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J-GLOBAL ID：202202249034814942   整理番号：22A0492011

抗HER2抗体を分泌するツカチニブと神経幹細胞の組み合わせは転移性脳腫瘍マウスの生存を延長する【JST・京大機械翻訳】

Combination of tucatinib and neural stem cells secreting anti-HER2 antibody prolongs survival of mice with metastatic brain cancer

著者 (32件)： Cordero Alex (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Cordero Alex (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Ramsey Matthew D. (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Ramsey Matthew D. (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Kanojia Deepak (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Kanojia Deepak (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Fares Jawad (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Fares Jawad (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Petrosyan Edgar (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Petrosyan Edgar (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Schwartz Charles W. (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Schwartz Charles W. (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Burga Rachel (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Burga Rachel (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Zhang Peng (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Zhang Peng (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Rashidi Aida (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Rashidi Aida (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Castro Brandyn (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Castro Brandyn (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Xiao Ting (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Xiao Ting (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Lee-Chang Catalina (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Lee-Chang Catalina (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Miska Jason (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Miska Jason (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Balyasnikova Irina V. (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Balyasnikova Irina V. (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Ahmed Atique U. (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Ahmed Atique U. (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Lesniak Maciej S. (Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, IL 60611) ,  Lesniak Maciej S. (Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, IL 60611)
資料名： Proceedings of the National Academy of Sciences of the United States of America  (Proceedings of the National Academy of Sciences of the United States of America)
巻： 119  号： 1  ページ： e2112491119  発行年： 2022年 
JST資料番号： D0387A  ISSN： 0027-8424  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： 脳転移は乳癌患者における死因である。臨床試験の欠如と血液脳関門の存在は治療選択肢を制限する。さらに,ヒト表皮成長因子受容体2(HER2)の過剰発現は,乳癌脳転移(BCBM)の発生を増加させる。モノクローナル抗体トラスツズマブおよびペルツズマブのようなHER2標的化剤は,乳癌および頭蓋外転移患者の転帰を改善した。しかし,乳癌患者における連続したBCBM進行は,頭蓋内転移に対する新規で効果的な標的化治療の必要性を強調した。本研究では,LM008細胞の幹細胞性を損なうことなく,HER2(抗HER2Ab)に対する高機能,安定,完全長抗体を連続的に分泌するために,高移動および脳腫瘍向性ヒト神経幹細胞(NSC)LM008を操作した。分泌された抗HER2Abは,PI3K-Aktシグナリング経路を阻害することにより,HER2+ BCBM細胞でin vitroで腫瘍細胞増殖を障害し,頭蓋内異種移植モデルに注射した場合,有意な利点を生じた。加えて,抗HER2Ab LM008 NSCsとチロシンキナーゼ阻害剤ツカチニブを用いた二重HER2遮断は,多発性HER2+ BCBMの臨床関連モデルでマウスの生存を有意に改善した。これらの知見は,HER2Ab分泌LM008 NSCsを,HER2+ BCBM患者に対する有望な治療処方として,ツカチニブとの組み合わせで,有力な証拠を提供する。Copyright 2022 The Author(s). Published by PNAS. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 腫瘍細胞 ,  *脳腫瘍 ,  ヒト ,  臨床試験 ,  異種移植 ,  モノクローナル抗体 ,  ターゲティング ,  乳房腫瘍 ,  EGF受容体 ,  死因
準シソーラス用語： トラスツズマブ ,  ペルツズマブ ,  *抗HER2抗体 ,  過剰発現 ,  脳転移 , 【Automatic Indexing@JST】

著者キーワード (4件)： HER2 ,  神経幹細胞 ,  ツカチニブ ,  脳転移

分類 (2件)： 腫ようの化学・生化学・病理学  (GE02030N) ,  生物学的機能  (EB03040U)

タイトルに関連する用語 (7件)： 抗HER2抗体 ,  分泌 ,  神経幹細胞 ,  組み合わせ ,  転移性脳腫瘍 ,  マウス ,  生存