• Journal of Biomedical Engineering Research
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• v.20 no.2
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• pp.173-182
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• 1999

Contrast-enhanced CT has an important role in assessing liver lesions, the optimal protocol to get most effective result is not clear. The mein goal when deciding injention protocol is to optimize lesion detectability with rapid scanning when lesion to liver contrast is maximum. For this purpose, we developed a physiological model of the contrast medium enhancement based on the compartment modeling and pharmacokinetics. Blood supply to liver is achieved in two paths. This dual supply characteristic distinguishes the CT enhancement of liver from that of the other organs. The first path is by hepatic artery and to second, by portal vein. However, it is assumed that only gepatic artery can supply blood to hepatocellular carcinoma(HCC) compartment, thus, the difference of contrast enhancement is resulted between normal liver tissue and hepatic tumor. By solving differential equations for each compartment simultaneously using the computer program Matlab, CT contrast-enhancement curves were simulated. The simulated enhancement curves for aortic, hepatic, portal vein, and HCC compartments were compared with the mean enhancement curves from 24 patients exposed to the same protocols as the simulation. These enhancement curves showed a good agreement. Furthermore, we simulated lesion-to-liver curves for various injection protocols, and the effects were analyzed. The variables to be considered in the injection protocol were injection rate, dose, and concentration of contrast material. These data may help to optimize scanning protocols for better diagnosis.

• Journal of Life Science
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• v.21 no.4
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• pp.529-533
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• 2011

Metallothioneins (MT) are a group of low-molecular weight, cysteine-rich, intracellular proteins that are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins is associated with protection against DNA damage, oxidative stress, and apoptosis. Many studies have shown increased expression of MT in various human tumors, whereas MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. Using Northern blot analysis, we found that laminin induced expression of MT-1 in HSG and PC12 cells, which can be differentiated by laminin, but had no effect on MB-231, MDA-435, and PC-3 cells, which cannot be differentiated by laminin. In addition, we analyzed the expression level of the MT-1 gene in five prostate cancer cell lines possessing different metastatic potential. The expression of MT-1 in normal and less malignant cells (RWPE-1 and WPE1-NA22) was high and up-regulated by laminin, whereas the expression of MT-1 in WPE1-NB14, WPE1-NB11, and WPE1-NB26 cells (malignant) was extremely low and not elevated by laminin. These results suggest that the MT-1 gene is involved in laminin-mediated differentiation and affects the metastatic potential of tumor cells.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2006.02a
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• Tuberculosis and Respiratory Diseases
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• v.69 no.6
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• pp.469-473
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• 2010

Nocardia farcinia, an aerobic, gram-positive bacilli actinomycetes of the genus Nocardia, is an uncommon pathogen found in humans. The most common Nocardia infection sites are the lung, central nervous system, and skin. Even though hematogenous dissemination can occur, isolation of the organism from blood cultures is very rare. We report a case of Nocardia infection that was isolated on blood cultures. A 59-year-old male with a medical history that includes a liver transplantation 6-years prior due to hepatocellular carcinoma secondary to chronic hepatitis B, developed pneumonia and was transferred to Severance Hospital. At the time of admission, the patient's initial exam showed hypothermia, tachypnea, and hypotension. His chest radiograph showed severe pneumonia and a large abscess on left upper lobe. Under the presumptive diagnosis of bacterial pneumonia or other opportunistic infection, we started broad spectrum antibiotics. However, he developed Nocardia sepsis, rapidly deteriorated, and subsequently died.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.443-455
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• 2020

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.39-50
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• 2002

Hepatitis B viral infection which affect about 10% of Korean population manifests asymptomatic carrier, chronic hepatitis and liver cirrhosis and even associates with hepatocellular carcinoma. Clinical manifestations induced by hepatitis B virus vary depending on the degree of immune response by cytotoxic T cells against viral epitope-presenting liver cells. Since hepatitis B virus presents high rate of mutaton that might change the presented epitope and eventually alter immune response, viral mutations, especially in promoters and enhancers, have an important implication in hepatic inflammation and viral replication. To identify mutations related to the hepatic inflammation, we investigated sequence variations of hepatitis B viral promotor regions in the presence or absence of symptoms in hepatitis B carriers. For this, sera from persistently hepatitis B virus-infected mother-child pairs were collected. After PCR amplifiation of all hepatitis B viral promoters (C promoter, S1 promoter, S2/S promoter, X promoter) using serum DNA from each pair, viral promotors were sequenced by automatic sequencer and then sequence data were analyzed by ClustalW. In most cases, the dominant type of maternal virus was transmitted to the child. However, in some children, some new host specific viral variants could be observed in Cp, S1p and S2/Sp. The mutations in C promoter did not seem to be vertically transmitted but arose in new host independently after the wild type had been transmitted. Enhancer I containing X promoter revealed high host specific variations as has been reported before. Two S promoters, S1p and S2/Sp, have shown some point mutations in children, but no deletion mutations were detected as in chronic hepatitis patients in whom deletion mutations are frequently found. In conclusion, the children with the vertically transmitted hepatitis B virus mostly retain the dominant type virus that had been transmitted. However, host specific variants tended to accumulate over time, possibly as clinical symptoms develop.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.936-940
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• 2004

Doenjang (Korean soy paste) is one of the popular soybean based fermented foods in Korea. This study investigated the growth and DNA synthesis inhibitory effect of doenjang methanol extracts on AGS human gastric adenocarcinoma cells, Hep 3B human hepatocellular carcinoma cells and HT-29 human colon cancer cells. In order to determine an anticancer effect of doenjang methanol extracts, other soybean fermented foods and original materials were compared. The treatment of doenjang methanol extracts (200 $\mu\textrm{g}$/mL) to the AGS, Hep 3B and HT-29 cancer cells inhibited the growth of cancer cells by 80%, 77% and 86%, respectively. Compared to other soybean fermented foods and original materials, doenjang methanol extracts showed the highest growth inhibitory effect on different cancer cells. In addition, doenjang methanol extracts (200 $\mu\textrm{g}$/mL) significantly inhibited DNA synthesis of AGS and Hep 3B cancer cells by 76% and 59%, respectively. These results suggested that this anticancer effect of doenjang may be due to specific active compounds, which will be newly produced during soybean fermented process and not contained in soybean.

• Journal of Yeungnam Medical Science
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• v.12 no.1
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• pp.96-104
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• 1995

The transarterial embolization has been widely used to control bleeding. It has a variety of clinical utility; to reduce bleeding on the surgical field, to reduce the size of malignant tumor as a preopearative treatment, to treat arteriovenous malformation or arterial aneurysm as a curative method and to promote life quality of patient with diffuse or multiple hepatocellular carcinoma as a palliative treatment, etc. With the advance of modem technology, various embolic materials have been also developed. However, it has not been fully investigated of histopathologic changes of the embolized organs according to the embolic materials used. This study was undertaken to investigate the histopathologic changes of embolized renal artery in rabbit by various embolic materials, according to each embolic material and to time passed by after embolization. Of the 5 arteries embolized by ethylene vinyl alcohol copolymer(EVAL), one showed abscess formation in embolized kidney. The other 4 allowed to perform further pathologic study: within a week after embolization there was no any specific change in vessels, however, minimal endothelial hypertrophy was observed following 2 weeks of embolization. Of the 8 renal arteries embolized by N-buthyl-2-cyanoacrylate(Histoacryl), 4 showed total occlusion of the main renal arteries as well as renal infarction, which reflects the strong adhesiveness of Histoacryl to vascular wall. The other 4 showed fibrinoid degeneration in vascular wall within a week. However, further change was not observed thereafter. In all the 5 renal arteries embolized by polyvinyl alcohol(Ivalon), there were infiltration of inflammatory cells along the vessel walls, within one week, which represents vasculitis. They showed some fibrosis with appearance of giant cells in the vessel wall two weeks after embolization and also showed marked fibrosis of connective tissues surrounding vessels two months after embolization, respectively. The results suggest that EVAL is useful for the embolization of hypervascular lesion with limited arteriovenous fistula, Histoacryl for the curative treatment of the lesion with high blood flow or severe arteriovenous fistula, and Ivalan for palliative treatment of malignant tumor or arteriovenous malformation, respectively.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.196-208
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• 2019

Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

• The Korean Journal of Nuclear Medicine Technology
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• v.23 no.1
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• pp.50-53
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• 2019

Purpose Yttrium-90 (Y-90) is high-energy beta emitters ($E{\beta}$, max = 2.28 MeV) with the mean penetration depth of 2.5 mm in tissue. Radioactive microspheres containing Y-90 is widely used for the transarterial radioembolization of hepatocellular carcinoma. However, bremsstrahlung radiation from Y-90 can cause the external radiation exposure to medical staff who handle the Y-90 microspheres. In this study, shielding device for Y-90 microspheres was developed to minimize the external radiation exposure. Materials and Methods Y-90 microsphere shielding device was made from 6 mm thicknesses of tungsten including the lead glass window. Radiation shielding ability of Y-90 microsphere shielding device was evaluated using 4 GBq of $SIR-Spheres^{(R)}$ Y-90 microspheres. The bremsstrahlung radiation was measured using radiation survey meter. Results The mean radiation dose of Y-90 microspheres in acrylic shield was $261.7{\pm}2.3{\mu}Sv/h$ (n=5) at 10 cm away from the shield. With the additional tungsten shielding device, it was $23.7{\pm}1.3{\mu}Sv/h$ (n=5). Thus, the bremsstrahlung radiation dose was decreased by 90.9%. At 50 cm away from the shield, bremsstrahlung radiation was reduced by 89.2% after using tungsten shielding device. Conclusion During the preparation and radioembolization of Y-90 microsphere, medical staff are exposed to external radiation. In this study, we demonstrated that the use of tungsten shielding device devices significantly reduced the amount of bremsstrahlung radiation. Y-90 microsphere tungsten shielding device can be highly effective in reducing the bremsstrahlung radiation.