Premium
Effect of low‐energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer
Author(s) -
Elkashef Ahmed,
Barakat Nashwa,
Khater Sherry M.,
Awadalla Amira,
Belal Fathallah,
ElAssmy Ahmed M.,
Sheir Khaled Z.,
Shokeir Ahmed A.
Publication year - 2021
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.15173
Subject(s) - medicine , bladder cancer , epirubicin , urology , saline , urinary bladder , toxicity , immunostaining , pathology , gastroenterology , cancer , andrology , immunohistochemistry , breast cancer
Objectives To study the efficacy of low‐energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). Materials and Methods A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa induction by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 mL of EPI diluted in 0.3 mL saline) or saline (0.6 mL) was administered and retained in the bladders for 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm 2 ). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p 53 immunostaining, miR‐210, hypoxia‐inducible factor (HIF)‐1α, tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. Results The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p 53 , miR‐210, HIF‐1α, TNF‐α and IL‐6. LESW increased urothelial concentration of EPI by 5.7‐fold ( P < 0.001). No laboratory variable exceeded the reference ranges in any of the groups. There was an improvement of the indicators of EPI‐induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes ( P = 0.068, 0.003 and 0.046, respectively) in the EPI plus LESW group. Conclusions The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.