ID | 119321 |
Title Alternative | 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
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Author |
Maruhashi, Tomoko
Tokushima University
Miki, Hirokazu
Tokushima University
Tokushima University Educator and Researcher Directory
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Oda, Asuka
Tokushima University
Takahashi, Mamiko
Tokushima University
Fujii, Shiro
Tokushima University
Tokushima University Educator and Researcher Directory
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Nakamura, Shingen
Tokushima University
Tokushima University Educator and Researcher Directory
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Endo, Itsuro
Tokushima University
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Abe, Masahiro
Tokushima University|Kawashima Hospital
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Keywords | multiple myeloma
hyperthermia
carfilzomib
translation
and drug resistance
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
International Journal of Hematology
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ISSN | 09255710
18653774
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NCID | AA10797094
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Publisher | Springer Nature
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Volume | 119
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Issue | 3
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Start Page | 291
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End Page | 302
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Published Date | 2024-01-22
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Remark | 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 | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
jpn
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TextVersion |
その他
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MEXT report number | 甲第3790号
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Diploma Number | 甲医第1603号
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Granted Date | 2024-03-21
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
University Hospital
Medical Sciences
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