Low expression of SLC22A1 is associated with a poor prognosis of hepatocellular carcinoma: analysis of 303 patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the association between SLC22A1 expression and the outcomes of hepatocellular carcinoma (HCC) patients.</p><p><b>METHODS</b>A tissue microarray of 303 HCC and matched adjacent noncancerous liver tissues (ANLTs) were constructed. The expression of SLC22A1 was tested by immunohistochemistry (IHC) and scored by two pathologists according to a 12-score scale (a score>6 was defined as high expression, and a score≤6 as low expression). The correlation of SLC22A1 expression with the clinicopathological features and the patients' outcome was analyzed.</p><p><b>RESULTS</b>All the ANLTs had a IHC score of 12, as compared to only 29 (9.6%) of the HCC tissues. The patients were divided into 2 groups based on the IHC scores: 59% (180/303) in low expression group and 41% (123/303) in high expression group. The disease-free survival (DFS) rates and overall survival (OS) rates were significantly lower in low SLC22A1 expression group than in the high expression group. The 1-, 3-, and 5-year DFS rates were 43%, 31% and 27% in the low expression group, and were 58%, 47% and 43% in the high expression group, respectively. The 1-, 3-, and 5-year OS rates were 66%, 38% and 32% in low expression group, and were 80%, 57% and 50% in the high expression group, respectively. A low expression of SLC22A1 was positively correlated with the tumor diameter, BCLC stage, tumor differentiation, and AFP levels (P<0.05), and was an independent predictor of poor overall survival (HR=1.454; 95% CI, 1.050-2.013).</p><p><b>CONCLUSIONS</b>Down-regulation of SLC22A1 is a malignant feature and a potential prognostic marker of HCC.</p>

Long-term outcome and prognostic factors of intrahepatic cholangiocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The management of intrahepatic cholangiocarcinoma (ICC) remains a challenge due to poor prognosis. The aim of this study was to summarize the surgical management experience in recent 10 years and to identify the influencing factors related to outcome of patients with ICC in a single hepatobiliary center.</p><p><b>METHODS</b>From January 1995 to June 2005, 136 patients with ICC undergoing surgery were reviewed retrospectively. Survival rates of patients were calculated using the Kaplan-Meier method and compared by using the log-rank test. The prognostic factors were identified by the Cox regression model.</p><p><b>RESULTS</b>Seventy-nine of 136 patients underwent resection, and 65 of 79 patients were curative (R0). The surgical mortality was 2.2%. The 1-, 3- and 5-year survival rates of patients undergoing R0 resection were 72.1%, 35.6% and 20.1% respectively, which were significantly longer than those who underwent palliative resection and exploration, respectively (P < 0.01). At stage IV of the disease, 10 patients who underwent aggressive curative resection achieved a better median survival than those (n = 12) without resection (14 months vs 3 months, P < 0.001). The independent prognostic factors of the whole group were TNM stage (OR, 2.013, P = 0.008) and curative resection (OR, 2.957, P = 0.003). Higher TNM stage (OR, 1.894, P = 0.004) and lymph node metastasis (OR, 4.248, P = 0.005) linked to poor prognosis after R0 resection. For patients without lymph node metastasis, the median survival of those who underwent regional lymphadenectomy was comparable with those who did not (18 months vs 22 months, P = 0.817).</p><p><b>CONCLUSIONS</b>R0 resection is mandatory for ICC patient to achieve long-term survival. Aggressive resection benefits for selected patients with local advanced disease. Higher TNM stage and lymph node metastasis were poor prognostic factors for ICC patients after R0 resection.</p>

Changes in TGF-beta1/Smads signaling pathway in rats with chemical hepatocarcinogenesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in transforming growth factor beta 1 (TGF-beta1)/Smads signaling pathway in rats with chemical hepatocarcinogenesis.</p><p><b>METHODS</b>Fresh diethylnitrosamine (DENA) solution was administered in SD rats to induce hepatocellular carcinoma (HCC). The protein expressions of TGF-beta1, phosphorylated Smad2, Smad4 and Smad7 were detected in these rats with immunohistochemistry, and the mRNA expression of Smad4 was evaluated with RT-PCR.</p><p><b>RESULTS</b>Cirrhotic nodules occurred in the rats 8 weeks after DENA treatment, and HCC nodules were found 16 weeks after the treatment. In the normal liver tissue, very low levels of TGF-beta1 and Smad4 expressions, low Smad7 expression and high phosphorylated Smad2 expression were detected. The development of liver cirrhosis was accompanied by increased expressions of TGF-beta1, Smad4 and Smad7 but at 8 weeks after DENA treatment, the expression of phosphorylated Smad2 was significantly decreased, followed then by gradual increment till nearly the normal level. Twenty-two weeks after DENA treatment, Smad4 expression in liver tissue decreased markedly as compared with the levels at 8 and 16 weeks. The expressions of Smad4 and phosphorylated Smad2 in the HCC tissue was significantly lower than those in normal liver tissue.</p><p><b>CONCLUSION</b>Hepatocarcinogenesis involves very complex mechanisms, can can be related partially to the decreased Smad4 and phosphorylated Smad2 expression and TGFbeta1 and Smad7 overexpression in advanced stage of liver cirrhosis.</p>

The study of inhibition effect of octreotide on the growth of hepatocellular carcinoma xenografts in situ in nude mice / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effect of octreotide (OCT) on inhibiting hepatocellular carcinoma (HCC) and investigate its mechanisms.</p><p><b>METHODS</b>Nude mice bearing xenografts in situ were treated with OCT or saline control for 7 weeks since tumor implantation. The immunohistochemistry for somatostatin receptor 2 (SSTR2), cMet, transforming growth factor beta1 (TGFbeta1), phospho-Smad2, Smad4 and Smad7 was performed. SSTR2 and Smad4 mRNA expression was measured by semi-quantitative RT-PCR.</p><p><b>RESULTS</b>After OCT treatment, the mean tumor weight in mice given OCT (0.17 +/- 0.14 g) was significantly lower than that of the control group (0.53 +/- 0.06 g). The inhibition rate of tumor was 67.9%. mRNA and protein expression of SSTR2, Smad4 in tumor cells of the treatment group were significantly more than that of the control group. cMet expression in OCT group was remarkably lower than that in control group. Between two groups, the expression of TGFbeta1, phospho-Smad2 and Smad7 were not remarkably different. In addition, phospho-Smad2 expression in HCC was significantly less than that of the normal hepatic cell.</p><p><b>CONCLUSION</b>OCT can inhibit the growth of HCC xenografts markedly. The mechanisms of OCT-induced inhibition effect may be related to up-regulating SSTR2 expression, down-regulating cMet, and recovering the function of TGFbeta/Smads-induced antitumor. In addition, the decreased expression of phospho-Smad2 may be an important feature of Bel7402 cells.</p>