Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/32255
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    Title: Homoharringtonine induced immune alteration for an Efficient Anti-tumor Response in Mouse Models of Non-small Cell Lung Adenocarcinoma Expressing Kras Mutation
    Authors: Weng, Tzu-Yang
    Wu, Hsuan Franziska
    Li, Chung-Yen
    Hung, Yu-Hsuan
    Chang, Yu-Wei
    Chen, Yi-Ling
    Hsu, Hui-Ping
    Chen, Yu-Hung
    Wang, Chih-Yang
    Chang, Jang-Yang
    Lai, Ming-Derg
    Contributors: Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg
    Natl Cheng Kung Univ, Dept Med
    Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci
    Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management
    Natl Hlth Res Inst, Natl Inst Canc Res
    Keywords: Antigen-Presenting Cells
    B-Cells
    Translational Control
    Myeloid-Leukemia
    Stat3 Activation
    Signal Pathway
    In-Vitro
    Cancer
    Apoptosis
    Chemotherapy
    Date: 2018-05-29
    Issue Date: 2019-11-15 15:47:02 (UTC+8)
    Publisher: NATURE PUBLISHING GROUP
    Abstract: Homoharringtonine (HHT), an inhibitor of protein synthesis, has been used to treat leukemia. Its therapeutic effects on non-small cell lung adenocarcinoma carrying KRAS mutation and their immune system are less understood. The present study examined the therapeutic efficacy and the immune effects of HHT in two murine lung tumor models, xenograft and transgenic, carrying the Kras mutation G12D and G12C respectively. HHT exhibited efficient anticancer activity, significantly suppressing lung tumor growth in vitro and in vivo. The levels of 22 cytokines and chemokines in splenocytes of tumor-bearing mice were examined. Interleukin-12 expression was lower in splenocytes of HHT-treated mice when compared to the controls as demonstrated by a cytokine array and an enzyme-linked immunosorbent assay. The expression levels of CD80, CD86, and CD69 in B220(+) B cells from splenocytes of HHT-treated mice were higher than that of control mice in two mouse tumor models. Furthermore, antitumor effect of HHT was attenuated with depletion of B cells. Increased numbers of CD80(+) and CD86(+) B cells were observed in the mice treated with narciclasine, another translation inhibitor. In conclusion, HHT changed the features of immune cells, and exhibited efficient anti-tumor activity against lung tumor carrying mutant Kras expression.
    ???metadata.dc.relation.uri???: http://dx.doi.org/10.1038/s41598-018-26454-w
    Relation: Scientific Reports, v.8, 8216
    Appears in Collections:[Dept. of Senior Service and Health Management] Periodical Articles

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