title: Characterization of non-alcoholic steatohepatitis-derived hepatocellular carcinoma as a human stratification model in mice.
abstract: The therapeutic strategy against hepatocellular carcinoma (HCC) is determined by tumor stage and liver function. Improvements of stratification contribute to extending the survival of patients. However, stratification has been attributed little attention in animal models largely due to the lack of suitable models. Herein we showed that the recently-reported, non-alcoholic steatohepatitis-derived HCC model (STAM model) is the first murine model in which the concept of human stratification is applicable by demonstrating the following features: (i) at least 4 detectable tumor nodules; (ii) average tumor growth rate of 150 % from 16 to 20 weeks of age; (iii) no visible metastasis; and (iv) relatively preserved liver function. These observations suggested that HCC in STAM mice is equivalent to stages B to C of the Barcelona Clinic Liver Cancer (BCLC) staging system for humans. Application of the stratification concept to experimental animals will create new avenues to establish pharmacological intervention against HCC.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan ktakakura@jikei.ac.jp shigeo_koido@jikei.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takakura
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan ktakakura@jikei.ac.jp shigeo_koido@jikei.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.affiliation: Stelic Institute & Co., Inc, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Stelic Institute & Co., Inc, Tokyo, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hashiguchi
authors.affiliation: Stelic Institute & Co., Inc, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shibazaki
authors.affiliation: Stelic Institute & Co., Inc, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.affiliation: Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Katagi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Department of Oncology, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D065626:Non-alcoholic Fatty Liver Disease; D047368:Tumor Burden; D055114:X-Ray Microtomography
keywords: Barcelona Clinic Liver Cancer staging system; Child-Pugh grade; Hepatocellular carcinoma; murine model; non-alcoholic steatohepatitis