111 results on '"Dongsheng Xiong"'
Search Results
102. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells.
- Author
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Dongmei Fan, Wei Li, Yuqi Yang, Xiaolong Zhang, Qing Zhang, Yan Yan, Ming Yang, Jianxiang Wang, and Dongsheng Xiong
- Subjects
LYMPHOBLASTIC leukemia treatment ,CYTARABINE ,CANCER chemotherapy ,IMMUNOTHERAPY ,LYSIS ,CYTOKINES ,CLINICAL trials - Abstract
Background: B-acute lymphoblastic leukemia (B-ALL) is derived from B cell progenitors. Recently, the development of appropriate combinations of chemotherapy and immunotherapy represents a promising approach for eliminating cancer. We previously constructed an anti-CD3 × anti-CD19 bi-specific antibody in a diabody configuration and its disulfide-stabilized format (ds-diabody). The combination of the diabody or ds-diabody and Ara-C was highly effective in enhancing the cytotoxicity of T cells against the CD19+ human leukemia cell-line, Nalm-6, both in vitro and in vivo. This study verified whether B-ALL patient-derived cells were sensitive to the diabody or ds-diabody and low-dosage Ara-C combination. Methods: This study aimed to detect the B7 family members B7.1 (CD80) and B7.2 (CD86) that were expressed in B-ALL patient-derived cells pre-treated by Ara-C (0.25 μM) and to determine the targeted killing ability of T cell subtypes induced by the diabody or ds-diabody combination with Ara-C both in vitro and in vivo. We also determined the levels of the cytokines that were released by activated CD4+ or CD8+ T cells during therapy. Result: Low-dose Ara-C enhanced CD80 and CD86 expression in nearly 50 % of specimens of B-ALL patient-derived cells. A combination of diabody or ds-diabody and Ara-C enhanced T cell against B-ALL cells in vitro and in vivo. Both CD8+ and CD4+ T cells were potently activated. Expression of CD25 and CD69 was augmented equally by CD4+ or CD8+ T cells. However, CD8+ T cells made the major contribution by redirecting target cell lysis in a granzyme B and perforin-dependent mechanism. CD4+ T cells played an important immunomodulatory role by secreting IL2. Consequently, IL3, IL6, TNFα, and IFNγ were also released by CD4+ or CD8+ T cells following diabody-mediated T cell activation. Conclusion: T cell therapy induced by diabody or ds-diabody combined with low dose of Ara-C was effective against cancer cell-lines and in clinical trials. In vivo, the ds-diabody was more efficient than its parent diabody due to its enhanced stability. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
103. AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells.
- Author
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Dongmei Fan, Zhenzhen Li, Xiaolong Zhang, Yuqi Yang, Xiangfei Yuan, Xiuli Zhang, Ming Yang, Yizhi Zhang, and Dongsheng Xiong
- Subjects
ACUTE myeloid leukemia ,STEM cells ,GENETIC overexpression ,INTERLEUKIN-3 ,ANTIGEN receptors - Abstract
Background: Leukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (IL3)-receptor α chain, has been identified as a potential immunotherapeutic target due to its overexpression on LSCs in AML as well as on AML blasts, rather than normal hematopoietic stem cells. Methods: We constructed a CD123-targeted fusion protein antiCD3Fv-◢IL3, with one binding site for T cell antigen receptor (TCRCD3) and the other for CD123, by recombinant gene-engineering technology. Cysteine residues were introduced into the V domains of the antiCD3Fv segment to enhance its stability by locking the two chains of Fv together with disulfide covalent bonds. The stability and cytotoxicity of the two fusion proteins were detected in vitro and in vivo. Results: Both fusion proteins were produced and purified from Escherichia coli 16C9 cells with excellent yields in fully active forms. High-binding capability was observed between these two fusion proteins and human IL3R, leading to the specific lysis of CD123-expressing cell lines KG1a; also, mononuclear cells from primary AML patients were inhibited in a colony forming assay in vitro, presumably by redirecting T lymphocytes in vitro. In addition, they displayed an antileukemic activity against KG1a xenografts in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, especially disulfide-stabilized (ds)-antiCD3Fv-◢IL3 for its improved stability. Conclusions: These results suggest that both fusion proteins display the antileukemic activity against CD123-expressing cell lines as well as leukemic progenitors in vitro and in vivo, especially ds-antiCD3Fv-◢IL3. They could be the promising candidates for future immunotherapy of AML. [ABSTRACT FROM AUTHOR]
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- 2015
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- View/download PDF
104. Improvement of tumor targeting and antitumor activity by a disulphide bond stabilized diabody expressed in Escherichia coli.
- Author
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Juanni Liu, Ming Yang, Jinhong Wang, Yuanfu Xu, Yan Wang, Xiaofeng Shao, Chunzheng Yang, Yingdai Gao, and Dongsheng Xiong
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TUMORS ,ANTINEOPLASTIC agents ,ESCHERICHIA coli ,MULTIDRUG resistance ,CYSTEINE proteinases - Abstract
We have generated an anti-Pgp/anti-CD3 diabody which can effectively inhibit the growth of multidrug-resistant human tumors. However, the two chains of the diabody are associated non-covalently and are therefore capable of dissociation. Cysteine residues were introduced into the V-domains to promote disulphide cross-linking of the dimer as secreted by Escherichia coli. Compared with the parent diabody, the ds-Diabody obtained was more stable in human serum at 37°C, without loss of affinity or cytotoxicity activity in vitro. Furthermore, the ds-Diabody showed improved tumor localization and a twofold improved antitumor activity over the parent diabody in nude mice bearing Pgp-overexpressing K562/A02 xenografts. Our data demonstrate that ds-Diabody may be more useful in therapeutic applications than the parent diabody. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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105. Tools for Mind Map and technology research: The method of presenting mind map online.
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Dongsheng, Xiong and Xiao, Xu
- Abstract
This paper briefly introduces the knowledge of Mind Map, compares various softwares for making mind map, and also compares several correlative technologies for presenting mind map online. It concretely introduces the usage of FreeMindFlashBrower and the method of displaying Chinese correctly in FreeMindFlashBrower. It finally provides a free tool chain which can make Chinese mind map and present them online. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
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106. Classification of Imaginary Movements in ECoG.
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Lijun Li, Dongsheng Xiong, and Xiaoming Wu
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- 2011
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107. Overexpression of Cell Surface Cytokeratin 8 in Multidrug-Resistant MCF-7/MX Cells Enhances Cell Adhesion to the Extracellular Matrix
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Jinhong Wang, Chunzheng Yang, Fang Liu, Xiao-Feng Shao, Ziyou Cui, Zhong Chen, Dongsheng Xiong, and Zhenping Zhu
- Subjects
Proteomics ,Cancer Research ,Cell ,Down-Regulation ,Breast Neoplasms ,lcsh:RC254-282 ,Polymerase Chain Reaction ,Statistics, Nonparametric ,Cell membrane ,Mice ,Tandem Mass Spectrometry ,Cell Line, Tumor ,medicine ,Cell Adhesion ,Animals ,Humans ,Vitronectin ,RNA, Small Interfering ,Cell adhesion ,skin and connective tissue diseases ,Cellular localization ,Microscopy, Confocal ,biology ,Keratin-8 ,HEK 293 cells ,Cell Membrane ,Antibodies, Monoclonal ,Transfection ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,Drug Resistance, Multiple ,Extracellular Matrix ,Fibronectins ,Fibronectin ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Cell culture ,Drug Resistance, Neoplasm ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Female ,Mitoxantrone ,Research Article - Abstract
Accumulating evidence suggests that multiple complex mechanisms may be involved, simultaneously or complementarily, in the emergence and development of multidrug resistance (MDR) in various cancers. Cell adhesion-mediated MDR is one such mechanism. In the present study, we initially observed increased cell adhesion to extracellular matrix proteins by the MDR human breast tumor cell line MCF-7/MX compared to its parental cells. We then used a strategy that combined antibody-based screening technique and mass spectrometry-based proteomics to identify membrane proteins that contribute to the enhanced adhesion of MCF-7/MX cells. Using MCF-7/MX cells as immunogen, we isolated a mouse monoclonal antibody, 9C6, that preferentially reacts with MCF-7/MX cells over the parental MCF-7 cells. The molecular target of 9C6 was identified as cytokeratin 8 (CK8), which was found to be overexpressed on the cell surface of MCF-7/MX cells. We further observed that down-regulation of cell surface levels of CK8 through siRNA transfection significantly inhibited MCF-7/MX cell adhesion to fibronectin and vitronectin. In addition, anti-CK8 siRNA partially reversed the MDR phenotype of MCF-7/MX cells. Taken together, our results suggest that alterations in the expression level and cellular localization of CK8 may play a significant role in enhancing the cellular adhesion of MDR MCF-7/MX cells.
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108. AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells
- Author
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Yizhi Zhang, Dongmei Fan, Zhenzhen Li, Xiuli Zhang, Xiaolong Zhang, Dongsheng Xiong, Xiangfei Yuan, Ming Yang, and Yuqi Yang
- Subjects
Cancer Research ,Myeloid ,CD3 Complex ,T cell ,Recombinant Fusion Proteins ,T-Lymphocytes ,Immunoblotting ,Interleukin-3 Receptor alpha Subunit ,Mice, SCID ,Biology ,Mice ,AntiCD3Fv ,Mice, Inbred NOD ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Progenitor cell ,Molecular Biology ,Interleukin 3 ,Leukemic stem cells ,Research ,Myeloid leukemia ,Hematology ,Flow Cytometry ,Fusion protein ,Virology ,Xenograft Model Antitumor Assays ,Haematopoiesis ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Fusion proteins ,Oncology ,CD123 ,Cancer research ,Neoplastic Stem Cells ,Female ,Immunotherapy ,Stem cell - Abstract
Background Leukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (IL3)-receptor α chain, has been identified as a potential immunotherapeutic target due to its overexpression on LSCs in AML as well as on AML blasts, rather than normal hematopoietic stem cells. Methods We constructed a CD123-targeted fusion protein antiCD3Fv-⊿IL3, with one binding site for T cell antigen receptor (TCRCD3) and the other for CD123, by recombinant gene-engineering technology. Cysteine residues were introduced into the V domains of the antiCD3Fv segment to enhance its stability by locking the two chains of Fv together with disulfide covalent bonds. The stability and cytotoxicity of the two fusion proteins were detected in vitro and in vivo. Results Both fusion proteins were produced and purified from Escherichia coli 16C9 cells with excellent yields in fully active forms. High-binding capability was observed between these two fusion proteins and human IL3R, leading to the specific lysis of CD123-expressing cell lines KG1a; also, mononuclear cells from primary AML patients were inhibited in a colony forming assay in vitro, presumably by redirecting T lymphocytes in vitro. In addition, they displayed an antileukemic activity against KG1a xenografts in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, especially disulfide-stabilized (ds)-antiCD3Fv-⊿IL3 for its improved stability. Conclusions These results suggest that both fusion proteins display the antileukemic activity against CD123-expressing cell lines as well as leukemic progenitors in vitro and in vivo, especially ds-antiCD3Fv-⊿IL3. They could be the promising candidates for future immunotherapy of AML. Electronic supplementary material The online version of this article (doi:10.1186/s13045-015-0109-5) contains supplementary material, which is available to authorized users.
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109. A novel calmodulin antagonist O-(4-ethoxyl-butyl)-berbamine overcomes multidrug resistance in drug-resistant MCF-7/ADR breast carcinoma cells.
- Author
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Rong Liu, Yanjun Zhang, Yanhong Chen, Jing Qi, Simei Ren, Ming Yang Xushi, Chunzheng Yang, Huifang Zhu, and Dongsheng Xiong
- Subjects
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CALMODULIN , *MULTIDRUG resistance , *DRUG resistance , *BREAST cancer , *CANCER chemotherapy - Abstract
Multidrug resistance (MDR) mediated by the overexpression of the drug efflux protein P-glycoprotein is one of the major obstacles to successful cancer chemotherapy. The development of safe and effective MDR-reversing agents is an important approach to addressing this problem clinically. In this study, we evaluated the P-gp-modulatory potential of O-(4-ethoxyl-butyl)-berbamine (EBB), a novel calmodulin antagonist and derivative of bisbenzylisoquinoline alkaloid, which significantly improved the chemosensitivity of P-glycoprotein-mediated multidrug-resistant cells to doxorubicin compared with the efficacy of a conventional P-glycoprotein inhibitor, verapamil. EBB not only blocked the function of P-glycoprotein confirmed by the fact that EBB increased intracellular accumulation of rhodamine 123 and doxorubicin but also inhibited the expression of P-glycoprotein actualized by downregulating P-glycoprotein. Furthermore, our results showed that cotreatment with EBB and doxorubicin resulted in marked G2/M arrest and apoptosis of MCF-7/ADR cells, accompanied by down-regulation of the proteins cdc2/p34 and cyclin B1 and increased the levels of calcium ions. Taken together, these results suggest that cotreatment with EBB and doxorubicin could strongly potentiate the antitumor activity of doxorubicin, thus may have significant clinical application in cancer chemotherapy. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3266–3275, 2010 [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
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