Rei-Ping Tang

Prognostic Value of Signal Transducers and Activators of Transcription 3 in Breast Cancer

Introduction: Constitutively activated signal transducers and activators of transcription (STAT) proteins are found in various types of tumors. However, there is still very limited information about the role of STATs in breast cancer. The power of tissue microarray technique is the capability of doing a series of analyses of thousands specimens in a parallel fashion with minimal damage to the origin blocks. This study was designed with the application of tissue microarray to analyze the STAT3 status in breast cancer. Materials and Methods: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected, and STAT3 expression was analyzed by immunohistochemical staining with tissue microarray. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histologic grading, and tumor-node-metastasis staging were also collected. Results: By multivariate analysis, the STAT3 expression turned out to be significantly related to the overall 5-year survival rate (P = 0.024). Conclusion: Immunohistochemical staining with tissue microarray was convenient and feasible for the analysis of STAT3 expression status in breast cancer. Our preliminary results are promising and deserve further evaluation. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2286–90)

Cellular changes in hepatocytes and intestinal endothelium after hepatoduodenal ligament occlusion and protective effects of caspase inhibition.

Introduction:Hepatic vascular control is used by many surgeons to prevent massive hemorrhage during hepatectomy. However, this may carry a risk of ischemic damage to the hepatocytes. Another major drawback of intraoperative occlusion of the hepatoduodenal ligament is portal stasis with resultant intestinal congestion which may cause adverse effects on the intestinal functions. CD44 is a transmembrane glycoprotein present in many types of epithelial cells. By mediating the attachment of dividing crypt cells to the basal lamina via hyaluronan, CD44 is considered to play a role in maintaining the intestinal villus integrity. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. ZVAD-fmk is a cell-permeable irreversible inhibitor of caspase and might block the processing of many caspases. This study is designed with the purpose to evaluate the impact of intraoperative occlusion of the hepatoduodenal ligament on hepatocyte and intestine functions and also to evaluate the potential influence of ZVAD-fmk on the hepatocyte and intestine functions. Materials and Methods:Male Sprague-Dawley rats were randomized to 5 groups. Group 1(C) underwent sham operation. Group 2 (HDL30) underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 3 (HDL 15) underwent occluding the hepatoduodenal ligament by for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. Group 4 (ZHDL30) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament by for 30 minutes. Group 5 (ZHDL15) first received ZVAD-fmk, then underwent occluding the hepatoduodenal ligament for 15 minutes, releasing for 5 minutes, underwent occlusion for another 15 minutes. After removing the temporary occlusion, liver tissue and proximal jejunum were harvested. Hepatocyte and intestine apoptosis were quantitated using the TUNEL method. CD 44 status of jejunum were determined by immunohistochemical staining. Results:Hepatocyte apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). Jejunal apoptosis was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk effectively attenuated this phenomenon in both groups. There was no significant difference between group (HDL30) and group (HDL15). CD44 expression on jejunum was significantly increased in group (HDL30) and group (HDL15) when compared with group (C). ZVAD-fmk failed to effectively diminish this phenomenon. Conclusion:Occlusion of the hepatoduodenal ligament significantly increased both hepatocyte and jejunal apoptosis and pretreatment with ZVAD-fmk could effectively diminish such phenomenon. CD44 expression on jejunum was also significantly increased by intraoperative occlusion of the hepatoduodenal ligament, yet pretreatment with ZVAD-fmk failed to show significant effect on such phenomenon.

Antithrombin-III attenuates hepatocyte apoptosis in bile duct ligated rat: a striking cellular change.

Background and purpose: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. This study was designed with the purpose of evaluating the possible effect of antithrombin-III on hepatocyte apoptosis in bile duct ligated rat. Materials and methods: The rats were randomized to 3 groups: group 1 (control, C) underwent sham operation; group 2 (obstructive jaundice, OB) underwent common bile duct ligation; and group 3 (obstructive jaundice with antithrombin-III, OBAT-III) underwent common bile duct ligation and simultaneously were treated with antithrombin-III. Liver tissues were harvested on the fifth postoperative day. Results: Hepatocyte apoptosis was significantly increased in bile duct ligated group when compared with the sham operation group. The administration of antithrombin-III effectively attenuates such phenomenon in obstructive jaundice with antithrombin-III group. Conclusion: Bile duct ligation significantly increased hepatocyte apoptosis and the administration of antithrombin-III effectively attenuates such phenomenon.

The kinetic expression of lipopolysaccharide-binding protein and CD14 gene in obstructive jaundice.

ABSTRACT Background: Binding lipopolysaccharide (LPS) with high-affinity, lipopolysaccharide-binding protein (LBP) and CD14 lower the threshold stimulatory concentrations of LPS dramatically and enhance the rate of cytokine production markedly. This study aimed to investigate the kinetic expression of LBP/CD14 and its possible relationship with tumor necrosis factor alpha (TNF-α) to better understand the pathophysiology of obstructive jaundice. Materials and Methods: The tissues (liver, spleen, intestine, and lung) of male Sprague-Dawley rats were harvested at pre-bile duct ligation in controls and at specific time points (24, 48, 72, 96, and 120 hr) after bile duct ligation. LBP, CD14, and TNF-α mRNA expression were measured in tissues harvested from controls and at the specific time points. Results: Hepatic LBP mRNA expression increased significantly at five days after bile duct ligation. CD 14 mRNA expression increased significantly after five days of bile duct ligation in liver, lung, spleen, and ileum. TNF-α mRNA expression increased significantly in all four organs (liver, lung, spleen, and ileum) after four days of bile duct ligation. Conclusion: Five days of bile duct ligation upregulated CD 14 mRNA expression in liver, lung, spleen, and ileum and increased TNF-α mRNA expression simultaneously in the liver, lung, spleen, and ileum. In addition, five days of bile duct ligation also upregulated LBP mRNA expression in the liver and increased hepatic TNF-α mRNA expression simultaneously. The kinetic expressions of LBP and CD 14 in obstructive jaundice are intriguing and further evaluation is warranted.

Glypican-3 Expression in Breast Cancer

Background: The protein Glypican-3 has been found in various types of tumors and has shown promise as a tumor marker. However, there is still very limited information about the role of Glypican-3 in breast cancer. Tissue microarray (TMA) analyzes thousands of specimens in parallel with minimal damage to the origin blocks. The purpose of this study was to ascertain the role of Glypican-3 status in breast cancer using TMA. Materials and Methods: Archival tissue specimens from 99 patients with primary invasive breast cancer were analyzed for Glypican-3 expression by immunohistochemical staining with TMA. The results were compared to clinicopathologic data by the use of multivariate analysis. Results: TNM stage was significantly related to the overall 5-year survival rate. Nevertheless, Glypican-3 expression has no significant relationship to overall five-year survival. Conclusions: Immunohistochemical staining with TMA was convenient and feasible for analyzing Glypican-3 expression status in breast cancer. However, our preliminary results show that Glypican-3 expression had no significant prognostic value in breast cancer.