title: Therapeutic and analysis model of intrahepatic metastasis reflects clinical behavior of hepatocellular carcinoma.
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 suppressed 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.
authors.affiliation: Department of Pathogenic Biochemistry, Institute of Natural Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Sawada
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaura
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Mitani
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D009368:Neoplasm Transplantation; D010647:Phenyl Ethers / Q000494:pharmacology
chemical_list: C414368:N-hydroxy-5-ethoxymethyloxy-2-methyl-4-(4-phenoxybenzoyl)aminopentanamide; D010647:Phenyl Ethers; D004317:Doxorubicin; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin