Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy. Materials and Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series. Multivariable Cox regression models including substaged pT3 established clinicopathological features, and the expression of the predictive immunohistochemical feature E-cad was used to identify independent predictors on progression-free (PFS), cancer-specific (CSS) and overall survival (OS), respectively. Results: No significant differences were found addressing clinicopathological data and substaged pT3. In multivariable Cox regression models, lymph node involvement was an independent predictor for PFS (p < 0.001), CSS (p < 0.001) and OS (p = 0.002), respectively. Lymphovascular invasion (LVI) significantly influenced PFS (p = 0.016). ASA score 3/4 independently predicted CSS (p = 0.049) and OS (p = 0.032). Neither pT3 substages nor E-cad expression were significant prognosticators for survival. Conclusions: In pT3 UCB patients with ASA 3/4, positive lymph node status and/or presence of LVI, administration of chemotherapy should be considered due to the high risk of poor oncological outcome. The immunohistochemical marker E-cad was not an independent predictor

Disease proteomics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62680/1/nature01514.pd

Enzymatic Fuel Cells Solely Supplied with Unpurified Cellbiose Dehydrogenase and Laccase in Microorganism's Culture Supernatants

Enzymatic electrodes have great potential for catalysing the direct conversion of chemical compounds into electricity with the use of redox enzymes. However, expensive and time-consuming enzyme purification and the frequent need to add mediators are considered as drawbacks of enzymatic electrodes. We report a biofuel cell at pH 5, supplied with the unpurified enzymes laccase and cellobiose dehydrogenase (CDH) in crude culture supernatant, without the further addition of mediators. A maximum power output of 6.2±1.2 μW cm−2 was achieved by using supernatants containing laccase from Trametes versicolor (2.84 UmL−1) and CDH (0.90 UmL−1) from a recombinant yeast Yarrowia lipolytica YPC4. In comparison, the supply of purified enzymes (laccase: 2.40 UmL−1, CDH: 0.15 UmL−1) in a buffer solution yielded only about a twofold higher power density. Our results demonstrate the feasibility of using unpurified laccase and CDH in an enzymatic biofuel cell, which can simplify its construction and operation

Overcoming Bottlenecks of Enzymatic Biofuel Cell Cathodes: Crude Fungal Culture Supernatant Can Help to Extend Lifetime and Reduce Cost

Enzymatic biofuel cells (BFCs) show great potential for the direct conversion of biochemically stored energy from renewable biomass resources into electricity. However, enzyme purification is time-consuming and expensive. Furthermore, the long-term use of enzymatic BFCs is hindered by enzyme degradation, which limits their lifetime to only a few weeks. We show, for the first time, that crude culture supernatant from enzyme-secreting micro-organisms (Trametes versicolor) can be used without further treatment to supply the enzyme laccase to the cathode of a mediatorless BFC. Polarization curves show that there is no significant difference in the cathode performance when using crude supernatant that contains laccase compared to purified laccase in culture medium or buffer solution. Furthermore, we demonstrate that the oxygen reduction activity of this enzymatic cathode can be sustained over a period of at least 120 days by periodic resupply of crude culture supernatant. This is more than five times longer than control cathodes without the resupply of culture supernatant. During the operation period of 120 days, no progressive loss of potential is observed, which suggests that significantly longer lifetimes than shown in this work may be possible. Our results demonstrate the possibility to establish simple, cost efficient, and mediatorless enzymatic BFC cathodes that do not require expensive enzyme purification procedures. Furthermore, they show the feasibility of an enzymatic BFC with an extended lifetime, in which self-replicating microorganisms provide the electrode with catalytically active enzymes in a continuous or periodic manner

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC.</p> <p>Method</p> <p>AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test.</p> <p>Results</p> <p>59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025).</p> <p>Conclusions</p> <p>Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.</p