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Activity of T Cells Stimulated by Hemagglutinin-neuraminidase of Newcastle Disease Virus in vivo

Chemical Research in Chinese Universities 2011年第3期27卷 455-460页

作者： piao Bing-guo LI Xiao SUN Li-li KAN Shi-fu LIU Lei HUANG Hai-yan YANG guo-hua WANG Yu-hang WANG Zhuo-yue SUN Jiu-hua piao Yun-feng JIN Ning-yi The First Hospital of Jilin University Changehun 130021 P. R. ChinA Genetic Engineering Laboratory of PLA 3. Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changehun 130062 P. R. China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changchun 130062 P. R. China Department of Gastroenterology 209 Hospital of PLA Mudanjiang 157000 P. R. China Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130001 P R. China

To investigate the stimulated activity of T cells and the anti-tumor properties of hemagglutinin-neuraminidase（HN） of Newcastle disease virus（NDV） strain Changchun（NDVcc）, the expression of HN gene in hepatoma cells（human HepG-2 and mouse H22 cells） infected with the recombinant adenovirus（Ad-HN） was identified by Western blot analysis and flow cytometry. Sialidase activity of NDVcc HN expressed by Ad-HN was assayed by the periodate-resorcinol method. The in vivo anti-tumor effects of NDVcc HN were evaluated in the H22 solid tumor model. Regional lymph nodes of the mouse model treated with Ad-HN were removed to harvest T lymphocytes and evaluating the specific cytotoxicity of cytotoxic T lymphocyte（CTL） and natural killer（NK） cells by an L-lactate dehydrogenase（LDH） assay, in the mean time, the secretion of cytokines was analyzed by enzyme linked immunosorbent assays（ELISA）. The results show that NDVcc HN was effectively expressed by Ad-HN in HepG-2 and H22 cells. The sialidase activity assay showed that Ad-HN significantly reduced sialic acid level of the hepatoma cells compared with the cells infected the empty adenovirus vector（Ad-mock）. When treated with Ad-HN, the growth of subcutaneous H22 primary tumors in C57BL/6 mice was suppressed, and the mean mice survival increased. In addition, the treatment of Ad-HN elicited strong NK and CTL responses, and high levels of Th1 cytokines, such as IL-2 and IFN-γ. In conclusion, NDVcc HN effectively elicits T cell-mediate anti-tumor cytotoxicity via sialidase activity and may be a novel strategy for cancer immunotherapy.

关键词： Newcastle disease virus Hemagglutinin-neuraminidase Hepatoma T Cell Anti-tumor immunity

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Cytosolic phospholipase A2α modulates cell-matrix adhesion via the FAK/paxillin pathway in hepatocellular carcinoma

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Cancer Biology & Medicine 2019年第2期16卷 377-390页

作者： piao guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua guo Department of Tumor Cell Biology Department of Hepatobiliary Cancer Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer/ Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Objective: To explore the effect of cytosolic phospholipase A2α(cPLA2α) on hepatocellular carcinoma(HCC) cell adhesion and the underlying ***: Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody *** signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression ***: Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in HepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC ***: Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.

关键词： Hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin

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Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma

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Cancer Biology & Medicine 2019年第1期16卷 89-99页

作者： Lu Chen Xiangdong Tian Wenchen Gong Bo Sun Guangtao Li Dongming Liu piao guo Yuchao He Ziye Chen Yuren Xia Tianqiang Song Hua guo Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was ***: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by ***: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated ***: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and *** study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

关键词： Periostin hepatoblastoma EMT MAPK/ERK

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The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing

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Cancer Biology & Medicine 2020年第1期17卷 142-153页

作者： Lu Chen Xianfu Yi piao guo Hua guo Ziye Chen Chunyu Hou Lisha Qi Yongrong Wang Chengwen Li Peng Liu Yucun Liu Yuanfu Xu Ning Zhang The concrete information of affiliations should be presented for instanceDepartment of Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300070China School of Biomedical Engineering and Technology Tianjin Medical UniversityTianjin 300070China The Center for Translational Cancer Research Peking University First HospitalBeijing 100034China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection Tianjin 300020China Cytogenetics Laboratory Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still ***,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver ***:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted *** and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the *** cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ ***:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient ***,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse ***-induced HCCs exhibited a similar histological phenotype and genomic profile as human ***:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.

关键词： Hepatocellular carcinoma bone marrow-derived cells(BMDCs) origination genome sequencing copy number alteration

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Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

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Chemical Research in Chinese Universities 2011年第4期27卷 646-650页

作者： ZHU Ji-hong LI Xiao SUN Li-li ZHANG Mu-chun KAN Shi-fu LIU Lei HUANG Hai-yan YANG guo-hua piao Bing-guo JIN Ning-yi Department of Gynecology and Obstetrics the First Hospital of Jilin University Changchun 130021 P. R. China Laboratory of Genetic Engineering of PLA Academy of Military Medical Sciences Changchun 130062 P. R. China Department of Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130012 P R. China Department of Urology China-Japan Union Hospital of Jilin University Changchun 130033 P. R. China Department of Gastroenterology the First Hospital of Jilin University Changchun 130021 P. R. China

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid *** explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,*** results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect *** results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean *** results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

关键词： Apoptin gene Chicken anemia virus Human cervical carcinoma Anti-tumor effect

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Induction of Effective Antitumor Immune Response by Combined Administration of hIL-18 and NDV HN

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Chemical Research in Chinese Universities 2011年第5期27卷 836-840页

作者： HUANG Hai-yan MENG Xiang-wei LI Xiao SUN Li-li KAN Shi-fu LIU Lei piao Bing-guo YANG guo-hua WANG Zhuo-yue WANG Yu-hang QI Yan-xin JIN Ning-yi Department of Gastroenterology the First Hospital of Jilin University Changchun 130021 P. R. China Laboratory of Genetic Engineering of PLA Military Veterinary Institute Academy of Military Medical Sciences Changchun 130062 P. R. China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences Changchun 130062 P. R. China Department of Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130012 P. R. China Digestive lnternal Medicine Xuzhou Center Hospital Xuzhou 221009 P. R. China

To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus （NDV） hemagglutinin-neuraminidase（HN） and human interleukin 18（hIL-18） gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus（Ad）-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector（Ad-mock）. Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte（CTL） responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN＋Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ （IFN-γ）, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.

关键词： Newcastle disease virus Human interleukin 18(hlL-18) Hemagglutinin-neuraminidase(HN) Hepatoma Antitumor immunity

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Anti-tumor Immune Response Mediated by Newcastle Disease Virus HN Gene

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Chemical Research in Chinese Universities 2011年第2期27卷 282-286页

作者： PENG Li-ping LI Xiao SUN Li-li WEN Zhong-mei LIU Yan GAO Peng HUANG Hai-yan piao Bing-guo JIN Jing J1N Ning-yi Department of Respiratory Medicine the First Hospital of Jilin University Changchun 130021 P R. China Genetic Engineering Laboratory of PLA the Eleventh Institute of Academy of Military Medical Sciences of PLA Changchun 130062 P R. China Head and Neck Surgery the Tumor Hospital of Jilin Province Changchun 130012 P R. China Department of Gastroenterology First Hospital of Jilin University Changchun 130021 P R. China Department of Hematology and Oncology People＇s Hospital of Jilin Province Changchun 130021 P R. China College of Pharmacy Changchun University of Chinese Medicine Changchun 130117 P R. China

Hemagglutinin-neuramidinase（HN） is one of the most important surface structure proteins of the Newcastle disease virus（NDV）. HN not only mediates receptor recognition but also possesses neuraminidase（NA） activity, which gives it the ability to cleave a component of those receptors, NAcneu. Previous studies have demonstrated that HN has interesting anti-neoplastic and immune-stimulating properties in mammalian species, including humans. To explore the application of the HN gene in cancer gene therapy, we constructed a Lewis lung carcinoma（LLC） solid tumor model using C57BL/6 mice. Mice were injected intratumorally with the recombinant adenovirus expressing HN gene（Ad-HN）, and the effect of HN was explored by natural killer cell activity assay, cytotoxic lymphocyte activity assay, T cell subtype evaluation, and Th1/Th2 cytokines analysis. The results demonstrate that HN not only can elicit clonal expansion of both CD4＋ and CD8＋ T cell populations and cytotoxic T lymphocyte（CTL） and killer cell response, but also skews the immune response toward Th1. Thus, vaccination with Ad-HN may be a potential strategy for cancer gene therapy.

关键词： HN gene Recombined adenovirus Cytokine Cell immunity Anti-tumor activity

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基于CPSO的PID神经网络及偏航电机控制策略

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电机与控制学报 2010年第9期14卷 55-62页

作者：朴海国王志新上海交通大学电气工程系上海200240

风电机组偏航系统具有高度的非线性与不确定性,采用传统的基于精确数学模型控制方法用于风电机组偏航系统,难以获得期望的稳定性、鲁棒性等控制性能。针对以上问题,借鉴传统静态神经网络的逆系统控制方法,并根据非线性自回归平均模型(NA... 详细信息

风电机组偏航系统具有高度的非线性与不确定性,采用传统的基于精确数学模型控制方法用于风电机组偏航系统,难以获得期望的稳定性、鲁棒性等控制性能。针对以上问题,借鉴传统静态神经网络的逆系统控制方法,并根据非线性自回归平均模型(NARMA-L2),给出了基于合作粒子群算法(CPSO)的PID神经网络控制策略(PIDNNC),并基于该策略设计了PIDNNC积分合成控制系统,提出了基于该策略的PIDNN神经网络控制系统设计方法。通过建立偏航系统的仿真模型进行仿真实验,并与PID控制器的控制效果进行比较,表明该控制策略能提高偏航系统的稳定性、鲁棒性和控制精度。通过偏航实验系统进行实验验证,结果表明该控制策略是可行和有效的。

关键词： PID神经网络粒子群算法稳定性鲁棒性偏航控制风电机组

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基于合作粒子群算法的PID神经网络非线性控制系统

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控制理论与应用 2009年第12期26卷 1317-1324页

作者：朴海国王志新张华强上海交通大学电气工程系上海200240

PID神经元网络(PIDNN)模型为一种新型的神经网络模型,兼有PID与神经网络的共同优点,应用于复杂的控制系统,取得优良控制性能,但其后向传播算法(BP)限制了该模型的应用范围.为实现对非线性多变量系统的有效控制,扩展神经网络的应有范围,... 详细信息

PID神经元网络(PIDNN)模型为一种新型的神经网络模型,兼有PID与神经网络的共同优点,应用于复杂的控制系统,取得优良控制性能,但其后向传播算法(BP)限制了该模型的应用范围.为实现对非线性多变量系统的有效控制,扩展神经网络的应有范围,本文采用PIDNN神经网络设计了多变量PIDNN神经网络(MPIDNN)控制器,并用本文作者提出的合作粒子群算法(CPSO)取代了传统BP后向传播算法,通过比较MPIDNN_CPSO、MPIDNN_CRPSO、MPIDNN_PSO和MPIDNN_BP4种控制器的控制性能,仿真结果表明,基于CPSO算法的MPIDNN控制器实现了对非线性多变量不对称系统的有效控制.与传统的BP算法相比,CPSO算法提高了控制系统的稳定性、精确性与鲁棒性.

关键词： PID神经网络粒子群算法非线性不对称控制稳定性鲁棒性合作粒子群最优算法

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视觉SLAM综述

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智能系统学报 2016年第6期11卷 768-776页

作者：权美香朴松昊李国哈尔滨工业大学多智能体机器人实验室黑龙江哈尔滨150000

视觉SLAM指的是相机作为唯一的外部传感器,在进行自身定位的同时创建环境地图。SLAM创建的地图的好坏对之后自主的定位、路径规划以及壁障的性能起到一个决定性的作用。本文对基于特征的视觉SLAM方法和直接的SLAM方法,视觉SLAM的主要标... 详细信息

视觉SLAM指的是相机作为唯一的外部传感器,在进行自身定位的同时创建环境地图。SLAM创建的地图的好坏对之后自主的定位、路径规划以及壁障的性能起到一个决定性的作用。本文对基于特征的视觉SLAM方法和直接的SLAM方法,视觉SLAM的主要标志性成果,SLAM的主要研究实验室进行了介绍,并介绍了SIFT,SURF,ORB特征的检测与匹配,关键帧选择方法,并对消除累积误差的闭环检测及地图优化的方法进行了总结。最后,对视觉SLAM的主要发展趋势及研究热点进行了讨论,并对单目视觉SLAM,双目视觉SLAM,RGB_D SLAM进行了优缺点分析。

关键词：视觉同步定位与创建地图单目视觉 RGBD SLAM 特征检测与匹配闭环检测

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