[Show abstract][Hide abstract] ABSTRACT: A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes (CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925) in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922, rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 "GG" genotype was associated with higher levels of CXCR5 than the "AG" and "AA" genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the "G" allele in rs3922 may lead to higher gene expression than the "A" allele, implicating that rs3922 might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism associated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination.
[Show abstract][Hide abstract] ABSTRACT: Alternative schedules are needed to provide greater immunogenicity in adults who fail to respond to the standard hepatitis B (HB) vaccine regimen.
To evaluate the immunogenicity and safety of high antigen content HB vaccine formulations administered to non-responders after routine primary vaccination.
This was a phase III, double-blind, controlled clinical trial in China. We enrolled healthy participants (16-60 years old) seronegative for HB surface (HBs) antigen after primary vaccination, who had HBs antibody (anti-HBs) titres <10mIU/ml at 28 days following routine vaccination with licensed HB vaccine containing 10μg of antigen. Participants were randomised (2:2:1) to receive three booster doses of HB vaccine formulations containing 60μg, 30μg or 10μg of antigen per dose 28 days apart. Blood samples were obtained pre-vaccination and 28 days after each dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28 days after each vaccine dose.
Seroconversion rates were ≥92.1% and ≥87.1% as from the second dose of the 60μg and 30μg HB vaccine formulations, respectively, with geometric mean concentrations (GMCs) of ≥286.0mIU/ml and ≥164.0mIU/ml. In the 10μg HB vaccine group the seroconversion rates were ≥83.0% and the GMCs ≥110.1mIU/ml as from the second vaccine dose. All HB vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported at least one injection-site or systemic adverse reaction (145/434 [33.4%] from the 60μg group; 138/435 [31.7%] from the 30μg group and 69/222 [31.1%] from the 10μg group). Most reactions were mild or moderate and resolved within 24h. No serious adverse events were reported.
Booster vaccination with a three-dose schedule of a high antigen content HB vaccine formulation was immunogenic and well tolerated in healthy adults.
[Show abstract][Hide abstract] ABSTRACT: The aggressive course of uveal melanoma is believed to reflect its unusually invasive and metastatic nature, which is associated with the nuclear factor kappaB (NF-κB) pathway. MicroRNAs (miRNAs) have been implicated in the regulation of various biological and pathological processes in cancer, however, the special role of miR-9 in uveal melanoma metastasis is largely unknown. In the present study, we showed that miR-9 is significantly reduced in highly invasive uveal melanoma cell lines, and suppressed migration and invasion of highly invasive cells. Furthermore, miR-9 negatively modulated NF-κB1 expression by direct targeting at its 3'-UTRs. Additionally, downstream targets of NF-κB1, such as MMP-2, MMP-9 and VEGFA, were regulated by miR-9 in the same pattern as NF-κB1. Therefore, miR-9 suppresses uveal melanoma cell migration and invasion partly through downregulation of the NF-κB1 signaling pathway.
[Show abstract][Hide abstract] ABSTRACT: Hand, foot, and mouth disease (HFMD) has been emerging as an important public problem over the past few decades, especially in Asian and Pacific regions. A national program on EV71 vaccine development against HFMD was initiated in China, in 2008, which called for a need for seroepidemiological study for the target population.
This was a retrospective study conducted in Jiangsu Province, in October, 2010. We measured the neutralizing antibodies against EV71 and CoxA16 in a cohort of infants aged of 2, 7, 12, and 27-38 months and their mothers just before delivery. Series sera samples from 975 infants and 555 mothers were collected and analyzed. Questionnaires on the history of HFMD were completed in the survey. A total of 143 HFMD cases were collected, but only 11.2% were reported to the National Infectious Disease Information Management System. The level of maternal antibody titers decreased dramatically during the first 7 month and remained at a relatively low level thereafter. But it increased significantly from month 12 to months 27-38. The accumulate incidence density of HFMD demonstrated a significant increase after 14 months of age, resulting in a accumulate incidence density of 50.8/1000 person-years in survey period. Seropositivity of EV71 antibody in infants at the age of 2 months seems to demonstrate a protective effect against HFMD.
High seropositive rate of EV71 and CoxA16 antibody was found in prenatal women in mainland China, and there is a need to enhance the HFMD case management and the current surveillance system. We suggest that infants aged between 6 to 14 months should have the first priority to receive EV71 vaccine.
PLoS ONE 05/2012; 7(5):e37206. DOI:10.1371/journal.pone.0037206 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the impact of the ITGA2 gene polymorphism on gastric cancer risk.
A hospital-based case-control study was conducted, including 307 gastric cancer patients and 307 age- and gender-matched control subjects. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism assay.
The frequencies of the wild and variant genotypes in cases were significantly different from those of controls (P = 0.019). Compared with individuals with the wild genotype CC, subjects with the variant genotypes (CT + TT) had a significantly higher risk of gastric cancer (adjusted odds ratio = 1.57, 95% CI = 1.13-2.17, P = 0.007). In stratified analyses, the elevated gastric cancer risk was especially evident in older individuals aged > 58 years, nonsmokers and rural subjects. Further analyses revealed that the variant genotypes were associated with poor tumor differentiation and adjacent organ invasion in the sub-analysis of gastric cancer patients.
The ITGA2 gene C807T polymorphism may be associated with an increased risk of gastric cancer, differentiation and invasion of gastric cancer.
World Journal of Gastroenterology 06/2011; 17(23):2860-6. DOI:10.3748/wjg.v17.i23.2860 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the possible relationship between the Ku80 gene polymorphism and the risk of gastric cancer in China.
In this hospital-based case-control study of gastric cancer in Jiangsu Province, China, we investigated the association of the Ku80 G-1401T (rs828907) polymorphism with gastric cancer risk. A total of 241 patients with gastric cancer and 273 age- and sex-matched control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism.
The frequencies of genotypes GG, GT and TT were 65.6%, 22.8% and 11.6% in gastric cancer cases, respectively, and 75.8%, 17.6% and 6.6% in controls, respectively. There were significant differences between gastric cancer and control groups in the distribution of their genotypes (P = 0.03) and allelic frequencies (P = 0.002) in the Ku80 promoter G-1401T polymorphism.
The T allele of Ku80 G-1401T may be associated with the development of gastric cancer.
World Journal of Gastroenterology 04/2011; 17(16):2131-6. DOI:10.3748/wjg.v17.i16.2131 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is well documented that 5-10% hepatitis B adult vaccinees are non- and hypo-responders and probably are not adequately protected against hepatitis B virus (HBV) infection. The sequence variations of genes involved in processes such as pathogen recognition, antigen processing and presentation, and differentiation/maturation of lymphocytes may affect the duration and intensity of protective humoral immune response to the hepatitis B vaccine. In this study, frequencies of 53 known SNPs within 21 candidate genes were analyzed among 46 responders and 24 non-responders. Four SNPs (rs2243248, rs1805015, rs1295686 and rs3804100) in IL-4, IL-4RA, IL-13 and TLR2 genes were found significantly associated with the vaccinees' status of serum anti-HBV response triggered by the vaccine (P<0.05). Two SNPs (rs1295686 and rs1805015) also showed significant association with the vaccine-induced immune response when analyzed together with risk factors such as age and gender, by multivariable logistic regression analysis (P<0.05). Further, haplotype analysis showed that the AG haplotype defined by SNPs rs1143633 (IL-1B; intron) and rs1143627 (IL-1B; intron) was present more frequently in non-responders than in responders (P=0.035). Thus, specific SNPs in genes of cytokines/cytokine receptors and TLR2 were associated with status of the hepatitis B vaccine-induced protective humoral immune response.
[Show abstract][Hide abstract] ABSTRACT: Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single-nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa-mir-27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR-27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case-control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06-2.05; P = 0.019). The elevated risk was especially evident in older subjects (age >58 years), men, nonsmokers and rural subjects. A significant association of hsa-mir-27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR-27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR-27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa-mir-27a, by modulating miR-27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility.
Cancer Science 10/2010; 101(10):2241-7. DOI:10.1111/j.1349-7006.2010.01667.x · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the association between pre-miR-146a C/G polymorphism and gastric cancer risk.
We performed a hospital-based, case-control study using polymerase chain reaction-restriction fragment length polymorphism method in 608 individuals (304 gastric cancer patients and 304 age and sex matched cancer-free controls).
The frequencies of pre-miR-146a C/G genotypes in the case group were significantly different from those in the control groups (P = 0.037). Compared with CC genotype carriers, subjects with the variant genotypes (GC + GG) had a 58% increased risk of gastric cancer (adjusted OR = 1.58, 95% CI: 1.11-2.20, P = 0.009). Moreover, a higher gastric cancer risk was especially evident in younger individuals aged < or =58 years, nonsmokers, and males (adjusted OR = 1.76, 95% CI: 1.08-2.87, P = 0.024; adjusted OR = 1.55, 95% CI: 1.06-2.28, P = 0.025; adjusted OR = 1.53, 95% CI: 1.04-2.27, P = 0.033; respectively).
Pre-miR-146a C/G polymorphism might be associated with an elevated risk of gastric cancer in Chinese population.
World Journal of Gastroenterology 07/2010; 16(28):3578-83. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were: to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.
Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.
Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P < 0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.
The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.
Chinese medical journal 07/2010; 123(13):1679-84. · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genistein, an isoflavone isolated from soybean, has been found to be a potent antitumor agent. However, both the effect of genistein on human uveal melanoma cells and the precise mechanism by which genistein suppresses tumorigenesis remain unclear. In the present study, we explored the possible activity of genistein to inhibit human uveal melanoma cell growth and investigated the possible role of genistein on microRNA-27a (miR-27a) as well as its target gene zinc finger and BTB domain containing 10 (ZBTB10) expression levels. The results suggested a significant inhibition of uveal melanoma cell growth in a time- and dose-related manner. In vivo study also indicated treatment groups with genistein could significantly inhibit the growth of xenografts. Further functional assays revealed that the levels of miR-27a and its target gene ZBTB10 were significantly different based on the dose of genistein. In conclusion, the present study demonstrates that genistein exerts growth inhibitory activities in human uveal melanoma cells. Moreover, we for the first time report a correlation between antitumor activity of genistein and miR-27a mediated regulatory mechanism.
[Show abstract][Hide abstract] ABSTRACT: Vasculogenic mimicry (VM) was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells.
VM structure was detected by periodic acid-Schiff (PAS) staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR) and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin) mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining.
Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 microM Genistein-treatment groups but not in 100 and 200 microM. RT-PCR and Western Blot showed that 100 and 200 microM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P < 0.05). However, the 25 and 50 microM Genistein slightly decreased the VE-cadherin level in vitro (P > 0.05).
Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.
Journal of Experimental & Clinical Cancer Research 09/2009; 28(1):124. DOI:10.1186/1756-9966-28-124 · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been shown that the expression of the receptor for advanced glycation end products (RAGE) is closely associated with invasion and metastasis in gastric cancer. A Gly82Ser polymorphism in exon 3 of RAGE gene was identified and thought to have an effect on the functions of its protein. Therefore, the goal of the present study was to investigate whether the polymorphism is involved in the development or progression of gastric cancer.
In the hospital-based case-control study, the RAGE genotypes were determined using PCR-RFLP in 566 individuals (283 gastric cancer patients and 283 age- and sex-matched controls).
The distribution of genotype was significantly different between cases and controls (P = 0.038). Compared with the wild-type 82Gly/Gly carriers, subjects with the variant genotypes (82Gly/Ser and 82Ser/Ser) had a significantly higher risk of gastric cancer (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Moreover, the elevated gastric cancer risk was especially evident in younger individuals (ages < or =58 years), nonsmokers, and rural subjects. Further analyses revealed that the variant genotypes were associated with adjacent organ invasion in the subanalysis of gastric cancer patients.
Our findings indicate that the RAGE Gly82Ser polymorphism may confer not only an increased risk of gastric cancer but also with invasion of gastric cancer in the Chinese population.
Clinical Cancer Research 06/2008; 14(11):3627-32. DOI:10.1158/1078-0432.CCR-07-4808 · 8.72 Impact Factor