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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2002 Feb;93(2):190–197. doi: 10.1111/j.1349-7006.2002.tb01258.x

Therapeutic and Analysis Model of Intrahepatic Metastasis Reflects Clinical Behavior of Hepatocellular Carcinoma

Shigeaki Sawada 1,✉, Koji Murakami 1, Takeshi Yamaura 1, Noriyasu Mitani 1, Kazuhiro Tsukada 2, Ikuo Saiki 1,✉
PMCID: PMC5926959  PMID: 11856483

Abstract

This study was designed to establish an intrahepatic metastasis model to investigate the biology and therapy of hepatocellular carcinoma (HCC) in mice. A fragment of mouse HCC tumor CBO140C12 was orthotopically implanted into the mouse liver. The number of intrahepatic metastatic colonies and the volume of the implanted tumor increased in a time‐dependent manner. At 28 days after fragment implantation, all mice showed intrahepatic metastasis. Intravenous administrations of cisplatin and doxorubicin at 7 and 21 days after the implantation significantly sup‐ pressed the growth of the primary tumor nodule, but tended to inhibit intrahepatic metastasis. However, a marked decrease of body weight was observed during the experiment. On the other hand, an inhibitor of matrix metalloproteinases (MMPs), ONO–4817, decreased the gelatinase activity of MMP–9 secreted by CBO140C12 cells, and significantly reduced the number of colonies of intrahepatic metastasis when administered orally. Our established model, which is focused on intrahepatic metastasis, is suitable for evaluating the therapeutic effect of HCC and for analyzing intrahepatic metastasis, because this model reflects the clinical features of HCC and all the steps of tumor metastasis.

Keywords: Intrahepatic metastasis, Hepatocellular carcinoma, Metastasis model, Orthotopic implantation, MMP inhibitor

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