OBJECTIVES: To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up. MATERIALS AND METHODS: Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder. RESULTS: Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease. CONCLUSIONS: This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.
OBJECTIVES: To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic ratbladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up. MATERIALS AND METHODS: Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 ratbladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder. RESULTS: Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease. CONCLUSIONS: This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.
Authors: J Falke; J Parkkinen; L Vaahtera; C A Hulsbergen-van de Kaa; E Oosterwijk; J A Witjes Journal: Biomed Res Int Date: 2018-06-10 Impact factor: 3.411
Authors: Kyle G Potts; Chad R Irwin; Nicole A Favis; Desmond B Pink; Krista M Vincent; John D Lewis; Ronald B Moore; Mary M Hitt; David H Evans Journal: EMBO Mol Med Date: 2017-05 Impact factor: 12.137
Authors: Johannes Falke; Christina A Hulsbergen-van de Kaa; Roberto Maj; Egbert Oosterwijk; J Alfred Witjes Journal: World J Urol Date: 2018-05-16 Impact factor: 4.226
Authors: F Johannes P van Valenberg; Dalit Strauss-Ayali; Yael Agmon-Gerstein; Astar Friedman; Harm C Arentsen; H Ewout Schaafsma; J Alfred Witjes; Egbert Oosterwijk Journal: Ther Adv Urol Date: 2018-03-19