We found evidence for acute and prolonged effects of PIP on bladder contractility, which seem to be mediated through TRPV1. Furthermore, we found evidence for involvement of TRPV1 in afferent signaling of mechanical stimuli.

PurposeIn this preclinical study we examined the biodistribution of hypericin formulated as its watersoluble PVP-hypericin complex in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY-27 tumor cells. The results were compared with the biodistribution of hexaminolevulinate (HAL) induced protoporphyrin IX (PpIX). MethodsFreshly prepared PVP-hypericin and HAL solutions were instilled in both normal as well as tumor bearing rat bladders. Following instillation, bladders were removed and snap frozen in liquid nitrogen. Fluorescence of PVP-hypericin or PpIX induced HAL was measured in the bladder layers and quantified using image analysis software. ResultsThe results of these experiments show that PVP-hypericin (30 µM) accumulated about 3.5-fold more in malignant urothelial tissue as compared to normal urothelium, whereas PpIX accumulated to the same extent in malignant and normal urothelium, both after intra-bladder instillation of 8 or 16 mM HAL. Besides, PVP-hypericin and PpIX accumulated selectively in the urothelium with a tumor-to-muscle ratio of 30.6 for PVP-hypericin and 3.7 to 8.3 for 16 and 8 mM HAL, respectively. ConclusionsThis study shows that PVP-hypericin appears to have great potential as a photodynamic agent against non-muscle invasive bladder cancers after intravesical administration, with a limited risk of affecting the deeper layers of the bladder.

No abstract

Polyvinylpyrrolidone (PVP)-hypericin is a potent photosensitizer that is used in the urological clinic to photodiagnose with high-sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differential accumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cell carcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessed using fluorescence image analysis of 5-μm cryostat sections of spheroids that were incubated with PVP-hypericin. The results show that PVP-hypericin accumulated to a much higher extent in T24 spheroids as compared to NHU spheroids, thereby reproducing the clinical situation. Subsequently, spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18J/cm 2 . When using low fluence rates, only minor differences in cell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantial difference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids. It was concluded that further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic for NMIBC, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

A major challenge to urologists with respect to bladder cancer is the high rate of tumor recurrence after transurethral resection (TUR). Implantation of resected tumor cells on traumatized bladder urothelium is believed to be the main cause of tumor recurrence. The aim of this study was to find a safe irrigant fluid and modality that prevents reimplantation of malignant cells during TUR. Therefore, the cytotoxicity and antiadherence effects of polyethylene glycol 400 (PEG400) and PEG4000 were investigated and compared with currently used irrigant fluids, water and 1.5% glycine (G-IF), on the RT112 urothelial cell carcinoma cell line. PEG400 (20%), G-IF, water and to a lesser extent 10% PEG400 and PEG4000 showed dramatic cytotoxic effects, besides exhibiting interesting antiadherence characteristics. The presence of serum proteins did not interfere with the activity of PEG400. In a clonogenic assay, both water and 20% PEG400 showed a better cytotoxic profile than G-IF, and it was found that these two fluids were able to induce a 5-log kill. This study shows that a solution of 20% PEG400 in water is a promising irrigant with antiadhesive and cytotoxic properties, which could be used to prevent tumor cell reimplantation during TUR. The irrigant remains active in the presence of serum proteins, is transparent, inexpensive and possesses an excellent safety profile.