Fig. 2. Findings of liver tissues. Focal necrosis of liver cells and invasion of inflammatory cells in portal areas were found in both groups. However, fibrosis or piecemeal necrosis was not obvious. (a: control group, b: KurozuM group; HE ×200). Fig. 3. Findings of GSTP staining. Large GSTPpositive foci with a diameter of 20 mm was noted in liver in the control group (a). On t he other hand, in the KurozuM group, no lesion of more than 3 mm in diameter was found in liver (b). Fig. 4. Numbers and size of GSTPpositive foci. The numbers of GSTP positive foci were 12.2 ± 6.8 in the control group, and 10.7 ± 5.3 in the KurozuM group. There was no significant difference between the two groups. The size (mm) of GSTPpositive foci in the KurozuM group (0.89 ± 0.46) was significantly (p<0.001) reduced compared with the control (7.35 ± 5.31). T. Shizuma et al. 0.19 ng/mg protein, respectively. Total and activated MMP-2 and MMP-9 levels were all significantly (p<0.001) reduced in the Kurozu-M group compared with the control group (Fig. 5). Survival. In the control group, all 8 rats died within 36 weeks after initial DEN administration. On the other hand, the survival rate in the Kurozu-M group was 37.5% (3/8) at 48 weeks. The survival rate in the Kurozu-M group was significantly higher than that in the control group (p<0.001) (Fig. 6). Discussion Kurozu-M treatment markedly inhibited growth of HCC and improved survival in the DEN-induced HCC animal model. One of the mechanisms of its anti-cancer effects was considered to be suppression of activated MMP-2 and MMP-9, which degrade the extracellular matrix, thereby promoting the growth and metastasis of various solid cancers. Occurrence of HCC is generally associated with liver fibrosis or inflammatory changes. Clinically, chronic hepatitis or liver cirrhosis (LC) with HCV infection often leads to HCC. For example, the occurrence rate of HCC in LC patients with HCV infection is 6–8%/year in Japan.(12) In patients with hepatitis, inflammation and regeneration in the liver are associated with J. Clin. Biochem. Nutr. | July 2011 | vol. 49 | no. 1 | 33 ©2011 JCBN