Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity

• 資料種別: 博士論文
• タイトル: Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity
• 著者・編者: Fujii, Shiro; Nakamura, Shingen; Oda, Asuka; Miki, Hirokazu; Tenshin, Hirofumi; Teramachi, Jumpei; Hiasa, Masahiro; Bat-Erdene, Ariunzaya; Maeda, Yusaku; Oura, Masahiro; Takahashi, Mamiko; Iwasa, Masami; Endo, Itsuro; Yoshida, Sumiko; Aihara, Ken-ichi; Kurahashi, Kiyoe; Harada, Takeshi; Kagawa, Kumiko; Nakao, Michiyasu; Sano, Shigeki; Abe, Masahiro
• 著者標目: Fujii, Shiro; Nakamura, Shingen; Oda, Asuka; Miki, Hirokazu; Tenshin, Hirofumi; Teramachi, Jumpei; Hiasa, Masahiro; Bat-Erdene, Ariunzaya; Maeda, Yusaku; Oura, Masahiro; Takahashi, Mamiko; Iwasa, Masami; Endo, Itsuro; Yoshida, Sumiko; Aihara, Ken-ichi; Kurahashi, Kiyoe; Harada, Takeshi; Kagawa, Kumiko; Nakao, Michiyasu; Sano, Shigeki; Abe, Masahiro
• 出版事項: Wiley
• 出版年月日等: 2018-01-12
• 出版年（W3CDTF）: 2018-01-12
• 並列タイトル等: Pim阻害活性を有するチアゾリジン-2,4-ジオン誘導体のユニークな抗骨髄腫活性; Anti-myeloma Activity by Thiazolidine-2,4-dione compounds
• タイトル（掲載誌）: British Journal of Haematology
• 巻号年月日等（掲載誌）: 180 2
• 掲載巻: 180
• 掲載号: 2
• 掲載ページ: 246-258
• ISSN（掲載誌）: ISSN : 0007-1048; ISSN : 1365-2141
• 授与機関名: 徳島大学
• 授与年月日: 2018-09-13
• 報告番号: 甲第3206号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: multiple myeloma; PIM2; thiazolidine‐2; 4-dione compounds; breast cancer resistance protein; proteasome inhibitor; BCRP
• 対象利用者: 一般
• 一般注記: Proviral Integrations of Moloney virus 2 (PIM2) kinase is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX 6258 and PIM447. SMI 16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations, and reduced in vitro colony forming capacity and in vivo tumorigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistently, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI 16a mitigated the PIM2 protein increase and cooperatively enhanced anti MM effects in combination with carfilzomib. Collectively, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned.
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1111/bjh.15033
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/112752/20181205174131278770/k3206_abstract_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/112752/20181205174131605693/k3206_fulltext.pdf fulltext