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

Satoru Kikuchi, Hiroyuki Kishimoto, Hiroshi Tazawa, Yuuri Hashimoto, Shinji Kuroda, Masahiko Nishizaki, Takeshi Nagasaka, Yasuhiro Shirakawa, Shunsuke Kagawa, Yasuo Urata, Robert M. Hoffman, Toshiyoshi Fujiwara

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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.

Original languageEnglish
Pages (from-to)501-509
Number of pages9
JournalMolecular Therapy
Volume23
Issue number3
DOIs
Publication statusPublished - Mar 5 2015

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Gastrointestinal Neoplasms
Lymph Nodes
Neoplasm Metastasis
Rectal Neoplasms
Green Fluorescent Proteins
Telomerase
Rectum
Heterografts
Adenoviridae
Colonic Neoplasms
Sentinel Lymph Node
Viruses
Recurrence
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer. / Kikuchi, Satoru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Hashimoto, Yuuri; Kuroda, Shinji; Nishizaki, Masahiko; Nagasaka, Takeshi; Shirakawa, Yasuhiro; Kagawa, Shunsuke; Urata, Yasuo; Hoffman, Robert M.; Fujiwara, Toshiyoshi.

In: Molecular Therapy, Vol. 23, No. 3, 05.03.2015, p. 501-509.

Research output: Contribution to journalArticle

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