• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.167-174
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• 2023

Development of hepatocellular carcinoma (HCC) is driven by a multistep and long-term process. Because current therapeutic strategies are limited for HCC patients, there are increasing demands for understanding of immunotherapy, which has made technological and conceptual innovations in the treatment of cancer. Here, I discuss HCC immunotherapy in the view of interaction between liver resident cells and immune cells.

• 약학회지
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• 제56권6호
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• pp.352-357
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• 2012

FGFR3 is a member of the fibroblast growth factor receptor family which interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance. Accumulated evidence suggests that aberrant regulation of FGFR3 and genetic alterations are implicated in the development and progression of various cancers. Despite a high incidence of FGFR3 over-expression, no such investigation has been performed in hepatocellular carcinoma. Thus, we investigated genetic alterations of the FGFR3 gene in 73 cases of hepatocellular carcinoma by single-strand conformational polymorphism (SSCP) and sequencing. One silent mutation (A369A) was found in the extracellular domain of FGFR3, and one genetic alteration in the immunoglobulin-like III domain of FGFR3 appeared to be polymorphism. Taken together, we concluded that over-expression of FGFR3 in hepatocellular carcinoma is not associated with genetic alterations of FGFR3 gene, and we suggest that there could be another underlying mechanism of aberrant FGFR3 expression in hepatocellular carcinoma.

• 대한수의학회지
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• 제37권3호
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• pp.509-523
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• 1997

This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4509-4513
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• 2013

Chronic hepatitis B virus (HBV) infection has long been the most common cause of hepatocellular carcinoma (HCC). However, some aspects of the pathogenesis of HBV infection and genesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still inconclusive. An increasing number of published studies indicate that hepatitis B virus mutations are associated with risk of HCC. These variations include, in particular, mutations in ORF S,C,X gene regions. This mini-review summarizes results of clinical studies and molecular mechanisms on the possible relations of HBV mutations with the development of hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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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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• 제14권3호
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• pp.1579-1583
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• 2013

Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-${\kappa}B$) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4769-4775
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• 2015

Background: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and thirdly leading cause of cancer-related death worldwide. The estimated risk of hepatocellular carcinoma is 15 to 20 times as high among persons infected with HCV as it is among those who are not infected, with most of the excess risk limited to those with advanced hepatic fibrosis or cirrhosis. Glypican3 (GPC3) plays a key role in relation to signaling with growth factors, regulating the proliferative activity of cancer cells. Glutamine synthetase (GS) catalyzes the synthesis of glutamine from glutamate and ammonia in the mammalian liver. GS was suggested as a specific marker for tracing cell lineage relationships during hepatocarcinogenesis. In normal liver, GS expression is seen in pericentral hepatocytes, but not by midzonal or periportal hepatocytes. In HCC, strong and diffuse GS expression in seen in tumor cells. Results: Glypican3 immunopositvity was highly specific and sensitive indicator for hepatocellular carcinoma as well as glutamine synthetase which was found to be a sensitive and specific indicator for development of hepatocellular carcinoma when compared to cirrhosis, liver cell dyspalsia and metastatic carcinomas. Statistical analysis revealed a significant association between GPC3 and GS with tumor size (P=0.003, p=0.006, respectively). Diffuse staining significantly associated with large tumor size while, focal and mixed staining was detected more with small tumor size. Studying the relation with tumor grade also revealed significant association between diffuse GPC3 and GS staining with high tumor grade. Diffuse staining was detected in 91.7% and 100% respectively of poorly differentiated specimens and only in 33.3% and 22.2% of well differentiated specimens. Conclusions: While using GPC3 and GS to screen for premalignant hepatic lesions remains controversial, our data suggest that GPC3 and GS may be a reliable diagnostic immunomarkers to distinguish HCC from benign hepatocellular lesions. However, negative immunostaining should not exclude the diagnosis of HCC.

• Journal of Yeungnam Medical Science
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• 제32권1호
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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.

• Genomics & Informatics
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• 제6권4호
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• pp.192-201
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• 2008

Erythropoietin-producing human hepatocellular carcinoma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular system development. Eph receptor overexpression has been observed in various cancers and is related to the malignant transformation, metastasis, and differentiation of cancers, including hepatocellular carcinoma (HCC). Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. EphrinB1, the ligand of EPHB1, has been shown to regulate HCC carcinogenesis. Here, we sought to determine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, including chronic liver disease (CLD) and HCC. We genotyped 26 EPHB1 single nucleotide polymorphisms (SNPs) in 399 Korean CLD, HCC, and LD (CLD+HCC) cases and seroconverted controls (HBV clearance, CLE) using the GoldenGate assay. Two SNPs (rs6793828 and rs11717042) and 1 haplotype that were composed of these SNPs were associated with an increased risk for CLD, HCC, and LD (CLD+HCC) compared with CLE. Haplotypes that could be associated with HBV-infected liver diseases by affecting downstream signaling were located in the Eph tyrosine kinase domain of EPHB1. Therefore, we suggest that EPHB1 SNPs, haplotypes, and diplotypes may be genetic markers for the progression of HBV-associated acute hepatitis to CLD and HCC.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.