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  • 2017  (11)
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  • 2017  (11)
  • 1
    Language: English
    In: Translational andrology and urology, December 2017, Vol.6(6), pp.1067-1080
    Description: Radical cystectomy (RC) is the standard of care treatment of localized muscle-invasive bladder cancer (BC). However, about 50% of patients develop metastases within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival (OS) in patients with muscle-invasive BC. Pathological response to neoadjuvant treatment is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from chemotherapy. The identification of reliable biomarkers enabling clinicians to identify patients who might benefit from chemotherapy is a very important clinical task. An identification tool could lead to individualized therapy, optimizing response rates. In addition, unnecessary treatment with chemotherapy which potentially leads to a loss of quality of life and which might also might cause a delay of cystectomy in a neoadjuvant setting could be avoided. The present review aims to summarize and discuss the current literature on biomarkers for the prediction of response to systemic therapy in muscle-invasive BC. Tremendous efforts in genetic and molecular characterization have led to the identification of predictive candidate biomarkers in urothelial carcinoma (UC), although prospective validation is pending. Ongoing clinical trials examining the benefit of individual therapies in UC of the bladder (UCB) by molecular patient selection hold promise to shed light on this question.
    Keywords: Bladder Cancer (Bc) ; Biomarker ; Chemotherapy ; Immunotherapy ; Urothelial Carcinoma (Uc)
    ISSN: 2223-4691
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  • 2
    Language: English
    In: Central European journal of urology, 2017, Vol.70(3), pp.275-279
    Description: Vasectomy is the simplest, safest, and most effective form of definitive fertility control in men [1]. Vasectomy is used for 10% of contraception worldwide but only for 2% in Germany [2]. The aim of this study was to investigate the impact of vasectomy on the sexual satisfaction of sterilized men and their partners. Vasectomized men and their partners were surveyed by means of the IIEF (International Index for Erectile Function) and the FSFI (Female Sexual Function Index) questionnaires. A total of 294 couples were surveyed; 90 men answered the IIEF, and 74 women answered the FSFI. The results of the questionnaires were compared to a historical comparison group. The men were also surveyed with a not validated questionnaire, which was returned by 95 men. The two-sample t-test for independent samples, the chi-squared test, and the Wilcoxon-Mann-Whitney test were carried out. The vasectomized men had significantly better results than the healthy historical comparison group in the IIEF domains of erectile function, orgasm, sexual desire, and intercourse satisfaction. For the female partners of the sterilized men, there were almost no significant differences in any questions of the FSFI in comparison to the control group. A significant difference was observed only in the domain 'arousal'. Vasectomy does not have a negative impact on the sexual satisfaction of the affected couples. In fact, sexual satisfaction improved for the sterilized men, while the satisfaction of the women was not reduced by the vasectomy.
    Keywords: Fsf ; Iief ; Sexual Satisfaction ; Vasectomy
    ISSN: 2080-4806
    E-ISSN: 20804873
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  • 3
    In: Vallo, Stefan and Rutz, Jochen and Kautsch, Miriam and Winkelmann, Ria and Michaelis, Martin and Wezel, Felix and Bartsch, Georg and Haferkamp, Axel and Rothweiler, Florian and Blaheta, Roman A and Cinatl, Jindrich (2017) Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines. Oncology letters, 14 (5). pp. 5513-5518.
    Description: Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer.
    Keywords: RM Therapeutics. Pharmacology
    ISSN: 1792-1074
    Source: University of Kent
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  • 4
    Language: English
    In: Scandinavian Journal of Urology, 04 July 2017, Vol.51(4), pp.342-344
    Keywords: Angiomyolipoma ; Flank Pain ; Kidney ; Selective Arterial Embolization ; Ureteral Stone ; Medicine
    ISSN: 2168-1805
    E-ISSN: 2168-1813
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  • 5
    Language: English
    In: Journal of Cancer Education, 2017, Vol.32(1), pp.135-140
    Description: Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term “prostate cancer.” After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients’ access of health information online.
    Keywords: Prostatic neoplasms ; Internet ; Consumer health information ; Health services research ; Decision making
    ISSN: 0885-8195
    E-ISSN: 1543-0154
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  • 6
    In: Vallo, Stefan and K�pp, Raoul and Michaelis, Martin and Rothweiler, Florian and Bartsch, Georg and Brandt, Maximilian and Gust, Kilian and Wezel, Felix and Blaheta, Roman and Haferkamp, Axel and Cinatl, Jindrich (2017) Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells. Oncology Letters, 13 (6).
    Description: Nanoparticle albumin‑bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro‑apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'‑triphosphate‑binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab‑paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC‑SUP, as well as sub‑lines with acquired resistance against gemcitabine (T24rGEMCI20 and TCC‑SUPrGEMCI20) and vinblastine (T24rVBL20 and TCC‑SUPrVBL20) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1‑inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab‑paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab‑paclitaxel and paclitaxel in the same dose‑dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab‑paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.
    ISSN: 1792-1074
    Source: University of Kent
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  • 7
    Language: English
    In: Oncology Letters, 11/2017, Vol.14(5), pp.5513-5518
    Description: Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo .
    Keywords: Adhesion ; Acquired Resistance ; Cancer Cell Line Collection ; Chemotaxis ; Cisplatin ; Gemcitabine ; Integrin Β1 ; Urothelial Cancer
    ISSN: 1792-1074
    E-ISSN: 1792-1082
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  • 8
    Language: English
    In: Oncology Letters, 06/2017, Vol.13(6), pp.4085-4092
    Description: Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5′-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab-paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC-SUP, as well as sub-lines with acquired resistance against gemcitabine (T24 r GEMCI 20 and TCC-SUP r GEMCI 20 ) and vinblastine (T24 r VBL 20 and TCC-SUP r VBL 20 ) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1-inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab-paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.
    Keywords: Abcb1 ; Acquired Resistance ; Bladder Cancer ; Cabozantinib ; Cancer Cell Line Collection ; Crizotinib ; Nanoparticle Albumin-Bound Paclitaxel
    ISSN: 1792-1074
    E-ISSN: 1792-1082
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  • 9
    Language: English
    In: Clinical Genitourinary Cancer, October 2017, Vol.15(5), pp.e809-e817
    Description: This prospective multicenter study analyzed the effect of hospital and surgeon case volume on perioperative quality of care and short-term complications and mortality in 479 patients undergoing radical cystectomy for bladder cancer. We found that hospital volume might represent an at least equally important factor regarding postoperative complications as the surgeon case volume itself at European tertiary care centers. Case volume has been suggested to affect surgical outcomes in different arrays of procedures. We aimed to delineate the relationship between case volume and surgical outcomes and quality of care criteria of radical cystectomy (RC) in a prospectively collected multicenter cohort. This was a retrospective analysis of a prospectively collected European cohort of patients with bladder cancer treated with RC in 2011. We relied on 479 and 459 eligible patients with available information on hospital case volume and surgeon case volume, respectively. Hospital case volume was divided into tertiles, and surgeon volume was dichotomized according to the median annual number of surgeries performed. Binomial generalized estimating equations controlling for potential known confounders and inter-hospital clustering assessed the independent association of case volume with short-term complications and mortality, as well as the fulfillment of quality of care criteria. The high-volume threshold for hospitals was 45 RCs and, for high-volume surgeons, was 〉 15 cases annually. In adjusted analyses, high hospital volume remained an independent predictor of fewer 30-day (odds ratio, 0.34;  = .002) and 60- to 90-day (odds ratio, 0.41;  = .03) major complications but not of fulfilling quality of care criteria or mortality. No difference between surgeon volume groups was noted for complications, quality of care criteria, or mortality after adjustments. The coordination of care at high-volume hospitals might confer a similar important factor in postoperative outcomes as surgeon case volume in RC. This points to organizational elements in high-volume hospitals that enable them to react more appropriately to adverse events after surgery.
    Keywords: High Volume ; Postoperative Complications ; Quality of Health Care ; Urinary Bladder Neoplasms ; Volume-Outcome Relationship ; Medicine
    ISSN: 1558-7673
    E-ISSN: 1938-0682
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  • 10
    In: Acta Chiropterologica, December 2017, Vol.19(2), pp.347-355
    Description: Noack's round-leaf bat Hipposideros cf. ruber is widely distributed in sub-Saharan Africa. Here, we present some aspects of its ecology from two caves in central Ghana. Our main objective was to assess the nightly and annual flight activity and to examine the influences of ambient temperature on flight activity. We tested the hypothesis that flight activity of the species is concentrated at certain periods of the night and the year using mist-netting data from 2,712 captured bats. We found no evidence for annual fluctuations in flight activity, probably due to no distinct seasonal limitation of food resources, no migration, and the lack of extreme environmental conditions in the study area. Our hypothesis of concentrated nightly flight activity was confirmed for one cave but not for the other. Flight activity was concentrated early in the night (20:00, 21:00 and 22:00 hours) at one cave, possibly to take advantage of locally available early active prey insects, while it was uniformly distributed throughout the night at the other. Lastly, we found a reduction in the flight activity of H. cf. ruber when there was a distinct drop in temperature over the night. We therefore suggest the reduction in flight activity may result from the direct effects of temperature on prey abundance as the bats responded by reducing activity to avoid excessive prey search costs.
    Keywords: Flight Activity ; Hipposideros Cf. Ruber ; Caves ; Insects ; Temperature ; Prey
    ISSN: 1508-1109
    E-ISSN: 17335329
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