Characterization of non-alcoholic steatohepatitis-derived hepatocellular carcinoma as a human stratification model in mice

Anticancer Res. 2014 Sep;34(9):4849-55.

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.

Keywords: Barcelona Clinic Liver Cancer staging system; Child-Pugh grade; Hepatocellular carcinoma; murine model; non-alcoholic steatohepatitis.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / mortality
  • Disease Models, Animal
  • Fatty Liver / complications*
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / mortality
  • Male
  • Mice
  • Neoplasm Staging
  • Non-alcoholic Fatty Liver Disease
  • Tumor Burden
  • X-Ray Microtomography