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  • 1
    Language: English
    In: Expert Review of Anticancer Therapy, 01 June 2011, Vol.11(6), pp.941-948
    Description: Radical cystectomy represents the gold-standard of treatment for invasive bladder cancer. Following cystectomy, various options for urinary diversion may be offered to patients. This article represents an overview of the history of urinary diversion, explains the current selection criteria used at one of the most experienced bladder cancer centers worldwide, and provides an update on the current understanding of continence mechanisms. Furthermore, we review the current literature on quality of life for patients with different forms of urinary diversion. Excellent functional results can be achieved with continent forms of urinary diversion. It is important to consider the relative and absolute contraindications when choosing any form of urinary diversion. Proper patient selection and thorough standardized preoperative counseling is critical in achieving optimal results.
    Keywords: Continent Cutaneous Diversion ; Ileal Conduit ; Orthotopic Ileal Neobladder ; Radical Cystectomy ; Quality of Life ; Urinary Diversion ; Medicine
    ISSN: 1473-7140
    E-ISSN: 1744-8328
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  • 2
    Language: English
    In: BJU international, June 2011, Vol.107(12), pp.1967-72
    Description: • 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.
    Keywords: Ureteroscopy ; Biocompatible Materials -- Administration & Dosage ; Dextrans -- Administration & Dosage ; Hyaluronic Acid -- Administration & Dosage ; Kidney Transplantation -- Adverse Effects ; Urinary Tract Infections -- Prevention & Control ; Vesico-Ureteral Reflux -- Therapy
    ISSN: 14644096
    E-ISSN: 1464-410X
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  • 3
    Language: English
    In: World Journal of Urology, 2014, Vol.32(1), pp.221-228
    Description: Byline: Georg Bartsch (1,2), Siamak Daneshmand (1), Eila C. Skinner (3), Sumeet Syan (1), Donald G. Skinner (1), David F. Penson (4) Keywords: Female; Bladder cancer; Urinary diversion; Neobladder; Urinary function Abstract: Purpose The ratio between orthotopic and non-orthotopic diversions in women is far lower than in male patients. Data on urinary function in female patients with neobladders are therefore sparse. Methods We investigated the urinary function of female neobladder patients utilizing the Bladder Cancer Index, a validated and reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we tried to identify preoperative factors that may influence functional results. All living female patients with an orthotopic neobladder (N = 82) from the University of Southern California Bladder Cancer Database were sent a questionnaire including the University of Michigan Bladder Cancer Index. Univariate analyses were performed using the Kruskal--Wallis test followed by a multivariate stepwise regression model. Results Fifty-six patients (68.3 %) responded and were included in the analysis. Thirty-five (62.5 %) of these patients had to catheterize their neobladder to a certain amount, while 25 patients (44.6 %) depend on catheterization to empty their neobladder. Univariate analyses showed that patient age (〉65 years) was the only variable associated with a statistically significant lower rate of neobladder catheterization. Better urinary bother scores were associated with organ-confined disease (p = 0.038) and education level (p = 0.01). However, these variables were not significant in a multivariate stepwise linear regression model. Conclusion Considerably more women require urinary catheterization to void than previously reported. In this study, representing the largest investigated cohort in this topic, we were unable to identify any predictors of this outcome or any other urinary HRQOL in this cohort. Author Affiliation: (1) Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA, 90089, USA (2) Department of Urology, Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany (3) Department of Urology, Stanford University, 300 Pasteur Dr Suite S287, Palo Alto, Stanford, CA, 94305, USA (4) Department of Urologic Surgery, Center of Surgical Quality and Outcomes Research, Vanderbilt University, 2525 West End Ave Suite 600, Nashville, TN, 37203, USA Article History: Registration Date: 25/11/2013 Received Date: 25/10/2013 Accepted Date: 25/11/2013 Online Date: 07/12/2013
    Keywords: Female ; Bladder cancer ; Urinary diversion ; Neobladder ; Urinary function
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 4
    Language: English
    In: The Journal of Urology, 2010, Vol.183(4), pp.e654-e654
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 5
    Language: English
    In: PLoS ONE, August 19, 2014, Vol.9(8)
    Description: Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
    Keywords: DNA Polymerases – Growth ; Proteins – Growth
    ISSN: 1932-6203
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(8), p.e105590
    Description: Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    In: PLoS ONE, 2013, Vol.8(12)
    Description: Scientists who are members of an editorial board have been accused of preferentially publishing their scientific work in the journal where they serve as editor. Reputation and academic standing do depend on an uninterrupted flow of published scientific work and the question does arise as to whether publication mainly occurs in the self-edited journal. This investigation was designed to determine whether editorial board members of five urological journals were more likely to publish their research reports in their own rather than in other journals. A retrospective analysis was conducted for all original reports published from 2001–2010 by 65 editorial board members nominated to the boards of five impact leading urologic journals in 2006. Publications before editorial board membership, 2001–2005, and publications within the period of time as an editorial board member, 2006–2010, were identified. The impact factors of the journals were also recorded over the time period 2001–2010 to see whether a change in impact factor correlated with publication locality. In the five journals as a whole, scientific work was not preferentially published in the journal in which the scientists served as editor. However, significant heterogeneity among the journals was evident. One journal showed a significant increase in the amount of published papers in the ‘own’ journal after assumption of editorship, three journals showed no change and one journal showed a highly significant decrease in publishing in the ‘own’ journal after assumption of editorship.
    Keywords: Research Article ; Science Policy
    E-ISSN: 1932-6203
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  • 8
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(1), p.e53100
    Description: Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into "responders" and "non-responders" to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 9
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 2012, Vol.109(17), pp.6686-6691
    Description: Copy number variants (CNVs) are a recently recognized class of human germ line polymorphisms and are associated with a variety of human diseases, including cancer. Because of the strong genetic influence on prostate cancer, we sought to identify functionally active CNVs associated with susceptibility of this cancer type. We queried low-frequency biallelic CNVs from 1,903 men of Caucasian origin enrolled in the Tyrol Prostate Specific Antigen Screening Cohort and discovered two CNVs strongly associated with prostate cancer risk. The first risk locus (P = 7.7 x 10–4, odds ratio = 2.78) maps to 15q21.3 and overlaps a noncoding enhancer element that contains multiple activator protein 1 (AP-1) transcription factor binding sites. Chromosome conformation capture (Hi-C) data suggested direct cis-interactions with distant genes. The second risk locus (P = 2.6 x 10–3, odds ratio = 4.8) maps to the α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase C (MGAT4C) gene on 12q21.31. In vitro cell-line assays found this gene to significantly modulate cell proliferation and migration in both benign and cancer prostate cells. Furthermore, MGAT4C was significantly overexpressed in metastatic versus localized prostate cancer. These two risk associations were replicated in an independent PSA-screened cohort of 800 men (15q21.3, combined P = 0.006; 12q21.31, combined P = 0.026). These findings establish noncoding and coding germ line CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression. ; p. 6686-6691.
    Keywords: Binding Sites ; Genes ; Metastasis ; Transcription Factors ; Loci ; Humans ; Prostatic Neoplasms ; Risk ; Cell Proliferation ; Germ Cells ; Screening ; Enhancer Elements ; Human Diseases ; Odds Ratio ; Men ; Risk Factors ; Antigens
    ISSN: 0027-8424
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  • 10
    Language: English
    In: Expert Review of Anticancer Therapy, 01 December 2010, Vol.10(12), pp.1945-1954
    Description: Despite being a common cancer worldwide, management of transitional cell carcinoma of the bladder currently relies primarily on clinical staging and histopathologic parameters. Assaying alterations in molecular pathways can contribute valuable information that can accurately predict outcome and chemotherapeutic response in individual patients with bladder cancer. Medium- to high-throughput gene-expression profiling technologies are now allowing multiplexed assessment of alterations responsible for the genesis and progression of bladder tumors. These investigations employ global or pathway-based approaches to define molecular signatures that can predict prognosis independent of traditional clinical performance metrics. Prognostic panels generated using these strategies can also elucidate the biology of tumor progression and identify potential therapeutic targets.
    Keywords: Gene-Expression Profiling ; Global Approach ; Microarray ; Multimarker Analysis ; Pathway-Specific Approach ; Urothelial Carcinoma ; Medicine
    ISSN: 1473-7140
    E-ISSN: 1744-8328
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