• Title/Summary/Keyword: Hepatitis C

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C-terminal truncated HBx reduces doxorubicin cytotoxicity via ABCB1 upregulation in Huh-7 hepatocellular carcinoma cells

  • Jegal, Myeong-Eun;Jung, Seung-Youn;Han, Yu-Seon;Kim, Yung-Jin
    • BMB Reports
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    • v.52 no.5
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    • pp.330-335
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    • 2019
  • Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.

Incidence Density of Antibody against Hepatitis C Virus in Seoul and Gyeonggi Area; A Retrospective Cohort Study - Based on Medical Screening Data from a General Hospital - (서울 경기지역 성인의 C형 간염 바이러스 항체 양성자 평균발생률; 후향적 코호트 연구 - 일개 병원의 종합검진 자료를 중심으로 -)

  • Ryu, Seung-Ho;Kim, Dong-Il;Suh, Byung-Seong;Kim, Woon-Sool;Chang, Yoo-Soo;Beck, Sung-Ho;Lee, Soo-Jin;Kim, Yong-Kyu;Song, Jae-Chul
    • Journal of Preventive Medicine and Public Health
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    • v.37 no.4
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    • pp.337-344
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    • 2004
  • Objectives : This study was performed to determine the incidence density and the prevalence of sero-positive hepatitis C from 1999 to 2002 among adults aged 20 and over residing in Seoul and the Gyeonggi province. Method : The data for period was obtained from 114,635 adults, residing in Seoul or the Gyeonggi province, who had undertaken comprehensive health screening tests from Jan 1999 to Dec 2002 in a University hospital in Seoul. Among them, subjects with sero-negative status against hepatitis C were selected (21,408 in 1999, 28,830 in 2000) and then followed up until Dec 2002 to determine the incidence of hepatitis C during this period. The serum was tested with the immunoradiometric assay (IRMA) which uses third generation HCV antibody. Age adjusted rates were estimated by direct standardization using a reference population of 2000 aged from 20 to 80 years. Results : The prevalence of anti-HCV from 1999 to 2002 was 2.1 per 1000 persons(95% CI $1.8{\sim}2.4$). Male showed 1.7 per 1000 persons (95% CI $1.4{\sim}2.1$), while female showed 2.7 per 1000 persons(95% CI $2.2{\sim}3.2$). Age?sex adjusted rate showed 2.8 per 1000 persons (95% CI $2.64{\sim}2.96$), which is lower than the results of some previous study. The prevalence showed a significantly increasing pattern with age both in males and females (p<0.05). The incidence density of anti-HCV among the population aged 20 and over was 1.1 per 104 person-years at risk (95% CI $0.6{\sim}2.4$); 1.2 (95% CI $0.6{\sim}2.7$) for males and 0.8 (95% CI $0.6{\sim}4.2$) for females. Age adjusted incidence density was 2.91 per 104 person-years at risk (95% CI $2.43{\sim}3.38$) for those aged 20 and over. It showed an increasing pattern with age (p<0.05), especially for those age over 50 years. Conclusion : The study subjects for this study were supposedly healthier than the general population so the prevalence and incidence for the general population are thought to be higher than the results of the present study.

Role of IL-18 Gene Promoter Polymorphisms, Serum IL-18 Levels, and Risk of Hepatitis B Virus-related Liver Disease in the Guangxi Zhuang Population: a Retrospective Case-Control Study

  • Lu, Yu;Bao, Jin-Gui;Deng, Yan;Rong, Cheng-Zhi;Liu, Yan-Qiong;Huang, Xiu-Li;Song, Liu-Ying;Li, Shan;Qin, Xue
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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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.

Age Related Prevalence of Antibodies to Hepatitis A Virus, Performed in Korea in 2005 (국내에서 2005년에 실시한 연령별 A형 간염 바이러스 항체 보유율)

  • Choi, Hea Jin;Lee, Soo Young;Ma, Sang Hyuk;Kim, Jong Hyun;Hur, Jae Kyun;Kang, Jin-Han
    • Pediatric Infection and Vaccine
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    • v.12 no.2
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    • pp.186-194
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    • 2005
  • Purpose : Hepatitis A viral infections have been continued after re-emerging since mid 1990s in Korea. The incidence of this disease has been increased in young adults younger than 30 years of age since 2000. This study was performed to evaluate the prevalence of antibody to hepatitis A in Korea(two regions; Incheon and Changwon) in 2005, and was compared with the results of similar studies in mid 1990s. Methods : The study was conducted from January 2005 to June 2005, and consisted of 1,301 enrolled subjects, neonates to 50 years old, living in Incheon and Changwon in Korea. All sera were frozen and stored at $-70^{\circ}C$ until assayed. Anti-HAV IgG antibodies were measured by microparticle enzyme immunoassay(HAVAB, Abbott Lab., IL, USA). Results : The prevalence of anti-HAV IgG was 61.1% in infants younger than 1 year old, 30.5% in 1~5 years, 14.6% in 6~10 years, 1.7% in 11~15 years, 6.5% in 16~20 years, 36.6%in 21~30 years, 77.5% in 31~40 years, and 99.8% in 41~50 years. Statistical differences were not found between male and female, but there was statistical difference in 6~10 years old age group between the two areas. Conclusion : Our study indicate that the prevalence of antihepatitis A virus antibody has shifted from children to old adolescents and young adults. This result suggests that the risk of sudden outbreaks or increasing incidence of hepatitis A viral infections in young adults may be expected in our society. The preventive strategies of hepatitis A including vaccination should be prepared.

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A study of the current(2003-2005) prevalence of anti-HBs and immunologic memory of hepatitis B vaccine in children from the central area of Korea (최근(2003-2005) 우리나라 중부지역 소아에서 B형 간염 항체 보유율과 백신의 면역학적 기억에 대한 연구)

  • An, Young Won;Chung, Eun Hee;Rheem, Insoo
    • Clinical and Experimental Pediatrics
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    • v.49 no.6
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    • pp.630-634
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    • 2006
  • Purpose : This study was conducted to assess the current(2003-2005) prevalence of anti-HBs and immunologic memory for Hepatitis B vaccine in children from the central area of Korea. Methods : Subjects were chosen from children and adolescents who received tests for hepatitis B surface antigen(HBsAg) and anti-HBs at Dankook University Hospital from March 2003 to May 2005. Among these, antibodies to hepatitis B core antigen(IgG anti-HBc) were checked. A single booster vaccination was performed on children whose anti-HBs titers were under 10 mIU/mL. One month after booster vaccination we rechecked the anti-HBs titer. Results : A total of 3,277 subjects were tested for HBsAg/anti-HBs, and 1,913(58.4 percent) of them were positive for anti-HBs. Of these, 29 subjects(0.9 percent) were positive for HBsAg. Positive results for anti-HBs by age were 78.6 percent for 6-12 months of age, 62.7 percent for 1-3 years of age, 51.9 percent for 4-6 years of age, 49.5 percent for 7-12 years of age, 63.4 percent for 13-15 years of age and 72.2 percent for 16-18 years of age. The 80 subjects who were tested negative for HBsAg/anti-HBs received a single booster vaccine, 71 subjects were tested positive for antibodies. IgG anti-HBc titer was checked for 169 of the subjects, 5 subjects were positive. Conclusion : In our study, a significant anamnestic response was observed in 88.8 percent of children. This is believed to be a result of the relatively long immunologic memory effect of the hepatitis B vaccination in children from the central area of Korea.

The Anti-Migratory Effect of Cirsium japonicum Pharmacopuncture in C6 Glioma Cell (대계 약침액의 C6 신경교종 세포에 대한 이주 억제 효과)

  • Park, Juyeon;Lee, Kangpa;Chang, Haeryong;Moon, Jinyoung
    • Korean Journal of Acupuncture
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    • v.30 no.4
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    • pp.212-219
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    • 2013
  • Objectives : Cirsium japonicum is a traditional Korean medicine that has been used in the treatment of inflammatory diseases such as appendicitis, hepatitis, pulmonary abscess and tumor. The aim of study was to elucidate anti-migratory activity of CJP(Cirsium japonicum pharmacopuncture) through regulation of inflammatory mediators in C6 glioma cell. Methods : Nitric oxide(NO) production was determined by using nitrite assay. The cell migration was analyzed by wound-healing assay and Boyden chamber assay. The expression levels of iNOS, and protein kinase C(PKC)-${\alpha}$ were measured by western blotting assay. Results : CJP showed a significant decrease on NO production. Moreover, glioma cell migration was effectively suppressed by CJP. Furthermore, CJP inhibited the expressions of iNOS and PKC-${\alpha}$ in C6 glioma cells. Conclusions : These results suggest that CJP inhibits glioma cell migration and iNOS expression through regulation of PKC-${\alpha}$. Therefore, it is expected that CJP could be an effective agents for blocking malignant progression of glioma.

Aptamers (nucleic acid ligands) for trypsin-like serine proteases

  • Gal, Sang-Wan;Jeong, Yong-Kee;Satoshi Nishikawa
    • Journal of Life Science
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    • v.12 no.1
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    • pp.14-18
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    • 2002
  • Subpopulations of nucleotides that bind specifically to a variety of proteins have been isolated from a population of random sequence RNA/DNA molecules. Roughly one in $10^{13}$ random sequence RNA/DNA molecules folds in such a way as to create a specific binding site for small ligands. Since the development of in vitro selection procedure, more than 50 nucleic acid ligands (aptamers) have been isolated. These molecules are very useful for the study of molecular recognition between nucleic acid and protein/organic compound. In addition to these basic studies this method gives us a dream to produce new drugs against several diseases. We focused on several aptamers which specifically binds to trypsin-like serine proteases (thrombin, human neutrophil elastase, activated protein C and NS3 protease of human hepatitis C virus) and want to introduce their structural characteristics and some functions.

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Production and characterization of monoclonal antibody against bovine coronavirus (소 코로나바이러스에 대한 단크론항체 생산과 특성)

  • Ahn, Jae-moon;Kang, Shien-young
    • Korean Journal of Veterinary Research
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    • v.38 no.3
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    • pp.581-588
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    • 1998
  • Eight monoclonal antibodies(MAbs) against bovine coronavirus(BCV) were produced and characterized. Three MAbs(1G9, 4H12, 5C1) specific to the S glycoprotein and two HE glycoprotein-specific MAbs(2A5, 5G4) were found to neutralize the BCV in fluorescence focus neutralization(FFN) test. Two HE-specific MAbs from the neutralizing MAbs inhibited the hemagglutinating activity of the BCV. None of the N protein-specific MAbs(1C1, 5A12, 6H1) neutralized the virus infectivity. Bovine coronavirus and mouse hepatitis virus, which belong to group II coronaviruses, were differentiated from other groups of coronaviruses(porcine transmissible gastroenteritis virus, porcine epidemic diarrhea virus, canine coronavirus) by all MAbs in fluorescence antibody test(FA), but not in FFN test.

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Effects of Glucose and Glutamine Concentrations on Hybridoma Growth ann Anti-HBsAg MAb Production in Enriched Medium (농축배지에서 Glucose와 Glutamine 농도가 하이브리도마 증식과 간염표면항원에 대한 단일클론항체 생산에 미치는 영향)

  • 전복환;조의철김동일
    • KSBB Journal
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    • v.5 no.4
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    • pp.365-371
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    • 1990
  • To improve the growth of mouse hybridoma 2c3.1 secreting anti-Hepatitis B surface antigen monoclonal antibody (anti-HBsAg MAb), we had constructed an enriched medium and observed the effects of fetal bovine serum and serum-free supplements including human serum albumin, 'insulin and transferrin', and monoethanolamine. For further enhancement of growth, the concentrations of two major energy sources, glucose and glutamine, were strengthened with various ratios in the enriched medium. Maximum cell growth and monoclonal antibody production obtained in various ratios of glucose/glutamine with an inoculation concentration of 2$\times$105 cells/ml were 0.73$\times$106-4.62$\times$106 cells/ml and 65.1-422.6 $\mu\textrm{g}$/ml, respectively. Glutamine was round to be a major energy source and a limiting nutrient in comparison to glucose for 2c3.1 cell cultivation in enriched media with low serum.

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Effect of Scutellariae Radix Extract on Human CYP450 Mediated-Drug Metabolism

  • Yoo, Hye-Hyun;Lim, Sun-Young;Kim, Dong-Hyun
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.143-146
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    • 2011
  • Scutellariae Radix is widely used in the traditional herbal medicine for the treatment of fever, cough, dysentery, hepatitis and hypertension in Korea, China and Japan. In this study, we investigated the effects of 70% ethanolic extract of Scutellariae Radix (SRE) on CYP450-mediated drug metabolism in the in vitro systems using human liver microsomes and hepatocytes. The microsomal incubation assay showed that SRE inhibited the drug metabolism reactions catalyzed by CYP1A2, CYP2C8 and CYP2C9 in a dose-dependent manner. In particular, SRE was shown to strongly inhibit the metabolic activity of CYP1A2 with an $IC_{50}$ value of 4.6 ${\mu}g/mL$. When SRE was evaluated for its effect on the induction of CYP450 enzyme activities in cryopreserved human hepatocytes, SRE did not exhibit any effect.