Biodistribution of Evans blue in an orthotopic <scp>AY</scp>‐27 rat bladder urothelial cell carcinoma model: implication for the improved diagnosis of non‐muscle‐invasive bladder cancer (<scp>NMIBC</scp>) using dye‐guided white‐light cystoscopy

Elsen, Sanne; Lerut, Evelyne; Cleynenbreugel, Ben Van; Aa, Frank Van der; Poppel, Hein Van; Witte, Peter de

doi:10.1111/bju.13113

Cited by 12 publications

(20 citation statements)

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“…These data are in line with a previous study using an identical tumor model that quantified the fluorescence of EB at the microscopic level in the different layers of the bladder wall (10). Consequently, a differential uptake of EB by the malignant and normal inner bladder wall was also observed using WL stereomicroscopy.…”

Section: Discussionsupporting

confidence: 92%

“…All the experiments were performed 2 days after the inoculation of AY-27 cells into the rat bladder. At this timepoint, high-grade CIS was present, as confirmed by histological analysis (10). …”

Section: Methodsmentioning

confidence: 69%

“…AY-27 cells were used for tumor implantation experiments. Details regarding the catheterization of animals and the tumor inoculation procedure were previously described by our group (10). All the experiments were performed 2 days after the inoculation of AY-27 cells into the rat bladder.…”

Section: Methodsmentioning

confidence: 99%

“…In a study by Roelants et al (9), the accumulation of EB was significantly higher in spheroids composed of malignant urothelial cells compared with that in spheroids derived from normal human urothelial cells. Elsen et al (10) investigated the accumulation of EB in an orthotopic rat non-muscle-invasive bladder cancer (NMIBC) model. The biodistribution of EB was examined in the different layers of healthy rat bladders and rat bladders bearing a malignant urothelium by quantifying the fluorescence of EB.…”

Section: Introductionmentioning

confidence: 99%

“…The rat NMIBC tumor model was characterized in more detail by a transcriptome analysis of malignant and normal rat urothelium, with a specific focus on cell adhesion. The aim of this analysis was to further investigate our previous hypothesis (10) that EB is able to selectively accumulate in tumor tissue due to defects in the urothelial barrier.…”

Section: Introductionmentioning

confidence: 99%

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Evans blue-mediated white-light detection of non-muscle-invasive bladder cancer: A preclinical feasibility and safety study using a rat bladder urothelial cell carcinoma model

Elsen

Lerut

et al. 2016

Molecular and Clinical Oncology

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Photodynamic diagnosis (PDD) improves the detection of non-muscle-invasive bladder cancer (NMIBC). However, white-light (WL) cystoscopy remains the technique routinely used in urological clinics. A more cost-effective but equally performant alternative to PDD may encompass the use of an intense tumoritropic dye in combination with WL cystoscopy. Using a preclinical setting, we investigated the practical aspects of the use of Evans blue (EB) dye for the possible future detection of NMIBC using WL cystoscopy. A solution of 1 and 5 mM EB was instilled into healthy and AY-27 tumor-bearing rat bladders. The bladders were then rapidly dissected and the inner walls were inspected for EB using WL stereomicroscopy. EB present in the bladders and the plasma was also quantified using high performance liquid chromatography. To assess the effects of repeated instillations on normal rat bladders, EB was instilled for 7 consecutive days, after which time the bladder wall was investigated histologically. To gain insight into the mechanisms underlying the selective accumulation of EB in malignant urothelium, RNA sequencing of urothelial tissue and subsequent comparative analysis were performed, with a specific focus on cell adhesion. The concentrations of EB were substantially higher in malignant bladders compared with those in healthy bladders, matching the blue staining of the inner bladder wall observed by stereomicroscopy. EB was equally present in the plasma of healthy and tumor-bearing subjects, although at low concentrations. Importantly, EB did not cause any abnormalities in the urothelium after 7 days of repeated instillation in normal rats. RNA sequencing of the urothelium indicated an abnormal expression of several genes related to cell adhesion in malignant urothelium compared with the normal urothelium. Our findings may be important for future clinical developments in the field of diagnostics for bladder cancer. Implementing the more cost-effective protocol of EB instillations in combination with WL cystoscopy may offer a benefit to patients as well as the healthcare system.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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