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ID 119321
タイトル別表記
温熱療法による急速な翻訳抑制はカルフィルゾミブの抗骨髄腫活性を増強する
著者
丸橋, 朋子 徳島大学大学院医学研究科(医学専攻)
Oda, Asuka Tokushima University
Takahashi, Mamiko Tokushima University
キーワード
multiple myeloma
hyperthermia
carfilzomib
translation
and drug resistance
資料タイプ
学位論文
抄録
Hyperthermia is a unique treatment option for cancers. Multiple myeloma (MM) remains incurable and innovative therapeutic options are needed. We investigated the efficacy of hyperthermia and carfilzomib in combination against MM cells. Although MM cell lines exhibited different susceptibilities to pulsatile carfilzomib treatment, mild hyperthermia at 43℃ induced MM cell death in all cell lines in a time-dependent manner. Hyperthermia and carfilzomib cooperatively induced MM cell death even under suboptimal conditions. The pro-survival mediators PIM2 and NRF2 accumulated in MM cells due to inhibition of their proteasomal degradation by carfilzomib; however, hyperthermia acutely suppressed translation in parallel with phosphorylation of eIF2α to reduce these proteins in MM cells. Recovery of β5 subunit enzymatic activity from its immediate inhibition by carfilzomib was observed at 24 hours in carfilzomib-insusceptible KMS-11, OPM-2, and RPMI8226 cells, but not in carfilzomib-sensitive MM.1S cells. However, heat treatment suppressed the recovery of β5 subunit activity in these carfilzomib-insusceptible cells. Therefore, hyperthermia re-sensitized MM cells to carfilzomib. Our results suggest treatment of MM with hyperthermia in combination with carfilzomib. Further research is warranted on hyperthermia for drug-resistant extramedullary plasmacytoma.
掲載誌名
International Journal of Hematology
ISSN
09255710
18653774
cat書誌ID
AA10797094
出版者
Springer Nature
119
3
開始ページ
291
終了ページ
302
発行日
2024-01-22
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Tomoko Maruhashiの学位論文として提出され,学位審査・授与の対象となっている。
論文本文は2025-01-22以降公開予定
This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12185-023-03706-8
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
jpn
著者版フラグ
その他
文科省報告番号
甲第3790号
学位記番号
甲医第1603号
学位授与年月日
2024-03-21
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系