Associations of margin status with overall and cancer specific survival were not statistically significant. Of 1,397 patients 69 (4.9%) experienced upper tract recurrence at a median of 3.1 years. Positive initial margin status and final margin

status were associated with upper tract recurrence (p < 0.001).

Conclusions: Patients with positive ureteral margins at cystectomy are at increased risk for upper tract recurrence. With a serial sectioning strategy most positive initial margins can be converted to negative final margins. Patients who undergo conversion to a negative final margin with serial sectioning are at decreased risk for upper tract disease.”
“Cholinergic neurons rely on the sodium-dependent choline transporter CHT to provide choline see more for synthesis of acetylcholine. CHT cycles between cell surface and subcellular organelles, but little is known about selleck chemicals llc regulation of this trafficking. We hypothesized that activation of protein kinase C with phorbol ester modulates choline uptake by altering the rate of CHT internalization from or delivery to the plasma membrane. Using SH-SY5Y cells that stably

express rat CHT, we found that exposure of cells to phorbol ester for 2 or 5 min significantly increased choline uptake, whereas longer treatment had no effect. Kinetic analysis revealed that 5 min phorbol ester treatment significantly enhanced V of choline uptake, but had no effect on K, for solute binding. Cell-surface biotinylation assays showed that plasma membrane levels of CHT protein were enhanced following 5 min phorbol ester treatment; this was blocked by protein kinase C inhibitor bisindolylmaleimide-I. Moreover, CHT internalization was decreased and delivery of CHT to plasma membrane was increased by phorbol ester. Our results suggest that treatment of neural cells with the protein kinase C activator phorbol ester rapidly and transiently increases cell surface CHT levels and this corresponds with enhanced choline uptake activity which may play an important role in replenishing acetylcholine stores following its release by depolarization. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: We describe cancer

specific outcomes in patients with pT4 bladder urothelial carcinoma at radical cystectomy in a large international Cytoskeletal Signaling inhibitor Cohort.

Materials and Methods: We reviewed the records of 4,257 patients treated with radical cystectomy for bladder urothelial carcinoma at 12 centers. No patient received any preoperative systemic chemotherapy or radiotherapy.

Results: Of the 4,257 patients 583 (14%) had pT4 bladder urothelial carcinoma, of whom 83.7% were male, 85.2% had substage pT4a disease, 24.9% had positive soft tissue surgical margins, 57.8% had lymphovascular invasion and 53.5% had lymph node metastasis. Median followup was 55.0 months. Overall estimated 5-year recurrence-free and cancer specific survival was 29% (95% Cl 22-32) and 31% (95% Cl 25-36), respectively.