Hadaschik Boris A, Black Peter C, Sea Jason C, Metwalli Adam R, Fazli Ladan, Dinney Colin P, Gleave Martin E, So Alan I
The Prostate Centre at Vancouver General Hospital and Department of Urologic Services, University of British Columbia, Vancouver, BC, Canada.
BJU Int. 2007 Dec;100(6):1377-84. doi: 10.1111/j.1464-410X.2007.07165.x. Epub 2007 Sep 10.
To describe a technique for transurethral tumour inoculation, bioluminescence imaging (BLI) and validation of this approach using ex vivo magnetic resonance imaging (MRI), as a reproducible and quantifiable model of orthotopic bladder cancer is required to enable preclinical pharmacological studies of intravesically administered anticancer agents and the use of BLI provides a sensitive method to monitor tumour growth over time.
Human KU-7 bladder tumour cells were transduced with a lentiviral construct to stably express the firefly luciferase gene. These cells were then inoculated in female nude mice by intravesical instillation. BLI was performed weekly and the mice were killed after 4 weeks. Ex vivo MRI and whole-mount step-sections were obtained to assess bladder tumour volume.
KU-7 tumour cells were highly tumorigenic and were successfully inoculated in 96% of mice. After 4 weeks, all tumours were confined to the mucosa and submucosa (</=pT1). There was an excellent correlation between tumour volume and BLI for both ex vivo bladder MRI (R(2) = 0.929) and end-point histological measurements (R(2) = 0.836).
We have established and validated a reliable model of orthotopic bladder cancer that can be used to evaluate various methods of intravesical therapy. BLI allows excellent longitudinal surveillance and quantification of tumour burden.
描述一种经尿道肿瘤接种技术、生物发光成像（BLI）以及使用离体磁共振成像（MRI）对该方法进行验证，因为需要一种可重复且可量化的原位膀胱癌模型来开展膀胱内给药抗癌药物的临床前药理学研究，而BLI的使用提供了一种监测肿瘤随时间生长的灵敏方法。
用人KU-7膀胱肿瘤细胞转导慢病毒构建体以稳定表达萤火虫荧光素酶基因。然后通过膀胱内灌注将这些细胞接种到雌性裸鼠体内。每周进行一次BLI，4周后处死小鼠。获取离体MRI和整装连续切片以评估膀胱肿瘤体积。
KU-7肿瘤细胞具有高度致瘤性，成功接种于96%的小鼠体内。4周后，所有肿瘤均局限于黏膜和黏膜下层（≤pT1）。对于离体膀胱MRI（R² = 0.929）和终点组织学测量（R² = 0.836），肿瘤体积与BLI之间均具有良好的相关性。
我们已建立并验证了一种可靠的原位膀胱癌模型，可用于评估各种膀胱内治疗方法。BLI能够对肿瘤负荷进行出色的纵向监测和量化。
