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this study has many limitations, such as the sample size, age group, sex composition, and physical characteristics. Continuously observing the persistence of the protection provided by vaccines in real cases and the effectiveness of a booster dose (a third dose), conducting long-term clinical trials, and obtaining post-clinical data are essential tasks.To some extent, this study showed that serum neutralizing antibody levels decreased after the second dose of inactivated vaccines. Importantly, the results suggest that a booster dose (a third dose) is necessary to maintain the effectiveness of inactivated vaccines regardless of sex and two-dose immunization procedure.

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Enterovirus 71 (EV71), a major causative agent of hand-foot-and-mouth disease (HFMD), causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) of 30 infants (6 to 11 months) immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response. Clinical Trial Registration: NCT01391494 and NCT01512706.

We have previously found that expression of MARVELD1 was remarkably downregulated in multiple tumor tissues, but unclear in hepatocellular carcinoma (HCC) and its function has not been explored yet. In the present study, to uncover the underlying mechanism of MARVELD1 in the pathogenesis and development of HCC, we investigated the expression pattern of MARVELD1 and its effect on tumor proliferation in HCC. The results indicated the frequent downregulation of MARVELD1 in clinic samples and cell lines of HCC resulted from promoter methylation, as well as genetic deletion. Furthermore, treatment of MARVELD1 unexpressing Hep3B2.1-7 and PLC/PRF/5 cells with the demethylating agent 5-aza-2′ deoxycytidine restored its expression. Overexpression of MARVELD1 suppressed the proliferation of HCC cells in vitro and in vivo, whereas downregulation of endogenous MARVELD1 by shRNAs significantly enhanced these characters. MARVELD1 overexpression could enhance chemosensitivity of HCC cells to epirubicin and 10-hydroxycamptothecin. Corresponding to these results, the expression of p-ERK1/2 and cyclin D1 were decreased, whereas p16 and p53 were increased in MAR-VELD1-transfected cells. We also demonstrated that knockdown of MARVELD1 resulted in upregulation of p-ERK1/2 and cyclin D1, and downregulation of p16 and p53. Moreover, the effect of the decreased cell growth rate was significantly reversed when MAR-VELD1-overexpressing cells were trasfected with p53 or p16 siR-NA. Our findings suggest that MARVELD1 is a tumor suppressor by negatively regulating proliferation, tumor growth and chemosensitivity of HCC cells via increasing p53 and p16 in vitro and in vivo. MARVELD1 may be a potential target for HCC therapy. (Cancer Sci 2012; 103: 716-722) H epatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, and its incidence is still rising.(1) Currently there are about 600 000 cases of HCC each year, and nearly 78% of them are from Asian countries.(2) Substantial evidence from epidemiological studies indicates that HCC is strongly associated with alcohol abuse, chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and liver cirrhosis.(3-5) More than one million people die of liver cancer worldwide every year.(6) Few patients are diagnosed in the early stage, and <20% of HCCs can be resected completely. (7,8) Resistance to many of chemotherapy agents is a major obstacle to successful HCC treatment.(9-11) Therefore, a better understanding of the molecular mechanisms underlying HCC progression is urgently needed for leading to a more effective treatment.Genetic and epigenetic aberrations, leading to the activation of oncogenes and inactivation of tumor suppressor genes, are thought to play major roles in the pathogenesis of HCC. Recently, several MARVEL (proteins of the myelin and lymphocytes [MAL] and related proteins for vesicle trafficking and membrane link) domain-containing proteins have attracted increasing interest because they exhibit tumor suppressor activities a...