[Corrigendum] Downregulation of heparanase by RNA interference inhibits invasion and tumorigenesis of hepatocellular cancer cells in vitro and in vivo.

Following the publication of this article, an interested reader drew to the authors' attention that two images in Fig. 1B (the a and d panels) appeared to represent the same clone, albeit with different intensities and the panels were cropped differently. The authors were able to confirm that Figs. 1B(a) and B(d) were inadvertently selected from the same set of images but with different exposure times: Owing to an error in data handling, a wrong image was chosen during the grouping the figures. The corrected version of Fig. 1 is shown on the next page, featuring the correct image for Fig. 1B(d). The authors regret that this error was not picked up upon before the paper was sent to press, although the error did not affect the major conclusions reported in the paper. The authors thank the Editor of International Journal of Oncology for allowing them the opportunity to publish a Corrigendum. and regret any inconvenience caused to the readership. [the origional article was published on International Journal of Oncology 40: 1601­1609, 2012; DOI: 10.3892/ijo.2012.1338].

Prevalence and trends of transfusion-transmittable infections among blood donors in Southwest China.

BACKGROUND: The high prevalence of transfusion-transmitted infections (TTIs) is causing serious harm to human health worldwide. The aim of this research was to assess the prevalence and influencing factors of TTIs in Southwest China. METHODS: A retrospective study of blood donor records from January 2008 to December 2015 was conducted. All samples were screened for HBV, HCV, HIV and syphilis. The donor's data was recorded and analyzed statistically using SPSS software. RESULTS: We revealed that the prevalence of TTIs showed a decreasing trend from 2.39 to 1.98%, and this was slightly lower than that in other regions of China. Syphilis infection was the most serious issue among blood donors in Southwest China, which demonstrated a significantly higher rate than that in other areas of China. The high infection rate of the female and farmer groups in rural regions is worth noting. The logistic regression model showed that age, occupation and donor category was the influential factors for TTIs. CONCLUSIONS: The overall prevalence of TTIs demonstrated a decreasing trend from 2008 to 2015 in Southwest China, but there is still a sufficient threat to blood safety, and more efforts are needed to further guarantee blood safety in China.

Quantitative and multiplexed detection for blood typing based on quantum dot-magnetic bead assay.

BACKGROUND: Accurate and reliable blood grouping is essential for safe blood transfusion. However, conventional methods are qualitative and use only single-antigen detection. We overcame these limitations by developing a simple, quantitative, and multiplexed detection method for blood grouping using quantum dots (QDs) and magnetic beads. METHODS: In the QD fluorescence assay (QFA), blood group A and B antigens were quantified using QD labeling and magnetic beads, and the blood groups were identified according to the R value (the value was calculated with the fluorescence intensity from dual QD labeling) of A and B antigens. The optimized performance of QFA was established by blood typing 791 clinical samples. RESULTS: Quantitative and multiplexed detection for blood group antigens can be completed within 35 min with more than 105 red blood cells. When conditions are optimized, the assay performance is satisfactory for weak samples. The coefficients of variation between and within days were less than 10% and the reproducibility was good. The ABO blood groups of 791 clinical samples were identified by QFA, and the accuracy obtained was 100% compared with the tube test. Receiver-operating characteristic curves revealed that the QFA has high sensitivity and specificity toward clinical samples, and the cutoff points of the R value of A and B antigens were 1.483 and 1.576, respectively. CONCLUSION: In this study, we reported a novel quantitative and multiplexed method for the identification of ABO blood groups and presented an effective alternative for quantitative blood typing. This method can be used as an effective tool to improve blood typing and further guarantee clinical transfusion safety.

Meprin-ß regulates production of pro-inflammatory factors via a disintegrin and metalloproteinase-10 (ADAM-10) dependent pathway in macrophages.

Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as atherosclerosis. Meprin, an astacin metalloproteinase, has exhibited proinflammatory effects in vivo and in vitro studies. Here, we tried to further investigate the proinflammatory potential of meprin-ß and the possible underlying mechanisms in primary human peripheral blood macrophages. In our current study, ELISA assay revealed that meprin-ß increased the production of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-18 and interleukin-6 (IL-6) in macrophages. However, meprin-ß shows no effects on the level of ligands of epidermal growth factor receptor (EGFR), and the activation of EGFR. The molecular mechanism was associated with activation of a disintegrin and metalloproteinase 10 (ADAM10) and the phosphorylation of IκB. Further analysis of upstream mechanisms showed that activation of NF-κB by meprin-ß was mediated by inhibiting ADAM10-downstream extracellular signal regulated kinase (ERK1/2) pathway. Taken together, these results indicated that meprin-ß exhibited pro-inflammatory effects by targeting activating ADAM10, leading to ERK1/2-mediated activation of NF-κB in macrophages, and this would make meprin-ß a strong candidate for further study as proinflammatory target.

In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.

Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen. However, vaccine therapy targeting only one cytotoxic T lymphocyte (CTL) epitope is suboptimal in preventing cancer. In the present study, we designed heparanase multi-epitope vaccines to increase the immune response to standard single heparanase epitopes. The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo. Heparanase multi-epitope vaccines not only induced the heparanase-specific CTL to lyse tumor cells but also increased CTL secretion of interferon-γ. However, these heparanase-specific CTL did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirms the safety of these multi-epitope vaccines. Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.

microRNA detection in feces, sputum, pleural effusion and urine: novel tools for cancer screening (Review).

microRNAs (miRNAs) are short non-coding RNA sequences that play important roles in the regulation of gene expression. They have significant regulatory functions in basic cellular processes, including differentiation, proliferation and apoptosis. miRNAs are differentially expressed in tumors, compared with normal tissues. Importantly, miRNAs are also stable and abundantly present in body fluids and feces. The high reproducibility, sensitivity and specificity of miRNAs in body fluids and feces enable miRNAs to be used as potential molecular markers for cancer screening. An increasingly large number of research studies have reported the role of miRNAs in this field. In the present review, we focused mainly on the application of detecting miRNAs in stool, sputum, pleural effusion and urine, to detect colon, lung and urological cancers, highlighting the role of miRNAs in early diagnosis and prognosis.

Glucocorticoids can increase the survival rate of patients with severe viral hepatitis B: a meta-analysis.

OBJECTIVES: Severe viral hepatitis B is a disease associated with significant morbidity and mortality. Clinical controlled trials show that the efficacy of treatment of severe viral hepatitis B with glucocorticoids remains debatable. Therefore, we carried out this meta-analysis to evaluate the safety, efficacy, and side effects of glucocorticoid therapy for severe viral hepatitis B. METHODS: We searched PubMed, Medline, Embase, Cochrane Library, and Google Scholar for randomized-controlled trials published before April 2012 in which glucocorticoid therapy was compared with routine treatment for severe viral hepatitis B. The primary outcome was the survival rate of the two groups. RESULTS: We selected eight controlled clinical trials, which included 597 patients. We recorded a benefit of glucocorticoid treatment on the survival rate of patients with severe viral hepatitis B (597 patients) [risk ratio (RR)=1.188, 95% confidence interval (CI) 1.030-1.369, P=0.018]. The benefit was most noticeable in patients at the stage of preliver failure (409 patients) (RR=1.275, 95% CI 1.077-1.510, P=0.005), whereas there was no efficacy for patients with liver failure (188 patients) (RR=1.008, 95% CI 0.774-1.312, P=0.955). Glucocorticoid treatment was not associated with the development of secondary infection and bleeding. CONCLUSION: Treatment with glucocorticoids can significantly increase the survival rate of patients with severe hepatitis B. The benefit was most noticeable in patients at the stage of preliver failure. However, the incidence of secondary infection and bleeding did not change significantly. This finding suggests that prompt and timely glucocorticoid treatment is crucial.

hTERT-based therapy: a universal anticancer approach (Review).

Human telomerase reverse transcriptase (hTERT) has been identified as a major protein involved in aberrant cell proliferation, immortalization, metastasis and stemness maintenance in a majority of tumors, yet it has little or no expression in normal somatic cells. During the past few years, the development of hTERT-based therapies such as immunotherapy, suicide gene therapy and small-molecule interfering therapy have become critical and specific for eradicating all types of cancer. Here, current knowledge regarding hTERT and its involvement in various cancers and its role as a target of cancer therapies are reviewed. Additionally, hurdles to new cancer therapy development and new therapeutic opportunities are described, along with areas that require further investigation.

Macrophages in tumor microenvironments and the progression of tumors.

Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-ß, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.

microRNA-27b suppresses mouse MSC migration to the liver by targeting SDF-1αin vitro.

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.

Downregulation of heparanase by RNA interference inhibits invasion and tumorigenesis of hepatocellular cancer cells in vitro and in vivo.

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.

HCV infection in voluntary donors and its influence on recruitment of donors in Chongqing area.

Blood donor recruitment models have changed from paid donors to employer-organized donors and to voluntary donors in China. Reports on the hepatitis C virus (HCV) infection among voluntary blood donors in China have been rarely found at present. The prevalence of anti-HCV and genotypes among the first-time voluntary blood donors was investigated in Chongqing area of China. A total of 13,620 serum samples were collected from the first-time voluntary blood donors in Chongqing, China. Anti-HCV antibody was tested by ELISA. The Core/E2 region of HCV RNA from HCV seropositive samples was amplified by RT-PCR for genotyping. The results indicated that the prevalence of anti-HCV averaged 0.49% (67/13,620), and the highest rate (0.86%) was obtained in the group aged 40 to 49. A higher prevalence was observed among the more educated donors, and metropolitan donors. The ratios of following genotypes 1b, 2a, 3a and 3b were 4 (18%), 5 (23%), 9 (41%) and 4 (18%) in all the 22 samples respectively. Genotype 3 (3a and 3b) was the predominant genotype. In conclusion, the prevalence of anti-HCV was low among the population of voluntary blood donors in Chonqing area. The genotyping results showed the possibility of presence of druggies among the voluntary blood donors. Therefore, more attention should be paid to exclude those high-risk persons from the volunteers.