New gene therapy of Smad7 for hepatocellular carcinoma with liver cirrhosis

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In a cirrhotic liver, the regenerative ability and specific functions are impaires ; a hepatic resection increases the possibility of postoperative liver failure. A truncated type II transforming growth factor-β receptor (TβTR), which specifically inhibits TGF-β signaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of adenovirus-mediated TβTR gene transducation after partial hepatectomy for liver cirrhosis. Rats were treated with dimethylnitrosamine for 3 weeks, and they all had severe cirrhosis. After the 10% partial hepatectomy in rats of this model, we injected PBS, AdLacZ, and Ad TβTR, into the portal vein, which was followed by an additionl 2-week dimethylnitrosamine treatment. On histologic examination, fibrotic tissue had decreased in the livers of the Ad TβTR -treated rats compared with rats that were treated by PBS and AdLacZ. Ad TβTR treatment improved the survival rate after a partial hepatectomy. Our results suggest that the TβTR gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.