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Novel CD9-targeted therapies in gastric cancer

World Journal of Gastroenterology 2015年第11期21卷 3206-3213页

作者： Yoko Murayama kenji oritani Shusaku Tsutsui Department of Gastro-enterology and Hepatology Itami City Hospital Department of Hematology/Oncology Graduate School of MedicineOsaka University

There are 33 human tetraspanin proteins,emerging as key players in malignancy,the immune system,fertilization,cellular signaling,adhesion,morphology,motility,proliferation,and tumor ***9,a member of the tetraspanin family,associates with and influences a variety of cell-surface *** these interactions,CD9 modifies multiple cellular events,including adhesion,migration,proliferation,and ***9 is therefore considered to play a role in several stages during cancer *** CD9 expression is generally related to venous vessel invasion and metastasis as well as poor *** found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative,proapoptotic,and antiangiogenic effects,strongly indicating that CD9 is a possible therapeutic target in patients with gastric ***,we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer,which still shows poor prognosis.

关键词： CD9 Tetraspanin Gastric cancer Tumo-rigenicity The

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Current understanding of the role of tyrosine kinase 2 signaling in immune responses

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World Journal of Biological Chemistry 2022年第1期13卷 1-14页

作者： Ryuta Muromoto kenji oritani Tadashi Matsuda Department of Immunology Graduate School of Pharmaceutical SciencesHokkaido UniversitySapporo 060-0812Japan Department of Hematology International University of Health and WelfareNarita 286-8686Japan

Immune system is a complex network that clears pathogens,toxic substrates,and cancer *** self-antigens from non-self-antigens is critical for the immune cell-mediated response against foreign *** innate immune system elicits an early-phase response to various stimuli,whereas the adaptive immune response is tailored to previously encountered *** immune responses,B cells differentiate into antibody-secreting cells,while naïve T cells differentiate into functionally specific effector cells[T helper 1(Th1),Th2,Th17,and regulatory T cells].However,enhanced or prolonged immune responses can result in autoimmune disorders,which are characterized by lymphocytemediated immune responses against *** transduction of cytokines,which regulate the inflammatory cascades,is dependent on the members of the Janus family of protein *** kinase 2(Tyk2)is associated with receptor subunits of immune-related cytokines,such as type I interferon,interleukin(IL)-6,IL-10,IL-12,and *** studies on the therapeutic effects and the underlying mechanisms of Tyk2 inhibitors in autoimmune or chronic inflammatory diseases are currently *** review summarizes the findings of studies examining the role of Tyk2 in immune and/or inflammatory responses using Tyk2-deficient cells and mice.

关键词： Tyrosine kinase 2 Cytokines Signal transduction Immune system Inflammation

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Early B lymphocyte development: Similarities and differences in human and mouse

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World Journal of Stem Cells 2014年第4期6卷 421-431页

作者： Michiko Ichii kenji oritani Yuzuru Kanakura Department of Hematology and Oncology Osaka University Graduate School of MedicineOsaka 565-0871Japan

B lymphocytes differentiate from hematopoietic stem cells through a series of distinct stages. Early B cell development proceeds in bone marrow until immature B cells migrate out to secondary lymphoid tissues, such as a spleen and lymph nodes, after completion of immunoglobulin heavy and light chain rearrangement. Although the information about the regulation by numerous factors, including signaling molecules, transcription factors, epigenetic changes and the microenvironment, could provide the clinical application, our knowledge on human B lymphopoiesis is limited. However, with great methodological advances, significant progress for understanding B lymphopoiesis both in human and mouse has been made. In this review, we summarize the experimental models for studies about human adult B lymphopoiesis, and the role of microenvironment and signaling molecules, such as cytokines, transforming growth factor-β superfamily, Wnt family and Notch family, with point-by-point comparison between human and mouse.

关键词： Human B lymphopoiesis B cell cultures IL-7 Microenvironment Wnt signaling

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Signal transducer and activator of transcription 3 regulation by novel binding partners

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World Journal of Biological Chemistry 2015年第4期6卷 324-332页

作者： Tadashi Matsuda Ryuta Muromoto Yuichi Sekine Sumihito Togi Yuichi Kitai Shigeyuki Kon kenji oritani Department of Immunology Graduate School of Pharmaceutical SciencesHokkaido University Department of Hematology and Oncology Graduate School of Medicine Osaka University

Signal transducers and activators of transcription(STATs) mediate essential signals for various biological processes,including immune responses,hematopoiesis,and neurogenesis. STAT3,for example,is involved in the pathogenesis of various human diseases,including cancers,autoimmune and inflammatory disorders. STAT3 activation is therefore tightly regulated at multiple levels to prevent these pathological conditions. A number of proteins have been reported to associate with STAT3 and regulate its activity. These STAT3-interacting proteins function to modulate STAT3-mediated signaling at various steps and mediate the crosstalk of STAT3 with other cellular signaling pathways. This article reviews the roles of novel STAT3 binding partners such as DAXX,zipperinteracting protein kinase,Krüppel-associated box-associated protein 1,Y14,PDZ and LIM domain 2 and signal transducing adaptor protein-2,in the regulation of STAT3-mediated signaling.

关键词： Janus kinase/signal transducer and activator of tr

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