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Mol Ther. 2015 Mar;23(3):501-9. doi: 10.1038/mt.2014.244. Epub 2014 Dec 19.

Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer.

Author information

1
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
2
1] Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan [2] Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
3
Oncolys BioPharma, Inc., Tokyo, Japan.
4
1] Department of Surgery, University of California, San Diego, California, USA [2] AntiCancer, Inc., San Diego, California, USA.

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.

PMID:
25523761
PMCID:
PMC4351467
DOI:
10.1038/mt.2014.244
[Indexed for MEDLINE]
Free PMC Article

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