• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10917-10922
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• 2015

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$), alpha-fetoprotein (${\geq}100ng/ml$), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.44-49
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• 2005

The protective effects of the DWP-04 [DDB : selenium yeast: glutathione {31.1 : 6.8 : 62.1 (%, w/w)} against hepatotoxicity by carbon tetrachloride $(CCl_4)$ were studied in rats. The rats were intraperitoneally injected with $CCl_4$ (50% in com oil) at initial dose of 1 ml/kg followed by 0.5 ml/kg 3 times during 1 week. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was administered everyday before the start of $CCl_4$ injection for two weeks. $CCl_4$ induced hepatocelluar degeneration and necrosis, which led to a great increase in serum aminotransferase, alkaline phosphatase activity and serum lipid levels. It was found by biochemical analysis that $CCl_4$ treatment remarkably increased thiobarbituric acid reactive substances and physphatidylcholine hydroperoxide in hepatic tissues and induced antioxidant enzymes such as catalase and superoxide dismutase (SOD). Liver and serum lipids were significantly lower in rats fed on DWP-04 than in rats induced by $CCl_4$ only-treatment. These results suggested that the DWP-04 could be a promising candidate for the protection of liver injury based on the preventive effects against lipid peroxidation and serum biochemical parameters.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.166-169
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• 2006

Accumulated evidences have established that aberrant regulation of histone deacetylases (HDACs) is one of major causes for development of human malignancies. Mammalian HDACs can be divided into three subclasses consisting of 11 homologous of HDACs and 7 of sirtuins, but little is known about HDAC2 causes for carcinogenesis in solid tumors. Here, in order to investigate the roles of HDAC2 in carcinogenesis of liver cancer progression, we analyzed the expression of HDAC2 in 62 human hepatocellular carcinomas by utilizing Immunohistochemistry. Moderate to strong expression of HDAC2 was found in 54 (87%) out of total 62 tumors. The majority of positive tumors were detected in nucleous, but normal hepatocytes did not express of HDAC2 or showed weak positive staining. Interestingly, we were also noted that HDAC2 expression was appeared to be associated with aggressiveness of the tumors by the fact that HDAC2 expression was observed with significances in high grade tumors (Edmonson grade II, III). Taken together, we found the aberrant expression of HDAC2 in hepatocellular carcinomas, and this suggests that HDAC2 may play an important role in the development of liver cancer.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.742-746
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• 1993

Recent literature reveals that pulmonary embolism secondary of pulmonary tumor embolism are dyspnea, hemoptysis, pulmonary hypertension, and circulatory collapse. We experienced a case of pulmonary embolism secondary to hepatocelluar cancer in 53-year-old man. From 2 months before admission, he began to experience cough and mild shortness of breath. Within a few days these symptoms progressed to near total incapacity. Pulmonary embolism was confirmed by angiography and the diagnosis of hepatocellular cancer was estabillished by abdomen CT and $\alpha$-FP(21,000 ng/ml). There was no evidence of intravascular cogulation elsewhere in deep vein of the extremities or risk factors of deep vein thrombosis. Thus we consider that pulmonary embolism in this patients is related to hepatocellular cancer rather than deep vein thrombosis. Therefore we report the first case which hepatocellular cancer initially presented as pulmonary embolism in Korean literature.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.53-62
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• 2011

Radiation-induced liver disease (RILD) has been characterized as a veno-occlusive disease with anicteric elevation of alkaline phosphatase (ALP). However, some RILD patients present with elevated transaminase levels rather than with anicteric elevation of ALP, and these findings are common in the Asia-Pacific region where hepatitis B virus (HBV) infection is associated with 70~90% of hepatocelluar carcinoma (HCC) cases. In addition, the development of RILD is more common in patients with hepatitis B virus-related HCC. These findings indicate that susceptibility to RILD might be different in HBV carriers and non-carriers, and moreover, RILD in patients with HBV-related HCC might be associated with another unique pathogenesis such as HBV reactivation. However, HBV reactivation after hepatic irradiation has been reported in only a few studies. This study reports three cases of HBV reactivation alter hepatic tomotherapy for management of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.559-562
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• 2012

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

• Toxicological Research
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• v.23 no.1
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• pp.11-17
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• 2007

This study was carried out to investigate the effect of LAB (Lactic acid bacteria: Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus) on detoxication of damaged liver in carbon tetrachloride ($CCl_4$) and ethanol (25%)-treated rats. Rats had been daily (twice a day) pre-treated with saline (0.5 ml/kg: untreated group), $CCl_4$ (0.5 ml/kg: other groups) for 6 days. At seventh day, after treating rat with $CCl_4$ and then, mixture of LAB ($10^{11}$/0.5 ml: LAB group), saline (0.5 ml/kg: untreated group, $CCl_4$ group), and biphenyl dimethyl dicarboxylate (DDB) (50 mg/kg: DDB group) were treated orally with $CCl_4$ for 8 days. Ethanol is treated as the same manner instead of $CCl_4$. To investigate the hepatoprotective effect, rats treated with $CCl_4$ and ethanol were analyzed with serum GOT and GPT level. The GOT and GPT levels of LAB group was lower than the level of $CCl_4$ and DDB group. Especially, compared with data of $CCl_4$ group, GPT activity showed statistically significant result in the significance level of p < 0.05. The LAB group treated with ethanol also showed lower level of GOT and GPT than the other control groups treated with ethanol. The triglyceride level of serum decreased more in a group treated special materials (DDB and LAB group) than ethanol group. As well, the effect of LAB on the antifatigue has been investigated. The animals (10/group) were divided into 4 groups (untreated group, Carrier group, Red-ginseng group, LAB group). Each group was given carrier (0.9 mg/0.2 ml), red ginseng extract (200 mg/kg), and mixture of LAB ($10^{11}$/0.2 ml). Special materials were given for three weeks. After finishing treating through oral, horizontal wire test, rotarod test, and forced swimming test were performed. The time of resistance to fatigue of the group, fed with mixture of LAB, was longer than the time when mice treated with red-ginseng that the effect was already revealed. The result of this study revealed that LAB could decrease hepatocelluar injury compared with rats treated orally with $CCl_4$ and ethanol, and could also decrease fatigue.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.5-24
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• 2009

Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.85-90
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• 2010

Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.56-78
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• 1998

Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.