• BMB Reports
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• 제47권4호
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• pp.215-220
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• 2014

Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2753-2758
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• 2014

Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7213-7218
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• 2014

Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6227-6231
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• 2013

In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance.

• Journal of Ginseng Research
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• 제35권1호
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• pp.69-79
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• 2011

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.

• BMB Reports
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• 제52권8호
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.999-1003
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• 2014

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5025-5030
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• 2015

Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN- ${\gamma}$ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN ${\gamma}$ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN ${\gamma}$ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-${\gamma}$ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-${\gamma}$ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4).

• BMB Reports
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• 제53권6호
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• pp.299-310
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• 2020

Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1130-1139
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• 2018

Objective: To compare the therapeutic efficacy between conventional transarterial chemoembolization (cTACE) and combined therapy using cTACE and radiofrequency ablation (RFA) in ultrasound (US)-invisible early stage hepatocellular carcinoma (HCC). Materials and Methods: From January 2008 to June 2016, 167 patients with US-invisible early stage HCCs were treated with cTACE alone (cTACE group; n = 85) or cTACE followed by immediate fluoroscopy-guided RFA targeting intratumoral iodized oil retention (combined group; n = 82). Procedure-related complications, local tumor progression (LTP), time to progression (TTP), and overall survival (OS) were compared between the two groups. Multivariate analyses were performed to identify prognostic factors. Results: There was no major complication in either group. The cTACE group showed higher 1-, 3-, and 5-year LTP rates than the combined group; i.e., 12.5%, 31.7%, and 37.0%, respectively, in the cTACE group; compared to 7.3%, 16.5%, and 16.5%, respectively, in the combined group; p = 0.013. The median TTP was 18 months in the cTACE group and 24 months in the combined group (p = 0.037). Cumulative 1-, 3-, and 5-year OS rates were 100%, 93.2%, and 87.7%, respectively, in the cTACE group and 100%, 96.6%, and 87.4%, respectively, in the combined group (p = 0.686). Tumor diameter > 20 mm and cTACE monotherapy were independent risk factors for LTP and TTP. Conclusion: Combined therapy using cTACE followed by fluoroscopy-guided RFA is a safe and effective treatment in US-invisible early stage HCCs. It provides less LTP and longer TTP than cTACE alone.