Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells.

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.

High prevalence of hepatitis B virus infection in patients with B-cell non-Hodgkin's lymphoma in Korea.

This study assessed the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with non-Hodgkin's lymphoma in a highly HBV-endemic area. The prevalence of either HBV or HCV infection in 235 patients with non-Hodgkin's lymphoma was compared with that of an age- and sex-matched hospital control group of 235 patients. The prevalence of HBV infection was higher in B-cell non-Hodgkin's lymphoma (15.5%) than control (8.1%), but the prevalence of HCV infection in the non-Hodgkin's lymphoma patients (2.1%) and control group (3%) was similar. HBV prevalence increased significantly with age in the B-cell non-Hodgkin's lymphoma patients. The presence of HBV proteins and DNA in lymphoma tissues and peripheral blood mononuclear cells (PBMCs) from HBV-infected non-Hodgkin's lymphoma patients was also investigated using immunohistochemistry and PCR. HBV DNA was frequently detected in PBMCs from HBV-infected non-Hodgkin's lymphoma patients, but HBV antigens were not. Therefore, HBV infection, but not HCV infection, was associated with B-cell non-Hodgkin's lymphoma in Korea, suggesting a possible role for HBV in the development of non-Hodgkin's lymphoma.

The usefulness of colonoscopy as a screening test for detecting colorectal polyps.

BACKGROUND/AIMS: Colonic polyps are the most common lesions encountered during screening colonoscopy. The purpose of this study is to evaluate the usefulness of colonoscopy to detect colonic polyps in adults. METHODOLOGY: From January 2003 to September 2005, a total of 4,629 adults underwent colonoscopic screening as a part of a health evaluation program. We analyzed the completed questionnaires, and the colonoscopic and pathologic findings. RESULTS: Complete colonic evaluation was possible in 4,491 (97.0%) subjects, and 804 (17.9%) had adenomatous polyps, including 153 subjects (3.4%) with advanced adenomas. There were no significant complications such as bowel perforation or massive bleeding requiring transfusion in relation to the procedure. There was a trend toward an increased prevalence of adenomatous polyps with age. Among the subjects with polyps, 72.1% of the subjects had distal polyps and the relative risk for proximal polyp, according to the distal findings, was 5.4 (95% CI: 4.5-6.3) for adenomatous polyp, 5.1 (95% CI 3.6-7.0) for advanced adenoma as compared to the finding of no adenomatous polyp. CONCLUSIONS: Colonoscopy performed by experienced colonoscopists as a screening test is feasible for detecting subjects with colorectal polyps.

[Positron emission tomography with fluorine-18-fluorodeoxyglucose is useful for predicting the prognosis of patients with hepatocellular carcinoma].

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is heterogenous in terms of its glucose metabolism. Positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with HCC. This study was designed to assess the usefulness of FDG-PET for predicting the outcome of the patients with HCC. METHODS: FDG-PET was performed for 27 patients with HCC. The standardized uptake value (SUV) and SUV ratio (defined as the tumor-to-nontumor ratio of SUV) was calculated for each patient. The clinical factors of the outcome were analyzed by regression analysis using Cox's multivariate proportional hazard model. The survival rate was calculated by the Kaplan-Meier method. RESULTS: Among the analyzed clinical factors including tumor size, number of tumors, AFP, involvement of major vessels, presence of systemic metastases, Child-Pugh class the SUV and SUV ratio, only the SUV was the only significant independent prognostic factor (p=0.001). On the basis of the SUV, the patients were divided into two groups of roughly equal size: group A, SUV of <7; group B, SUV > or =7. The cumulative survival rate was significantly lower for group B than for group A, and the median survival time was significantly different (4 months vs 15 months, respectively) (p=0.003). CONCLUSIONS: These results suggest that FDG-PET is useful to predict the outcome for patients with hepatocellular carcinoma.

[Evaluation of various hepatic lesions with positron emission tomography].

BACKGROUND/AIMS: [18F]FDG-PET is a functional imaging modality reflecting cellular glucose metabolism. In most malignant cells, accumulation and trapping of [18F]FDG allows the visualization of increased uptake compared with normal cells. The aim of this study was to assess the value of PET in differentiating benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. METHODS: Eighty patients with liver lesions were enrolled (hepatocellular carcinoma 34, cholangiocarcinoma 8, metastatic liver cancer 25, hemangioma 6, liver abscess 7). Liver metastases were 22 adenocarcinoma, 2 lymphoma, 2 squamous cell carcinoma. The PET images of these patients were analyzed. SUV and lesion-to-normal liver background SUV ratio were obtained and compared among the disease groups. RESULTS: All liver metastases and all cholangiocarcinomas had increased uptake value, with SUV ratios greater than 2. Hepatocellular carcinoma had SUV ratios greater than 2 in 20 of 34 patients (59%). All hemangiomas had poor uptake, a SUV ratio of less than 2. All liver abscesses showed definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful in differentiating malignant from benign lesions of the liver in limited situations. Limitations included false negative results in some patients with hepatocellular carcinoma. Liver abscesses raised problems in differential diagnosis from malignant liver tumors. The findings of this study suggest that the PET technique might be applied in tumor staging and the detection of recurrence, as well as monitoring responses to therapy for all adenocarcinomas and some hepatocellular carcinomas.