• Bulletin of the Korean Chemical Society
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• v.26 no.9
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• pp.1385-1389
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• 2005

Human hepatitis B virus (HBV) is a pathogen related to the development of liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, the efficient methods to suppress HBV replication have not been developed yet. Therefore, we have used RNA interference (RNAi) as a potential tool for the suppression of HBV replication. Here, we designed a 21 nt small intefering dsRNA (siRNA) against hepatitis B virus X (HBx) RNA with 3' overhanging ends derived from T7 promoter. It has been reported that HBV X protein plays an important role in HBV gene expression and viral replication. The suppression of HBx gene expression by the 21 nt siRNA was investigated by Northern blot analysis and chloramphenicol acetyl transferase (CAT) assay. The level of HBx mRNA was decreased by siRNA in a dose-dependent manner. We also found that the 21 nt siRNA inhibited the HBV replication in hepatocellular carcinoma cell.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7069-7077
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• 2014

Background: This retrospective study aimed to validate the safety and effectiveness of hepatectomy for huge hepatocellular carcinoma (HCC). Materials and Methods: Data of patients who underwent hepatectomy for HCC between January 2006 and December 2012 were reviewed. The patients were divided into three groups: huge HCC(${\geq}10cm$ in diameter), large HCC(${\geq}5$ but<10 cm in diameter) and small HCC(<5cm in diameter). Results: Characteristics of pre-operative patients in all three groups were homogeneously distributed except for alpha fetal protein (AFP)(p<0.001).The 30, 60, 90-day post-operative mortality rates were not different among the three groups (p=0.785, p=0.560, and p=0.549). Laboratory data at 1, 3, and 7 days after surgery also did not vary. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates in the huge and large HCC groups were lower than that of the small HCC group (OS: 32.5% vs 36.3% vs 71.2%, p=0.000; DFS: 20.0% vs 24.8% vs 40.7%, p=0.039), but there was no difference between the huge and large HCC groups (OS: 32.5% vs 36.3%, p=0.667; DFS: 20.0% vs 24.8%, p=0.540). In multivariate analysis, five independent poor prognostic factors that affected OS were significantly associated with worse survival (p<0.05), namely, AFP level, macrovascular invasion, Edmondsone Steiner grade, surgical margin and Ishak score. AFP level, macrovascular invasion, microvascular invasion, and surgical margin influenced disease-free survival independently (p<0.05). Conclusions: The safety of hepatectomy for huge HCC is similar to that for large and small HCC; and this approach for huge HCC may achieve similar long-term survival and disease-free survival as for large HCC.

• The Korean Journal of Nuclear Medicine
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• v.39 no.3
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• pp.151-162
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• 2005

Hemangioma is the most common benign tumor of the liver, with a prevalence estimated as high as 7%. Tc-99m red blood cell (RBC) hepatic blood pool scan with single photon omission computed tomography (SPECT) imaging is extremely useful for the confirmation or exclusion of hepatic hemangiomas. The classic finding of absent or decreased perfusion and increased blood pooling ("perfusion/blood pool mismatch") is the key diagnostic element in the diagnosis of hemangiomas. The combination of early arterial flow and delayed blood pooling ("perfusion/blood pool match") is shown uncommonly. In giant hemangioma, filling with radioactivity appears first in the periphery, with progressive central fill-in on sequential RBC blood pool scan. However, the reverse filling pattern, which begins first in the center with progressive peripheral filling, is also rarely seen. Studies with false-positive blood pooling have been reported infrequently in nonhemangiomas, including hemangiosarcoma, hepatocellular carcinoma, hepatic adenoma, and metastatic carcinomas (adenocarcinoma of the colon, small cell carcinoma of the lung, neruroendocrine carcinoma). False-negative results have been also reported rarely except for small hemagniomas that are below the limits of spatial resolution of gamma camera.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.129-138
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• 2018

Purpose: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ${\leq}3cm$ in size. Materials and Methods: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. Conclusions: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3915-3920
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• 2014

Background: Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. Materials and Methods: This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. Results: During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was $56.5{\pm}7.7years$. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Conclusions: Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.82-82
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• 1997

The hepatitis B virus(HBV) is a small, enveloped virus with a circular, double-stranded DNA genome. HBV causes active and chronic hepatitis worldwide, including Korea, and is considered to be a major factor for liver cirrhosis and hepatocellular carcinoma. In contrast to the wealth of knowledge on the gene structure and expressional regulation, immunological and pathological mechanisms for HBV-induced hepatocellular injury are not well known. In the present study, vaccinia virus which has been demonstrated to be a useful eukaryotic expression vector was used to clone the gene for HBV surface antigen, L(S+preS2+preS1). The recombinant vaccinia virus vector, pMJ-L, which contains L surface antigen gene of adr-type HBV was constructed, and subseouently used for making recombinant vaccinia virus VV-$\textrm{HBV}_{L}$. Expression of the HBV antigen was examined by immunofluorescent antibody (IFA) test using mouse monoclonal anti-hepatitis B surface antigen. HBsAg was detected in the recombinant virus indicating that the VV-$\textrm{HBV}_{L}$ expressed S antigen successfully. The HBV-Vaccinia Virus recombinant obtained in this study is currently being used for studying the immunological aspects of HBV infection.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• Journal of Veterinary Clinics
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• v.33 no.4
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• pp.187-193
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• 2016

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions. This study aims to show that the actions of growth factors associated with PDGFR-${\alpha}$, PDGFR-${\beta}$, VEGFR-2, c-KIT, and c-ABL, which are used in veterinary medicine, are expressed in canine intractable tumors. This study used archival cases of canine paraganglioma, gastrointestinal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. Tissues had been immunohistochemical analysis. The antibodies used were PDGFR-${\alpha}$, PDGFR-${\beta}$, c-kit, VEGFR-2, and c-Abl. PDGFR-${\alpha}$ was expressed only in HCC, and PDGFR-${\beta}$ was expressed in all tumors. VEGFR was also only expressed in HCC, and c-KIT has been expressed in HCC, paraganglioma, and small intestinal adenocarcinoma. c-Abl was expressed in all cancers, but was weakly expressed in paraganglioma, while more than moderately expressed in other tissues. In conclusion, this study investigated how TKIs used in human medicine can be applied to canine intractable tumors, through immunohistochemistry. The results indicate that there may be an application for TKIs in treating canine intractable tumors.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.142-145
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• 2018

Metastases to the liver can be found in various malignancies, most commonly originating from the colon, rectum, pancreas, stomach, esophagus, breast, lung, and melanoma. Surgical resection of liver metastasis is generally considered to be the definitive therapy fore cure. However, many patients are unable to undergo surgical resection due to medical comorbidities or multifocal extent of malignant disease affecting the liver. Among patients not eligible for surgery, other therapies exist for treatment in order to down stage the disease for surgical resection or for palliation. Radioembolization of hepatic metastases has shown to improve outcomes among patients with variety of malignancies including more common malignancies such as colorectal cancer. Yttrium-90 (Y-90) radioembolization has been successfully used in the management of hepatic metastases. A small series of metastatic sarcoma to the liver treated with radioembolization showed a promising response. We report a case of metastatic gastric leiomyosarcoma to the liver treated with Y-90 glass microspheres therapy using the radiation segmentectomy approach, previously described for hepatocellular carcinoma.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1974-1984
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• 2021

Objective: This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). Materials and Methods: In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intention-to-treat and as-treated analyses were performed. Results: Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000-0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. Conclusion: NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.