EDTA‐induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

Abstract

Aim:The aim of this study was to determine the effect of intravesical EDTA instillation on the development of intravesically implanted tumor cells in normal mice. Methods: The mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate the amount of normal urothelial cell shedding, and the degree of tumor growth inhibition following intravesical EDTA instillation in comparison with phosphatebuffered saline (PBS) instillation. Results: At 1 h after instillation, the number of urothelial cells aspirated was 500-1000 per PBS-treated mouse and 10 000-20 000 per EDTA-treated mouse (P < 0.00001). The bladder weight, which reflected the effect of the agent on the tumor, was similar in the untreated and PBS-treated mice (105.46 ± 46 mg and 106.2 ± 50 mg, respectively). It was significantly lower in the EDTAtreated mice (80.4 ± 42 mg) (P = 0.0045). Conclusions: Intravesical administration of EDTA results in significant normal and neoplastic urothelial cell shedding. Intravesical irrigation with EDTA may prevent adherence of the malignant cells to the bladder wall following tumor resection.

Mouse orthotopic models for bladder cancer research

“…Complete emptying of the bladder before instillation prevents over-distension of the bladder. As expected, increasing the amount of cancer cells reportedly increases the tumour take rate [11][12][13][14]23]. Shapiro et al [24] reported a higher tumour take rate when more cells were used for implantation, which increase from 30% to > 90% when tumour cells used increased from 2.5 × 10 5 to 1 × 10 6 under similar conditions.…”

“…One of the concerns in any orthotopic bladder cancer model is the success rate of tumour implantation. The rate of tumour 'take' with various models is 30% [10] to 100% (Table 1) [4, [11][12][13][14][15][16][17][18][19][20][21][22]. Poor tumour take results in the waste of valuable time and resources, and can affect the interpretation of study results.…”

“…One approach of orthotopic tumour implantation involves direct injection of tumour cells into the bladder mucosa after exposing it through an abdominal incision [11,26,27]. This method is not ideal as it requires an open surgical procedure and might result in more muscle- Tumour take rate, % [11] No 45 min MBT-2/C3He 5 × 10 5 in 0.05 100 [12] 2 h MBT-2/C3He 1 × 10 7 in 0.1 83 [17] 3 h MBT-2/C3He 2 × 10 6 in 0.1 85 [14] 45-60 min MBT-2/C3He 1 × 10 5 in 0.1 50 [13] 3 h MBT-2/C3He 1 × 10 7 in 0.05 90 Chan et al…”

Rapid differentiation of superficial urothelial cells after chitosan-induced desquamation

“…However, the cytotoxic effect was found only in cells that were in direct contact with a suitably high concentration of chitosan. Such limited toxicity gives chitosan a new and very promising role for both theoretical studies of cell detachment and subsequent regeneration and in clinical application, especially in fighting chronic cystitis (Dalal et al 1994;Mulvey et al 1998Mulvey et al , 2001 and superficial bladder cancers (Nativ et al 2006).…”

“…By removing the layer of umbrella cells, it is highly probable that the majority of bacteria can be cleared from the bladder. Last but not least, induced desquamation has been proposed as a possibility for removing superficial tumours of the urinary bladder (Nativ et al 2006).…”