• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3583-3587
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• 2012

SUMOylation has emerged as an important post-translational modification that modulates the localization, stability and activity of a broad spectrum of proteins. A dynamic process, it can be reversed by a family of SUMO-specific proteases (SENPs). However, the biological roles of SENPs in mammalian development and pathogenesis remain largely elusive. Here, we demonstrated that SENP2 plays a critical role in the control of hepatocellular carcinoma cell growth. SENP2 was found to be down-regulated in hepatocellular carcinoma (HCC) tissues and over-expression suppressed the growth and colony formation of HCC cells. In contrast, silencing of SENP2 by siRNAs promoted cancer cell growth. We further found that stability of ${\beta}$-catenin was markedly decreased when SENP2 was over-expressed. Interestingly, the decrease was dependent on the de-SUMOylation activity of SENP2, because over-expression of a SENP2 catalytic mutant form had no obviously effects on ${\beta}$-catenin. Our results suggest that SENP2 might play a role in hepatocellular carcinoma cell growth control by modulating the stability of ${\beta}$-catenin.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4953-4960
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• 2013

Primary liver cancer is one of the most common cancers at the global level, accounting for half of all cancers in some undeveloped countries. This disease tends to occur in livers damaged through alcohol abuse, or chronic infection with hepatitis B and C, on a background of cirrhosis. Various cancer-causing substances are associated with primary liver cancer, including certain pesticides and such chemicals as vinyl chloride and arsenic. The strong association between HBV infection and liver cancer is well documented in epidemiological studies. It is generally acknowledged that the virus is involved through long term chronic infection, frequently associated with cirrhosis, suggesting a nonspecific mechanism triggered by the immune response. Chronic inflammation of liver, continuous cell death, abnormal cell growth, would increase the occurrence rate of genetic alterations and risk of disease. However, the statistics indicated that only about one fifth of HBV carries would develop HCC in lifetime, suggesting that individual variation in genome would also influence the susceptibility of HCC. The goal of this review is to highlight present level of knowledge on the role of viral infection and genetic variation in the development of liver cancer.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.264-269
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• 2020

The study aimed to characterize chemical composition and anticancer property of the n-hexane fraction derived from Asiasari Radix et Rhizoma. The anticancer activity was evaluated on a panel of cancer cell lines including HN22, HSC2, HSC3, and HSC4 cells (human oral cancer), HCC827 and HCC827GR cells (human lung cancer), and KYSE30 and KYSE450 (human esophageal cancer) by MTS assay. As a result, The least polar subfraction from n-hexane-soluble layer displayed notable cytotoxicity on the tumor cell lines with IC50 ranging from 1.20 to 17.0 ㎍/ml. The chemical composition of constituents in the active subfraction was determined by gas chromatography-mass spectrometry (GC-MS). The essential oils comprised of sesquiterpenes including β-gurjunene (7.45%), γ-amorphene (6.61%), guaia-6,9-diene (6.40%), δ-guaiene (5.21%) and a phenylpropanoid, safrole (0.49%) were mainly identified in addition to long-chain hydrocarbons including n-heptadecane (24.60%), 7-hexadecene (4.44%) and a diterpenoid, ent-kaur-16-ene (6.57%).

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Journal of Yeungnam Medical Science
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• v.32 no.1
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• pp.1-7
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• 2015

Over several decades, a hierarchical cancer stem cell (CSC) model has been established in development of solid cancers, including hepatocellular carcinoma(HCC). In terms of this concept, HCCs originate from liver CSCs. Clinically HCCs show a wide range of manifestations from slow growth to very aggressive metastasis. One of the reasons may be that liver CSCs originate from different cells. This review describes the basic concept of CSCs and the cellular origin of liver CSCs.

• Investigative Magnetic Resonance Imaging
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• v.20 no.4
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• pp.231-240
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• 2016

Purpose: To determine whether liver stiffness (LS) measured by magnetic resonance elastography (MRE) can predict the outcome of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients. Materials and Methods: A total of 107 patients with Child-Pugh class A liver function who were treated with RFA for single HCC and who had undergone a gradient-echo MRE within 6 months before RFA were included. We evaluated the relationship between the LS values and the ablation volume, local tumor progression (LTP), and intrahepatic distant recurrence (IDR). We also constructed receiver operating characteristic (ROC) curves to examine the role of LS in predicting liver function deterioration, which was defined as an increase of Child-Pugh score by one point or more at 1 year after RFA. Results: There was no significant correlation between LS and ablation volume, and neither time to LTP nor IDR was associated with LS. Among the 66 patients who did not have recurrence 1 year after RFA, 5 patients (7.6%) developed liver function deterioration. A high LS value was significantly associated with development of liver function deterioration after RFA and the area under the ROC curve was 0.764 (95% CI 0.598-0.929, P = 0.003). Conclusion: LS measured by MRE could not predict ablation volume and tumor recurrence. However, high LS values were significantly associated with development of liver function deterioration.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.28-31
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• 2017

The number of laparosocpic liver resection performed every years has been increasing. There is a trend than more major hepatectomy and complex liver resection is being reported. However there has been a major obstacles in many centers because open liver resection is still considered as a gold standard and many surgeons are still getting used to the old method of liver resection. To start a new procedure, education and training is essential in order to achieve a good outcome without compromising the safety of the patients. A gradual progression is crucial in order to avoid dreadful complication. The development of the consensus meeting and difficulty score has facility the understanding of safe practice in the development of laparoscopic liver resection. In a long run, development of registry system will improve transparency and safety of this operation.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.1
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• pp.105-109
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• 2000

X-linked agammaglobulinemia (XLA) is a primary inherited B-cell immunodeficiency. The prevalence of neoplastic disease in patients with XLA is approximatedly 0.7%. The most frequent tumor is lymphoreticular malignancy. We report a case of hepatocellular carcinoma (HCC) in a 13-year-old boy with XLA, after probable maternal transmission of hepatitis B virus. The authors consider that the vertical transmission of hepatitis B virus might play an important role in the development of HCC in a child with XLA who could not eliminate hepatitis B virus effectively.

• BMB Reports
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• v.53 no.6
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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.