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Proceedings Paper

Caspase-3-independent pathways proceeding in bystander effect of HSV-tk/GCV system
Author(s): Juqiang Lin; Yan Ma; Shaoqun Zeng; Zhihong Zhang
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Paper Abstract

HSV-tk/GCV system, which is the virus-directed enzyme/prodrug therapy of herpes simplex virus (HSV) thymidine kinase (tk) gene / the anti-viral reagent ganciclovir (GCV), is one of the promising approaches in the rapidly growing area of gene therapy. As gene therapy of cancer such as suicide gene therapy has entered the clinic, another therapy effect which is called 'bystander effect' was reported. Bystander effect can lead to killing of non-transduced tumor cells in the immediate vicinity of GCV-treated HSV-TK-positive cells. Now the magnitude of 'bystander effect' is an essential factor for this anti-tumor approach in vivo. However, the mechanism which HSV-tk/ACV brings "bystander effect" is poorly understood. In this study, we monitor the activation of caspase-3 in HSV-tk/GCV system by a FRET probe CD3, a FRET-based indicator for activity of caspase3, which is composed of an enhanced cyan fluorescent protein, a caspase-sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. Through application of CD3 we have visualized the activation of caspase-3 in tk gene positive human adenoid cystic carcinoma (ACC-M) cells but not in bystander effect of HSV-tk/GCV system induced by GCV. This finding provides needed information for understanding the mechanisms by which suicide gene approaches actually kill cancer cells, and may prove to be helpful for the clinical treatment of cancers.

Paper Details

Date Published: 13 February 2008
PDF: 7 pages
Proc. SPIE 6868, Small Animal Whole-Body Optical Imaging Based on Genetically Engineered Probes, 68680B (13 February 2008); doi: 10.1117/12.763385
Show Author Affiliations
Juqiang Lin, Fujian Normal Univ. (China)
Yan Ma, Huazhong Univ. of Science and Technology (China)
Shaoqun Zeng, Huazhong Univ. of Science and Technology (China)
Zhihong Zhang, Huazhong Univ. of Science and Technology (China)


Published in SPIE Proceedings Vol. 6868:
Small Animal Whole-Body Optical Imaging Based on Genetically Engineered Probes
Alexander P. Savitsky; Robert E. Campbell; Robert M. Hoffman, Editor(s)

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