Abstract
Abstract
Background
Conventional cystoscopy can detect advanced stages of bladder cancer; however, it has limitations to detect bladder cancer at the early stages. Fluorocoxib A, a rhodamine-conjugated analog of indomethacin, is a novel fluorescent imaging agent that selectively targets cyclooxygenase-2 (COX-2)-expressing cancers.
Methods
In this study, we have used a carcinogen N-butyl-N-4-hydroxybutyl nitrosamine (BBN)-induced bladder cancer immunocompetent mouse B6D2F1 model that resembles human high-grade invasive urothelial carcinoma. We evaluated the ability of fluorocoxib A to detect the progression of carcinogen-induced bladder cancer in mice. Fluorocoxib A uptake by bladder tumors was detected ex vivo using IVIS optical imaging system and Cox-2 expression was confirmed by immunohistochemistry and western blotting analysis. After ex vivo imaging, the progression of bladder carcinogenesis from normal urothelium to hyperplasia, carcinoma-in-situ and carcinoma with increased Ki67 and decreased uroplakin-1A expression was confirmed by histology and immunohistochemistry analysis.
Results
The specific uptake of fluorocoxib A correlated with increased Cox-2 expression in progressing bladder cancer. In conclusion, fluorocoxib A detected the progression of bladder carcinogenesis in a mouse model with selective uptake in Cox-2-expressing bladder hyperplasia, CIS and carcinoma by 4- and 8-fold, respectively, as compared to normal bladder urothelium, where no fluorocoxib A was detected.
Conclusions
Fluorocoxib A is a targeted optical imaging agent that could be applied for the detection of Cox-2 expressing human bladder cancer.
Funder
National Cancer Institute
University of Tennessee
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference47 articles.
1. Cancer of the Urinary Bladder [https://www.cancer.gov/types/bladder/hp].
2. Bladder Cancer Stages [https://www.cancer.org/cancer/bladder-cancer/detection-diagnosis-staging/staging.html].
3. Advanced Bladder Cancer Meta-analysis C. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361(9373):1927–34.
4. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.
5. Gill IS, Kaouk JH, Meraney AM, Desai MM, Ulchaker JC, Klein EA, Savage SJ, Sung GT. Laparoscopic radical cystectomy and continent orthotopic ileal neobladder performed completely intracorporeally: the initial experience. J Urol. 2002;168(1):13–8.
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献