• Radiation Oncology Journal
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• v.37 no.4
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• pp.286-292
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• 2019

Purpose: A mandibular metastasis is uncommon in patients with hepatocellular carcinoma (HCC). We report the clinical features of this rare lesion and evaluate the effectiveness of radiotherapy in affected patients. Materials and Methods: We retrospectively reviewed our institutional medical records for HCC patients who received radiotherapy for bone metastasis, and included cases of mandible metastasis. The clinical features of these cases, and the characteristics and outcomes of the treatments were assessed. Results: A total of 1,498 patients with a bone metastasis from HCC were treated with radiotherapy between July 1998 and April 2012 at our institution. We identified 9 patients (0.6%) in this cohort that received radiotherapy for a mandibular metastasis. The condyle was the most common location of mandibular metastasis. The median radiation dose was 40 Gy (range, 27.5 to 60 Gy), with a daily dose of 2-3 Gy. All of these 9 patients died during a median follow-up of 9 months (range, 1 to 19 months). Symptom relief was achieved in 7 of 8 patients who completed radiotherapy. Tumor size reduction was observed in 2 of 4 patients who underwent radiologic evaluation after radiotherapy. Conclusions: Metastasis to the mandible from HCC has a poor prognosis. Radiotherapy can be an effective local treatment option for symptomatic relief in these cases.

• Journal of Microbiology and Biotechnology
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• v.20 no.4
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• pp.821-827
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• 2010

Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase the transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested, including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.1
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• pp.11-14
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• 2010

Human tumors, including those of the hepatobiliary system, express a number of specific antigens that can be recognized by T cells, and may provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. The ability to culture sufficient numbers of DCs from human bone marrow or blood progenitors has attracted a great deal of interest in their potential utilization in human tumor vaccination. $CD34^+$ peripheral blood stem cells (PBSCs) were obtained from a patient with a hepatocellular carcinoma. The PBSCs were cultured in the X-VIVO 20 medium supplemented with the Flt-3 Ligand (FL), GM-CSF, IL-4 and TNF-$\alpha$ for 12 days. The morphology and functions of the cells were examined. The generated cells had the typical morphology of DCs. When the DCs were reinjected into the same patient, an augmentation of the cytotoxic T lymphocyte (CTL) activity was observed. Concomitantly, an increase in the natural killer (NK) cell activity was also detected in the patient. These results suggest that DCs-based cancer immunotherapy may become an important treatment option for cancer patients in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2985-2990
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• 2012

Background: Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. Materials and methods: In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. Results: A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. Conclusions: According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4853-4856
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• 2016

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.355-358
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• 2013

XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.5-9
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• 2013

Rhomboids were identified as the first intramembrane serine proteases about 10 years ago. Since then, the study of the rhomboid protease family has blossomed. Rhomboid domain containing 1 (RHBDD1), highly-expressed in human testis, contains a rhomboid domain with unknown function. In the present study, we tested the hypothesis that RHBDD1 was associated with proliferation and apoptosis in hepatocellular carcinoma using recombinant lentivirus-mediated silencing of RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA levels markedly suppressed proliferation and colony formation capacity of HepG2 human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In summary, it was demonstrated that RHBDD1 might be a positive regulator for proliferative and apoptotic characteristics of hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3697-3703
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• 2016

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sorafnib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival.

• BMB Reports
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• v.53 no.8
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• pp.431-436
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• 2020

Alpha-fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for Hepatocellular carcinoma（HCC). However, the underlying mechanism of AFP expression in HCC is poorly understood. In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic target for HCC.