Detection of carcinogen-induced bladder cancer by fluorocoxib A

Jennifer Bourn,Lawrence Marnett,Md Jashim Uddin,Wesley White,Maria Cekanova,Kusum Rathore,Robert Donnell

doi:10.1186/s12885-019-6366-x

Jennifer Bourn, Lawrence Marnett + Show 5 more

Open Access

https://doi.org/10.1186/s12885-019-6366-x

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Abstract

BackgroundConventional 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.MethodsIn 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.ResultsThe 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.ConclusionsFluorocoxib A is a targeted optical imaging agent that could be applied for the detection of Cox-2 expressing human bladder cancer.

Highlights

Conventional cystoscopy can detect advanced stages of bladder cancer; it has limitations to detect bladder cancer at the early stages
Standard treatments for Non-muscle invasive bladder papillary carcinoma (NMIBC) are a transurethral resection of bladder tumor (TURBT) or opened radical cystectomy depending on patient preferences and anatomy and location of cancer
Four hours after fluorocoxib A administration, mice were sacrificed, and dissected tissues were imaged by the IVIS imaging system to detect fluorocoxib A uptake

Summary

Introduction

Conventional cystoscopy can detect advanced stages of bladder cancer; it has limitations to detect bladder cancer at the early stages. Bladder cancer is the 6th most common type of cancer with an estimated 80,000 newly diagnosed cases and 17, 000 deaths per year in the United States [1]. Treatment management depends on whether the bladder cancer is diagnosed as NMIBC or MIBC. The gold-standard treatment for MIBC is neoadjuvant platinum-based chemotherapy followed by radical cystectomy [3, 4]. Standard treatments for NMIBC are a transurethral resection of bladder tumor (TURBT) or opened radical cystectomy depending on patient preferences and anatomy and location of cancer. The detection of bladder cancer at the early stages and more accurate detection of cancer during TURBT procedures is needed to improve patient treatment outcomes

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