To clarify whether preoperative transcatheter arterial chemoembolization (TAE) improves the prognosis of patients with hepatocellular carcinoma (HCC) after surgery, 120 patients who had undergone hepatectomy for HCC from 1988 to 1994 and satisfied the criteria of stages II and III were enrolled in this study. Forty-four patients underwent preoperative TAE (group A) and 76 patients did not (group B). No significant differences in the outcomes were observed between these two groups. To rectify the comparison, patients with tumors 2 to 8 cm were assigned to groups A1 (n = 24) and B1 (n = 57), and those with tumors > 8 cm were assigned to groups A2 (n = 20) and B2 (n = 19), respectively. Although no significant differences in survival between groups A1 and B1 were found, group A2 presented superior 1-, 2-, and 3-year tumor-free survival rates of 80%, 55%, and 32% and 1-, 3-, and 5-year cumulative survival rates of 90%, 53%, and 42%. These figures are in comparison with the tumor-free survival rates of 50%, 22%, and 11% (p = 0.06), and the cumulative survival rates of 72%, 33%, and 11% (p = 0.01) during the same periods for group B2, respectively. The Cox regression model revealed that for patients with tumors > 8 cm, the relative risk of preoperative TAE for overall survival was 0.38 (p = 0.017), indicating that preoperative TAE might benefit patients with tumors > 8 cm but not those with tumors 2 to 8 cm.

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Stress-induced premature senescence (SIPS), a state of cell growth arrest due to various stimuli, is implicated in the pathogeneses of hepatic fibrogenesis. Progerin, a permanently farnesylated mutant lamin A protein, likely leads to premature senescence to influent liver diseases. The previous reports showed that activation of insulin-like growth factor-1 (IGF-1) signaling could enhance cell longevity and attenuate liver fibrosis. However, the underlying mechanisms about hepatocyte premature senility in liver fibrosis, and how IGF-1 regulates cell premature aging and fibrogenesis, remain poorly understood. In the present study, we found the augment of hepatocyte oxidation and premature aging, along with the decrease of plasm IGF-1 level in patients with liver fibrosis and CCl 4 -induced liver injury rat models. Nevertheless, IGF-1 gene transfer to CCl 4 rats to overexpress intrahepatic IGF-1 relieved hepatocyte oxidative stress and premature senescence, which was likely mediated by the p53/progerin pathway, to improve hepatic steatosis and fibrogenesis. In vitro, H 2 O 2 caused abnormal accumulation of progerin in nuclear and activation of nuclear p53–progerin interaction to trigger primary rat hepatocyte premature senescence through the p21-independent pathway; while these effects were rescued by prolonged exogenous IGF-1 or the IGF-1 adenovirus vector. Furthermore, the IGF-1 adenovirus vector, transfected to H 2 O 2 -treated hepatocytes, reversed oxidative stress-induced premature senescence via enhancing cytoplasmic AKT1–p53 interaction and subsequently inhibiting nuclear p53–progerin interaction. Consequently, our data illuminate a novel role of IGF-1 in regulating stress-induced hepatocyte premature senescence in liver fibrosis: prolonged IGF-1 relieves oxidative stress-initiated hepatocyte premature senescence via inhibition of nuclear p53–progerin interaction to ameliorate hepatic steatosis and fibrogenesis.