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 language | English |
|---|---|
| Pages (from-to) | 501-509 |
| Number of pages | 9 |
| Journal | Molecular Therapy |
| Volume | 23 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 5 2015 |
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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 journal › Article
}
TY - JOUR
T1 - Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer
AU - Kikuchi, Satoru
AU - Kishimoto, Hiroyuki
AU - Tazawa, Hiroshi
AU - Hashimoto, Yuuri
AU - Kuroda, Shinji
AU - Nishizaki, Masahiko
AU - Nagasaka, Takeshi
AU - Shirakawa, Yasuhiro
AU - Kagawa, Shunsuke
AU - Urata, Yasuo
AU - Hoffman, Robert M.
AU - Fujiwara, Toshiyoshi
PY - 2015/3/5
Y1 - 2015/3/5
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84924030183&partnerID=8YFLogxK
U2 - 10.1038/mt.2014.244
DO - 10.1038/mt.2014.244
M3 - Article
C2 - 25523761
AN - SCOPUS:84924030183
VL - 23
SP - 501
EP - 509
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 3
ER -