Comparison of liver regeneration after a splenectomy and splenic artery ligation in a dimethylnitrosamine-induced cirrhotic rat model

AbstractAimA splenectomy and splenic artery ligation accelerate liver regeneration and improve liver function after a hepatectomy. However, there are no studies that directly compared the effects of a splenectomy and splenic artery ligation. In the present study, we compared the effects of a splenectomy and splenic artery ligation in cirrhotic rats.MethodsDimethylnitrosamine (DMN) was administered intraperitoneally for 4 weeks to induce cirrhosis. The rats were divided into three groups: sham operation (CT group), splenic artery ligation (SAL group) and splenectomy (SP group). Liver functions [alanine aminotransferase (ALT) and total bilirubin (T. Bil)], plasma TGF-β1, histopathological changes, extent of liver fibrosis (fibrotic rate) and regeneration [Ki-67 labelling index(LI)] were investigated in each group.ResultsALT and T. Bil levels were significantly lower in the SP group than the CT and SAL groups. TGF-β1 levels were significantly lower in the SP group than in the CT and SAL groups. The fibrotic rate was significantly lower in the SP group than in the CT and SAL groups. The Ki-67 labelling index was significantly higher in the SP group than in the CT and SAL groups.DiscussionA Splenectomy significantly improved liver regeneration with reduction of plasma TGF-β1 levels compared with splenic artery ligation in DMN-treated cirrhotic rats

N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition.

Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition

Infectious liver cyst in a 71-year-old woman.

<p>(a) Abdominal CT scan showed enhanced cystic wall. (b) Laparotomy view. (c) Intraoperative photograph of post-central hepatectomy. (d) Surgical sample: note the presence of an abscess separated by a septum from the tumor area.</p

Simple hepatic cyst in a 64-year-old woman.

<p>a) Abdominal CT scan shows a well-defined water attenuation lesion in the right hepatic lobe. (b) 3D-image showed a cyst capacity of 1800 ml. Note the Glisson’s pedicle in the base. (c) Laparoscopic aspiration and ethanol sclerosis using sand balloon catheter. (d) Wide unroofing in the right hepatic lobe.</p

Comparison of protein and mRNA expression levels of various factors between low and highly metastatic gastric cancer cell lines.

<p>(A) Western blot analysis of total cell lysates shows protein expression levels of NDRG1, growth factor receptor, EMT-related proteins, Wnt/β-catenin-related proteins, and other factors in HSC-58, 58As1 and 58As9 cells. (B) Comparison of mRNA expression levels of NDRG1, E-cadherin, vimentin, Snail, MMP-1 and β-catenin in HSC-58, 58As1 and 58As9 cells by qRT-PCR analysis. (C) Immunocytochemical analysis of E-cadherin and β-catenin in HSC-58 and 58As9, using specific antibodies against E-cadherin, β-catenin and DAP1. Magnification×200. (D) Western blot analysis shows expression of β-catenin and Snail in nucleus and cytosol fraction. CREB, a nuclear marker, and α-tubulin, a cytosol marker. (E,F) Comparison of luciferase activity driven by E-cadhrin promoter and β-catenin (TopFlash) driven promoter between HSC-58 and its highly metastatic cell lines. The relative promoter activity is presented when normalized by the activity in HSC-58. *p<0.01.</p

Altered expression of EMT-related factors by NDRG1 knockdown in highly metastatic 58As1.

<p>(A) Microarray analysis for the effect of NDRG1 knockdown on expression of genes that are up- or down- regulated in Asl/Sic50 versus As1/Mock3. Relative expression rates are presented on genes belonging to three biological functions. (B) Comparison of protein expression levels of NDRG1, EMT-related proteins, β-catenin, Akt, p-Akt, ERK1/2, p-ERK1/2, GSK-3β, p-GSK-3β and EGFR by western blot analysis with total cell lysate. (C) The mRNA expression of NDRG1, E-cadherin, vimentin, Snail, MMP-1 and β-catenin was determined by qRT-PCR analysis. (D) Comparison of luciferase activity driven by β-catenin (TopFlash) between As1/Mock3 and its NDRG1 knockdowned cell lines. Relative luminescence fold is presented when normalized by the value in As1/Mock3. Each column is average of triplicate trials±SD.</p