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原位膀胱肿瘤模型及膀胱内saRNA治疗的评估

An orthotopic bladder tumor model and the evaluation of intravesical saRNA treatment.

作者信息

Kang Moo Rim, Yang Glen, Charisse Klaus, Epstein-Barash Hila, Manoharan Muthiah, Li Long-Cheng

机构信息

Department of Urology and Helen Diller Comprehensive Cancer Center, University of California-San Francisco.

出版信息

J Vis Exp. 2012 Jul 28(65):4207. doi: 10.3791/4207.

DOI:10.3791/4207
PMID:22872227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3476411/
Abstract

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. The mouse model is established by urethral catheterization under inhaled general anesthetic. Chemical burn is then introduced to the bladder mucosa using intravesical silver nitrate solution to disrupt the bladder glycosaminoglycan layer and allows cells to attach. Following several washes with sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder tumors is confirmed and monitored by in vivo bladder ultrasound and bioluminescent imaging. The tumors are then treated intravesically with saRNA formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with ultrasound and bioluminescence. All steps of this procedure are demonstrated in the accompanying video.

摘要

我们在原位异种移植小鼠膀胱肿瘤模型中,展示了一种用膀胱内递送的小激活RNA(saRNA)治疗膀胱癌的新方法。小鼠模型通过在吸入全身麻醉下进行尿道插管建立。然后使用膀胱内硝酸银溶液对膀胱黏膜进行化学灼伤,以破坏膀胱糖胺聚糖层并使细胞附着。用无菌水冲洗几次后,通过导管将人膀胱癌KU-7-luc2-GFP细胞注入膀胱并停留2小时。随后通过体内膀胱超声和生物发光成像确认并监测膀胱肿瘤的生长。然后用脂质纳米颗粒(LNP)配制的saRNA对肿瘤进行膀胱内治疗。用超声和生物发光监测肿瘤生长。本程序的所有步骤均在随附视频中展示。

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