近藤 慎吾 (コンドウ シンゴ)

KONDO Shingo

写真a

所属(所属キャンパス)

薬学部 薬学科 化学療法学講座 (芝共立)

職名

助教

メールアドレス

メールアドレス

研究室住所

東京都港区芝公園1-5-30

研究室電話番号

03-5400-2795

研究室FAX番号

03-5400-2669

経歴 【 表示 / 非表示

  • 2017年04月
    -
    2019年03月

    東京医科歯科大学医学部附属病院, 薬剤部, 薬剤師

学歴 【 表示 / 非表示

  • 2013年04月
    -
    2017年03月

    慶應義塾

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(薬学), 慶應義塾, 課程, 2017年03月

免許・資格 【 表示 / 非表示

  • 薬剤師免許, 2013年07月

 

論文 【 表示 / 非表示

  • Effect of TNIK upregulation on JQ1-resistant human colorectal cancer HCT116 cells

    Takahashi C., Kondo S., Sadaoka K., Ishizuka S., Noguchi K., Kato Y., Sugimoto Y.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  530 ( 1 ) 230 - 234 2020年06月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0006291X

     概要を見る

    © 2020 Elsevier Inc. JQ1 disrupts the binding of bromodomain and extra-terminal (BET) family of proteins to acetylated histones, modulates the expression of various genes, and inhibits the proliferation of cancer cells. We established two JQ1-resistant sublines from human colorectal cancer HCT116 cells. These resistant cells showed an 8- to 9-fold higher resistance to JQ1, and a 2- to 4-fold higher resistance to various anti-cancer agents, such as doxorubicin, etoposide, mitoxantrone, SN-38, cisplatin, and methotrexate than the parental HCT116 cells. The JQ1-resistant cells expressed higher levels of TRAF2 and NCK-interacting protein kinase (TNIK), cyclin D1 (CCND1), cyclin E1 (CCNE1), and their corresponding mRNAs than the parental cells. TNIK is a regulator of Wnt/β-catenin signaling and is known to transactivate CCND1. Transient transfection of HCT116 cells with a TNIK expression plasmid resulted in the upregulation of cyclin D1, cyclin E1, and their corresponding mRNAs, as well as an increase in CCNE1 promoter activity. Furthermore, luciferase assay revealed that the JQ1-resistant cells showed high CCNE1 promoter activity. These results suggest that TNIK also transactivates CCNE1. Three stable TNIK transfectant clones of HEK293 cells expressed 1.5- to 2-fold higher levels of TNIK, cyclin D1, and cyclin E1 than the parental cells. The 293/TNIK-6 cells, which expressed the highest level of TNIK among the transfectants, showed a 2.3-fold higher resistance to JQ1 than the parental cells. These results suggest the possible involvement of TNIK in cellular resistance to JQ1.

  • STAT1 upregulates glutaminase and modulates amino acids and glutathione metabolism

    Kondo S., Kato Y., Minagawa S., Sugimoto Y.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  523 ( 3 ) 672 - 677 2020年01月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0006291X

     概要を見る

    © 2020 Elsevier Inc. We previously reported the upregulation of cellular Glu and glutathione levels in human ABCB5- and murine Abcb5-transfected cells. Here, we demonstrate the upregulation of STAT1 and glutaminase (GLS) in ABCB5/Abcb5-transfected cells. Among a total of four ABCB5/Abcb5 high-expressing clones with docetaxel resistance, three of the clones expressed STAT1 and GLS highly and showed resistance to docetaxel and buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis. Neither STAT1 nor GLS upregulation was observed in the remaining ABCB5 high-expressing clone, as well as in another two ABCB5 low-expressing clones; these three clones did not show BSO resistance. The ABCB5/STAT1 high-expressing clones showed higher cellular levels of Ala, Glu, and Asp and lower cellular levels of Phe, Trp, Leu, Ile, Gly, Met, Tyr, Val, and His compared to the ABCB5/STAT1 low-expressing clones. The former clones also showed a higher resistance to Glu. The STAT1-transfected clones expressed high levels of GLS and the corresponding mRNA, suggesting the transactivation of GLS by STAT1. These clones showed resistance to Glu and BSO, similar to the ABCB5/STAT1 high-expressing clones. The cellular glutathione levels of the STAT1-transfected clones were significantly higher than that of the control. The STAT1-transfected clones also showed greater resistance to the effect of BSO on the cellular glutathione depletion compared to the control. These results demonstrate that STAT1 upregulates GLS and modulates amino acids and glutathione metabolism. Although we were unable to directly prove STAT1 upregulation by ABCB5, our results suggest that ABCB5 expression, directly or indirectly, leads to the overexpression of STAT1.

  • SNAIL- and SLUG-induced side population phenotype of HCT116 human colorectal cancer cells and its regulation by BET inhibitors

    Kato Y., Kondo S., Itakura T., Tokunaga M., Hatayama S., Katayama K., Sugimoto Y.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  521 ( 1 ) 152 - 157 2019年10月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0006291X

     概要を見る

    © 2019 Elsevier Inc. Epithelial-mesenchymal transition (EMT) is associated with cancer malignancies such as invasion, metastasis, and drug resistance. In this study, HCT116 human colorectal cancer cells were transduced with SLUG or SNAIL retroviruses, and EMT cells with mesenchymal morphology were established. The EMT cells showed a high invasive activity and resistance to several anticancer agents such as methotrexate, SN-38, and cisplatin. Furthermore, they contained about 1–10% side population (SP) cells that were not stained by Hoechst 33342. This SP phenotype was not stable; the isolated SP cells generated both SP and non-SP cells, suggesting a potential for differentiation. Gene expression analysis of SP cells suggested the alteration of genes that are involved in epigenetic changes. Therefore, we examined the effect of 74 epigenetic inhibitors, and found that two inhibitors, namely I-BET151 and bromosporine, targeting the bromodomain and extra-terminal motif (BET) proteins, decreased the ratio of SP cells to <50% compared with the control, without affecting the immediate efflux of Hoechst 33342 by transporters. In addition, compared with the parental cells, the EMT cells showed a higher sensitivity to I-BET151 and bromosporine. This study suggests that EMT development and SP phenotype can be independent events but both are regulated by BET inhibitors in SLUG- or SNAIL-transducted HCT116 cells.

  • Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5-transfected cells.

    Kondo S., Hongama K., Hanaya K., Yoshida R., Kawanobe T., Katayama K., Noguchi K., Sugimoto Y.

    BMC Pharmacol Toxicol. 2015年12月

    研究論文(学術雑誌), 共著, 査読有り

KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • ヒスチジン異化はメトトレキサート感受性の主要な決定因子である

    近藤 慎吾

    ファルマシア (公益社団法人日本薬学会 )  55 ( 7 ) 702 2019年07月

    書評,文献紹介等, 単著

研究発表 【 表示 / 非表示

  • SLUG導入HCT116細胞におけるxCT発現上昇とフェロトーシス抵抗性

    加藤 優, 近藤 慎吾, 杉本 芳一

    第24回日本がん分子標的治療学会学術集会 (徳島グランヴィリオホテル) , 2020年10月, ポスター(一般)

  • STAT1が関与する薬剤耐性とその克服

    近藤 慎吾, 加藤 優, 杉本 芳一

    第79回日本癌学会学術総会, 2020年10月, ポスター(一般)

  • SLUG導入HCT116細胞におけるフェロトーシス感受性規定因子の解明

    加藤 優, 近藤 慎吾, 杉本 芳一

    第79回日本癌学会学術総会 (広島) , 2020年10月, ポスター(一般)

  • ABCB5発現細胞におけるGLS発現の増大

    近藤 慎吾, 加藤 優, 杉本 芳一

    第78回日本癌学会学術総会 (京都国際会館) , 2019年09月, ポスター(一般)

  • 上皮間葉転換に伴って誘導されるside population細胞の制御

    加藤 優, 近藤 慎吾, 片山 和浩, 杉本 芳一

    第78回日本癌学会学術総会 (京都国際会館) , 2019年09月, ポスター(一般)

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担当授業科目 【 表示 / 非表示

  • 課題研究(化学療法学)

    2020年度

  • 演習(化学療法学)

    2020年度

  • 卒業研究1(薬学科)

    2020年度

  • 英語演習(薬学科)

    2020年度

  • 分子腫瘍神経科学特論

    2020年度

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所属学協会 【 表示 / 非表示

  • 日本がん分子標的治療学会, 

    2019年04月
    -
    継続中
  • 日本癌学会, 

    2012年04月
    -
    継続中
  • 日本薬学会, 

    2011年04月
    -
    継続中