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Yang L.,Peking Union Medical College | Yang L.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | Yang H.,Kunming Medical University | Wu K.,Kunming Medical University | And 5 more authors.
Journal of Medical Virology | Year: 2014

Genetic variations of High-Risk HPV E6/E7 may be associated with the development of cervical cancer in specific geographic regions. Few data have been reported about the HPV prevalence and E6/E7 variants among cervical cancer patients in Southwest China. This study was designed to investigate the prevalence of HPV and E6/E7 variants of most prevalent HPV among cervical cancer patients in Southwest China. After genotyping, E6/E7 genes of most prevalent HR HPV samples were sequenced and analyzed. Phylogenetic trees were then constructed, followed by an analysis of the diversity of secondary structure and selection pressures. HPV 16 (73.8%) and HPV 18 (16.4%) are the most prevalent infection types among cervical cancer patients, followed by HPV 58, HPV 56 and HPV 59, which is different from the high HPV 58 infection rate of outpatients in this region. Eighteen single nucleotide changes were observed in HPV 16 E6 with 13/18 non-synonymous mutations (5 in beta sheet and 2 in alpha helix). Ten single nucleotide changes were identified among HPV 16 E7 with 3/10 non-synonymous mutations. Three single nucleotide changes were observed in HPV 18 E6 with one non-synonymous mutation, and only one synonymous mutation was identified in HPV 18 E7. HPV 16 E6-D25E, E7-N29S and E7-T846C (S95S) exhibited a prevalent linkage mutation. The phylogenetic tree demonstrates that European and Asian lineages were the main patterns. This study may help understand the intrinsic geographical relatedness and oncogenic potential of HR HPV and contributes further to research of diagnostic, therapeutic and therapeutic vaccine strategy. © 2014 Wiley Periodicals, Inc. Source


Ding X.,Peking Union Medical College | Ding X.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | Qiu L.,Peking Union Medical College | Qiu L.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | And 13 more authors.
OncoTargets and Therapy | Year: 2016

Background: Semaphorin 4D (Sema4D) belongs to the class IV semaphorins, and accumulating evidence has indicated that its elevated level may be one strategy by which tumors evade current anti- angiogenic therapies. The biological roles of Sema4D in colorectal cancer (CRC), however, remain largely undefined. This study was designed to investigate the effects of Sema4D on tumor angiogenesis and growth in CRC, especially in different vascular endothelial growth factor (VEGF) backgrounds. Methods: The expression of Sema4D in human CRC was evaluated by immunohistochemical analysis of tumors and their matching normal control tissues. The expression level of Sema4D and VEGF was investigated in different CRC cell lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and in vivo tumor angiogenic assays. Results: Immunohistochemical analysis of human CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive ratios of Sema4D staining for well, moderately, and poorly differenti- ated cancers were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five different CRC cell lines, while VEGF expression level varies among these cell lines. HCT- 116 showed the lowest VEGF level, while Caco-2 showed the maximum VEGF level. In vitro migration results show that regardless of cell type and VEGF background, Sema4D showed an enhanced in vitro proangiogenic effect to induce the migration of human umbilical vein endothelial cells. Finally, in vivo tumor angiogenic assays demonstrated that Sema4D alone can elicit a significant angiogenic response to promote tumor growth independently of VEGF. Conclusion: Targeting Sema4D might serve as a parallel option for antiangiogenic therapy for CRC, particularly when traditional anti-VEGF therapies fail or tumors develop resistance to strategies targeting a single angiogenic signaling pathway. © 2016 Ding et al. Source


Huang W.,Peking Union Medical College | Huang W.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | Yao Y.,Peking Union Medical College | Yao Y.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | And 17 more authors.
PLoS ONE | Year: 2014

Objective: Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections. Methods: Mice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay. Results: Intramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates. Conclusions: Utilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections. © 2014 Huang et al. Source


Long Q.,Peking Union Medical College | Long Q.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | Huang W.,Peking Union Medical College | Huang W.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | And 17 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis. © 2014 Landes Bioscience. Source


Yue Y.,Peking Union Medical College | Yue Y.,Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases | Yang H.,Kunming Medical University | Wu K.,Kunming Medical University | And 16 more authors.
PLoS ONE | Year: 2013

HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28) and HPV-58 (L1: n = 21, L2: n = 21) L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software), followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns). Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn) and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn). Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and contributes further to research on their infectivity, pathogenicity, and vaccine strategy. © 2013 Yue et al. Source

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