• Journal of Yeungnam Medical Science
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• v.32 no.1
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• pp.47-49
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• 2015

Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient's clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.276-282
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• 1998

Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF$\alpha$ (chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF$\beta$ repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.

• The Korean Journal of Mycology
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• v.39 no.3
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• pp.235-238
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• 2011

Agrobacterium harboring vector pCHBs with hygromycin phosphotransferase(hph) and hepatitis B virus surface antigen(HBsAg)gene was transformed into the mycelial culture of Flammulina velutipes. In particular, mild NaOH solution was treated to the mycelia before Agrobacterium infection step. This was purposed to generate putative surface wounds in the mycelial cell walls. The results showed that hygromycin-resistant($hyg^r$) mycelia could be obtained only from NaOH-treated mycelia but not from intact mycelia. The integration of $hyg^r$ gene in fungal genome was confirmed by PCR. In addition, a single transgene integration and heterologous protein expression in F. velutipes could be verified by Southern blot hybridization and western blot analysis, respectively. This study demonstrated an efficient tool for the Agrobacterium-mediated transformation of F. velutipes mycelia.

• The Journal of Korean Medicine
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• v.20 no.3 s.39
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• pp.54-65
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• 1999

Objectives: Hepatoma is a very serious disease in Korea and vvorldwiclc. Hepatitis B vims (HBV) has proved the most significant cause of hepatoma. We canied out this study to investigate the effect of Acanthopanax sessilifloms on inhibiting cell proliferation and DNA synthesis in HepG2.2.15 cell line and on inhibiting phosphorilation of oncogene (MAP kinase) in NIT/3T3-HBx ceIl. Methods: To investigate the anti-cancer effect of Acanthopanax sessiliflorus, we did the CellTiter 96 Aqueous Non-radioactive Cell Proliferation assay (Promega); MTS/PMS assay, [$^3H$]-thymicline incorporation assay, and we measured the gene expression through westem blotting. Results: Acanthopanax sessiliflorus showed an inhibiting effect on the increase of HepG2.2.15 in the NTS/PMS assay. It also showed an inhibiting effect on DNA synthesis of HepG2.2.15 in the [$^3H$]-thymidine incorporation assay. Acanthopanax sessiliflorus showed an inhibiting effect of phosphorilation of MAP kinase in HBV - X genes. too. Conclusions: The results suggested that this herb had an anti cancer effect. We may discover an effective anti-cancer herb medicine through further studies on this herb medicine.

• BMB Reports
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• v.37 no.2
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• pp.167-176
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• 2004

Although efficient antiviral lamivudine is used for HBV-infected patients, a prolonged treatment with nucleoside analogs often results in lamivudine-resistant variants. In this study, we evaluated the fidelity of the lamivudine-resistant variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A, M550V, and M550I) of HBV DNA polymerases were expressed in insect cells then purified. Like many other reverse transcriptases, no $3'{\rightarrow}5'$ exonuclease activity was detected in the HBV DNA polymerase. Since there is no proofreading activity, then the use of the site-specific nucleotide misincorporation method is beneficial. From the $f_{ins}$ value analysis, it is evident that M550I and M550V exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A exhibits similar fidelity values. It is therefore suggested that lamivudine resistance comes from the stringency to dNTP binding and the discrimination of dCTP and lamivudine in M550V and M550I.

• BMB Reports
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• v.38 no.3
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• pp.294-299
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• 2005

In this report, we describe the high-yield secretory expression of the recombinant human anti-HBsAg Fab fragment from Pichia pastoris that was achieved by co-integration of the genes encoding the heavy and light chains (both under the control of alcohol oxidase promoter) into the genome of the yeast cells. The fed-batch fermentations were carried out in a 5 L scale. Both chains of the Fab were successfully expressed upon methanol induction. The absorbance ($OD_{600}$) of the broth can reach 350~500 at the end of fed-batch phase. After the induction, the expression level of the recombinant Fab (soluble) reached 420~458 mg/L. The recombinant Fab fragment was purified from the crude culture supernatant by ion exchange chromatography and the purity of the recombinant Fab fragment was over 95%. The affinity activities of the crude fermentation supernatant and the purified Fab were analyzed by indirect ELISA, which showed that the purified recombinant Fab fragment had high affinity activity with hepatitis B surface antigen.

• KSBB Journal
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• v.26 no.2
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• pp.157-164
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• 2011

Five assays for anti-HBs were compared to improve potency test of Human lgG preparations. The three commercial EIA kits were optimized including dose response curve ranges and compared by conducting a co-laboratory study. After selecting the most reproducible EIA kit, methods comparison was performed with 22 samples in 5 different days. As a result, EIA (7.7 ${\pm}$ 5.3%) and MEIA (AxSYM: 3.7 ${\pm}$ 1.9%, IMx: 1.6 ${\pm}$ 0.8%) showed precision and accuracy (100.1 ${\pm}$ 12.6%). Therefore, the validated EIA assay was established and it is believed to be comparable to current MEIA.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.120-125
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• 1994

We obtained the total protein antibodies of Saccharomyces cerevisiae KCTC 1720 and Escherichia coli K-12 from the rabbit and the guinea pig to determine the host-derived proteins which may be remained in biotechnological products. The protein concentration of rabbit antibodies was 4.05 mg/mι in the case of yeast, 7.14 mg/mι in the case of E. coli and that of guinea pig antibodies was 1.90 mg/mι in the case of yeast, 7.17 mg/mι in the case of E. coli, respectively. To determine remained host-derived proteins in biotechnological products which produced by the hosts, S. cerevisiae or E. coli, we used a sandwich enzyme linked immunosorbent assay method in 96 well microplate. When the method applied to determine the remained host-derived proteins in commercial biotechnological products, it detected less than 3.5 ng/vial in human growth hormone, less than 1 ng/vial in hepatitis B vaccine and interferon-${\gamma}$ and 2~23 ng/vial in interferon-$\alpha$. The method can be used to determine the remained host-derived protein in biotechnological products.

• Journal of the Korean Magnetic Resonance Society
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• v.9 no.2
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• pp.122-137
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• 2005

The hepatitis B virus X protein (HBx) is highly linked with liver diseases and the development of hepatocellular carcinoma. HBx-interacting protein (XIP) has been shown to abolish the transactivation functions of HBx. Here, we define the structural characteristics and HBx binding properties of XIP. Under physiological conditions, XIP was composed mainly of random-coils but significant helicity was induced in the hydrophobic condition. NMR spectroscopy defined the secondary structure of XIP in the presence of sodium dodecyl sulfate. Four putative helices were mapped to the amino acids 8-12, 32-38, 42-54 and 82-91. Any deletion of defined putative helices in XIP led to loss of binding to HBx, and truncated mutant lacking last putative helix decreased helicity more than that it could. Our results suggest that XIP requires its entire sequence for HBx binding and it may be under drastic conformational change when binds to HBx.

• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.