Marked antitumor effect of NK012, a SN-38-incorporating micelle formulation, in a newly developed mouse model of liver metastasis resulting from gastric cancer.
BACKGROUND
Gastric cancer with liver metastasis (LM) is associated with poor prognosis due to rapid progression. It is, therefore, important to develop a quantitative and highly reproducible animal model of LM using human gastric cancer cells.


METHODS
Cells of a human gastric cancer cell line, HSC-57, were injected into the portal vein to produce LMs. Cells from some of these metastatic foci were expanded in vitro and subsequently implanted into the portal veins of mice. This procedure was repeated nine times. The antitumor effects of CPT-11 and NK012 were compared using the LM model.


RESULTS
The potent metastatic clone 57L9 was obtained. NK012 exerted a stronger antitumor effect than CPT-11 against 57L9 cells integrated with the luciferase gene (57L9Luc). The survival rates on day 131 in the 57L9Luc mouse model were 100% and 0% for the NK012 and CPT-11 groups, respectively.


CONCLUSIONS
This 57L9Luc LM model was found to be useful for monitoring the responses to NK012 and CPT-11.
Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
Kazuyoshi
K
Yanagihara
Misato
M
Takigahira
Takanori
T
Kubo
Takahiro
T
Ochiya
Tetsuya
T
Hamaguchi
Yasuhiro
Y
Matsumura
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D008823:Micelles; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D000077146:Irinotecan; D008156:Luciferases; D002166:Camptothecin