Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after hepatectomy are the major obstacles of long-term survival. The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs of RNA and 103 pairs of protein from tumour and adjacent nontumour liver tissues of HCC patients were examined. About 85 and 60% of HCC tumour tissues were found to overexpress Six1 mRNA and protein, respectively, compared with nontumour liver tissues. No Six1 protein was detected in HCC nontumour liver tissues and normal liver tissues. Increased Six1 protein expression in HCC patients was significantly correlated with pathologic tumour-nodemetastasis (pTNM) stage (P ¼ 0.002), venous infiltration (P ¼ 0.004) and poor overall survival (P ¼ 0.0423). We concluded that Six1 is frequently overexpressed in HCC patients and elevated Six1 protein in HCC patients may be an indication of advanced stage and poor overall survival after hepatectomy.

The present work provides evidence that HI insult destroyed brain cholesterol homeostasis, which might be important in the molecular pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol balance may be effective for the recovery of white matter function.

Objective: Understanding the biological functions of cancer stem cells (CSCs) provide new avenues for therapeutic interventions, which is especially important in hepatocellular carcinoma (HCC), an often fatal malignancy. We aim to determine whether glypican-3 (GPC3), an over-expressed membrane protein in HCC, mediates CSC properties in HCC cells. Design:We determined the cell surface expression of GPC3 in HCC patients and HCC cell lines, and isolated GPC3-high/low sub-populations to study their abilities to self-renew. Additionally, we used HCC cell-based systems where GPC3 expression was either suppressed or induced, to validate the stem-like properties (spheroid formation, cell cycle progression, tumor initiation) that may be mediated by GPC3. Results:We observed highly specific cell surface expression of GPC3 in HCC cells only (and not in normal hepatocytes or tumor-associated fibroblasts). The GPC3-high sub-populations isolated from HCC cells possess higher levels of self-renewing ability, have lower percentages of cells in the G 0 /G 1 phase, and promoted tumor formation in vivo. These observations were confirmed in HCC cell-based systems where GPC3 expression was either suppressed or induced. The effects of GPC3 (and EpCAM and CD133) on spheroid formation and cell cycle were nullified by the starvation-induced autophagy inhibitor, 3-methyladenine (3-MA), indicating that these processes are partially regulated by autophagy. Conclusion:We provide first evidence that GPC3 is a novel CSC marker in HCC, and that it mediates selfrenewal, cell cycle progression, and tumor formation partly via autophagy induction. We also suggest that autophagy inhibition may be a general approach for intervening with liver CSC functions, regardless of cell surface marker expression.