[Show abstract][Hide abstract] ABSTRACT: ZNF689, a C2H2-type of zinc finger transcription factor, was suggested to play a key role in hepatocarcinogenesis. However, none of the target genes or potential roles of ZNF689 in hepatocellular carcinoma (HCC) have been elucidated. Here, we investigated the role of ZNF689 in HCC cell lines focusing on cell viability and apoptosis.We found that the knockdown of ZNF689 by its specific siRNA decreased cell viability of Huh7. Cell cycle analysis revealed that the ZNF689 knockdown increased the proportion of the sub-G1 population, accompanied by an increase of annexin V- and TUNEL-positive cells.Western blot analysis revealed that ZNF689 knockdown induced the expression of pro-apoptotic factors of Bcl-2 family, Bax, Bak and jBid. There was a correlation between the expression of ZNF689 and an anticancer drug 5-fluorouracil (5-FU) resistance of HCC cells. In vivo, ZNF689 siRNA reduced tumor viability in HepG2-bearing mice with statistical significance. Furthermore, immunohistochemical analysis demonstrated that nuclei of a significant portion of human HCC surgical specimens were positive for ZNF689. Taken together, our results indicate that ZNF689 blocks pro-apoptotic signaling by suppressing the Bak/Bax/Bid pathway, resulting in the progression of liver cancer and resistance to 5-FU. ZNF689 may be a promising chemotherapeutic target against liver cancer.
Experimental Cell Research 08/2011; 317(13):1851-9. DOI:10.1016/j.yexcr.2011.05.012 · 3.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: Patients infected with hepatitis C virus (HCV) genotype 2 are more sensitive to interferon (IFN) therapy than those infected with genotype 1, but 10-20% of patients do not achieve a sustained viral response (SVR) to combination therapy with pegylated (PEG) IFN and ribavirin (RBV). This study examines the prognostic factors associated with SVR in patients infected with HCV genotype 2 treated with PEG IFN and RBV. Methods: We treated 149 patients with chronic hepatitis C caused by HCV genotype 2. The patients received s.c. PEG IFN-α-2b (1.5 µg/kg) and a weekly weight-adjusted dose of RBV (600, 800 and 1000 mg per <60, 60-80 and >80 kg, respectively) for 24 weeks and then prognostic factors associated with the SVR were examined. Results: Among the 149 patients, 138 completed the combination therapy and a sustained viral response was achieved in 71.8% of them. Univariate analysis showed that age, as well as mean RBV and PEG IFN doses were factors affecting the SVR (P = 0.012, =0.021, =0.014). Multivariate analysis identified age and mean PEG IFN dose (P = 0.021, =0.018, respectively) as factors involved in the SVR, but not mean RBV dose. Conclusion: The SVR of patients infected with HCV genotype 2 depended on the dosage of PEG IFN, but not of RBV. Selecting sufficient doses of PEG IFN for combination with RBV is critical for treating such patients.
Hepatology Research 06/2011; 41(8):722-730. DOI:10.1111/j.1872-034X.2011.00816.x · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present report represents the case of a 36-year-old woman with congenital hepatic fibrosis (CHF). She was admitted to our hospital because of gastric varices. She was asymptomatic and her liver function tests were within normal limits. Computed tomography showed hepatomegaly, splenomegaly and collateral circulation, but no evidence of liver cirrhosis. Real-time tissue elastography suggested severe fibrosis of the liver. Laparoscopy showed wide and discrete white markings on the surface of the liver and she was diagnosed with CHF based on the histological examination. The findings obtained from elastography and laparoscopy were useful for making the diagnosis of CHF.
[Show abstract][Hide abstract] ABSTRACT: We describe laparoscopic findings of tuberculous peritonitis in a 68-year-old man and those at follow-up 8 months later. The initial laparoscopic findings revealed typical yellowish-white nodules on the liver surface, and histological findings showed granulomas with caseous necrosis. Laparoscopy 8 months later showed that anti-tubercular drugs had diminished the nodules and adhesions with a fibrin net appearance were evident. Laparoscopy and biopsy are useful for a rapid diagnosis of tuberculous peritonitis.
Internal Medicine 01/2010; 49(4):293-7. DOI:10.2169/internalmedicine.49.2809 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: There is a lack of information regarding the laparoscopic features and interobserver variation of histological diagnosis in patients with non-alcoholic fatty liver disease (NAFLD).
Methods: Thirty-five patients with NAFLD were studied for laparoscopic and histological findings. For the study of interobserver variation of histological diagnosis, two pathologists from different hospitals independently observed the 35 liver samples with patient names blinded to the pathologists. Assessment of laparoscopic findings on the diagnosis of non-alcoholic steatohepatitis (NASH) was also investigated.
Results: Histological diagnoses of the two pathologists were identical in 28 (five fatty liver, 23 NASH) patients, whereas they were not identical in seven patients (20%). The difference of diagnosis was mainly caused by the difference of judgment of minimal fibrosis and minimal necroinflammatory grade. Analysis of the laparoscopic findings revealed that small regular depressions were frequently found on the liver surface in patients with NASH. Scatter of dye on the liver surface facilitated the observation of this finding. Sensitivity and specificity of small depressions in the diagnosis of NASH was 73.9% and 80.0%, respectively.
Conclusion: Interobserver variation of the diagnosis was found in 20% of patients with NAFLD. Small regular depressions were characteristic findings of NASH. Laparoscopy is assessed to be useful for diagnosis of NAFLD, especially of early stage of NASH.
[Show abstract][Hide abstract] ABSTRACT: A 27-year-old man was admitted due to abdominal fullness. He had ascites and subcutaneous nodules on his head, with liver dysfunction and eosinophilia. Abdominal imaging revealed obstruction of the hepatic veins and stenosis of the inferior vena cava. Histological diagnosis of a subcutaneous nodule revealed obstructive thrombophlebitis with eosinophils. Tyrosine kinase created by fusion of the FIP1L1 and PDGFRA genes, which is characteristic of hypereosinophilic syndrome (HES), was detected. He was diagnosed with Budd-Chiari syndrome associated with HES. Liver function tests improved after interventional therapy followed by steroid therapy. It is important to diagnose the cause of Budd-Chiari syndrome.
Internal Medicine 02/2007; 46(14):1095-100. DOI:10.2169/internalmedicine.46.6438 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 63-year-old man was admitted to hospital in 2003 for treatment of a hepatocellular carcinoma (HCC). He was negative for HBs antigen (HBsAg) and anti-HCV antibody, and positive for anti-HBs. He had a past history of chronic hepatitis B. In 1986, HBsAg had become negative with the development of anti-HBs. In 2003, an HCC was detected and liver resection was carried out. Histological examination revealed moderately differentiated HCC and slightly fibrotic liver. It is suggested that a diagnosis of HCC, combined with negativity for HBsAg and anti-HCV antibody, may include cases of past recovery from chronic hepatitis B, such as this case.
Internal Medicine 02/2007; 46(1):29-33. DOI:10.2169/internalmedicine.46.1586 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH.
Thirteen older patients with AIH (mean age, 75.0+/-5.3 years; range, 70-89 years) and 27 middle-aged patients (mean age, 51.3+/-5.8 years; range, 41-60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined.
There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P<0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone.
This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH.
Hepatology Research 10/2006; 36(2):139-42. DOI:10.1016/j.hepres.2006.06.007 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some nodules cannot be visualized clearly on conventional sonography but can be visualized on CT. In the present study, we evaluated the usefulness of real-time percutaneous ablation therapy under virtual sonographic guidance for these nodules.
In vitro experiments were performed with gelatin gel to evaluate the accuracy of virtual sonography. We also studied 50 patients with 58 hepatocellular carcinoma nodules, of whom 18 patients (21 nodules) underwent radiofrequency ablation by virtual sonography. This was the initial treatment for seven of these patients and an additional treatment for 11 patients. Thirty-two patients (37 nodules) received radiofrequency ablation without virtual imaging. The patients receiving standard radiofrequency ablation were retrospectively selected as the historical control group under the same conditions as the study group.
The in vitro gelatin gel study revealed that all punctures had been performed accurately. In both the initial-treatment group and the additional-treatment group, the mean number of treatments with virtual sonography was significantly lower than that without virtual sonography (p = 0.003 for both groups). The rates of local recurrence and complications did not differ significantly between the two groups.
In the treatment of nodules not depicted on sonography, radiofrequency ablation assisted by virtual sonography is an efficacious alternative.
American Journal of Roentgenology 06/2006; 186(5 Suppl):S255-60. DOI:10.2214/AJR.04.1252 · 2.73 Impact Factor