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ABSTRACT: BACKGROUND: Hepatitis B virus (HBV) infection is reported to be associated with an increased risk of pancreatic cancer (PaC), but it remains controversial whether this is a causal relationship. In addition, it is unclear whether the status of HBV infection also affects PaC risk. Therefore, we conducted a meta-analysis to more closely examine the association between HBV infection and PaC. METHOD: The studies included in the meta-analysis were identified and retrieved from PubMed and several other databases. The literature search was conducted up until August 2012. We adopted the Cochrane Collaboration's RevMan 5.1 in a combined analysis of pooled relative risk (RR) with their corresponding 95 % confidence intervals (CIs) using a random-effects and a fixed-effects model. RESULTS: Nine studies including 6 case-control and 3 cohort studies met eligibility criteria. The meta-analysis showed that the PaC risk was positively correlated with HBV infection when comparing with 'never exposed to HBV' subgroup, the pooled RR was 1.39 (95 % CI 1.22-1.59, p < 0.00001) in chronic HBV carriers, 1.41 (95 % CI 1.06-1.87, p = 0.02) in past exposure to HBV, and 3.83 (95 % CI 1.76-8.36, p = 0.0007) in active HBV infection. Using a stratified analysis, we also found that the risk of PaC was independent of smoking, alcohol drinking, and diabetes. CONCLUSION: Findings from this meta-analysis strongly support that HBV infection is associated with an increased risk of PaC.
Cancer Causes and Control 01/2013; · 2.88 Impact Factor
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ABSTRACT: The SDF-1/CXCR4 axis is critical for inducing stem cell mobilization into the circulation, for homing stem cells to the site of injury, and for stem cell participation in the regeneration of liver tissue. In this study, we have gained insight into the molecular mechanisms involved in regulating the expression of SDF-1α by miRNAs. Using microarray and bioinformatics approaches, we identified six miRNAs with differential expression in damaged liver tissue (21 days after liver injury) compared to normal C57BL/6 murine liver tissue and further confirmed these observations by qPCR; miR-23a, which was identified by other researchers, was also included for comparative purposes. We found that miR-23a, miR-27a and miR-27b expression was significantly lower in the damaged liver than in the normal liver (p<0.05). We further confirmed that miR-27b could directly interact with the 3'UTR of SDF-1α to suppress SDF-1α protein expression using a luciferase reporter assay and Western blot analysis. In addition, we found that the over-expression of miR-27b significantly reduced the directional migration of primary cultured CRCX4-positive murine mesenchymal stem cells (mMSCs) in vitro using a transwell assay. These results suggest that miR-27b may be a unique signature of the stem cell niche in the damaged mouse liver and that mir-27b can suppress the directional migration of mMSCs by down-regulating SDF-1α expression by binding directly to the SDF-1α 3'UTR.
Biochemical and Biophysical Research Communications 04/2012; 421(2):389-95. · 2.48 Impact Factor
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Xu-Dong Tang,
Guo-Zhen Wang,
Jun Guo,
Mu-Han Lü,
Chuan Li,
Ning Li,
Ya-Ling Chao,
Chang-Zhu Li,
Yu-Yun Wu, Chang-Jiang Hu,
Dian-Chun Fang,
Shi-Ming Yang
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ABSTRACT: Accumulating research suggests that heparanase may be a universal tumor-associated antigen (TAA). Several heparanase T-cell epitopes from humans and mice have already been identified. However, because of low immunogenicity, polypeptide vaccines usually have difficulty inducing effective antitumor immune responses in vivo. In this study, to increase the immunogenicity of polypeptide vaccines, we designed and synthesized two four-branch multiple antigenic peptides (MAP) on the basis of mouse heparanase (mHpa) T-cell epitopes (mHpa398 and mHpa519). The dendritic cells (DC) from mice bone marrow loaded with above MAP vaccines from heparanase were used to evaluate immune response against various tumor cell lines, compared with immune response to their corresponding linear peptides, ex vivo and in vivo. We further assessed IFN-γ release both in CD4(+) T-cell-depleted and nondepleted mice. The results showed that effectors generated from DCs, loaded with MAP-vaccinated mice splenocytes, induced a stronger immune response against target cells expressing both heparanase and H-2K(b) than did effectors generated from mice vaccinated with their corresponding linear peptides. Heparanase-specific CD8(+) T-cell responses induced by MAP and linear peptide vaccination required synergy of CD4(+) T cells. In addition, heparanse-derived MAP vaccines significantly inhibited the growth of B16 murine melanoma in C57BL/6 mice, while also increasing the survival rate of tumor-bearing mice. Our data suggest that MAP vaccines based on T-cell epitopes from heparanase are efficient immunogens for tumor immunotherapy.
Molecular Cancer Therapeutics 03/2012; 11(5):1183-92. · 5.23 Impact Factor
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Zhen Xiong,
Mu-Han Lü,
Ya-Han Fan,
Ya-Ling Cao, Chang-Jiang Hu,
Yu-Yun Wu,
Shu-Min Wang,
Gang Luo,
Dian-Chun Fang,
Chuan Li,
Shi-Ming Yang
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ABSTRACT: Heparanase is an endoglycosidase that degrades heparan sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. The expression of heparanase is associated with invasion, as well as the angiogenic and metastatic potential of diverse malignant tumors. We used RNA interference strategies to evaluate the role of human heparanase in a liver cancer cell line and to explore the therapeutic potential of its specific targeting. Using an online siRNA tool, we designed three small interfering RNA sequences to target the heparanase coding region and cloned them into the pGenesil-1 vector. The siRNA vectors were transfected into HepG2 liver cancer cells. Heparanase expression was measured by real-time RT-PCR and Western blotting. Cell proliferation was detected by MTT staining and plate colony formation. Cell cycle analysis was performed by flow cytometry. In vitro invasion was measured by Matrigel invasion assay. We also analyzed tumorigenicity in heparanase-suppressed HepG2 cells in nude mice. We found that siRNA-1 (1214-1232) and siRNA-3 (611-629) targeting heparanase significantly downregulated the expression of heparanase in HepG2 liver cancer cells. Compared with its controls, siRNA-1 or siRNA-3 vectors efficiently inhibi-ted the proliferation and invasion of HepG2 liver cancer cells in vitro and tumorigenesis in vivo. These results suggest that heparanase-specific RNA interference has potential value as a novel therapeutic agent for human liver cancer.
International Journal of Oncology 01/2012; 40(5):1601-9. · 2.40 Impact Factor
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ABSTRACT: Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses.
Journal of Biomedicine and Biotechnology 01/2012; 2012:605045. · 2.44 Impact Factor
