Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease

Analysis of Syndecan-2 Methylation in Bowel Lavage Fluid for the Detection of Colorectal Neoplasm

BACKGROUND/AIMS: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF). METHODS: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA. RESULTS: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test forSDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively. CONCLUSIONS: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.

17-DMAG has the Potentiated Anticancer Effects Against Hepatocellular Carcinoma Cells by Transfection of the Gene Encoding Hepatitis B Viral X Protein

BACKGROUND/AIMS: Hepatitis B viral protein X (HBx) is implicated in the pathogenesis of hepatocellular carcinoma (HCC) as well as the elevation of heat shock proteins (HSPs) after hepatitis B virus (HBV) infection. We thus investigated the anticancer effects of an HSP90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in HBx-transfected hepatocellular carcinoma cells. METHODS: pcDNA-HBx was made by inserting the HBx gene derived from the HBV-infected patient into pcDNA3.1 using the restriction enzymes (XbaI/HindIII). HBx-expressing HepG2 cells were then generated by transfecting HepG2 cells with pcDNA containing HBx gene. To compare the anticancer effects of 17-DMAG between pcDNA-HBx transfected HepG2 cells and the control cells (pcDNA-transfected HepG2 cells), we performed various molecular studies, including Ez-cytox proliferation assay, Western blot analysis, and flow cytometry. RESULTS: 17-DMAG inhibited the proliferation of pcDNA-HBx transfected HepG2 cells better than control cells (P<0.05). After treating with a various concentration of 17-DMAG (50–1,000 nM), pcDNA-HBx transfected HepG2 cells exhibited higher expression of pro-apoptotic proteins (c-caspase-3, c-caspase-8, and c-caspase-9) than did control cells (P<0.05). pcDNA-HBx transfected HepG2 cells showed higher activities of caspase-3, caspase-8, and caspase-9 than did control cells (P<0.05). Finally, we found that the expression of pro-apoptotic proteins (PARP and c-caspase-3) was considerably decreased by the use of a caspase inhibitor suggesting that 17-DMAG induces the cell death of HepG2 cells caspase-dependently. CONCLUSIONS: Our study strongly suggests that 17-DMAG has antiviral effects against HBV as well as anticancer effects against HepG2 cells. Thus, the application of 17-DMAG appears to be particularly advantageous to the HCC patients related with HBV infection.