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ID 53079
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Author
Kikuchi, Satoru
Hashimoto, Yuuri
Kuroda, Shinji
Urata, Yasuo
Robert M Hoffman
Fujiwara, Toshiyoshi ORCID Kakenhi
Abstract
Currently, early gastrointestinal cancers are treated endoscopically, as long as there are no lymph node metastases. However, once a gastrointestinal cancer invades the submucosal layer, the lymph node metastatic rate rises to higher than 10%. Therefore, surgery is still the gold standard to remove regional lymph nodes containing possible metastases. Here, to avoid prophylactic surgery, we propose a less-invasive biological ablation of lymph node metastasis in submucosally invaded gastrointestinal cancer patients. We have established an orthotopic early rectal cancer xenograft model with spontaneous lymph node metastasis by implantation of green fluorescent protein (GFP)-labeled human colon cancer cells into the submucosal layer of the murine rectum. A solution containing telomerase-specific oncolytic adenovirus was injected into the peritumoral submucosal space, followed by excision of the primary rectal tumors mimicking the endoscopic submucosal dissection (ESD) technique. Seven days after treatment, GFP signals had completely disappeared indicating that sentinel lymph node metastasis was selectively eradicated. Moreover, biologically treated mice were confirmed to be relapse-free even 4 weeks after treatment. These results indicate that virus-mediated biological ablation selectively targets lymph node metastasis and provides a potential alternative to surgery for submucosal invasive gastrointestinal cancer patients.
Keywords
endoscopic treatment
adenovirus
colorectal cancer
lymphatic metastasis
Published Date
2014-12-19
Publication Title
Molecular Therapy
ISSN
1525-0016
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1038/mt.2014.244
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/53915
language
英語
Copyright Holders
© 2015 American Society of Gene & Cell Therapy
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True
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