Mechanisms of bone destruction and drug resistance in myeloma: a novel therapeutic strategy targeting a myeloma-bone marrow interaction

骨髓瘤骨质破坏和耐药机制：针对骨髓瘤-骨髓相互作用的新型治疗策略

• 批准号: 23591390
• 负责人: ABE Masahiro
• 金额: $ 3.24万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591390/
• 关键词: 血液腫瘍学; 多発性骨髄腫; 骨病変; Pimキナーゼ; 骨髄腫; 骨芽細胞; 薬剤耐性; アポトーシス

Pim-2 kinase is up-regulated in both myeloma cells and bone marrow stromal cells through their mutual interaction in bone lesions in myeloma, and plays a pivotal role in tumor survival and the suppression of osteoblastogenesis with bone loss in myeloma. Treatment with Pim inhibitiors appears to induce myeloma cell death and restore its drug sensitivity through abrogating a drug efflux pump function. Further, Pim inhibitors induce bone formation suppressed in myeloma. Therefore, Pim-2 inhibition may become an important therapeutic option to target a myeloma-bone marrow interaction, which causes drug resistance and bone destruction.

Pim-2激酶在骨髓瘤的骨病变中通过骨髓瘤细胞和骨髓基质细胞的相互作用在两者中上调，并且在肿瘤存活和骨髓瘤中骨丢失的成骨细胞生成的抑制中起关键作用。用Pim抑制剂治疗似乎诱导骨髓瘤细胞死亡，并通过废除药物外排泵功能恢复其药物敏感性。此外，Pim抑制剂诱导骨髓瘤中抑制的骨形成。因此，Pim-2抑制可能成为靶向骨髓瘤-骨髓相互作用的重要治疗选择，骨髓瘤-骨髓相互作用导致耐药性和骨破坏。

项目成果

An Acidic Milieu Aggravates Myeloma Growth And Drug Resistance But Triggers Anti-myeloma Activity Of Reveromycin A, A Novel Anti-resorptive Agent

酸性环境会加剧骨髓瘤生长和耐药性，但会触发新型抗吸收剂白藜芦醇 A 的抗骨髓瘤活性

• 发表时间: 2011
• 作者: Fukushima N;Itamura H;Urata C;Tanaka M;Hisatomi T;Kunota Y;Sueoka E;Kimura S;Abe M
• 通讯作者: Abe M

SY6-4 Targeting the interplay between myeloma cells and the bone marrow microenvironment

SY6-4 针对骨髓瘤细胞与骨髓微环境之间的相互作用

• 发表时间: 2012
• 作者: Fukata M;Ishikawa F;Najima Y;Yamauchi T;Saito Y; Takenaka K;Miyawaki K;Shimazu H;Shimoda K;Kanemaru T;Nakamura K;Odashiro K;Nagafuji K;Harada M;Akashi K;M Abe
• 通讯作者: M Abe

Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment.

• DOI: 10.7150/thno.5860
• 发表时间: 2013
• 期刊: Theranostics
• 影响因子: 12.4
• 作者: Hayashi K;Nakamura M;Sakamoto W;Yogo T;Miki H;Ozaki S;Abe M;Matsumoto T;Ishimura K
• 通讯作者: Ishimura K

Overview of the pathophysiology of MBD and acquired genetic events: Bench work for the targeted therapy to the microenvironmen of MBD. Session: Myeloma bone disease

MBD 的病理生理学和获得性遗传事件概述：针对 MBD 微环境的靶向治疗的基准工作。

• 发表时间: 2013
• 作者: Muto T;Sashida G;Oshima M;Wendt GR;Mochizuki-Kashio M;Nagata Y;Sanada M;Miyagi S;Saraya A;Kamio A;Nagae G;Nakaseko C;Yokote K;Shimoda K;Koseki H;Suzuki Y;Sugano S;Aburatani H;Ogawa S;Iwama A;M Abe
• 通讯作者: M Abe

骨髄腫骨病変と腫瘍免疫．シンポジウム5 骨免疫と炎症性疾患．

骨髓瘤骨病变与肿瘤免疫。

• 作者: Ando;T.;Xiao;W.;Gao;P.;Namiranian;S.;Matsumoto;K.;Tomimori;Y.;Hong;H.;Yamashita;H.;Kimura;M.;Kashiwakura;J.;Hata;T.R.;Izuhara;K.;Gurish;M.F.;Roers;A.;Rafaels;N.M.;Barnes;K.C.;Jamora;C.;Kawakami;Y.;and Kawakami;T.;安倍正博
• 通讯作者: 安倍正博