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Effective impairment of myeloma cells and their progenitors by hyperthermia

Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively a...

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Autores principales: Miki, Hirokazu, Nakamura, Shingen, Oda, Asuka, Tenshin, Hirofumi, Teramachi, Jumpei, Hiasa, Masahiro, Bat-Erdene, Ariunzaya, Maeda, Yusaku, Oura, Masahiro, Takahashi, Mamiko, Iwasa, Masami, Harada, Takeshi, Fujii, Shiro, Kurahashi, Kiyoe, Yoshida, Sumiko, Kagawa, Kumiko, Endo, Itsuro, Aihara, Kenichi, Ikuo, Mariko, Itoh, Kohji, Hayashi, Koichiro, Nakamura, Michihiro, Abe, Masahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828190/
https://www.ncbi.nlm.nih.gov/pubmed/29535808
http://dx.doi.org/10.18632/oncotarget.23121
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author Miki, Hirokazu
Nakamura, Shingen
Oda, Asuka
Tenshin, Hirofumi
Teramachi, Jumpei
Hiasa, Masahiro
Bat-Erdene, Ariunzaya
Maeda, Yusaku
Oura, Masahiro
Takahashi, Mamiko
Iwasa, Masami
Harada, Takeshi
Fujii, Shiro
Kurahashi, Kiyoe
Yoshida, Sumiko
Kagawa, Kumiko
Endo, Itsuro
Aihara, Kenichi
Ikuo, Mariko
Itoh, Kohji
Hayashi, Koichiro
Nakamura, Michihiro
Abe, Masahiro
author_facet Miki, Hirokazu
Nakamura, Shingen
Oda, Asuka
Tenshin, Hirofumi
Teramachi, Jumpei
Hiasa, Masahiro
Bat-Erdene, Ariunzaya
Maeda, Yusaku
Oura, Masahiro
Takahashi, Mamiko
Iwasa, Masami
Harada, Takeshi
Fujii, Shiro
Kurahashi, Kiyoe
Yoshida, Sumiko
Kagawa, Kumiko
Endo, Itsuro
Aihara, Kenichi
Ikuo, Mariko
Itoh, Kohji
Hayashi, Koichiro
Nakamura, Michihiro
Abe, Masahiro
author_sort Miki, Hirokazu
collection PubMed
description Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs.
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spelling pubmed-58281902018-03-13 Effective impairment of myeloma cells and their progenitors by hyperthermia Miki, Hirokazu Nakamura, Shingen Oda, Asuka Tenshin, Hirofumi Teramachi, Jumpei Hiasa, Masahiro Bat-Erdene, Ariunzaya Maeda, Yusaku Oura, Masahiro Takahashi, Mamiko Iwasa, Masami Harada, Takeshi Fujii, Shiro Kurahashi, Kiyoe Yoshida, Sumiko Kagawa, Kumiko Endo, Itsuro Aihara, Kenichi Ikuo, Mariko Itoh, Kohji Hayashi, Koichiro Nakamura, Michihiro Abe, Masahiro Oncotarget Research Paper Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs. Impact Journals LLC 2017-12-07 /pmc/articles/PMC5828190/ /pubmed/29535808 http://dx.doi.org/10.18632/oncotarget.23121 Text en Copyright: © 2018 Miki et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Miki, Hirokazu
Nakamura, Shingen
Oda, Asuka
Tenshin, Hirofumi
Teramachi, Jumpei
Hiasa, Masahiro
Bat-Erdene, Ariunzaya
Maeda, Yusaku
Oura, Masahiro
Takahashi, Mamiko
Iwasa, Masami
Harada, Takeshi
Fujii, Shiro
Kurahashi, Kiyoe
Yoshida, Sumiko
Kagawa, Kumiko
Endo, Itsuro
Aihara, Kenichi
Ikuo, Mariko
Itoh, Kohji
Hayashi, Koichiro
Nakamura, Michihiro
Abe, Masahiro
Effective impairment of myeloma cells and their progenitors by hyperthermia
title Effective impairment of myeloma cells and their progenitors by hyperthermia
title_full Effective impairment of myeloma cells and their progenitors by hyperthermia
title_fullStr Effective impairment of myeloma cells and their progenitors by hyperthermia
title_full_unstemmed Effective impairment of myeloma cells and their progenitors by hyperthermia
title_short Effective impairment of myeloma cells and their progenitors by hyperthermia
title_sort effective impairment of myeloma cells and their progenitors by hyperthermia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828190/
https://www.ncbi.nlm.nih.gov/pubmed/29535808
http://dx.doi.org/10.18632/oncotarget.23121
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