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J-GLOBAL ID：201802249478155850   整理番号：18A1868211

AbirateroneおよびEnzalutamide耐性前立腺癌の患者由来モデルはリボソーム指向療法に対する感受性を明らかにする【JST・京大機械翻訳】

Patient-derived Models of Abiraterone- and Enzalutamide-resistant Prostate Cancer Reveal Sensitivity to Ribosome-directed Therapy

著者 (111件)： Lawrence Mitchell G. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Lawrence Mitchell G. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Lawrence Mitchell G. (Melbourne Urological Research Alliance (MURAL), Melbourne, VIC, Australia) ,  Obinata Daisuke (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Sandhu Shahneen (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Sandhu Shahneen (Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Sandhu Shahneen (Cancer Tissue Collection After Death (CASCADE) Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Selth Luke A. (Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men’s Health, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia) ,  Wong Stephen Q. (Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Wong Stephen Q. (Molecular Biomarkers and Translational Genomics Lab, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Porter Laura H. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Lister Natalie (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Pook David (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Pook David (Medical Oncology, Monash Health, Clayton, VIC, Australia) ,  Pezaro Carmel J. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Pezaro Carmel J. (Eastern Health and Monash University Eastern Health Clinical School, Box Hill, VIC, Australia) ,  Goode David L. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Goode David L. (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Goode David L. (Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Rebello Richard J. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Rebello Richard J. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Clark Ashlee K. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Papargiris Melissa (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Papargiris Melissa (Melbourne Urological Research Alliance (MURAL), Melbourne, VIC, Australia) ,  Papargiris Melissa (Australian Prostate Cancer Bioresource, VIC Node, Monash University, Clayton, VIC, Australia) ,  Van Gramberg Jenna (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Van Gramberg Jenna (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Van Gramberg Jenna (Australian Prostate Cancer Bioresource, VIC Node, Monash University, Clayton, VIC, Australia) ,  Hanson Adrienne R. (Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men’s Health, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia) ,  Banks Patricia (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Wang Hong (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Niranjan Birunthi (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Keerthikumar Shivakumar (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Keerthikumar Shivakumar (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Keerthikumar Shivakumar (Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Hedwards Shelley (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Hedwards Shelley (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Huglo Alisee (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Huglo Alisee (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Yang Rendong (Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA) ,  Henzler Christine (Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA) ,  Li Yingming (Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA) ,  Lopez-Campos Fernando (Spanish National Cancer Research Centre, Madrid, Spain) ,  Castro Elena (Spanish National Cancer Research Centre, Madrid, Spain) ,  Toivanen Roxanne (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Toivanen Roxanne (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Azad Arun (Medical Oncology, Monash Health, Clayton, VIC, Australia) ,  Azad Arun (Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia) ,  Bolton Damien (Department of Urology, Austin Hospital, The University of Melbourne, Melbourne Heidelberg, VIC, Australia) ,  Bolton Damien (Department of Surgery, The University of Melbourne, Parkville, VIC, Australia) ,  Goad Jeremy (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Goad Jeremy (Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia) ,  Goad Jeremy (Epworth Healthcare, Melbourne, VIC, Australia) ,  Grummet Jeremy (Epworth Healthcare, Melbourne, VIC, Australia) ,  Grummet Jeremy (Department of Surgery, Central Clinical School, Monash University, Clayton, VIC, Australia) ,  Grummet Jeremy (Australian Urology Associates, Melbourne, VIC, Australia) ,  Harewood Laurence (Department of Surgery, The University of Melbourne, Parkville, VIC, Australia) ,  Harewood Laurence (Epworth Healthcare, Melbourne, VIC, Australia) ,  Kourambas John (Department of Medicine, Monash Health, Casey Hospital, Berwick, VIC, Australia) ,  Lawrentschuk Nathan (Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia) ,  Lawrentschuk Nathan (Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia) ,  Moon Daniel (Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia) ,  Moon Daniel (Epworth Healthcare, Melbourne, VIC, Australia) ,  Moon Daniel (Australian Urology Associates, Melbourne, VIC, Australia) ,  Moon Daniel (Central Clinical School, Monash University, Clayton, VIC, Australia) ,  Moon Daniel (The Epworth Prostate Centre, Epworth Hospital, Richmond, VIC, Australia) ,  Murphy Declan G. (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Murphy Declan G. (Division of Cancer Surgery, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia) ,  Murphy Declan G. (Epworth Healthcare, Melbourne, VIC, Australia) ,  Sengupta Shomik (Eastern Health and Monash University Eastern Health Clinical School, Box Hill, VIC, Australia) ,  Sengupta Shomik (Department of Urology, Austin Hospital, The University of Melbourne, Melbourne Heidelberg, VIC, Australia) ,  Sengupta Shomik (Epworth Healthcare, Melbourne, VIC, Australia) ,  Sengupta Shomik (Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia) ,  Sengupta Shomik (Epworth Freemasons, Epworth Health, East Melbourne, VIC, Australia) ,  Snow Ross (Australian Urology Associates, Melbourne, VIC, Australia) ,  Thorne Heather (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Thorne Heather (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Thorne Heather (kConFab, Research Department, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Mitchell Catherine (Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Pedersen John (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Pedersen John (TissuPath, Mount Waverley, VIC, Australia) ,  Clouston David (TissuPath, Mount Waverley, VIC, Australia) ,  Norden Sam (TissuPath, Mount Waverley, VIC, Australia) ,  Ryan Andrew (TissuPath, Mount Waverley, VIC, Australia) ,  Dehm Scott M. (Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA) ,  Dehm Scott M. (Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, MN, USA) ,  Tilley Wayne D. (Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men’s Health, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia) ,  Pearson Richard B. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Pearson Richard B. (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Pearson Richard B. (Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia) ,  Pearson Richard B. (Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia) ,  Pearson Richard B. (Oncogenic Signaling and Growth Control Program, Cancer Research Division, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia) ,  Hannan Ross D. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Hannan Ross D. (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Hannan Ross D. (Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia) ,  Hannan Ross D. (Oncogenic Signaling and Growth Control Program, Cancer Research Division, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia) ,  Hannan Ross D. (ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, ACT, Australia) ,  Frydenberg Mark (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Frydenberg Mark (Epworth Healthcare, Melbourne, VIC, Australia) ,  Frydenberg Mark (Australian Urology Associates, Melbourne, VIC, Australia) ,  Frydenberg Mark (Department of Surgery, Monash University, Clayton, VIC, Australia) ,  Furic Luc (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Furic Luc (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Furic Luc (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia) ,  Taylor Renea A. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Taylor Renea A. (Melbourne Urological Research Alliance (MURAL), Melbourne, VIC, Australia) ,  Taylor Renea A. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Physiology, Monash University, Clayton, VIC, Australia) ,  Risbridger Gail P. (Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia) ,  Risbridger Gail P. (Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) ,  Risbridger Gail P. (Melbourne Urological Research Alliance (MURAL), Melbourne, VIC, Australia) ,  Risbridger Gail P. (Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia)
資料名： European Urology  (European Urology)
巻： 74  号： 5  ページ： 562-572  発行年： 2018年 
JST資料番号： A0910B  ISSN： 0302-2838  CODEN： EUURAV  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 去勢抵抗性前立腺癌(CRPC)の細胞内性は,アンドロゲン受容体(AR)軸とAR非依存性表現型への多様な変化を含む腫瘍不均一性により悪化する。この不均一性を網羅する追加モデルの利用可能性は,CRPCに対するより効果的な治療法の同定を容易にするであろう。CRPCの不均一性を示す患者由来モデルを利用することにより治療戦略を発見する。2人の患者の独立した転移から4つの新しい患者由来異種移植(PDXs)を確立し,統合的ゲノミクスを用いて特性化した。合理的に選択された薬剤のパネルを,革新的ex vivo PDX培養システムを用いて試験した。以下の薬物を評価した:Arシグナル伝達阻害剤(アザルタミドとガレテロン),PARP阻害剤(タラゾパリブ),化学療法(シスプラチン),CDK4/6阻害剤(リボシブ),ブロモドメインと末端外(BET)蛋白質阻害剤(iBET151とJQ1),及びリボソーム生合成/機能阻害剤(RNAポリメラーゼI阻害剤CX-5461と汎-PIMキナーゼ阻害剤CX-6258)。PDX組織のex vivo培養における薬物有効性をKi67に対する免疫組織化学を用いて評価し,カスパーゼ-3レベルを切断した。候補薬物は,腫瘍容積が一次エンドポイントであるin vivoでの抗腫瘍効果も試験した。2尾t検定を用いて,薬物と対照処理を比較した。統合ゲノミクスにより,新規PDXsは既知及び新規AR突然変異,AR遺伝子のゲノム構造再編成及び神経内分泌様ARヌル表現型を含む耐性の不均一機構を示すことを明らかにした。それらの不均一性にもかかわらず,すべてのモデルはリボソーム標的化剤CX-5461とCX-6258の組合せに敏感であった。本研究により,リボソーム標的薬物はARヌル疾患を含む多様なCRPCサブタイプに対して効果的であり,臨床翻訳のための治療戦略を優先するための最新の患者由来モデルの可能性を強調することを示した。治療抵抗性前立腺癌の多様なタイプは,癌細胞における蛋白質合成経路を阻害する薬剤の新しい組み合わせに敏感である。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： *前立腺腫瘍 ,  細胞情報伝達 ,  *患者 ,  抗腫瘍作用 ,  培養 ,  突然変異 ,  *感受性 ,  表現型 ,  シスプラチン ,  腫瘍細胞 ,  薬物療法 ,  *リボソーム ,  タンパク質
準シソーラス用語： 阻害剤 ,  ゲノミクス , 【Automatic Indexing@JST】

著者キーワード (10件)： アビラテロン ,  アンドロゲン受容体 ,  去勢抵抗性前立腺癌 ,  エンザルタミド ,  Explant ,  神経内分泌前立腺癌 ,  organノイド ,  患者由来異種移植 ,  前立腺癌 ,  リボソーム

分類 (2件)： 泌尿生殖器の腫よう  (GM04000S) ,  性ホルモン  (EB08050O)

タイトルに関連する用語 (7件)： 耐性 ,  前立腺癌 ,  患者 ,  モデル ,  リボソーム ,  療法 ,  感受性