• IMMUNE NETWORK
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• 제21권5호
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• 한국자기공명학회논문지
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• 제4권1호
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• pp.41-49
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• 2000

To design more efficient peptide antagonist against the HBV, preSl(21-47) which carries the HBV receptor binding site for hepatocytes was synthesized and the solution structure of preSl(21-47) was investigated using CD spectroscopy and NMR spectroscopy in membrane-mimicking environments. According to CD spectra, preSl(21-47) has a random structure in aqueous solution, while conformational change was induced by addition of TFE and SDS micelle. Tertiary structures as determined by NMR spectroscopy shows that preSl(21-47) has a very flexible structure even in SDS micelle.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2000년도 제30회 학술심포지엄
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• pp.39-43
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• 2000

HBV는 인체에 감염하여 간염, 간경변 및 간암을 유발하는 hepadnaviruses의 일종으로써 임상적으로 매우 중요한 바이러스이다. 그러나 이 바이러스에 의한 간암(HCC)의 발생 메커니즘은 아직 불확실하다. 최근에는 HBV의 X 단백질(HBx)이 간암 발생에 중요한 역할을 수행하는 것으로 보고되고 있다. HBx 단백질은 전사 활성인자(transcriptional activator)로써 숙주세포의 유전자발현에 영향을 미치어 세포증식 및 분화에 영향을 줄 수 있다. 본 연구에서는 HBx 단백질이 NIH 3T3 cell의 증식 및 형질전환에 미치는 영향을 조사하였다. HBx 단백질을 발현하는 세포주는 정상세포에 비하여 증식 속도가 2배 정도 빠르며, soft agar assay 결과에 의하면 대조군과 비교하여 더 많은 수의 colony를 형성하였다. 또한, 이들 HBx 발현 세포들은 접촉 저해 능력을 상실하여 HBx가 세포 형질 전환 능력을 가짐을 알수 있다 또한 HBx 발현 세포주에 있어서 p21의 RNA 및 protein수준이 정상세포에 비하여 낮으므로 HBx에 의한 증식 촉진 및 세포 형질 전환이 p21을 매개하여 이루어 짐을 알 수 있었다. HBx에 의한 p21 유전자의 발현 감소는 p21의 전사 수준에서 이루어지며 이는 p53-비의존적 경로에 의하여 이루어졌다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.173-173
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• 2001

The acute toxicity study of MBRI-98304, a new Hepatitis B virus (HBV) immunotherapeutic agent, was performed in Sprague-Dawley rats (7 weeks old) and Beagle dogs (4 months old). MBRI-98304 was injected intramuscularly at a single dosage of 0, 20, 100, 500, 2, 500, and 12, 500 $\mu\textrm{g}$/kg in rats and 0, 200, 1, 000, and 5, 000 $\mu\textrm{g}$/kg in Beagle dogs for 2 weeks daily. There were no deaths or clinical signs.(omitted)

• Genomics & Informatics
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• 제7권4호
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• pp.187-194
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• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

• 한국미생물·생명공학회지
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• 제14권6호
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• pp.455-460
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• 1986

간염 보균자의 혈액으로부터 Dane 입자를 분리하였다. Dane 입자의 핵으로부터 분리해낸 DNA는 $\alpha$-($^{32}$P) dNTP 존재하의 DNA 폴리머레이즈 반응 후 액체 씬틸레이션 카운터와 한천 전기영동 및 가이거 뮐러 카운터에 의하여 간염의 DNA임이 확인되었다. 간염 바이러스에 의한 감염을 막기 위한 백신으로서의 B형 간염 바이러스 표면항원을 생산하기 위하여 산성포스파테이즈 프로모터를 갖는 재조합 프라스미드를 함유하는 효모균주를 사용하였다. 재조합 프라스미드는 pHBV 130 및 pAM 82로부터 제작되었으며 대장균에 변환되어진 후 효모균주에 전달되었다. 간염 표면항원은 조절된 무기 인산 농도하에서 버크홀더 최소배지에서의 저해 해제로 생산되었다. 간염 표면항원의 생산 속도도 조사하였다. 전체 간염 표면항원 활성은 인산이 없는 배지에 옮겨진 뒤 3시간 내지 6시간에서 급격히 증가하였으며 9시간째에 최대에 도달하였다. 인산이 없는 배지에 옮기는 것은 고농도 인산 배지에서의 세포 배양을 6시간동안 수행한 뒤에 하는 것이 최적의 결과를 나타내었다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제6권1호
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• pp.32-38
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• 2003

목 적: HBcAb 양성인 공여자로부터 생체 부분 간이식을 시행할 때 HBsAg 음성인 수혜자가 B형 간염 바이러스에 감염될 가능성이 높다. 본 연구에서는 삼성서울병원의 소아 생체 부분 간이식에서 능동 면역을 주로 사용하였던 초창기와 Hepatitis Bimmunoglobulin (HBIg) 단독 요법을 사용하였던 후기를 비교 분석하여 간이식 후 de novo hepatitis B발생에 대한 HBIg 단독 요법의 예방 효과에 대해 조사해 보고자 하였다. 방 법: 1996년 5월부터 2002년 6월까지 시행한 생체 부분 간이식에서 공여자가 HBcAb 양성이었으며 수혜자가 HBsAg 음성인 소아는 15명이었다. 다른 이유로 사망한 2명을 제외한 13명 중 11명은 HBsAb 양성, 2명은 naive (HBsAb 음성, HBcAb 음성)였다. 모든 환자는 간이식 전 B형 간염 바이러스 예방 접종을 실시하였다. 초기 단계에는(1997년 1월~1997년 11월, 3명) 수혜자가 HBsAb 양성인 경우 간이식 후 B형 간염 추가접종을 실시하였다. 후기 단계에서는(1997년 12월 이후, 10명) 간이식 전후에 모두 B형 간염 예방 접종을 실시한 이후 항체 양성인 수혜자에게 HBsAb 항체가를 200 IU/L 이상 유지하기 위해 HBIg를 단독 유지요법으로 사용하였다. HBIg의 심한 부작용으로 인해 1명의 경우 Lamivudine을 사용하였다. De novo hepatitis B의 예방효과를 병력 고찰을 통하여 후향적으로 분석하였다. 결 과: 13명 중 3명(23.1%)에서 de novo hepatitis B가 발생하였다. 능동 면역만을 시행한 초기 단계에서 3명 중 3명 모두 7~19개월에 HBsAg 양성으로 혈청 변환을 하였다. 1명은 간이식 전 naive 혈청 소견이었고 2명은 HBsAb 양성인 상태였다. HBIg를 사용한 후기 단계에서는 10명 모두 관찰 기간 7~55개월 동안 HBsAg 음성으로 남아 있다. 결 론: HBIg 단독 요법은 HBcAb 양성인 공여자의 간을 이식받은 HBsAg 음성 수혜자에서 de novo hepatitis B를 예방하는데 효과적이다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6019-6026
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• 2015

Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1705-1712
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• 2016

Background: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. Materials and Methods: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). Results: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (P<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (p<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). Conclusions: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

• The Korean Journal of Physiology and Pharmacology
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• 제8권4호
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• pp.213-218
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• 2004

Primary fish-odor syndrome (FOS) is a genetic disorder caused by defective flavin-containing mono-oxygenase 3 gene (FMO3) with deficient N-oxidation of trimethylamine (TMA), causing trimethylaminuria (TMAU). By contrast, secondary FOS can be acquired by decreased FMO activities in patients with chronic liver diseases, but the underlying mechanisms are unknown. In the present study, we examined plasma NOx concentrations and viral DNA contents as well as in vivo FMO activities and their correlations in chronic viral hepatitis (CVH) patients. Plasma concentration of NOx was significantly increased by 2.1 fold $(56.2{\pm}26.5\;vs.\;26.6{\pm}5.4\;{\mu}M,\;p<0.01)$, and it was positively correlated with plasma hepatitis B virus (HBV) DNA contents $(r^2=0.2838,\;p=0.0107)$. Furthermore, the elevated plasma NOx values were inversely and significantly correlated with in vivo FMO activities detected by ranitidine-challenged test $(8.3%\;vs.\;20.0%,\;r^2=0.2109,\;p=\0.0315)$. TMA N-oxidation activities determined in CVH patients without challenge test were also significantly low (73.6% vs. 95.7%, p< 0.05). In conclusion, these results suggested that secondary FOS could be acquired by the endogenously elevated NO in patients with CVH.