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一种实时非侵入性自体生物发光膀胱癌异种移植模型。

A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.

作者信息

John Bincy Anu, Xu Tingting, Ripp Steven, Wang Hwa-Chain Robert

机构信息

Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.

Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN, USA.

出版信息

Mol Imaging Biol. 2017 Feb;19(1):10-14. doi: 10.1007/s11307-016-0989-y.

DOI:10.1007/s11307-016-0989-y
PMID:27443377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5599112/
Abstract

PURPOSE

The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research.

PROCEDURE

The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination.

RESULTS

Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals.

CONCLUSIONS

Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

摘要

目的

本研究旨在开发一种用于临床前研究的自动生物发光膀胱癌(UBC)异种移植动物模型。

程序

本研究使用了一种人源化的、细菌起源的lux报告系统,该系统由六个(luxCDABEfrp)基因组成,可在无需外源底物的情况下,在人UBC J82、J82-Ras和SW780细胞中表达产生生物发光信号所需的成分。将表达Lux的UBC细胞接种到免疫缺陷裸鼠体内,以形成自动生物发光异种移植肿瘤,并通过成像和体格检查进行监测。

结果

建立了表达Lux的自动生物发光J82-Lux、J82-Ras-Lux和SW780-Lux细胞系。源自致瘤性表达Lux的自动生物发光J82-Ras-Lux细胞的异种移植肿瘤,在动物出现可触及肿瘤之前,能够通过成像对肿瘤发展进行连续、非侵入性的实时监测。

结论

使用表达Lux的自动生物发光致瘤细胞,使我们能够通过肿瘤细胞植入、适应和生长,直至在动物体内形成可见/可触及肿瘤,来监测异种移植肿瘤发展的全过程。

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Systematic Review: Characteristics and Preclinical Uses of Bladder Cancer Cell Lines.系统评价:膀胱癌细胞系的特征及临床前应用
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Co-Cultured Continuously Bioluminescent Human Cells as Bioreporters for the Detection of Prodrug Therapeutic Impact Pre- and Post-Metabolism.共培养持续生物发光人细胞作为前代谢和后代谢的前药治疗效果检测的生物报告器。
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本文引用的文献

1
Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells.人源化病毒2A介导的lux操纵子的表达在人细胞中有效地产生自主生物发光。
PLoS One. 2014 May 2;9(5):e96347. doi: 10.1371/journal.pone.0096347. eCollection 2014.
2
VEGF targets the tumour cell.VEGF 靶向肿瘤细胞。
Nat Rev Cancer. 2013 Dec;13(12):871-82. doi: 10.1038/nrc3627.
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In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals.体内生物发光成像(BLI):在活体动物中对生物过程进行非侵入性可视化和检测。
Sensors (Basel). 2011;11(1):180-206. doi: 10.3390/s110100180. Epub 2010 Dec 28.
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Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶慢性诱导人乳腺细胞癌变的干预。
Carcinogenesis. 2012 Apr;33(4):876-85. doi: 10.1093/carcin/bgs097. Epub 2012 Feb 3.
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Autonomous bioluminescent expression of the bacterial luciferase gene cassette (lux) in a mammalian cell line.细菌荧光素酶基因盒(lux)在哺乳动物细胞系中的自主生物发光表达。
PLoS One. 2010 Aug 27;5(8):e12441. doi: 10.1371/journal.pone.0012441.
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Non-invasive detection of a small number of bioluminescent cancer cells in vivo.体内无创检测少量生物发光癌细胞。
PLoS One. 2010 Feb 23;5(2):e9364. doi: 10.1371/journal.pone.0009364.
7
In vivo bioluminescence imaging in an experimental mouse model for dendritic cell based immunotherapy against malignant glioma.基于树突状细胞的恶性胶质瘤免疫治疗实验小鼠模型中的体内生物发光成像
J Neurooncol. 2009 Jan;91(2):127-39. doi: 10.1007/s11060-008-9691-5. Epub 2008 Sep 12.
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A quantitative study of factors affecting in vivo bioluminescence imaging.影响活体生物发光成像的因素的定量研究
Luminescence. 2008 Sep-Oct;23(5):292-5. doi: 10.1002/bio.1032.
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Noninvasive bioluminescence imaging in small animals.小动物的非侵入性生物发光成像
ILAR J. 2008;49(1):103-15. doi: 10.1093/ilar.49.1.103.
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Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells.致癌性H-Ras在人类癌细胞中促进组蛋白去乙酰化酶抑制剂诱导凋亡的促凋亡能力。
Mol Cancer Ther. 2007 Mar;6(3):1099-111. doi: 10.1158/1535-7163.MCT-06-0586.