• BMB Reports
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• v.55 no.5
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• pp.220-225
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• 2022

Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis.

• BMB Reports
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• v.55 no.9
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• pp.459-464
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• 2022

Various mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite the growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of our study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells. The results showed that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, however, increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. Nevertheless, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin can be used as an adjuvant agent for therapy of liver cancer.

• Investigative Magnetic Resonance Imaging
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• v.26 no.1
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• pp.60-65
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• 2022

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used to detect and characterize focal hepatic lesions. Because gadoxetic acid is a hepatocyte-specific contrast agent, its patterns during hepatobiliary phase enhancement provide useful information for differential diagnoses of focal hepatic lesions. Hepatic angiomyolipoma (AML) is a rare mesenchymal hepatic neoplasm composed of blood vessels, epithelioid cells, and varying amounts of adipose tissue components. Hepatic AMLs usually show marked hypointensity during the hepatobiliary phase of gadoxetic acid-enhanced MRI as hepatic AMLs are devoid of hepatocytes and fibrotic components. The present study describes a patient with hepatic AML and an atypical imaging feature. This tumor showed hyperintensity during the hepatobiliary phase of gadoxetic acid-enhanced MRI, mimicking hepatocellular tumors such as hepatocellular adenoma. The hepatobiliary hyperintensity of this lesion was likely due to multifocal entrapped hepatocytes resulting from an intrasinusoidal growth pattern of tumor cells and insufficient hepatic parenchymal enhancement during the hepatobiliary phase of gadoxetic acid-enhanced MRI.

• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.92-98
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• 2016

The barcelona clinic liver cancer (BCLC) staging systemis regarded as the optimal staging system to predict prognosis and guide treatmentfor hepatocellular carcinoma (HCC) .According to the BCLC classification, only patients with BCLC A stage should undergo liver resection. In contrast, patients with intermediate-advanced HCC should be scheduled for palliative therapies,such as transcatheter arterial chemoembolization (TACE) and target therapy, even if the lesion is resectable. More and more studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by radical resection and many patients benefited from curative resection. The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations. A revision of the BCLC algorithm should be proposed.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.5-5
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• 2021

Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• Korean Journal of Radiology
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• v.20 no.1
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• pp.34-49
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• 2019

Conventional transcatheter arterial chemoembolization (c-TACE) is a widely used first-line palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). Despite the effectiveness of c-TACE, to date, technique and procedure scheduling has not yet been standardized. Drug-eluting microspheres (DEMs) were therefore introduced to ensure more sustained and tumor-selective drug delivery for permanent embolization. These DEMs can load various drugs and release them in a sustained manner over a prolonged period. This approach ensures the delivery of high concentrations of chemotherapeutic agents to tumors, without increasing systemic concentrations, and promote tumor ischemia and necrosis. This review summarizes the recent advances in the use of DEM-TACE to treat HCC.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.123-129
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• 2002

Purpose : The purpose of this study 띤as to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. Materials and Methods : Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from $36\~60\;Gy$ (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at $4\~8$ weeks following the completion of treatment. The acute and subacute toxicities were monitored. Results : An objective response was observed in 11 out of 17 patients, giving a response rate of $64.7\%$. The actuarial survival rate at 2 years was $21.2\%$ from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 30-CRT were gastro-duodenitis $(\geq\;grade\;2)$ in 2 patients. There were no treatment related deaths and radiation induced hepatitis. Conclusion : The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.211-220
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• 1985

Serum HBsAg, AntiHBs, HBeAg, AntiHBe and AntiHBc were detected by radioimmunoassay in 39 patients with acute viral hepatitis, 79 patients with chronic hepatitis, 30 patients with liver cirrhosis, 16 patients with primary hepatocellular carcinoma, 14 patients of HBsAg carriers and 129 cases of controls:78 cases of normal level of SGOT, SGPT, and 51 cases of elevated level of SGOT, SGPT. Following results were obtained: 1. HBsAg was detected in 66.7% of acute viral hepatitis, 63.3% of chronic hepatitis, 36.7% of liver cirrhosis, 81.3% of primary hepatocellular carcinoma and 27.1% of controls. 2. AntiHBs was positive in 0% of acute viral hepatitis, 21.5% of chronic hepatitis, 36.7% of liver cirrhosis, 31.3% of primary hepatocellular carcinoma, 0% of carrier and 44.2% of controls. 3. HBeAg was detected in 45.6% of chronic hepatitis, 23.3% of liver cirrhosis and 31.3% of primary hepatocellular carcinoma. 4. Among chronic liver diseases, antiHBe was positive in 56.3% of primary hepatocellular carcinoma, 23.3% of liver cirrhosis and 20.3% of chronic hepatitis. 5. AntiHBc was detected in most of all examines and the significance of presence of AntiHBc does not seem to represent liver disease itself but the evidence of infection of HBV. 6. Among 14 HBV carriers, 6 cases presented with abnormal SGOT, SGPT. 7. All HBV markers were negative in 5.1% of acute viral hepatitis, 5.1% of chronic hepatitis and 14.7% of controls: 17.6% of subjects with abnormal SGOT, SGPT and 12.8% of subjects with normal SGOT, SGPT. 8. Beside of HBV, other causes, such as non A, non B virus, Delta-agent, other viruses or related factors should be excluded among the patients with evidence of HBV infection associated with elevation of SGOT & SGPT.

• Journal of the Korean Society of Radiology
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• v.81 no.6
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• pp.1424-1435
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• 2020

Purpose The purpose of this study was to evaluate the usefulness of multiphasic CT and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT for the differentiation of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) from hepatocellular carcinoma (HCC). Materials and Methods From January 2007 to April 2016, 93 patients with pathologically confirmed HCC (n = 84) or cHCC-CCA (n = 9) underwent CT and PET/CT imaging. Contrast enhancement patterns were divided into three types based on the attenuation of the surrounding liver parenchyma: type I (early arterial enhancement with delayed washout), type II (early arterial enhancement without delayed washout), and type III (early hypovascular, infiltrative appearance, or peripheral rim enhancement). Results cHCC-CCAs (89%) had a higher PET/CT positive rate than did HCCs (61%), but the PET/CT positive rate did not differ significantly (p = 0.095). Among the 19 cases of the type II enhancement pattern, 3 (21%) of 14 HCCs and 4 (80%) of 5 cHCC-CCAs were PET/CT positive. cHCC-CCAs had a significantly higher PET/CT positive rate (p = 0.020) in the type II enhancement pattern. Conclusion The PET/CT positive rate of cHCC-CCA was significantly higher than that of HCC in lesions with a type II enhancement pattern. The ¹⁸F-FDG PET/CT can be useful for the differentiation of cHCC-CCA from HCC in lesions with a type II enhancement pattern on multiphasic CT.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.118-126
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• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.