BIRC5 (Survivin) belongs to the inhibitor of apoptosis gene family. The BIRC5 protein inhibits caspases and consequently blocks apoptosis. Thus, BIRC5 contributes to the progression of cancer allowing for continued cell proliferation and survival. In this study, we identified eight sequence variants of BIRC5 through direct DNA sequencing. Among the eight single nucleotide polymorphisms (SNPs), six common variants with frequencies higher than 0.05 were selected for larger-scale genotyping (n=1,066). Results of the study did not show any association between the promoter region polymorphisms and the clearance of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence. This is in line with a previous study in which polymorphisms in the promoter region does not influence the function of BIRC5. Initially, we were able to detect a signal with the +9194A>G, which disappeared after multiple corrections but led to a change in amino acid. Similarly, we were also able to detect an association signal between two haplotypes (haplotype-2 and haplotype-5) on the onset age of HCC and/or HCC occurrence, but the signals also disappeared after multiple corrections. As a result, we concluded that there was no association between BIRC5 polymorphisms and the clearance HBV infection and/or HCC occurrence. However, our results might useful to future studies.
Li, Zhi;He, Ming-Liang;Yao, Hong;Dong, Qing-Ming;Chen, Yang-Chao;Chan, Chu-Yan;Zheng, Bo-Jian;Yuen, Kwok-Yung;Peng, Ying;Sun, Qiang;Yang, Xiao;Lin, Marie C.;Sung, Joseph J.Y.;Kung, Hsiang-Fu
BMB Reports
/
v.42
no.1
/
pp.59-64
/
2009
Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.
Serpin peptidase inhibitor, Clade B (ovalbumin), Member 5 (SERPINB5), also known as maspin, is a potent tumor suppressor gene. It has correlations with many tumor cells, from pancreas cancer to breast cancer, so it is possible that it may also affect liver cancer. There has also been a report that SERPINB12, a gene placed right next to SERPINB5, is expressed in liver. For this study, 32 polymorphisms were identified in SERPINB5 by direct DNA sequencing, and 11 of them were selected to be tested with a larger scale subjects. The association of the 11 SERPINB5 polymorphisms with Hepatitis B virus (HBV) clearance, hepatocellular carcinoma (HCC) occurrence and the onset age of HCC were analyzed. There were no significant associations found between 11 SERPINB5 polymorphisms and HBV clearance. In the case of HCC occurrence, one of the haplotypes (ht) showed association with HCC occurrence (OR=2.26, p=0.005, $P^{Cor}=0.05$), albeit with a low statistical power (40.8%) and haplotype frequency (0.052). Further study with a bigger sample size will be needed to clearly verify the association between ht5 and HCC occurrence.
Serum HBsAg, AntiHBs, HBeAg, AntiHBe and AntiHBc were detected by radioimmunoassay in 39 patients with acute viral hepatitis, 79 patients with chronic hepatitis, 30 patients with liver cirrhosis, 16 patients with primary hepatocellular carcinoma, 14 patients of HBsAg carriers and 129 cases of controls:78 cases of normal level of SGOT, SGPT, and 51 cases of elevated level of SGOT, SGPT. Following results were obtained: 1. HBsAg was detected in 66.7% of acute viral hepatitis, 63.3% of chronic hepatitis, 36.7% of liver cirrhosis, 81.3% of primary hepatocellular carcinoma and 27.1% of controls. 2. AntiHBs was positive in 0% of acute viral hepatitis, 21.5% of chronic hepatitis, 36.7% of liver cirrhosis, 31.3% of primary hepatocellular carcinoma, 0% of carrier and 44.2% of controls. 3. HBeAg was detected in 45.6% of chronic hepatitis, 23.3% of liver cirrhosis and 31.3% of primary hepatocellular carcinoma. 4. Among chronic liver diseases, antiHBe was positive in 56.3% of primary hepatocellular carcinoma, 23.3% of liver cirrhosis and 20.3% of chronic hepatitis. 5. AntiHBc was detected in most of all examines and the significance of presence of AntiHBc does not seem to represent liver disease itself but the evidence of infection of HBV. 6. Among 14 HBV carriers, 6 cases presented with abnormal SGOT, SGPT. 7. All HBV markers were negative in 5.1% of acute viral hepatitis, 5.1% of chronic hepatitis and 14.7% of controls: 17.6% of subjects with abnormal SGOT, SGPT and 12.8% of subjects with normal SGOT, SGPT. 8. Beside of HBV, other causes, such as non A, non B virus, Delta-agent, other viruses or related factors should be excluded among the patients with evidence of HBV infection associated with elevation of SGOT & SGPT.
Kim, Kyoung-Yeon;Lee, Seung-Ku;Kim, Min-Ho;Cheong, Jae-Youn;Cho, Sung-Won;Yang, Kap-Seok;Kwack, Kyu-Bum
Genomics & Informatics
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v.6
no.4
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pp.192-201
/
2008
Erythropoietin-producing human hepatocellular carcinoma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular system development. Eph receptor overexpression has been observed in various cancers and is related to the malignant transformation, metastasis, and differentiation of cancers, including hepatocellular carcinoma (HCC). Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. EphrinB1, the ligand of EPHB1, has been shown to regulate HCC carcinogenesis. Here, we sought to determine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, including chronic liver disease (CLD) and HCC. We genotyped 26 EPHB1 single nucleotide polymorphisms (SNPs) in 399 Korean CLD, HCC, and LD (CLD+HCC) cases and seroconverted controls (HBV clearance, CLE) using the GoldenGate assay. Two SNPs (rs6793828 and rs11717042) and 1 haplotype that were composed of these SNPs were associated with an increased risk for CLD, HCC, and LD (CLD+HCC) compared with CLE. Haplotypes that could be associated with HBV-infected liver diseases by affecting downstream signaling were located in the Eph tyrosine kinase domain of EPHB1. Therefore, we suggest that EPHB1 SNPs, haplotypes, and diplotypes may be genetic markers for the progression of HBV-associated acute hepatitis to CLD and HCC.
Kim, Mae-Ja;Lee, Sun-Oak;Shin, Gye-Young;Kim, Eun-Kyung;Jang, Mi-Ra
Research in Community and Public Health Nursing
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v.13
no.1
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pp.57-67
/
2002
Purpose: Chronic hepatic disease is caused by inappropriate management of the hepatitis B virus. In Korea. there is an increasing number of chronic hepatic patients. who are at risk of dying from liver failure or hepatocellular carcinoma. Therefore it is important to manage the hepatitis B virus appropriately. Method: The patients diagnosed with chronic hepatic disease or HBV carrier who registered at a community health center or hospital were assessed regarding health man agement status and educational needs. The data was collected from 179 persons by convenient sampling between May, 2000 and April. 2001. The data were was analyzed for general characteristics using the descriptive method, factors influencing educational needs and health management using t-test and ANOVA. Results: 1. The average health management score was 18.2 from 12 to 24 range. Those who unknown were unaware of the presence of HBsAg, attending the educational program and keeping undergoing treatment at the community health center or hospital were had a higher management score(p< .05). 2. The educational needs regarding nutritional management(64.8%) was the highest topic with chronic hepatitis patients. The second highest topic was spreading prevention among family members (52.0%), and keeping medication (45.8%), the degree of physical activities(44.1%), and spreading prevention in public(39.1%). Those who were unaware of the presence of HBsAg (p< .001), less than 12 months after HBsAg (+)(p< .05), keeping treatment (p< .05) were higher educational needs. 3. The use of alternative therapy was 27.9% of subjects. The subjects thought it was helpful for disease management(42.1%), mostly, family members and relatives recommended to use (57.9%), and medical regimen was ignored during the alternative therapy. Conclusion: Based on the results, an educational program about prevention of type B hepatitis and management for patients having type B hepatitis should be developed.
We investigated HBV markers in serum and cerebrospinal fluid of 50 subjects with neurologic disorders or other disorders, who visited Dept. of neurology, college of medicine, Yeungnam University, from April-1 to August-31 1994 and were performed cerebrospinal fluid analysis to investigate the detection rate of HBV markers in cerebrospinal fluid and the possibility of neurologic disorders associated with HBV infection. The results were as follows. The positivity of HBsAg and HBV prevalence rate in serum were 6(12.0%) and 37(74.0%). The number of patient with HBsAg, only anti-HBV and no markers were 6(12.0%), 31(62.0%) and 13(26.0%), respectively. The positivity of HBsAg and HBV prevalence rate in cerebrospinal fluid were 3(6%) and 18(36.0%). The number of patient with HBsAg, only anti-HBV and no markers were 6(100.0%), 12(38.7%) and 0(0.0%) respectively. The number of patient with virus associated diseases(VAD) and non virus associated diseases(NVAD) were 26(52%) and 24(48%). The HBV prevalence rate in serum of VAD and NVAD groups were 88.5% and 58.3% (p<0.05). The HBV prevalence rate in CSF of VAD and NVAD groups were 53.8% and 16.7%(P<0.05). The HBV prevalence rate in serum and CSF of VAD and NVAD groups were 60.9% and 28.6%. Aa a conclusion, the HBV markers in the CSF were partially detected at the presence of the HBV markers in serum. The prevalance rate of HBV in the CSF was increased at the HBsAg positive in the serum and the serum and the CSF was significantly increased at the VAD group than the NVAD group.
Nelumbo nucifera (lotus) is known to be a useful medicinal plant and leaf extract contains several flavonoids and alkaloids. To analyze the effect of Nelumbo nucifera leaves extract (NNL) on the HBsAg production, we treated NNL on HepG2.2.15 cells which contain the hepatitis B viral genome and secrete surface antigen into media. NNL suppressed the production of hepatitis B surface antigen as a dose-dependent manner. To analyze the effect of NNL on HBV DNA replication, PCR analysis was performed. NNL was not affected the HBV DNA replication and HBsAg mRNA expression. To understand the effect of NNL on the production of HBsAg, we carried out the analysis of lipid-metabolizing gene expression using one-step RT-PCR. NNL reduced the gene expression of FASN and SREBP2 and increased the expression of LDLR. Triglyceride content of HepG2.2.15 cells was not decreased by treatment of NNL. This result suggests a possibility that NNL may have an effect for the inhibition of hepatitis B surface antigen by modulation of lipid and cholesterol metabolism.
Medical personnek are one of several groups that have been reported to have a high incidence of hepatiris B. It is also thought that the occurrence rate of hepatitis B surface antigen(HBsAg), aserologic marker for hepatitis B virus(HBV), is expected to be high in the dental personnel who are frequently exposed to the blood and saliva of the patients. Although many studies have been done to determine the HBsAg status of virus groups, limited investigations have been performed on dental personnel, especially in this country. The main purpose of this study was to identify HBsAg positivity among dental students, interns, and residents who would be expected to be a high risk group of hepatitis B infection. Screening test for HBsAg of a dental school population was performed by indirect hemagglutination(IHA)in 1982. The results were as follows : 1. Thirty four out of a total 362 persons(9.4%)tested in the study had positive response for HBsAg in their serum samples. 2. Twenty seven out of 320 dental students(8.4%)had positive for HBsAg, and in Senior class 12 out of 82 dental students (14.6%)had positive response that was the highest incidence among dental students group. 3. Seven out of 42 interns and residents(16.7%)had positive for HBsAg, and it was the highest incidence in this dental school population.
Choi, Yujung;Bae, Kil Seoung;Kim, Ki Hwan;Koh, Dae Kyun;Kim, Jong-Hyun
Pediatric Infection and Vaccine
/
v.25
no.2
/
pp.72-81
/
2018
Purpose: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. Methods: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. Results: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). Conclusions: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.
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