2025/07/01 更新

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写真a

イソベ タイチ
磯部 大地
ISOBE TAICHI
所属
医学研究院 基礎医学部門 助教
医学研究院 附属総合コホートセンター(併任)
九州大学病院 血液・腫瘍・心血管内科(併任)
医学部 医学科(併任)
職名
助教
プロフィール
基礎および臨床研究 がん診療
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研究分野

  • ライフサイエンス / 血液、腫瘍内科学

  • ライフサイエンス / 腫瘍診断、治療学

  • ライフサイエンス / 腫瘍生物学

  • ライフサイエンス / 消化器内科学

学位

  • 博士(医学)

経歴

  • 九州大学大学院 医学研究院 連携社会医学分野 助教 

    2020年10月 - 2024年3月

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    国名:日本国

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  • 九州大学大学院 連携腫瘍学分野 助教 

    2024年4月 - 現在

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    国名:日本国

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  • 九州大学病院 血液・腫瘍・心血管内科  

    2020年10月 - 現在

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  • 2012.5-2018.9 米国Stanford大学 研究員   

学歴

  • 九州大学   医学系学府   病態修復内科学

    2006年4月 - 2012年3月

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    国名:日本国

  • 大分医科大学   医学部   医学科

    1997年4月 - 2003年3月

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    国名:日本国

研究テーマ・研究キーワード

  • 研究テーマ: がん幹細胞

    研究キーワード: がん幹細胞

    研究期間: 2024年

  • 研究テーマ: エピジェネティクス

    研究キーワード: エピジェネティクス

    研究期間: 2024年

  • 研究テーマ: バイオマーカー

    研究キーワード: バイオマーカー

    研究期間: 2024年

  • 研究テーマ: 乳癌

    研究キーワード: 乳癌

    研究期間: 2024年

  • 研究テーマ: 大腸癌

    研究キーワード: 大腸癌

    研究期間: 2024年

  • 研究テーマ: 老化

    研究キーワード: 老化

    研究期間: 2024年

  • 研究テーマ: 胃癌

    研究キーワード: 胃癌

    研究期間: 2024年

  • 研究テーマ: クローン性造血で引き起こされるがん微小環境内の免疫応答の解明

    研究キーワード: クローン性造血、がん、微小環境

    研究期間: 2021年4月

  • 研究テーマ: 染色体異常を起因としたヒト大腸がんの新規疾患モデルの確立

    研究キーワード: がん、染色体異常

    研究期間: 2019年4月

論文

  • Spatial dynamics of CD39<SUP>+</SUP>CD8<SUP>+</SUP> exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer 国際誌

    Tanoue, K; Ohmura, H; Uehara, K; Ito, M; Yamaguchi, K; Tsuchihashi, K; Shinohara, Y; Lu, P; Tamura, S; Shimokawa, H; Isobe, T; Ariyama, H; Shibata, Y; Tanaka, R; Kusaba, H; Esaki, T; Mitsugi, K; Kiyozawa, D; Iwasaki, T; Yamamoto, H; Oda, Y; Akashi, K; Baba, E

    NATURE COMMUNICATIONS   15 ( 1 )   9033 - 9033   2024年10月   eISSN:2041-1723

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Communications  

    Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39<sup>+</sup>PD-1<sup>+</sup>CD8<sup>+</sup> T cells, specifically the TCF1<sup>+</sup> subset, precursor exhausted T (CD39<sup>+</sup> Tpex) cells, which positively correlate with ICB benefit. CD39<sup>+</sup> Tpex cells are predominantly in the stroma, while differentiated CD39<sup>+</sup> exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39<sup>+</sup> Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39<sup>+</sup> Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39<sup>+</sup>PD-1<sup>+</sup>CD8<sup>+</sup> T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.

    DOI: 10.1038/s41467-024-53262-w

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  • Impact of Genomic Alterations on Efficacy of Trastuzumab Deruxtecan Against Human Epidermal Growth Factor Receptor-2-Positive Advanced Gastric Cancer. 国際誌

    Yamaguchi K, Ito M, Isobe T, Koreishi S, Taguchi R, Uehara K, Ueno S, Imajima T, Kitazono T, Tsuchihashi K, Ohmura H, Yoshihiro T, Tanoue K, Nishiyori S, Iwama E, Maeda T, Akashi K, Baba E

    JCO precision oncology   8 ( 8 )   e2300681   2024年5月   eISSN:2473-4284

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JCO Precision Oncology  

    PURPOSE The impact of genomic alterations on response and resistance to trastuzumab deruxtecan (T-DXd) has not been elucidated. Thus, we sought to identify factors predicting sensitivity to T-DXd in gastric or gastroesophageal junction (G/GEJ) cancer. METHODS We conducted a retrospective study using real-world clinical data and next-generation sequencing–based comprehensive genomic profiling (CGP) data from patients with advanced G/GEJ cancers, collected by the nationwide database in Japan. We analyzed the associations between genomic alterations and the patients’ survivals after T-DXd treatment. RESULTS In 114 patients with human epidermal growth factor receptor-2 (HER2)–positive G/GEJ cancer treated with T-DXd, the most frequently altered genes were TP53 (82%), ERBB2 (80%), and CCNE1 (36%). Multivariate Cox regression analysis revealed CCNE1 amplification to be a significant predictor of shorter progression-free survival (PFS) after T-DXd treatment among 91 patients whose CGP samples were obtained before T-DXd (median PFS, 131 days v 189 days; hazard ratio [HR], 1.90 [95% CI, 1.02 to 3.53]; P 5 .044). Analyses of 1,450 G/GEJ cancers revealed significant CCNE1/ERBB2 coamplification (41% relative to 11% CCNE1 amplification in ERBB2-nonamplified tumors; P < .0001). ERBB2-activating mutations were also detected in 3.7% of G/GEJ cancers and in 8.8% of HER2-positive G/GEJ cancers treated with T-DXd. Patients with ERBB2-mutated tumors showed shorter PFS than those without ERBB2 mutations after T-DXd treatment (mPFS, 105 v 180 days; P 5 .046). CONCLUSION CCNE1 amplification may confer primary resistance to T-DXd in HER2-positive G/GEJ cancer, suggesting that the cell cycle could be a potential therapeutic target in CCNE1/ERBB2 coamplified tumors. ERBB2-activating mutation may also attenuate T-DXd efficacy in HER2-positive G/GEJ cancer.

    DOI: 10.1200/po.23.00681

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  • An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome 査読

    Shixuan Liu, Camille Ezran, Michael F. Z. Wang, Zhengda Li, Kyle Awayan, Snigdha Agarwal, Aditi Agrawal, Ahmad Al-Moujahed, Alina Alam, Megan A. Albertelli, Paul Allegakoen, Thomas Ambrosi, Jane Antony, Steven Artandi, Fabienne Aujard, Ankit Baghel, Isaac Bakerman, Trygve. E. Bakken, Jalal Baruni, Philip Beachy, Biter Bilen, Olga Botvinnik, Scott. D. Boyd, Deviana Burhan, Kerriann M. Casey, Charles Chan, Charles. A. Chang, Stephen Chang, Ming Chen, Michael F. Clarke, Sheela Crasta, Rebecca Culver, Jessica D’Addabbo, Spyros Darmanis, Roozbeh Dehghannasiri, Song-Lin Ding, Connor V. Duffy, F. Hernán Espinoza, Jean Farup, Hannah K. Frank, Margaret Fuller, Astrid Gillich, Elias Godoy, Dita Gratzinger, Lisbeth A. Guethlein, Yan Hang, Kazuteru Hasegawa, Rebecca D. Hodge, Malachia Hoover, Franklin W. Huang, Kerwyn C. Huang, Shelly Huynh, Taichi Isobe, Carly Israel, SoRi Jang, Qiuyu Jing, Robert C. Jones, Jengmin Kang, Caitlin J. Karanewsky, Jim Karkanias, Justus Kebschull, Aaron Kershner, Lily Kim, Seung K. Kim, E. Christopher Kirk, Winston Koh, Silvana Konermann, William Kong, Corinne Lautier, Song Eun Lee, Ed S. Lein, Rebecca Lewis, Peng Li, Shengda Lin, Yin Liu, Gabriel Loeb, Wan-Jin Lu, Katherine Lucot, Liqun Luo, Ashley Maynard, Aaron McGeever, Ross Metzger, Jingsi Ming, Tom Montine, Antoine de Morree, Maurizio Morri, Karim Mrouj, Shravani Mukherjee, Ahmad Nabhan, Saba Nafees, Norma Neff, Patrick Neuhöfer, Patricia Nguyen, Jennifer Okamoto, Julia Olivieri, Youcef Ouadah, Honor Paine, Peter Parham, Jozeph L. Pendleton, Lolita Penland, Martine Perret, Angela Oliveira Pisco, Zhen Qi, Stephen R. Quake, Ute Radespiel, Thomas A. Rando, Hajanirina Noëline Ravelonjanahary, Andriamahery Razafindrakoto, Julia Salzman, Nicholas Schaum, Robert Schopler, Bronwyn Scott, Liza Shapiro, Hosu Sin, Rahul Sinha, Rene Sit, Geoff Stanley, Lubert Stryer, Varun Ramanan Subramaniam, Aditi Swarup, Michelle Tan, Weilun Tan, Alexander Tarashansky, Aris Taychameekiatchai, Kyle J. Travaglini, Andoni Urtasun, Sivakamasundari, Avin Veerakumar, Venkata N. P. Vemuri, Jean-Michel Verdier, Douglas Vollrath, Bo Wang, Bruce Wang, Gefei Wang, James Webber, Hannah Weinstein, Irving L. Weissman, Amanda L. Wiggenhorn, Cathy V. Williams, Patricia Wright, Albert Y. Wu, Angela Ruohao Wu, Timothy Ting-Hsuan Wu, Tony Wyss-Coray, BaoXiang Li, Jia Yan, Can Yang, Jinxurong Yang, Anne D. Yoder, Brian Yu, Andrea R. Yung, Yue Zhang, Jia Zhao, Zicheng Zhao, Jonathan Z. Long, Iwijn De Vlaminck, Sheng Wang, Jacques Epelbaum, Christin S. Kuo, Jérémy Terrien, Mark A. Krasnow, James E. Ferrell

    Nature Communications   15 ( 1 )   2024年3月   eISSN:2041-1723

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Communications  

    Abstract

    Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, and health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, hormone signaling by its very nature connects cells of different organs and involves crosstalk of different hormones. Here, we leverage the organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), to systematically map source and target cells for 84 classes of hormones. This work uncovers previously-uncharacterized sites of hormone regulation, and shows that the hormonal signaling network is densely connected, decentralized, and rich in feedback loops. Evolutionary comparisons of hormonal genes and their expression patterns show that mouse lemur better models human hormonal signaling than mouse, at both the genomic and transcriptomic levels, and reveal primate-specific rewiring of hormone-producing/target cells. This work complements the scale and resolution of classical endocrine studies and sheds light on primate hormone regulation.

    DOI: 10.1038/s41467-024-46070-9

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    その他リンク: https://www.nature.com/articles/s41467-024-46070-9

  • Adversarial domain translation networks for integrating large-scale atlas-level single-cell datasets 査読 国際誌

    Jia Zhao, Gefei Wang, Jingsi Ming, Zhixiang Lin, Yang Wang, Snigdha Agarwal, Aditi Agrawal, Ahmad Al-Moujahed, Alina Alam, Megan A. Albertelli, Paul Allegakoen, Thomas Ambrosi, Jane Antony, Steven Artandi, Fabienne Aujard, Kyle Awayan, Ankit Baghel, Isaac Bakerman, Trygve E. Bakken, Jalal Baruni, Philip Beachy, Biter Bilen, Olga Botvinnik, Scott D. Boyd, Deviana Burhan, Kerriann M. Casey, Charles Chan, Charles A. Chang, Stephen Chang, Ming Chen, Michael F. Clarke, Sheela Crasta, Rebecca Culver, Jessica D’Addabbo, Spyros Darmanis, Roozbeh Dehghannasiri, Song-Lin Ding, Connor V. Duffy, Jacques Epelbaum, F. Hernán Espinoza, Camille Ezran, Jean Farup, James E. Ferrell Jr, Hannah K. Frank, Margaret Fuller, Astrid Gillich, Elias Godoy, Dita Gratzinger, Lisbeth A. Guethlein, Yan Hang, Kazuteru Hasegawa, Rebecca D. Hodge, Malachia Hoover, Franklin W. Huang, Kerwyn Casey Huang, Shelly Huynh, Taichi Isobe, Carly Israel, SoRi Jang, Qiuyu Jing, Robert C. Jones, Jengmin Kang, Caitlin J. Karanewsky, Jim Karkanias, Justus Kebschull, Aaron Kershner, Lily Kim, Seung K. Kim, E. Christopher Kirk, Winston Koh, Silvana Konermann, William Kong, Mark A. Krasnow, Christin Kuo, Corinne Lautier, Song Eun Lee, Ed S. Lein, Rebecca Lewis, Peng Li, Shengda Lin, Shixuan Liu, Yin Liu, Gabriel Loeb, Jonathan Z. Long, Wan-Jin Lu, Katherine Lucot, Liqun Luo, Aaron McGeever, Ross Metzger, Jingsi Ming, Tom Montine, Antoine de Morree, Maurizio Morri, Karim Mrouj, Shravani Mukherjee, Ahmad Nabhan, Saba Nafees, Norma Neff, Patrick Neuhöfer, Patricia Nguyen, Jennifer Okamoto, Julia Olivieri, Youcef Ouadah, Honor Paine, Peter Parham, Jozeph L. Pendleton, Lolita Penland, Martine Perret, Angela Oliveira Pisco, Zhen Qi, Stephen R. Quake, Ute Radespiel, Thomas A. Rando, Hajanirina Noëline Ravelonjanahary, Andriamahery Razafindrakoto, Julia Salzman, Nicholas Schaum, Robert Schopler, Bronwyn Scott, Liza Shapiro, Hosu Sin, Rahul Sinha, Rene Sit, Geoff Stanley, Lubert Stryer, Varun Ramanan Subramaniam, Aditi Swarup, Weilun Tan, Alexander Tarashansky, Aris Taychameekiatchai, Jérémy Terrien, Kyle J. Travaglini, Andoni Urtasun, Sivakamasundari, Avin Veerakumar, Venkata Naga Pranathi Vemuri, Jean-Michel Verdier, Iwijn De Vlaminck, Douglas Vollrath, Bo Wang, Bruce Wang, Gefei Wang, Michael F. Z. Wang, Sheng Wang, James Webber, Hannah Weinstein, Irving L. Weissman, Amanda L. Wiggenhorn, Cathy V. Williams, Patricia Wright, Albert Y. Wu, Angela Ruohao Wu, Tony Wyss-Coray, Bao Xiang, Jia Yan, Can Yang, Jinxurong Yang, Anne D. Yoder, Brian Yu, Andrea R. Yung, Yue Zhang, Jia Zhao, Zicheng Zhao, Angela Ruohao Wu, Can Yang

    Nature Computational Science   2 ( 5 )   317 - 330   2022年5月   eISSN:2662-8457

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    記述言語:その他   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Computational Science  

    The rapid emergence of large-scale atlas-level single-cell RNA-seq datasets presents remarkable opportunities for broad and deep biological investigations through integrative analyses. However, harmonizing such datasets requires integration approaches to be not only computationally scalable, but also capable of preserving a wide range of fine-grained cell populations. We have created Portal, a unified framework of adversarial domain translation to learn harmonized representations of datasets. When compared to other state-of-the-art methods, Portal achieves better performance for preserving biological variation during integration, while achieving the integration of millions of cells, in minutes, with low memory consumption. We show that Portal is widely applicable to integrating datasets across different samples, platforms and data types. We also apply Portal to the integration of cross-species datasets with limited shared information among them, elucidating biological insights into the similarities and divergences in the spermatogenesis process among mouse, macaque and human.

    DOI: 10.1038/s43588-022-00251-y

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    その他リンク: https://www.nature.com/articles/s43588-022-00251-y

  • Molecular hallmarks of heterochronic parabiosis at single-cell resolution 査読 国際誌

    Róbert Pálovics, Andreas Keller, Nicholas Schaum, Weilun Tan, Tobias Fehlmann, Michael Borja, Fabian Kern, Liana Bonanno, Kruti Calcuttawala, James Webber, Aaron McGeever, Nicole Almanzar, Jane Antony, Ankit S. Baghel, Isaac Bakerman, Ishita Bansal, Ben A. Barres, Philip A. Beachy, Daniela Berdnik, Biter Bilen, Douglas Brownfield, Corey Cain, Charles K. F. Chan, Michelle B. Chen, Michael F. Clarke, Stephanie D. Conley, Aaron Demers, Kubilay Demir, Antoine de Morree, Tessa Divita, Haley du Bois, Hamid Ebadi, F. Hernán Espinoza, Matt Fish, Qiang Gan, Benson M. George, Astrid Gillich, Rafael Gòmez-Sjöberg, Foad Green, Geraldine Genetiano, Xueying Gu, Gunsagar S. Gulati, Oliver Hahn, Michael Seamus Haney, Yan Hang, Lincoln Harris, Mu He, Shayan Hosseinzadeh, Albin Huang, Kerwyn Casey Huang, Tal Iram, Taichi Isobe, Feather Ives, Robert C. Jones, Kevin S. Kao, Guruswamy Karnam, Aaron M. Kershner, Nathalie Khoury, Seung K. Kim, Bernhard M. Kiss, William Kong, Mark A. Krasnow, Maya E. Kumar, Christin S. Kuo, Jonathan Lam, Davis P. Lee, Song E. Lee, Benoit Lehallier, Olivia Leventhal, Guang Li, Qingyun Li, Ling Liu, Annie Lo, Wan-Jin Lu, Maria F. Lugo-Fagundo, Anoop Manjunath, Andrew P. May, Ashley Maynard, Marina McKay, M. Windy McNerney, Bryan Merrill, Ross J. Metzger, Marco Mignardi, Dullei Min, Ahmad N. Nabhan, Katharine M. Ng, Patricia K. Nguyen, Joseph Noh, Roel Nusse, Rasika Patkar, Weng Chuan Peng, Lolita Penland, Katherine Pollard, Robert Puccinelli, Zhen Qi, Thomas A. Rando, Eric J. Rulifson, Joe M. Segal, Shaheen S. Sikandar, Rahul Sinha, Rene V. Sit, Justin Sonnenburg, Daniel Staehli, Krzysztof Szade, Michelle Tan, Cristina Tato, Krissie Tellez, Laughing Bear Torrez Dulgeroff, Kyle J. Travaglini, Carolina Tropini, Margaret Tsui, Lucas Waldburger, Bruce M. Wang, Linda J. van Weele, Kenneth Weinberg, Irving L. Weissman, Michael N. Wosczyna, Sean M. Wu, Jinyi Xiang, Soso Xue, Kevin A. Yamauchi, Andrew C. Yang, Lakshmi P. Yerra, Justin Youngyunpipatkul, Brian Yu, Fabio Zanini, Macy E. Zardeneta, Alexander Zee, Chunyu Zhao, Fan Zhang, Hui Zhang, Martin Jinye Zhang, Lu Zhou, James Zou, Jian Luo, Angela Oliveira Pisco, Jim Karkanias, Norma F. Neff, Spyros Darmanis, Stephen R. Quake, Tony Wyss-Coray

    Nature   603 ( 7900 )   309 - 314   2022年3月   ISSN:0028-0836 eISSN:1476-4687

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    記述言語:その他   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

    DOI: 10.1038/s41586-022-04461-2

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  • Ageing hallmarks exhibit organ-specific temporal signatures 査読

    Nicholas Schaum, Benoit Lehallier, Oliver Hahn, Róbert Pálovics, Shayan Hosseinzadeh, Song E. Lee, Rene Sit, Davis P. Lee, Patricia Morán Losada, Macy E. Zardeneta, Tobias Fehlmann, James T. Webber, Aaron McGeever, Kruti Calcuttawala, Hui Zhang, Daniela Berdnik, Vidhu Mathur, Weilun Tan, Alexander Zee, Michelle Tan, Tabula Muris Consortium, Angela Oliveira Pisco, Jim Karkanias, Norma F. Neff, Andreas Keller, Spyros Darmanis, Stephen R. Quake, Tony Wyss-Coray

    Nature   583 ( 7817 )   596 - 602   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41586-020-2499-y

  • A single-cell transcriptomic atlas characterizes ageing tissues in the mouse 査読

    Tabula Muris Consortium

    Nature   583 ( 7817 )   590 - 595   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41586-020-2496-1

  • miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells. 査読 国際誌

    Junko Mukohyama, Taichi Isobe, Qingjiang Hu, Takanori Hayashi, Takashi Watanabe, Masao Maeda, Hisano Yanagi, Xin Qian, Kimihiro Yamashita, Hironobu Minami, Koshi Mimori, Debashis Sahoo, Yoshihiro Kakeji, Akira Suzuki, Piero Dalerba, Yohei Shimono

    Cancer research   79 ( 20 )   5151 - 5158   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1158/0008-5472.CAN-18-3544

  • Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. 査読

    Tabula Muris Consortium

    Nature   562   367 - 372   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris.

    DOI: 10.1038/s41586-018-0590-4

  • E‑cadherin regulates proliferation of colorectal cancer stem cells through NANOG. 査読 国際誌

    Tamura S, Isobe T, Ariyama H, Nakano M, Kikushige Y, Takaishi S, Kusaba H, Takenaka K, Ueki T, Nakamura M, Akashi K, Baba E

    Oncology reports   40 ( 2 )   693 - 703   2018年8月

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    記述言語:英語  

    DOI: 10.3892/or.2018.6464

  • miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway 査読

    Taichi Isobe, Shigeo Hisamori, Daniel J. Hogan, Maider Zabala, David G. Hendrickson, Piero Dalerba, Shang Cai, Ferenc Scheeren, Angera H. Kuo, Shaheen S. Sikandar, Jessica S. Lam, Dalong Qian, Frederick M. Dirbas, George Somlo, Kaiqin Lao, Patrick O. Brown, Michael F. Clarke, Yohei Shimono

    ELIFE   3   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.7554/eLife.01977

  • Analysis of Adverse Events of Bevacizumab-containing Systemic Chemotherapy for Metastatic Colorectal Cancer in Japan 査読

    Taichi Isobe, Keita Uchino, Chinatsu Makiyama, Hiroshi Ariyama, Shuji Arita, Shingo Tamura, Masato Komoda, Hitoshi Kusaba, Tsuyoshi Shirakawa, Taito Esaki, Kenji Mitsugi, Shigeo Takaishi, Koichi Akashi, Eishi Baba

    ANTICANCER RESEARCH   34 ( 4 )   2035 - 2040   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Human STEAP3 maintains tumor growth under hypoferric condition 査読

    Taichi Isobe, Eishi Baba, Shuji Arita, Masato Komoda, Shingo Tamura, Tsuyoshi Shirakawa, Hiroshi Ariyama, Shigeo Takaishi, Hitoshi Kusaba, Takashi Ueki, Koichi Akashi

    EXPERIMENTAL CELL RESEARCH   317 ( 18 )   2582 - 2591   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.yexcr.2011.07.022

  • Effective monotherapy with amrubicin for a refractory extrapulmonary small-cell carcinoma of the liver. 査読

    Isobe T, Yanai S, Kusaba H, Yada S, Kuroda Y, Tamiya S, Matsumoto T, Baba E, Harada M

    Case reports in medicine   2009   538081   2009年6月

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    記述言語:英語  

    Effective monotherapy with amrubicin for a refractory extrapulmonary small-cell carcinoma of the liver.

    DOI: 10.1155/2009/538081

  • Autoimmune thrombocytopenia with clonal expansion of CD8-positive T cells after autologous peripheral blood stem cell transplantation for diffuse large B-cell lymphoma 査読

    T Isobe, TE Tanimoto, G Nakaji, T Miyamoto, S Yamasaki, K Takase, A Numata, T Fukuda, K Nagafuji, S Inaba, M Harada

    BONE MARROW TRANSPLANTATION   35 ( 3 )   315 - 316   2005年2月

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    記述言語:英語  

    DOI: 10.1038/sj.bmt.1704750

  • Elucidation of the mechanism of carcinogenic transformation of human gastric epithelial cells in atrophic gastritis 国際誌

    Yoshihiro, T; Yamaguchi, K; Ariyama, H; Koreishi, S; Uehara, K; Ohmura, H; Ito, M; Tsuchihashi, K; Isobe, T; Shindo, K; Ohuchida, K; Nakamura, M; Nagao, Y; Oda, Y; Akashi, K; Baba, E

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   1871 ( 6 )   167843 - 167843   2025年8月   ISSN:0925-4439 eISSN:1879-260X

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Biochimica Et Biophysica Acta Molecular Basis of Disease  

    Background: Helicobacter pylori infection and subsequent atrophic gastritis (AG) and intestinal metaplasia (IM) are regarded as precursor conditions for gastric cancer (GC). Though diverse mechanisms of carcinogenesis from AG and IM have been clarified using mouse models, few studies using human models have been reported. Here, we describe in vitro modeling of IM, as well as in vivo modeling of the oncogenic transformation from AG using human gastric organoids. Methods: Organoids derived from patients with AG were established and characterized by immunohistochemistry and in situ hybridization. Niche factor withdrawal and genetic engineering using CRISPR/Cas9 were conducted for modeling IM, and manipulated organoids were xenografted subcutaneously in mice to establish a GC model. Results: AG organoids (AGOs) were maintained by Wnt niche factors; withdrawal of these factors led to differentiation toward foveolar cells. Knockout of Runt-related transcription factor 3 (RUNX3), or activation of bone morphogenetic protein (BMP) signaling, resulted in accumulation of the key IM markers caudal-type homeobox 2 (CDX2) and mucin 2 (MUC2) in AGOs; disruption of SMAD4 counteracted the induction of these markers. Organoids doubly deficient for TP53 and SMAD4 formed larger and more proliferative p21 -negative subcutaneous tumors than did RUNX3-deficient organoids, suggesting that induction of a senescent state is a key barrier in stepwise carcinogenesis from AG. Conclusions: Wnt signaling is essential for homeostasis of AG, and SMAD4-dependent activation of BMP signaling promotes intestinal differentiation. Combined disruption of TP53 and SMAD4 confers tumorigenic potential to AGOs by inhibiting p21 induction.

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  • Lymphoproliferative Disorder in an Esophageal Cancer Patient Treated with Pembrolizumab

    Matsumura Takashi, Tsuchihashi Kenji, Yamamoto Takeo, Jinnouchi Fumiaki, Kusano Wataru, Kusumoto Yota, Arimizu Kohei, Ohmura Hirofumi, Kuma Yuki, Moriyama Shohei, Yamaguchi Kyoko, Ito Mamoru, Isobe Taichi, Ariyama Hiroshi, Oda Yoshinao, Akashi Koichi, Baba Eishi

    Internal Medicine   64 ( 11 )   1728 - 1732   2025年6月   ISSN:09182918 eISSN:13497235

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    記述言語:英語   出版者・発行元:一般社団法人 日本内科学会  

    <p>A 75-year-old man diagnosed with esophageal cancer and lung metastasis received a combination of fluorouracil, cisplatin, and pembrolizumab. During pembrolizumab maintenance therapy, lymphoproliferative lesions at the lips and mouth and multiple lymph node swellings appeared. Histologically, Epstein-Barr virus (EBV)-encoded RNA was positive, and EBV-DNA was detected in the blood. The patient was diagnosed with other iatrogenic immunodeficiency-associated lymph proliferative disorders (OIIA-LPDs) related to EBV activation induced by pembrolizumab. Rituximab was administered, resulting in the improvement of the OIIA-LPD. The emergence of an OIIA-LPD merits close attention in patients receiving immune checkpoint inhibitors. </p>

    DOI: 10.2169/internalmedicine.3743-24

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  • Metastatic urachal carcinoma treated with trifluridine/tipiracil and bevacizumab: a case report

    Kitazono, T; Isobe, T; Nishiyori, S; Kusano, W; Tanoue, K; Yoshihiro, T; Ohmura, H; Yamaguchi, K; Ito, M; Tsuchihashi, K; Akashi, K; Baba, E

    INTERNATIONAL CANCER CONFERENCE JOURNAL   2025年5月   ISSN:2192-3183

  • Treatment of malignant primary cardiac tumors requires attention to cardiovascular complications: a single-center, retrospective study

    Furukawa Kanami, Ohmura Hirofumi, Moriyama Shohei, Uehara Koki, Ito Mamoru, Tsuchihashi Kenji, Isobe Taichi, Ariyama Hiroshi, Fukata Mitsuhiro, Kusaba Hitoshi, Shiose Akira, Akashi Koichi, Baba Eishi

    Japanese Journal of Clinical Oncology   55 ( 2 )   113 - 122   2025年2月   ISSN:0368-2811

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    記述言語:英語   出版者・発行元:Oxford University Press  

  • The E2F4 transcriptional repressor is a key mechanistic regulator of colon cancer resistance to irinotecan (CPT-11).

    Matsubara J, Li YF, Koul S, Mukohyama J, Salazar LEV, Isobe T, Qian D, Clarke MF, Sahoo D, Altman RB, Dalerba P

    bioRxiv : the preprint server for biology   2025年1月

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    記述言語:英語  

    DOI: 10.1101/2025.01.22.633435

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  • Efficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes

    Yamaguchi, K; Tsuchihashi, K; Ueno, S; Uehara, K; Taguchi, R; Ito, M; Isobe, T; Imajima, T; Kitazono, T; Tanoue, K; Ohmura, H; Akashi, K; Baba, E

    ESMO OPEN   10 ( 1 )   104108   2025年1月   eISSN:2059-7029

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    記述言語:英語   出版者・発行元:ESMO Open  

    Background: Pembrolizumab, an immune checkpoint inhibitor (ICI), shows significant survival benefits in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but its efficacy in microsatellite-stable (MSS) mCRC is limited. Although ICIs are effective in tumor mutational burden-high (TMB-H) solid tumors, the impact on MSS-TMB-H mCRC, a rare subset within MSS mCRC, remains unclear. Materials and methods: We conducted a retrospective analysis using clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository in Japan. Patients with MSS-TMB-H mCRC who underwent tissue-based comprehensive genomic profiling and were treated with pembrolizumab or other later-line therapies were included. Pembrolizumab's efficacy was compared with that of trifluridine/tipiracil (FTD/TPI) and regorafenib. Genomic profiles of MSS-TMB-H, MSI-H-TMB-H, and MSS-TMB-low (TMB-L) CRCs were analyzed across 71 cancer-related genes. Results: Among 127 TMB-H mCRC cases treated with pembrolizumab in the C-CAT repository, 77 were MSS and 50 were MSI-H. Pembrolizumab showed significantly shorter time to treatment failure (TTF) and overall survival (OS) in patients with MSS-TMB-H mCRC compared with those with MSI-H-TMB-H mCRC [median TTF 2.0 versus 10.6 months; hazard ratio (HR) 4.79, 95% confidence interval (CI) 2.65-8.64, median OS 4.5 versus 33.6 months; HR 9.86, 95% CI 3.93-24.77, both P < 0.0001]. Among MSS-TMB-H mCRC patients, 19 received pembrolizumab, 73 received FTD/TPI (±bevacizumab), and 18 received regorafenib as their first later-line therapy. Pembrolizumab showed significantly shorter TTF and OS compared with FTD/TPI (median TTF 1.6 versus 4.1 months; HR 2.66, 95% CI 1.41-5.02, P = 0.0017, median OS 5.4 versus 13.8 months; HR 2.42, 95% CI, 1.09-5.38, P = 0.025). Genomic analysis of 6737 CRCs revealed that MSS-TMB-H CRCs harbored fewer pathogenic alterations than MSI-H-TMB-H CRCs but had a profile similar to MSS-TMB-L CRCs. Conclusions: Pembrolizumab may be less effective than FTD/TPI in later-line treatment of MSS-TMB-H mCRC, potentially due to genomic similarities between MSS-TMB-H and MSS-TMB-L CRC, suggesting the need for alternative therapeutic strategies in this subgroup.

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  • Treatment of malignant primary cardiac tumors requires attention to cardiovascular complications: a single-center, retrospective study 国際誌

    Furukawa, K; Ohmura, H; Moriyama, S; Uehara, K; Ito, M; Tsuchihashi, K; Isobe, T; Ariyama, H; Fukata, M; Kusaba, H; Shiose, A; Akashi, K; Baba, E

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   55 ( 2 )   113 - 122   2024年10月   ISSN:0368-2811 eISSN:1465-3621

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Clinical Oncology  

    Background: Malignant primary cardiac tumors require multimodal approaches including surgery, chemotherapy and radiotherapy, but these treatments can be associated with cardiovascular complications. However, few reports have described the cardiovascular complications related to primary cardiac tumor treatment because of their rarity. Methods: Clinical records of patients with primary cardiac tumors treated at Kyushu University Hospital from January 2010 to August 2021 were retrospectively examined. Results: Of the 47 primary cardiac tumor patients, 13 (28%) were diagnosed with malignancy, including 5 angiosarcomas, 3 intimal sarcomas, 3 diffuse large B-cell lymphomas, 1 Ewing’s sarcoma and 1 fibrosarcoma. Cardiovascular events were observed in 10 patients (77%), including cardiac dysfunction in 6 patients, arrhythmias in 5 patients, right heart failure in 2 patients, and excessively prolonged prothrombin time due to the combination of warfarin and chemotherapy in 1 patient. Two patients who showed notable cardiac complications are described. Case A involved a 69-year-old woman who underwent surgery for a left atrial intimal sarcoma, followed by postoperative chemotherapy with doxorubicin plus ifosfamide and radiotherapy. After three cycles of chemotherapy and sequential radiotherapy, her left ventricular ejection fraction decreased to 34%, and ongoing heart failure therapy was required. Case B involved a 66-year-old man who received chemotherapy for primary cardiac lymphoma, resulting in tumor shrinkage. However, due to tumor involvement of the intraventricular septum, atrioventricular block developed, requiring cardiac pacemaker implantation. Conclusion: High incidences of cardiac failure and arrhythmias were observed during multimodal treatments for malignant primary cardiac tumors. Proper management of complications may lead to a favorable prognosis in patients with malignant primary cardiac tumors.

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  • Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan 査読 国際誌

    Tsuchihashi, K; Ito, M; Arita, S; Kusaba, H; Kusano, W; Matsumura, T; Kitazono, T; Ueno, S; Taguchi, R; Yoshihiro, T; Doi, Y; Arimizu, K; Ohmura, H; Kajitani, T; Nio, K; Nakano, M; Oshima, K; Tamura, S; Shirakawa, T; Shimokawa, H; Uchino, K; Hanamura, F; Okumura, Y; Komoda, M; Isobe, T; Ariyama, H; Esaki, T; Hashimoto, K; Komune, N; Matsuo, M; Matsumoto, K; Asai, K; Yoshitake, T; Yamamoto, H; Oda, Y; Akashi, K; Baba, E

    BMC CANCER   23 ( 1 )   1046 - 1046   2023年10月   eISSN:1471-2407

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    記述言語:その他   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Cancer  

    Abstract

    Background

    Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy.

    Methods

    We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy.

    Results

    Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions.

    Conclusion

    The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

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    その他リンク: https://link.springer.com/article/10.1186/s12885-023-11528-4/fulltext.html

  • Preferential B cell differentiation by combined immune checkpoint blockade for renal cell carcinoma is associated with clinical response and autoimmune reactions 査読 国際誌

    Uehara, K; Tanoue, K; Yamaguchi, K; Ohmura, H; Ito, M; Matsushita, Y; Tsuchihashi, K; Tamura, S; Shimokawa, H; Isobe, T; Shibata, Y; Ariyama, H; Tanaka, R; Kusaba, H; Yamamoto, H; Oda, Y; Akashi, K; Baba, E

    CANCER IMMUNOLOGY IMMUNOTHERAPY   72 ( 11 )   3543 - 3558   2023年8月   ISSN:0340-7004 eISSN:1432-0851

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Immunology, Immunotherapy  

    Combined immune checkpoint blockade (ICB) is effective therapy for renal cell carcinoma (RCC). However, the dynamic changes in circulating B cells induced by combined ICB have not been clarified. The present study prospectively examined 22 patients scheduled to receive ICB for unresectable or metastatic RCC between March 2018 and August 2021. Eleven patients received combined therapy with anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab), and the other 11 patients received nivolumab monotherapy. Comprehensive phenotypes of circulating immune cells obtained prior to and after ICB therapy were analyzed by flow cytometry. Although the proportion of naïve B cells among total B cells was significantly decreased, that of switched memory B cells was significantly increased after combined therapy. In responders, the proportion of B cells among peripheral blood mononuclear cells was significantly higher prior to ICB therapy, and the proportion of switched memory B cells among total B cells tended to increase after ICB therapy. Of note, the proportion of plasmablasts among total B cells was significantly increased after ICB therapy in patients who developed severe immune-related adverse events (irAEs), and the proportion of B cells among peripheral blood decreased significantly. Furthermore, in four of five patients who developed immune-related hypophysitis following combined therapy, anti-pituitary antibody was detected in the serum. These results suggested that immune-related hypophysitis was closely related to the increase in circulating plasmablasts. Collectively, this study suggests that combined ICB promotes the differentiation of B cell populations, which is associated with efficient tumor suppression and development of irAEs.

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  • RHAMM marks proliferative subpopulation of human colorectal cancer stem cells.

    Nakano Michitaka, Taguchi Ryosuke, Kikushige Yoshikane, Isobe Taichi, Miyawaki Kohta, Mizuno Shinichi, Tsuruta Nobuhiro, Hanamura Fumiyasu, Yamaguchi Kyoko, Yamauchi Takuji, Ariyama Hiroshi, Kusaba Hitoshi, Nakamura Masafumi, Maeda Takahiro, Kuo Calvin J., Baba Eishi, Akashi Koichi

    Cancer Science   114 ( 7 )   2895 - 2906   2023年7月   ISSN:1347-9032

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    記述言語:英語   出版者・発行元:John Wiley & Sons Australia, Ltd  

    大腸癌幹細胞の中で増殖状態にあるものの特徴を決定するため、オルガノイドと大腸癌組織を材料に、それらのトランスクリプトミクスを解析した。その結果、CD44陽性を示す通常のヒト大腸癌幹細胞の分画の中に、ヒアルロン酸媒介運動性受容体(RHAMM)を発現している亜集団があることを発見した。細胞種の多様性を再構成することで腫瘍組織のミニチュア版としたオルガノイドを材料に、単一細胞トランスクリプトミクス解析を施行したところ、増殖性を示し、様々な細胞種の中にあって独特の特徴を示すRHAMM陽性細胞があることに注目された。ヒト大腸癌組織からRHAMM陽性CD44陽性の細胞を予期的に分離した結果、分離された同細胞は他の癌細胞と比較して高い増殖特性と自己新生能を現した。RHAMMを阻害するとin vitroでのオルガノイド形成は強く抑制され、in vivoでは腫瘍成長が阻害された。RHAMMは、通常の癌幹細胞分画内に含まれる増殖性の亜集団への特異的マーカーになりうると考えられた。

  • Inhibition of insulin-like growth factor-1 receptor enhances eribulin-induced DNA damage in colorectal cancer.

    Yoshihiro Tomoyasu, Ariyama Hiroshi, Yamaguchi Kyoko, Imajima Takashi, Yamaga Satoru, Tsuchihashi Kenji, Isobe Taichi, Kusaba Hitoshi, Akashi Koichi, Baba Eishi

    Cancer Science   113 ( 12 )   4207 - 4218   2022年12月   ISSN:1347-9032

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    記述言語:英語   出版者・発行元:John Wiley & Sons Australia, Ltd  

    クロイソカイメンから発見されたハリコンドリンBの誘導体である微小管標的薬エリブリン(Eri)に対する耐性のメカニズムについて検討した。Eri耐性大腸癌由来SW480細胞におけるインスリン様成長因子-1受容体(IGF-1R)/インスリン受容体(INSR)活性化に対するEri処理の影響を分析した。その結果、Eriへの曝露により、リン酸化されたIGF-1R/INSRとその下流エフェクターにおけるAktの蓄積量が増加し、IGFシグナルが活性化された。Eri処理はIGF-1Rの活性化とそれに続く核移行を誘導したが、IGF-1Rの活性化や核移行を阻害した場合、EriはDNA損傷を誘導し、G2/M停止を促進した。さらに、Eri耐性細胞株であるSW480を用いた異種移植マウスモデルにおいて、EriとIGF-1R阻害剤であるリンシチニブの併用は、いずれの単剤よりも腫瘍増殖を抑制した。以上より、EriとIGF-1R阻害剤の併用はEri耐性を克服することが示唆された。

  • IMPROVE bleeding score predicts major bleeding in advanced gastrointestinal cancer patients with venous thromboembolism 査読 国際誌

    Kusaba, H; Moriyama, S; Hieda, M; Ito, M; Ohmura, H; Isobe, T; Tsuchihashi, K; Fukata, M; Ariyama, H; Baba, E

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   52 ( 10 )   1183 - 1190   2022年10月   ISSN:0368-2811 eISSN:1465-3621

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese journal of clinical oncology  

    BACKGROUND: The incidence of venous thromboembolism has been reported as 20&#37; in cancer patients. Anticoagulation therapy is the standard treatment for venous thromboembolism. On the other hand, bleeding should be carefully managed, because advanced cancer, particularly gastrointestinal cancer, carries a high risk of bleeding. However, the optimal management for cancer-associated thromboembolism remains to be clarified. METHODS: We retrospectively examined patients with advanced gastrointestinal cancer, including gastric cancer and colorectal cancer, who were treated with chemotherapy between 2014 and 2018 for the incidence and characteristics of venous thromboembolism and bleeding. RESULTS: In total, 194 patients (120 men, 74 women) were enrolled in this study. The underlying pathology was gastric cancer in 74 cases and colorectal cancer in 120 cases. Of the 194 patients, 40 patients (20.6&#37;) were diagnosed with venous thromboembolism and 10 patients (5.2&#37;) were diagnosed with concomitant pulmonary thromboembolism. Conversely, bleeding was observed in 29 patients (15&#37;). The location of bleeding was the primary tumor in 17 cases, metastatic tumor in 9 and hemorrhagic gastric ulcer in 3. Within the venous thromboembolism group (n = 40), bleeding was observed in 10 patients (25&#37;). Multivariate analysis showed that International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding score ≥7 correlated significantly with major bleeding (P = 0.01). In patients with a low risk of bleeding, major bleeding was observed in only three patients. CONCLUSIONS: IMPROVE bleeding score may predict the risk for bleeding in gastrointestinal cancer patients with venous thromboembolism. Selecting patients with a low risk of bleeding using with IMPROVE bleeding score is expected to contribute to the safer management of anticoagulation therapy for cancer-associated thromboembolism.

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  • Potential therapeutic targets discovery by transcriptome analysis of an in vitro human gastric signet ring carcinoma model.

    Yamaguchi Kyoko, Yoshihiro Tomoyasu, Ariyama Hiroshi, Ito Mamoru, Nakano Michitaka, Semba Yuichiro, Nogami Jumpei, Tsuchihashi Kenji, Yamauchi Takuji, Ueno Shohei, Isobe Taichi, Shindo Koji, Moriyama Taiki, Ohuchida Kenoki, Nakamura Masafumi, Nagao Yoshihiro, Ikeda Tetsuo, Hashizume Makoto, Konomi Hiroyuki, Torisu Takehiro, Kitazono Takanari, Kanayama Tomohiro, Tomita Hiroyuki, Oda Yoshinao, Kusaba Hitoshi, Maeda Takahiro, Akashi Koichi, Baba Eishi

    Gastric Cancer   25 ( 5 )   862 - 878   2022年9月   ISSN:1436-3291

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    記述言語:英語   出版者・発行元:シュプリンガー・ジャパン(株)  

    E-カドヘリン欠損胃印環細胞癌(SRCC)における新規治療標的を同定することを目的とした。E-カドヘリンをコードするCDH1遺伝子をノックアウト(KO)したヒト胃オルガノイド(hGO)を用いて、in vitroのE-カドヘリン欠損胃癌モデルを作製し、新規治療標的を探索した。CDH1 KO hGO細胞は、SRCCに類似した特徴的な形態変化と高い細胞運動性を示した。RNA配列解析の結果、CDH1 KO hGO細胞では、野生型と比較して、マトリックスメタロプロテアーゼ(MMP)遺伝子の発現が増加していた。MMP阻害剤は、in vitroでCDH1 KO hGO細胞およびSRCC細胞株の細胞運動を抑制した。95例の臨床胃癌組織を用いた免疫蛍光分析により、MMP-3はE-カドヘリン異常のSRCCに特異的に多く存在することが示された。また、CDH1 KO後、CXCR4分子が細胞膜上に移行した。CXCR4のリガンドであるCXCL12を培養液に添加すると、CDH1 KO hGO細胞の細胞生存率が延長し、CXCR4アンタゴニストであるAMD3100によってその効果が消失した。SRCCの臨床サンプルでは、CXCL12を分泌する線維芽細胞が癌領域に著しく浸潤していることを確認した。以上より、MMPとCXCL12/CXCR4軸は、E-カドヘリン欠損SRCCの新規治療標的として有望な候補であると考えられた。

  • Upregulation of BMI1-suppressor miRNAs(miR-200c, miR-203) during terminal differentiation of colon epithelial cells.

    Hisamori Shigeo, Mukohyama Junko, Koul Sanjay, Hayashi Takanori, Rothenberg Michael Evan, Maeda Masao, Isobe Taichi, Valencia Salazar Luis Enrique, Qian Xin, Johnston Darius Michael, Qian Dalong, Lao Kaiqin, Asai Naoya, Kakeji Yoshihiro, Gennarino Vincenzo Alessandro, Sahoo Debashis, Dalerba Piero, Shimono Yohei

    Journal of Gastroenterology   57 ( 6 )   407 - 422   2022年6月   ISSN:0944-1174

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    記述言語:英語   出版者・発行元:シュプリンガー・ジャパン(株)  

    結腸癌組織8例(ヒト6例、マウス2例)から陰窩底部および陰窩頂部の上皮細胞を精製し、335個のmiRNA発現の差異を調べた。最終分化した頂部の上皮細胞で6個のmiRNA(miR-200a、miR-200b、miR-200c、miR-203、miR-210、miR-345)が最も上方制御されていた。ヒト大腸癌におけるこれらのmiRNA発現レベルは相互に正相関していた。相互の相関係数が高いmiRNA(miR-200a、miR-200b、miR-200c)の高発現は生存予後良好と関連した。最も上方制御された二つのmiRNA(miR-200c、miR-203)は、結腸上皮細胞において、幹細胞集団の自己複製の制御因子であるBMI1発現を相乗的に抑制し、増殖、オルガノイド形成および腫瘍形成性を阻害した。以上より、結腸上皮における最終分化ではmiR-200cとmiR-203が協調的に上方制御され、これらのmiRNAは協働してBMI1を抑制することにより上皮細胞の増殖を抑制すると考えられた。

  • Macrophages are primed to transdifferentiate into fibroblasts in malignant ascites and pleural effusions 査読 国際誌

    Ito, M; Nakano, M; Ariyama, H; Yamaguchi, K; Tanaka, R; Semba, Y; Sugio, T; Miyawaki, K; Kikushige, Y; Mizuno, S; Isobe, T; Tanoue, K; Taguchi, R; Ueno, S; Kawano, T; Murata, M; Baba, E; Akashi, K

    CANCER LETTERS   532   215597 - 215597   2022年2月   ISSN:0304-3835 eISSN:1872-7980

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Letters  

    Cancer-associated fibroblasts (CAFs) play an important role in cancer progression. However, the origin of CAFs remains unclear. This study shows that macrophages in malignant ascites and pleural effusions (cavity fluid-associated macrophages: CAMs) transdifferentiate into fibroblast-like cells. CAMs obtained from gastrointestinal cancer patients were sorted by flow cytometry and cultured in vitro. CD45+CD14+ CAMs transdifferentiated into CD45−CD90+ fibroblast-like cells that exhibited spindle shapes. Then, cDNA microarray analysis showed that the CD45−CD90+ fibroblast-like cells (macrophage-derived CAFs: MDCAFs) had a fibroblast-specific gene expression signature and produced growth factors for epithelial cell proliferation. Human colon cancer cells transplanted into immunodeficient mice with MDCAFs formed larger tumors than cancer cells alone. Gene ontology analyses showed the involvement of TGFβ signaling and cell-matrix adhesion in MDCAFs, and transdifferentiation of CAMs into MDCAFs was canceled by inhibiting TGFβ and cell adhesion. Furthermore, the acquired genetic alterations in hematopoietic stem cells (HSCs) were shared in CAMs and MDCAFs. Taken together, CAMs could be a source of CAFs and might originate from HSCs. We propose the transdifferentiation process of CAMs into MDCAFs as a new therapeutic target for fibrosis associated with gastrointestinal cancer.

    DOI: 10.1016/j.canlet.2022.215597

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  • Does the Use of Peripheral Immune-Related Markers Indicate Whether to Administer Pazopanib, Trabectedin, or Eribulin to Advanced Soft Tissue Sarcoma Patients? 国際誌

    Eijiro Shimada, Makoto Endo, Yoshihiro Matsumoto, Kenji Tsuchihashi, Mamoru Ito, Hitoshi Kusaba, Akira Nabeshima, Tomoya Nawata, Akira Maekawa, Tomoya Matsunobu, Nokitaka Setsu, Toshifumi Fujiwara, Keiichiro Iida, Makoto Nakagawa, Takeshi Hirose, Masaya Kanahori, Ryunosuke Oyama, Taichi Isobe, Hiroshi Ariyama, Kenichi Kohashi, Hidetaka Yamamoto, Yoshinao Oda, Yukihide Iwamoto, Koichi Akashi, Eishi Baba, Yasuharu Nakashima

    Journal of clinical medicine   10 ( 21 )   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/jcm10214972

  • Prominent PD-L1-positive M2 macrophage infiltration in gastric cancer with hyper-progression after anti-PD-1 therapy

    Kyoko Yamaguchi, Kenji Tsuchihashi, Kunihiro Tsuji, Yosuke Kito, Kenro Tanoue, Hirofumi Ohmura, Mamoru Ito, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, Eishi Baba

    Medicine   100 ( 19 )   e25773 - e25773   2021年5月

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    記述言語:その他   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/md.0000000000025773

  • Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab 査読

    Tanoue, Kenro, Tamura, Shingo, Kusaba, Hitoshi, Shinohara, Yudai, Ito, Mamoru, Tsuchihashi, Kenji, Shirakawa, Tsuyoshi, Otsuka, Taiga, Ohmura, Hirofumi, Isobe, Taichi, Ariyama, Hiroshi, Koreishi, Sakuya, Matsushita, Yuzo, Shimokawa, Hozumi, Tanaka, Risa, Mitsugi, Kenji, Akashi, Koichi, Baba, Eishi

    Scientific Reports   2021年2月

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    記述言語:その他   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/S41598-021-82448-1

  • Eribulin as a first-line treatment for soft tissue sarcoma patients with contraindications for doxorubicin 査読

    Kenji Tsuchihashi, Hitoshi Kusaba, Tomoyasu Yoshihiro, Toshifumi Fujiwara, Nokitaka Setsu, Makoto Endo, Yoshihiro Matsumoto, Takashi Imajima, Yudai Shinohara, Mamoru Ito, Satoru Yamaga, Kenro Tanoue, Kohei Arimizu, Hirofumi Ohmura, Fumiyasu Hanamura, Kyoko Yamaguchi, Taichi Isobe, Hiroshi Ariyama, Yasuharu Nakashima, Koichi Akashi, Eishi Baba

    Scientific Reports   10 ( 1 )   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-020-77898-y

  • Methylation of drug resistance‐related genes in chemotherapy‐sensitive Epstein–Barr virus‐associated gastric cancer 査読

    Hirofumi Ohmura, Mamoru Ito, Keita Uchino, Chihiro Okada, Shigeki Tanishima, Yuichi Yamada, Seiya Momosaki, Masato Komoda, Miyuki Kuwayama, Kyoko Yamaguchi, Yuta Okumura, Michitaka Nakano, Kenji Tsuchihashi, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba

    FEBS Open Bio   10 ( 1 )   147 - 157   2020年1月

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    記述言語:その他   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/2211-5463.12765

  • Organoid Culture of Human Cancer Stem Cells. 査読

    Shimono Y, Mukohyama J, Isobe T, Johnston DM, Dalerba P, Suzuki A

    Methods in molecular biology (Clifton, N.J.)   2016年9月

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    記述言語:その他  

    Organoid Culture of Human Cancer Stem Cells.

    DOI: 10.1007/7651_2016_13

  • Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy 査読

    Kenta Nio, Shuji Arita, Taichi Isobe, Hitoshi Kusaba, Kenichi Kohashi, Tatsuhiro Kajitani, Shingo Tamura, Gen Hirano, Kenji Mitsugi, Akitaka Makiyama, Taito Esaki, Hiroshi Ariyama, Yoshinao Oda, Koichi Akashi, Eishi Baba

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   75 ( 4 )   829 - 835   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00280-015-2706-y

  • Systemic chemotherapy for metastatic non-mucinous appendiceal adenocarcinoma: a case report and literature review 査読

    Kenji Tsuchihashi, Kotoe Takayoshi, Keita Uchino, Tsuyoshi Shirakawa, Hozumi Kumagai, Shingo Tamura, Masato Komoda, Taichi Isobe, Shigeo Takaishi, Hitoshi Kusaba, Shinichi Aishima, Koichi Akashi, Eishi Baba

    International Cancer Conference Journal   2 ( 1 )   36 - 40   2013年1月

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    記述言語:その他   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s13691-012-0060-z

  • Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells 査読

    Keita Uchino, Gen Hirano, Minako Hirahashi, Taichi Isobe, Tsuyoshi Shirakawa, Hitoshi Kusaba, Eishi Baba, Masazumi Tsuneyoshi, Koichi Akashi

    EXPERIMENTAL CELL RESEARCH   318 ( 15 )   1799 - 1807   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.yexcr.2012.04.011

  • Improvement of quality of life and survival using self-expandable metal stent placement for severe malignant stenosis of the gastric body: A case report 査読

    Hozumi Kumagai, Kenta Nio, Tsuyoshi Shirakawa, Keita Uchino, Hitoshi Kusaba, Taichi Isobe, Masato Komoda, Shingo Tamura, Ryo Maeyama, Eishi Nagai, Koichi Akashi, Eishi Baba

    Journal of Medical Case Reports   6 ( 1 )   315   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1752-1947-6-315

  • Irinotecan-based combination chemotherapy for metastatic small intestinal adenocarcinoma 査読

    Yoshihiro Shibata, Eishi Baba, Hiroshi Ariyama, Shuji Arita, Taichi Isobe, Hitoshi Kusaba, Kenji Mitsugi, Shuji Nakano, Koichi Akashi

    ONCOLOGY LETTERS   1 ( 3 )   423 - 426   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/ol_00000074

  • Schedule-dependent synergistic interaction between gemcitabine and oxaliplatin in human gallbladder adenocarcinoma cell lines 査読

    Akitaka Makiyama, Baoli Qin, Keita Uchino, Yoshihiro Shibata, Shuji Arita, Taichi Isobe, Gen Hirano, Hitoshi Kusaba, Eishi Baba, Koichi Akashi, Shuji Nakano

    ANTI-CANCER DRUGS   20 ( 2 )   123 - 130   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/CAD.0b013e3283218080

  • B cell activation regulates exosomal HLA production 査読

    Shuji Arita, Eishi Baba, Yoshihiro Shibata, Hiroaki Niiro, Shinji Shimoda, Taichi Isobe, Hitoshi Kusaba, Shuji Nakano, Mine Harada

    EUROPEAN JOURNAL OF IMMUNOLOGY   38 ( 5 )   1423 - 1434   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/eji.200737694

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書籍等出版物

  • 新臨床腫瘍学(改訂第7版)

    日本臨床腫瘍学会(担当:編集 範囲:コアメンバー)

    南江堂  2024年4月    ISBN:978-4-524-20426-7

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    記述言語:日本語   著書種別:教科書・概説・概論

講演・口頭発表等

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MISC

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所属学協会

  • 日本内科学会

  • 日本癌学会

  • 日本臨床腫瘍学会

  • American Association for Cancer Research (AACR)

  • American Society of Clinical Oncology (ASCO)

  • International Society for Stem Cell Research (ISSCR)

  • 日本消化器病学会

  • AACR

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  • ASCO

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  • ESMO

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  • 日本内科学会

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  • 日本消化器病学会

      詳細を見る

  • 日本癌学会

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  • 日本癌治療学会

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  • 日本臨床腫瘍学会

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  • 日本遺伝性腫瘍学会

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学術貢献活動

  • 第83回日本癌学会学術総会

    役割:企画立案・運営等

    赤司浩一  2024年9月

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    種別:大会・シンポジウム等 

    researchmap

  • 第20回日本臨床腫瘍学会学術集会

    役割:企画立案・運営等

    馬場 英司  2023年3月

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    種別:大会・シンポジウム等 

    researchmap

  • Scientific Reports 国際学術貢献

    2022年8月 - 2032年8月

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    種別:学会・研究会等 

  • 学術論文等の審査

    役割:査読

    2021年

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    種別:査読等 

    外国語雑誌 査読論文数:2

共同研究・競争的資金等の研究課題

  • クローン性造血を鑑みた老化細胞除去薬による新規消化器がん治療の開発基盤の構築

    研究課題/領域番号:24K11170  2024年 - 2026年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    磯部 大地

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    担当区分:研究代表者  資金種別:科研費

    患者由来腫瘍組織を用い、細胞老化について腫瘍細胞および微小環境中の細胞について解析を行い、治療標的候補を同定する。また腫瘍浸潤白血球に認められるクローン性造血が老化細胞の惹起する炎症にどのように影響するかについて詳らかにする。本研究により得られる知見は、がん治療において新たな治療戦略に繋がる可能性がある。

    CiNii Research

  • クローン性造血で引き起こされるがん微小環境内の免疫応答の解明

    研究課題/領域番号:21K07152  2021年 - 2023年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    磯部 大地, 菊繁 吉謙

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    担当区分:研究代表者  資金種別:科研費

    体細胞遺伝子変異を生じた造血幹細胞がクローン性に増殖し、造血の一部を担うことがあり、これをクローン性造血と呼ぶ。このクローン性造血を合併する固形がん症例は、がんの進展のため予後が悪化する。体細胞遺伝子変異を有する白血球が、がんの進展に有利な状況を生み出していることが原因と想定される。
    本研究では、大腸がん患者の臨床検体を用い、末梢血検体及びがん組織検体に含まれる白血球の各分画の遺伝子変異をそれぞれ解析し、クローン性造血と大腸がん微小環境における免疫応答との関連を詳らかにすることを目的とする。本研究により得られる知見は、クローン性造血の合併を考慮した新たな治療戦略に繋がる可能性がある。

    CiNii Research

  • 染色体異常を起因としたヒト大腸がんの新規疾患モデルの確立

    研究課題/領域番号:19K17831  2019年 - 2020年

    日本学術振興会  科学研究費助成事業  若手研究

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    担当区分:研究代表者  資金種別:科研費

  • 新規疾患モデルを用いた染色体変異による大腸発がんメカニズムの解明

    2019年 - 2020年

    公益財団法人新日本先進医療研究財団 令和元年度(第5回)研究助成金

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    担当区分:研究代表者  資金種別:受託研究

  • 細胞順応による初期転移巣成立機構解析の基盤構築

    研究課題/領域番号:15K14381  2015年 - 2016年

    科学研究費助成事業  挑戦的萌芽研究

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    担当区分:研究分担者  資金種別:科研費

教育活動概要

  • 医学系学府博士課程学生の研究指導
    医学科臨床実習の指導

担当授業科目

  • 個別化医療を推進する臨床腫瘍学コース

    2024年10月 - 現在  

  • 次世代の病理診断学

    2024年4月 - 現在  

  • 希少がんを含む各種がんの治療

    2023年10月 - 2024年3月  

  • 臨床腫瘍学の基本

    2023年4月 - 2023年9月   前期

  • 基盤がん医療

    2021年10月 - 現在   後期

FD参加状況

  • 2022年12月   役割:参加   名称:医学系学府教育FD「医学系大学院プログラムの進化と深化をめざして」

  • 2022年8月   役割:参加   名称:医学部医学科・生命科学科FD「医学教育分野別評価受審の振り返りについて」

  • 2021年12月   役割:参加   名称:医学系学府教育FD「学術論文の購読と投稿とこれから」

その他教育活動及び特記事項

  • 2023年  クラス担任  学部

  • 2022年  クラス担任  学部

海外渡航歴

  • 2012年5月 - 2018年9月

    滞在国名1:アメリカ合衆国   滞在機関名1:Stanford University

  • 2010年4月 - 2010年5月

    滞在国名1:アメリカ合衆国   滞在機関名1:Stanford University

専門診療領域

  • 生物系/医歯薬学/内科系臨床医学/内科学一般(含心身医学)

    腫瘍内科

臨床医資格

  • 総合内科専門医

    日本内科学会

  • 認定内科医

    日本内科学会

  • 指導医

    日本内科学会

  • 認定医

    日本がん治療認定医機構

医師免許取得年

  • 2003年

特筆しておきたい臨床活動

  • 腫瘍内科