In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation
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Kishimoto-2009-In vivo internal tum.pdf
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Author(s) • • • • • • •
Penman, Sheldon
Hoffman, Robert M.
Fujiwara, Toshiyoshi
Tanaka, Noriaki
Urata, Yasuo
Hayashi, Katsuhiro
Zhao, Ming
Kishimoto, Hiroyuki
Date Issued
August 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
United States National Academy of Sciences
Citation
Kishimoto, Hiroyuki et al. “In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation.” Proceedings of the National Academy of Sciences 106.34 (2009): 14514-14517. © 2009 National Academy of Sciences
Version
Final published version
Abstract
Cancer surgery requires the complete and precise identification of malignant tissue margins including the smallest disseminated lesions. Internal green fluorescent protein (GFP) fluorescence can intensely illuminate even single cells but requires GFP sequence transcription within the cell. Introducing and selectively activating the GFP gene in malignant tissue in vivo is made possible by the development of OBP-401, a telomerase-dependent, replication-competent adenovirus expressing GFP. This potentially powerful adjunct to surgical navigation was demonstrated in 2 nude mouse models that represent difficult surgical challenges—the resection of widely disseminated cancer. HCT-116, a model of intraperitoneal disseminated human colon cancer, was labeled by virus injection into the peritoneal cavity. A549, a model of pleural dissemination of human lung cancer, was labeled by virus administered into the pleural cavity. Only the malignant tissue fluoresced brightly in both models. In the intraperitoneal model of disseminated cancer, fluorescence-guided surgery enabled resection of all tumor nodules labeled with GFP by OBP-401. The data in this report suggest that adenoviral-GFP labeling tumors in patients can enable fluorescence-guided surgical navigation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0906388106