia Krobitsch,
Georg Schaefer,
Irmgard Verdorfer, Georg Bartsch,
Helmut Klocker,
Hans Lehrach,
Michal R Schweiger
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ABSTRACT: Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings.
Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.
We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance.Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations.
The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - in the long term - result in a more reliable prediction of individual cancer therapies.
BMC Medical Genomics 09/2011; 4:68. · 3.69 Impact Factor
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ABSTRACT: To describe two predictive models that predict for prostate cancer on biopsy derived from a large screening population. There are no published predictive models that predict prostate cancer in a screened population.
The patients from the Tyrol screening study of known age, total prostate-specific antigen (PSA) level, digital rectal examination (DRE) findings, prostate volume, and percentage of free PSA, and who underwent an initial prostate biopsy from January 1992 to June 2004 were included (n = 2271). Multivariate logistic regression models were used to develop the biopsy positivity predictive models: nomogram 1, age, DRE, and total PSA; and nomogram 2, age, DRE, total PSA, and percentage of free PSA. The predictive accuracy of the models was assessed in terms of discrimination and calibration. External validation of the nomograms was performed using a urologically referred population of patients who underwent prostate biopsy (n = 599).
Both nomograms were well-calibrated internally and externally and discriminated well between patients with positive and negative biopsy findings for both the European and U.S. cohorts (model 2 better than model 1).
Our nomogram with age, total PSA, and DRE had good predictive ability to differentiate between screened patients with cancer on the initial prostate biopsy and those without. Adding the percentage of free PSA improves this predictive power further. These models might aid in clinical decision making regarding the need for biopsy in both European and U.S. populations.
Urology 08/2011; 78(4):924-9. · 2.43 Impact Factor
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ABSTRACT: The objective of this study was to update an in-depth analysis of the time trend for prostate cancer (PCA) mortality in the population of Tyrol by 5 years, namely to 2008. In Tyrol, prostate-specific antigen (PSA) tests were introduced in 1988/89; more than three-quarters of all men in the age group 45-74 had at least one PSA test in the past decade.
We applied the same model as in a previous publication, i.e., an age-period-cohort model using Poisson regression, to the mortality data covering more than three decades from 1970 to 2008.
For Tyrol from 2004 to 2008 in the age group 60+ period terms show a significant reduction in prostate cancer mortality with a risk ratio of 0.70 (95% confidence interval 0.57, 0.87) for Tyrol, and for Austria excluding Tyrol a moderate reduction with a risk ratio of 0.92 (95% confidence interval 0.87, 0.97), each compared to the mortality rate in the period 1989-1993.
This update strengthens our previously published results, namely that PSA testing offered to a population at no charge can reduce prostate cancer mortality. The extent of mortality reduction is in line with that reported in the other recent publications. However, our data do not permit us to fully assess the harms associated with PCA screening, and no recommendation for PSA screening can be made without a careful evaluation of overdiagnosis and overtreatment.
International Journal of Public Health 06/2011; 57(1):57-62. · 2.54 Impact Factor
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ABSTRACT: Prostate cancer has become one of the most common malignancies worldwide. Morphological and histomorphological evaluation of this disease is a well established technique for the cancer classification and has remained relatively unchanged since several decades, although it remains a time consuming and subjective technique, with unsatisfactory levels of inter- and intra-observer discrepancy. Novel approaches for histological recognition are necessary to identify and to investigate cancer in detail. Fourier transform infrared (FTIR) spectroscopic imaging has become an essential tool for the detection, identification and characterization of the molecular components of biological processes, such as those responsible for the dynamic properties of cancer progression. Major advantage of this new technique is the acquisition of local molecular expression profiles while maintaining the topographic integrity of the tissue and avoiding time-consuming extraction, purification and separation steps. By using this method it is possible to investigate the spatial distribution of proteins, lipids, carbohydrates, cholesterols, nucleic acids, phospholipids and small molecules within biological systems by in situ analysis of tissue sections. We applied this technique on prostate cancer patients radical prostatectomy specimens in order to develop new tools for histomorphological analysis and the characterization of snap frozen prostate cancer tissues. As a first step, an optimization of sample preparation, tissue section thickness and IR slide material was performed. Special preparation methods for FTIR imaging are the essential requirements to maintain the spatial arrangement of compounds and avoid delocalization and degradation of the analytes. Subsequently, selected cancer samples were characterized with the prior optimized parameters and analyzed by univariate and cluster analysis. For the interpretation and calibration of the system we correlated the FTIR-images with the histopathological information. With this method it is possible to distinguish between cancer and noncancer areas within a prostate cancer tissue with a resolution of 6.25 μm × 6.25 μm on frozen sections.
Molecular BioSystems 11/2010; 6(11):2287-95. · 3.53 Impact Factor
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ABSTRACT: • To evaluate the success of endoscopic dextranomer/hyaluronic acid copolymer (DHAC) application in the treatment of patients with recurrent urinary tract infections (UTIs) and vesico-ureteric reflux (VUR) into the transplanted graft after renal transplantation.
• Between January 2008 and April 2009, 19 patients with recurrent UTIs presented VUR proven by voiding cystourethrography. • To correct VUR of the transplanted ureter, DHAC was injected endoscopically using hydrodistention technique. • Pre- and postoperative serum creatinine levels, the number of pre- and postoperative UTIs, postoperative complications and reflux resolution rate were recorded. The mean follow-up was 6.5 months.
• The average number of UTIs was reduced significantly from 4.89 (range 2-14) to 1.31 (range 0-4) on pre- and postoperative follow-up, respectively, of 6 months (P < 0.001). The success rate increased from 57.9% after the first injection to 78.9% after the second injection. • The remaining four patients with residual VUR received long-term low dose antibiotic prophylaxis. In total, two (10.5%) patients developed increasing creatinine levels postoperatively as a result of distal ureteral obstruction, and temporary urinary drainage was necessary in both patients.
• DHAC appears to be an efficient and minimal invasive method for treating VUR after renal transplantation with respect to short-term success. • Further investigation with a larger group of patients and longer follow-up is needed to evaluate the prolonged effect, as well as any potential side effects.
BJU International 11/2010; 107(12):1967-72. · 2.84 Impact Factor
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ABSTRACT: Novel markers for prostate cancer (PCa) detection are needed. Total prostate-specific antigen (tPSA) and percent free prostate-specific antigen (%fPSA=tPSA/fPSA) lack diagnostic specificity.
To evaluate the use of prostate-specific antigen (PSA) isoforms p2PSA and benign prostatic hyperplasia-associated PSA (BPHA).
Our study included 405 serum samples from the Rotterdam arm of the European Randomised Study of Screening for Prostate Cancer and 351 samples from the Urology Department of Innsbruck Medical University.
BPHA, tPSA, fPSA, and p2PSA levels were measured by Beckman-Coulter Access Immunoassay. In addition, the Beckman Coulter Prostate Health Index was calculated: phi=(p2PSA/fPSA)×√(tPSA).
The p2PSA and phi levels differed significantly between men with and without PCa. No difference in BPHA levels was observed. The highest PCa predictive value in both cohorts was achieved by phi with areas under the curve (AUCs) of 0.750 and 0.709, a significant increase compared to tPSA (AUC: 0.585 and 0.534) and %fPSA (AUC: 0.675 and 0.576). Also, %p2PSA (p2PSA/fPSA) showed significantly higher AUCs compared to tPSA and %fPSA (AUC: 0.716 and 0.695, respectively). At 95% and 90% sensitivity, the specificities of phi were 23% and 31% compared to 10% and 8% for tPSA, respectively. In both cohorts, multivariate analysis showed a significant increase in PCa predictive value after addition of p2PSA to a model consisting of tPSA and fPSA (increase in AUC from 0.675 to 0.755 and from 0.581 to 0.697, respectively). Additionally, the specificity at 95% sensitivity increased from 8% to 24% and 7% to 23%, respectively. Furthermore, %p2PSA, phi, and the model consisting of tPSA and fPSA with or without the addition of p2PSA missed the least of the tumours with a biopsy or pathologic Gleason score ≥7 at 95% and 90% sensitivity.
This study shows significant increases in PCa predictive value and specificity of phi and %p2PSA compared to tPSA and %fPSA. p2PSA has limited additional value in identifying aggressive PCa (Gleason score ≥7).
European urology 02/2010; 57(6):921-7. · 7.67 Impact Factor
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BJU International 11/2009; 104(9 Pt B):1376-80. · 2.84 Impact Factor
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C Shad Thaxton,
Robert Elghanian,
Audrey D Thomas,
Savka I Stoeva,
Jae-Seung Lee,
Norm D Smith,
Anthony J Schaeffer,
Helmut Klocker,
Wolfgang Horninger, Georg Bartsch,
Chad A Mirkin
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ABSTRACT: We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is approximately 300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies.
Proceedings of the National Academy of Sciences 11/2009; 106(44):18437-42. · 9.68 Impact Factor
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ABSTRACT: To compare outcomes of patients with asynchronous tumours detected before and after the introduction of scrotal ultrasonography (SUS) during routine follow-up examinations.
Since January 2001 SUS was also used during the follow-up of patients with testicular cancer. A series of 16 consecutive patients with asynchronous bilateral testicular tumours diagnosed while still complying with routine follow up investigations were identified and divided into two groups; group A was diagnosed by palpation only, before 2001, and group B was diagnosed after 2000. The groups were compared statistically for the interval between asynchronous tumours, clinical stage, tumour diameter at the time of diagnosis and rate of testis-sparing surgery.
All tumours in group A were diagnosed by palpation, but only two in group B were palpable at the time of diagnosis. The mean tumour diameter was statistically significantly smaller in group B (1.2 cm) than in group A (2.68 cm); testis-sparing surgery was used in all of group B and only three patients in group A. After organ-sparing surgery all patients had normal testosterone levels. All patients after organ-sparing surgery had adjuvant scrotal radiotherapy because of germ cell tumour, and no patient had a local recurrence.
Our data indicate that using SUS for the remaining testicle in routine follow-up visits of patients with testicular cancer leads to the earlier detection of smaller tumours and, consequently, a higher rate of organ preservation. The maintenance of physiological endocrine function might finally result in a better quality of life.
BJU International 09/2009; 105(8):1118-20. · 2.84 Impact Factor
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ABSTRACT: Abstract
Background
Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer.
Results
Using 52 microdissected cell populations of low- and high-risk prostate tumors, we identified via global cDNA microarrays analysis almost 1200 genes being differentially expressed among these groups. These genes were analyzed by statistical, pathway and gene enrichment methods. Twenty selected candidate genes were verified by quantitative real time PCR and immunohistochemistry. In concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic role of this gene in PC3 prostate cancer cells.
Conclusions
Our analyses provide deeper insights into the molecular changes occurring during prostate cancer progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of prostate cancer and therefore provide novel potential biomarkers.
Molecular Cancer. 01/2009;
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ABSTRACT: Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer.
Using 52 microdissected cell populations of low- and high-risk prostate tumors, we identified via global cDNA microarrays analysis almost 1200 genes being differentially expressed among these groups. These genes were analyzed by statistical, pathway and gene enrichment methods. Twenty selected candidate genes were verified by quantitative real time PCR and immunohistochemistry. In concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic role of this gene in PC3 prostate cancer cells.
Our analyses provide deeper insights into the molecular changes occurring during prostate cancer progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of prostate cancer and therefore provide novel potential biomarkers.
Molecular Cancer 01/2009; 8:130. · 3.99 Impact Factor
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ABSTRACT: To report our surgical technique of robotic-assisted laparoscopic partial nephrectomy (RLPN) for renal tumours of <7 cm and present their clinical outcomes, as minimally invasive PN is an increasingly viable option for small renal tumours.
From July 2005 to December 2006, 20 consecutive patients (mean age 58.2 years, sd 7.9) had RLPN and a follow-up of > or =1 year, all surgery being undertaken by one surgeon. All cases were elective except in one patient with a solitary kidney. We used the three-arm da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA) in a four-port, transperitoneal approach. Transient vascular occlusion was applied in all cases using a tourniquet technique. The tumour was excised with a 5-mm margin using cold-cut scissors, and the margins were assessed by frozen sections. The specimen was placed in an impervious bag for subsequent removal via the camera port. Under direct vision, we repaired all pelvicalyceal system entries with absorbable sutures. After the entire tumour bed surface was lined with Floseal (Baxter Healthcare, Deerfield, IL, ISA) the capsule/parenchyma was closed with running suture, reinforced by haemostatic clips.
The mean (sd) operative and warm ischaemia times were 82.7 (17.0) and 21.7 (2.4) min, respectively, and the mean estimated blood loss was 189 (32) mL. There were no intraoperative complications or conversion to open surgery. There was also no bleeding after surgery, perinephric haematoma or urinary leakage. The mean (sd) tumour size was 30.2 (2.4) mm, while margins were negative in all cases of malignancy. At the 1-year follow-up there was no local recurrence, renal functional deterioration or late surgical complications.
Our RLPN technique is a safe and feasible option for small renal tumours. Reproducible technique and good team co-ordination are pivotal for obtaining good oncological and surgical outcomes.
BJU International 11/2008; 103(5):663-8. · 2.84 Impact Factor
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ABSTRACT: Surgical haemostatic agents have been increasingly applied for the control of bleeding, and have excellent potential in laparoscopy. Several factors are important when evaluating the use of sealants. We present a brief overview of the history, composition and mechanism of action of sealants, together with a report on experimental studies and clinical experience with haemostatic sealants. We searched for reports on haemostatic agents and their use in renal parenchymal haemostasis; 15 animal models studies and 11 papers on clinical experience were included. The development of haemostatic agents and instruments is allowing the wider diffusion of challenging procedures. Several experimental animal studies have shown the efficacy and safety of sealants for haemostasis during nephron-sparing surgery. Clinical studies confirm the effectiveness of synthetic or fibrin glue, in particular during laparoscopic surgery. Sealants are effective and safe topical agents to control bleeding during nephron-sparing surgery. They should not be viewed as an alternative, but as complementary agents to be used to improve surgical outcomes. Further prospective studies are necessary to validate their role in relation to other haemostatic support techniques.
BJU International 11/2008; 102(11):1502-8. · 2.84 Impact Factor
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ABSTRACT: To develop a logistic regression-based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate-specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone.
We retrospectively analysed the data of 1280 men who had a biopsy while enrolled in a prospective, multicentre clinical trial. Of these, 1108 had all relevant clinical and pathological data available, and no previous diagnosis of prostate cancer. Using the PCPT risk calculator, we calculated the risks of prostate cancer and of high-grade disease (Gleason score > or =7) for each man. Receiver operating characteristic (ROC) curves for the risk calculator, PSA level and the novel regression-based model were compared.
Prostate cancer was detected in 394 (35.6%) men, and 155 (14.0%) had Gleason > or =7 disease. For cancer prediction, the area under the ROC curve (AUC) for the risk calculator was 66.7%, statistically greater than the AUC for PSA level of 61.9% (P < 0.001). For predicting high-grade disease, the AUCs were 74.1% and 70.7% for the risk calculator and PSA level, respectively (P = 0.024). The AUCs increased to 71.2% (P < 0.001) and 78.7% (P = 0.001) for detection and high-grade disease, respectively, with our novel regression-based models.
ROC analyses show that the PCPT risk calculator modestly improves the performance of PSA level alone in predicting an individual's risk of prostate cancer or high-grade disease on biopsy. This predictive tool might be enhanced by including percentage free PSA and the number of biopsy cores.
BJU International 11/2008; 103(5):609-14. · 2.84 Impact Factor
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ABSTRACT: To investigate the behaviour of donor myoblasts at the vesico-ureteric junction (VUJ) and to evaluate their potential as an autologous bulking agent, as myoblast transplantation has been shown to regenerate damaged or degenerated tissue, and it was postulated that they could be used to treat vesico-ureteric reflux.
Muscle biopsies were obtained from the lower limb muscles of 10 pigs. The quality of the cells was evaluated by electrophysiological and immunohistochemical tests. The cell membranes of myoblasts were labelled with PKH26, a fluorescent dye. Six weeks after taking of the muscle biopsies all pigs underwent cell transplantation; 30 x 10(6) cells suspended in transplantation medium (in 1-mL syringes) were injected at the VUJ, into the proximal urethra and the rhabdosphincter. At the VUJ volumes of 1 mL were injected, whereas in the urethra and rhabdosphincter small cell depots (0.1 mL) were injected. All the pigs were killed 8 weeks later, and the myoblasts and newly formed myofibres were identified using fluorescence microscopy, with a histological evaluation and investigation of potential local inflammatory reaction.
Two to three intact layers of autologous myoblasts were found in the outer aspects of the large cell depots in the VUJ. Immunohistochemistry further showed that the myoblasts were only viable at these outermost borders of the large bulking areas, whereas necrosis with red fluorescent cell detritus was visible in the remaining central aspects of the large bulk of cells. By contrast, cells survived and formed myotubes in the wall of the proximal urethra and the rhabdosphincter where the small cell depots had been injected.
In small depots, transplanted autologous myoblasts can survive and differentiate into myofibres, while in a large bulk of cells the vast majority of cells become necrotic. The present results show that myoblasts cannot be used for augmentation of large volumes of tissue or as a bulking agent.
BJU International 10/2008; 102(11):1731-6. · 2.84 Impact Factor
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ABSTRACT: Prostate cancer is the most prevalent tumor in males and its incidence is expected to increase as the population ages. Prostate cancer is treatable by excision if detected at an early enough stage. The challenges of early diagnosis require the discovery of novel biomarkers and tools for prostate cancer management.
We developed a novel feature selection algorithm termed as associative voting (AV) for identifying biomarker candidates in prostate cancer data measured via targeted metabolite profiling MS/MS analysis. We benchmarked our algorithm against two standard entropy-based and correlation-based feature selection methods [Information Gain (IG) and ReliefF (RF)] and observed that, on a variety of classification tasks in prostate cancer diagnosis, our algorithm identified subsets of biomarker candidates that are both smaller and show higher discriminatory power than the subsets identified by IG and RF. A literature study confirms that the highest ranked biomarker candidates identified by AV have independently been identified as important factors in prostate cancer development.
The algorithm can be downloaded from the following http://biomed.umit.at/page.cfm?pageid=516.
Bioinformatics 10/2008; 24(24):2908-14. · 5.47 Impact Factor
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ABSTRACT: Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors.
Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence.
All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-beta stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors.
We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma--particularly reactivated stroma--is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions.
The Prostate 09/2008; 68(11):1165-78. · 3.48 Impact Factor
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ABSTRACT: We describe our technique of achieving transient vascular occlusion utilizing Hem-o-Lok clips during robotassisted laparoscopic partial nephrectomy (RLPN) A once-folded vascular loop is threaded through a 2-cm feeding tube. After passing around the renal vessel, its tail goes through the U-loop, creating a tourniquet. Vascular occlusion begins when the tube slides towards the vessel and a Hem-o-Lok clip is applied on the vascular loop next to the exposed end of the tube. When no longer needed, it is released. Since July 2006, 25 patients underwent RLPN utilizing this technique, which required <15 seconds to deploy for any vessel size. There were eight patients with multiple vessels. The mean operative time was 82.6 minutes, and the mean warm ischemia time was 22 minutes (range 17-27 minutes). There were no cases of intraoperative or postoperative bleeding. The technique is simple, inexpensive, and applicable to multiple vessels. It is a viable alternative to standard vascular occlusion techniques, such as laparoscopic bulldog or Satinsky clamps.
Journal of endourology / Endourological Society 09/2008; 22(8):1677-80. · 1.75 Impact Factor
