2021/11/17 更新

写真a

セノオ マサハル
妹尾 昌治
SENO Masaharu
所属
ヘルスシステム統合科学学域 教授
職名
教授
外部リンク

学位

  • 工学博士 ( 大阪大学 )

研究キーワード

  • 再生医療

  • Biotechnology

  • Molecular Cell Biology

  • DDS

  • Bioinformatics

  • Tissue regeneration

  • がん幹細胞

  • 生物工学

  • 分子細胞生物学

  • ドラッグデリバリーシステム

  • バイオインフォマティクス

  • Cancer Stem Cells

研究分野

  • 情報通信 / 生命、健康、医療情報学

  • ライフサイエンス / 生体医工学

  • ライフサイエンス / 生体材料学

  • ものづくり技術(機械・電気電子・化学工学) / バイオ機能応用、バイオプロセス工学

  • ライフサイエンス / 細胞生物学

所属学協会

  • Japanese Association of Molecular Biology

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  • New York Academy of Science

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  • American Society of Cell Biology

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  • Japanese Cancer Association

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  • 日本分子生物学会

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  • New York Academy of Science

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  • American Society of Cell Biology

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  • 日本再生医療学会

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  • 日本癌学会

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  • 日本バイオインフォマティックス学会

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  • The New York Academy of Sciences ニューヨーク科学アカデミー

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  • American Association of Cancer Research

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  • 米国細胞生物学会(American Association for Cell Biology)

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▼全件表示

委員歴

  • 日本バイオインフォマティックス学会   中国・四国地域部会長  

    2005年   

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    団体区分:学協会

    日本バイオインフォマティックス学会

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論文

  • Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro. 査読

    Ghmkin Hassan, Said M. Afify, Kitano, S, Seno, A, Ishii, H, Shang, Y, Matsusaki, M, Seno, M

    Processes   2021年9月

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  • Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells.

    Abu Quora HA, Zahra MH, El-Ghlban S, Nair N, Afify SM, Hassan G, Nawara HM, Sheta M, Monzur S, Fu X, Osman A, Seno A, Seno M.

    Am J Cancer Res   2021年7月

  • Metformin suppresses self-renewal and stemness of cancer stem cell models derived from pluripotent stem cells.

    Zahra MH, Afify SM, Hassan G, Nawara HM, Kumon K, Seno A, Seno M

    Cell Biochem Funct.   2021年7月

  • Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells. 査読

    Abu Quora HA, Zahra MH, El-Ghlban S, Nair N, Afify SM, Hassan G, Nawara HM, Sheta M, Monzur S, Fu X, Osman A, Seno A, Seno M

    Am J Cancer Res.   2021年7月

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  • Metformin suppresses self-renewal and stemness of cancer stem cell models derived from pluripotent stem cells. 査読

    Zahra MH, Afify SM, Hassan G, Nawara HM, Kumon K, Seno A, Seno M

    Cell Biochem Funct.   2021年7月

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  • Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy.

    Hiroko Ishii, Said M. Afify, Ghmkin Hassan, David S. Salomon, Masaharu Seno

    Cancers (Basel)   2021年5月

  • Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy.

    Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M.

    Biomedicines   2021年5月

  • Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy. 査読

    Hiroko Ishii, Said M. Afify, Ghmkin Hassan, David S. Salomon, Masaharu Seno

    Cancers (Basel)   2021年5月

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  • Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy. 査読

    Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M

    Biomedicines.   2021年5月

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  • How can we turn the PI3K/AKT/mTOR pathway down? Insights into inhibition and treatment of cancer.

    Afify SM, Oo AKK, Hassan G, Seno A, Seno M.

    Expert Rev Anticancer Ther.   2021年4月

  • An assay for cancer stem cell-induced angiogenesis on chick chorioallantoic membrane. 査読

    Nawara HM, Afify SM, Hassan G, Zahra MH, Atallah MN, Seno A, Seno M

    Cell Biol Int.   2021年4月

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  • How can we turn the PI3K/AKT/mTOR pathway down? Insights into inhibition and treatment of cancer. 査読

    Afify SM, Oo AKK, Hassan G, Seno A, Seno M

    Expert Rev Anticancer Ther.   2021年4月

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  • Cancer Stem Cell Initiation by Tumor-Derived Extracellular Vesicles.

    Afify SM, Hassan G, Yan T, Seno A, Seno M

    Methods Mol Biol   2021年3月

  • Cancer Stem Cell Initiation by Tumor-Derived Extracellular Vesicles. 査読

    Afify SM, Hassan G, Yan T, Seno A, Seno M

    Methods Mol Biol.   2021年3月

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  • Isolation and characterization of cancer stem cells derived from human glioblastoma

    Hiroko Ishii1, Yuki Mimura, Maram H. Zahra, Shota Katayama, Ghmkin Hassan, Said M. Affify, Masaharu Seno

    Am J Cancer Res   2021年2月

  • A Novel Artificially Humanized AntiCripto-1 Antibody Suppressing Cancer Cell Growth.

    Ishii, H.; Zahra, M.H.; Takayanagi, A.; Seno, M.

    Int. J. Mol. Sci.   2021年2月

  • A Novel Artificially Humanized AntiCripto-1 Antibody Suppressing Cancer Cell Growth. 査読

    Ishii, H, Zahra, M.H, Takayanagi, A, Seno, M

    Int. J. Mol. Sci.   2021年2月

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  • Isolation and characterization of cancer stem cells derived from human glioblastoma, 査読

    Hiroko Ishii, Yuki Mimura, Maram H. Zahra, Shota Katayama, Ghmkin Hassan, Said M. Affify, Masaharu Seno

    Am J Cancer Res 2021   2021年2月

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  • Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro.

    Ghmkin Hassan, Said M. Afify. Kitano, S.; Seno, A.; Ishii, H.; Shang, Y.; Matsusaki, M.; Seno, M

    Processes 2021   2020年12月

  • An assay for cancer stem cell-induced angiogenesis on chick chorioallantoic membrane.

    Nawara HM, Afify SM, Hassan G, Zahra MH, Atallah MN, Seno A, Seno M

    Cell Biol Int   2020年12月

  • Tumor-associated macrophages derived from cancer stem cells.

    Osman A, Oze M, Afify SM, Hassan G, El-Ghlban S, Nawara HM, Fu X, Zahra MH, Seno A, Winer I, Salomon DS, Seno M.

    Acta Histochem   2020年9月

  • Tumor-associated macrophages derived from cancer stem cells. 査読

    Osman A, Oze M, Afify SM, Hassan G, El-Ghlban S, Nawara HM, Fu X, Zahra MH, Seno A, Winer I, Salomon DS, Seno M

    Acta Histochem.   2020年9月

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  • Metastasis Model of Cancer Stem Cell-Derived Tumors.

    Mansour H, Hassan G, Afify SM, Yan T, Seno A, Seno M

    Methods Protoc.   2020年8月

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    記述言語:英語  

  • Metastasis Model of Cancer Stem Cell-Derived Tumors. 査読

    Mansour H, Hassan G, Afify SM, Yan T, Seno A, Seno M

    Methods Protoc.   2020年8月

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  • Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in the Tumor Microenvironment 査読

    Du, J, Xu, Y, Sasada,, S. Oo, AKK, Hassan, G, Hafizah Mahmud, Apriliana Cahya Khayrani, Md Jahangir Alam, Kazuki Kumon, Ryo Uesaki, Said M. Afify, Hager M. Mansour, Neha Nair, Maram H. Zahra, Akimasa Seno, Nobuhiro Okada, Ling Chen, Ting Yan, Masaharu Seno

    Scientific Reports   2020年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Paclitaxel and Sorafenib: the effective combination of suppressing the self-renewal of cancer stem cells. 査読 国際誌

    Nawara HM, Afify SM, Hassan G, Zahra MZ, Atallah MN, Mansour H, Abu Quora HA, Alam MJ, Osman A, Kakuta H, Hamada H, Seno A, Seno M

    Cancers   12 ( 6 )   2020年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/cancers12061360

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  • Blood and cancer: Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments. 査読

    Hassan G, Seno M

    Cells   2020年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Cancer stem cell generation by silenced MAPK enhancing PI3K/AKT signaling. 査読

    Hassan G, Du J, Afify SM, Seno A, Seno M

    Medical Hypotheses   2020年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs. 査読

    Osman A, Afify SM, Hassan G, Fu X, Seno A, Seno M

    Cancers (Basel)   2020年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A novel model of liver cancer stem cells developed from induced pluripotent stem cells. 査読

    Afify SM, Sanchez Calle A, Hassan G, Kumon K, Nawara HM, Zahra MH, Mansour HM, Khayrani AC, Alam MJ, Du J, Seno A, Iwasaki Y, Seno M

    British Journal of Cancer   2020年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Upregulated Ccl20 and Ccr6 in cancer stem cells converted from mouse iPS cells. 査読

    Du J, Seno A, Sasada S, Xu Y, Oo AKK, Hassan G, Ueno S, Afify SM, Zahra MH, Okada N, Chen L, Fu X, Tokutaka H, Yan T, SenoM

    Journal of Research in Medical and Dental Science   2020年1月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells. 査読 国際誌

    Hassan G, Afify SM, Nair N, Kumon K, Osman A, Du J, Mansour H, Abu Quora HA, Nawara HM, Satoh A, Zahra MH, Okada N, Seno A, Seno M

    Cancers (Basel)   12 ( 1 )   2019年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/cancers12010082

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  • Cancer Stem Cell Induction from mouse Embryonic Stem Cell. 査読 国際誌

    Seno A, Murakami C, El-Aarag B, Iwasaki Y, Ohara T, Seno M.

    Oncology Letters   18 ( 3 )   2756 - 2762   2019年9月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/ol.2019.10614

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  • Metastasis of Cancer Stem Cells Developed in the Microenvironment of Hepatocellular Carcinoma. 査読 国際誌

    Afify SM, Hassan G, Osman A, Calle AS, Nawara HM, Zahra MH, El-Ghlban S, Mansour H, Alam MJ, Abu Quora HA, Du J, Seno A, Iwasaki Y, Seno M

    Bioengineering (Basel)   6 ( 3 )   2019年8月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/bioengineering6030073

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  • Method to Convert Stem Cells into Cancer Stem Cells. 査読

    Afify SM, Chen L, Yan T, Calle AS, Nair N, Murakami C, Zahra MH, Okada N, Iwasaki Y, Seno A, Seno M

    Methods and protocols   2019年8月

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  • Daunorubicin can eliminate iPS-derived cancer stem cells via ICAD/CAD-independent DNA fragmentation. 査読

    Akimasa Seno, Akifumi Mizutani, Kazuki Aizawa, Ryoma Onoue, Junko Masuda, Naotaka Ochi, Saki Taniguchi, Tatsuyuki Sota, Yuki Hiramoto, Taisuke Michiue, Neha Nair, Masaharu Seno

    Cancer Drug Resistance   2   335 - 350   2019年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.20517/cdr.2019.01

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  • Conversion of Stem Cells to Cancer Stem Cells: Undercurrent of Cancer Initiation. 査読 国際誌

    Afify SM, Seno M.

    Cancers (Basel).   11 ( 3 )   pii:E345   2019年3月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/cancers11030345

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  • Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel. 査読 国際誌

    Khayrani AC, Mahmud H, Oo AKK, Zahra MH, Oze M, Du J, Alam MJ, Afify SM, Quora HAA, Shigehiro T, Calle AS, Okada N, Seno A, Fujita K, Hamada H, Seno Y, Mandai T, Seno M.

    International Journal of Molecular Sciences   20 ( 5 )   pii:E1042   2019年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms20051042

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  • A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness. 査読 国際誌

    Katsura Y, Ohara T, Noma K, Ninomiya T, Kashima H, Kato T, Sato H, Komoto S, Narusaka T, Tomono Y, Xing B, Chen Y, Tazawa H, Kagawa S, Shirakawa Y, Kasai T, Seno M, Matsukawa A, Fujiwara T.

    Cancers (Basel).   11 ( 2 )   pii:E177   2019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: 10.3390/cancers11020177

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  • Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells. 査読 国際誌

    Kunoh T, Shimura T, Kasai T, Matsumoto S, Mahmud H, Khayrani AC, Seno M, Kunoh H, Takada J.

    Nanotechnology.   30 ( 5 )   055101 - 055101   2019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: 10.1088/1361-6528/aaedd5

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  • Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model. 査読 国際誌

    International Journal of Molecular Sciences   19 ( 11 )   2018年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms19113345

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  • Five Fibrosis Biomarkers Together with Serum Ferritin Level to Diagnose Liver Fibrosis and Cirrhosis 査読 国際誌

    Clinical Laboratory   64 ( 10 )   1685 - 1693   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)  

    DOI: 10.7754/Clin.Lab.2018.180502

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  • HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. 査読 国際誌

    Ono K, Eguchi T, Sogawa C, Calderwood SK, Futagawa J, Kasai T, Seno M, Okamoto K, Sasaki A, Kozaki KI

    Journal of Cellular Biochemistry   119 ( 9 )   7350 - 7362   2018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: 10.1002/jcb.27039

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  • Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment. 査読 国際誌

    Oo AKK, Calle AS, Nair N, Mahmud H, Vaidyanath A, Yamauchi J, Khayrani AC, Du J, Alam MJ, Seno A, Mizutani A, Murakami H, Iwasaki Y, Chen L, Kasai T, Seno M

    Translational Oncology   11 ( 3 )   653 - 663   2018年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.tranon.2018.03.001

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  • Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide. 査読 国際誌

    Masuda J, Shigehiro T, Matsumoto T, Satoh A, Mizutani A, Umemura C, Saito S, Kijihira M, Takayama E, Seno A, Murakami H, Seno M

    International Journal of Molecular Sciences   19 ( 4 )   2018年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms19041261

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  • Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. 査読 国際誌

    Mahmud H, Kasai T, Khayrani AC, Asakura M, Oo AKK, Du J, Vaidyanath A, El-Ghlban S, Mizutani A, Seno A, Murakami H, Masuda J, Seno M

    International Journal of Molecular Sciences   19 ( 3 )   2018年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms19030659

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  • 異なる転移能を有する口腔扁平上皮癌細胞由来エクソソームに含まれるプロテオームの特性

    小野 喜章, 江口 傑徳, 十川 千春, 村上 純, 藤原 敏史, 笠井 智成, 妹尾 昌治, 佐々木 朗, 小崎 健一, 岡元 邦彰

    生命科学系学会合同年次大会   2017年度   [1LBA - 052]   2017年12月

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    記述言語:日本語   出版者・発行元:生命科学系学会合同年次大会運営事務局  

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  • Iron depletion is a novel therapeutic strategy to target cancer stem cells 査読 国際誌

    Takayuki Ninomiya*,Toshiaki Ohara*,Kazuhiro Noma*,Yuki Katsura,Ryoichi Katsube,Hajime Kashima,Takuya Kato,Yasuko Tomono,Hiroshi Tazawa*,Shunsuke Kagawa*,Yasuhiro Shirakawa*,Fumiaki Kimura,Ling Chen,Tomonari Kasai*,Masaharu Seno*,Akihiro Matsukawa*,Toshiyoshi Fujiwara*

    Oncotarget   8 ( 58 )   98405 - 98416   2017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: 10.18632/oncotarget.21846

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  • Practical liposomal formulation for taxanes with polyethoxylated castor oil and ethanol with complete encapsulation efficiency and high loading efficiency 査読 国際誌

    Tsukasa Shigehiro, Junko Masuda, Shoki Saito, Apriliana, C. Khayrani, Kazumasa Jinno, Akimasa Seno, Arun Vaidyanath, Akifumi Mizutani, Tomonari Kasai, Hiroshi Murakami, Ayano Satoh, Tetsuya Ito, Hiroki Hamada, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno

    Nanomaterials   7 ( 10 )   1391 - 1398   2017年9月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/nano7100290

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  • 舌癌細胞株由来エクソソーム解析による頸部リンパ節転移マーカーの探索

    小野 喜章, 江口 傑徳, 十川 千春, 村上 純, 笠井 智成, 妹尾 昌治, 佐々木 朗, 小崎 健一

    日本癌学会総会記事   76回   J - 1062   2017年9月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • Synthesis and assembly of Hepatitis B virus envelope protein-derived particles in Escherichia coli 査読 国際誌

    Hao Li, Keisuke Onbe, Qiushi Liu, Masumi Iijima, Kenji Tatematsu, Masaharu Seno, Hiroko Tada, Shun’ ichi Kuroda

    Biochemical and Biophysical Research Communications   490 ( 2 )   155 - 160   2017年8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.bbrc.2017.06.015

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  • A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment 査読 国際誌

    Neha Nair,Anna Sanchez Calle,Maram, Hussein Zahra,Marta Prieto-Vila,Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno

    Scientific Reports   7 ( 1 )   6838 - 6838   2017年7月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-017-07144-5

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  • Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities 査読 国際誌

    Junko Masuda, Eiji Takayama, Warren Strober, Ayano Satoh, Yuji Morimoto, Yasuko Honjo, Tatsuo Ichinohe, Shin Ichi Tokuno, Toshiaki Ishizuka, Takahiro Nakata, Akifumi Mizutani, Naoki Umemura, Atsushi Kitani, Ivan J. Fuss, Tsukasa Shigehiro, Harumi Kawaki, Masako Mizuno-Kamiya, Nobuo Kondoh, Masaharu Seno

    Oncology Reports   38 ( 1 )   449 - 455   2017年7月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/or.2017.5646

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  • A Novel Model of Meibomian Gland Dysfunction Induced with Complete Freund's Adjuvant in Rabbits. 査読 国際誌

    Hideki Miyake, Tomoko Oda, Osamu Katsuta, Masaharu Seno, Masatsugu Nakamura

    Vision (Basel, Switzerland)   1 ( 1 )   2017年2月

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    記述言語:英語  

    A novel meibomian gland dysfunction (MGD) model induced by the injection of complete Freund's adjuvant (CFA) in rabbits was developed to facilitate the understanding of the pathophysiology of MGD with meibomitis. In addition, we sought to evaluate treatment with steroid eye drops in this model. Male Japanese white rabbits were subcutaneously injected with CFA into the upper eyelid margin. The eyelid margins of the rabbits were chronologically observed through slit lamp examination. The development of meibomitis was assessed through histopathology. We evaluated the effects of topically applied tobramycin/dexamethasone (Tob/Dex) eye drops on the plugged orifices and telangiectasia. After the injection of CFA, slit lamp examination revealed markedly plugged orifices, telangiectasia around the orifices and a toothpaste-like meibum, as compared with the normal eyelids. Histopathology revealed granulation tissue with infiltration of inflammatory cells, hyperkeratinization of the ductal epithelium, and cystic dilatation of ducts in the meibomian gland. The orifices were plugged with a proteinaceous substance. Tob/Dex eye drops significantly suppressed the plugging and telangiectasia around the orifices. Through the injection of CFA, we successfully established a novel rabbit MGD that mimics the symptoms observed in humans meibomitis. This model should be useful in the evaluation of the efficacy of drug candidates.

    DOI: 10.3390/vision1010010

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  • Hyaluronic Acid Mediated Enrichment of CD44 Expressing Glioblastoma Stem Cells in U251MG Xenograft Mouse Model. 査読

    Vaidyanath A, Mahmud HB, Khayrani AC, Oo AK, Seno A, Asakura A, Kasai T, Seno M

    Journal of Stem Cell Research and Therapy   2017年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4172/2157-7633.1000384

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  • 腫瘍を標的とした抗体提示リポソームの開発と製剤化 査読

    妹尾昌治, 重廣司

    DDS先端技術の製剤への応用開発   249 - 262   2017年

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    担当区分:筆頭著者  

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  • Immunoliposomes: Recent Progress of Liposomal Drug Delivery System Coupled with Antibodies. in “Liposomes: Historical, Clinical and Molecular Perspectives 査読

    Shigehiro T, Seno, M

    Liposomes Historical,Clinical and Molecular Perspectives   189 - 209   2017年

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    担当区分:責任著者  

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  • Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting 査読

    Masuda J, Kawamoto H, Strober W, Takayama E, Mizutani A, Murakami H, Ikawa T, Kitani A, Maeno N, Shigehiro T, Satoh A, Seno A, Arun V, Kasai T, Fuss IJ, Katsura Y, Seno M.

    Appl Biochem Biotechnol.   180 ( 8 )   1559 - 1573   2016年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12010-016-2187-4

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  • Meibomian gland dysfunction model in hairless mice bred under special diet limiting lipid content

    Hideki Miyake, Tomoko Oda, Osamu Katsuta, Masaharu Seno, Masatsugu Nakamura

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   57 ( 12 )   2016年9月

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    記述言語:英語   出版者・発行元:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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  • Characterization of Gene Expression Patterns among Artificially Developed Cancer Stem Cells Using Spherical Self-Organizing Map. 査読

    Seno A, Kasai T, Ikeda M, Vaidyanath A, Masuda J, Mizutani A, Murakami H, Ishikawa T, Seno M.

    Cancer Inform.   15   163 - 178   2016年8月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4137/CIN.S39839

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  • Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells 査読

    Neha Nair, Arun Vaidyanath, Kenta Hoshikawa, Anna Sanchez Calle, Tomonari Kasai, Masaharu Seno

    CANCER RESEARCH   76   2016年7月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-LB-278

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  • The significance of c-Kit protooncogene in iCSC-derived PDAC model 査読

    Anna Sanchez Calle, Kenta Hoshikawa, Neha Nair, Marta Prieto-Vila, Arun Vaidyanath, Tomonari Kasai, Masaharu Seno

    CANCER RESEARCH   76   2016年7月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-1725

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  • Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

    Miyake H, Oda T, Katsuta O, Seno M, Nakamura M

    Invest Ophthalmol Vis Sci.   57 ( 7 )   3268 - 3275   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1167/iovs.16-19227

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  • Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses 査読

    Masashi Okada,Zhen Wu Mei,Md Imran Hossain,Li Wang,Taihei Tominaga,Takeshi Takebayashi,Masaharu Murakami,Mizuki Yasuda,Tsukasa Shigehiro,Tomonari Kasai*,Akifumi Mizutani*,Hiroshi Murakami*,Ibrahim El Tantawy El Sayed ,Shingo Dan,Takao Yamori,Masaharu Seno

    Medicinal Chemistry Research   25 ( 5 )   879 - 892   2016年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00044-016-1508-z

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  • Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient. 査読

    Shigehiro T, Zhai W, Vaidyanath A, Masuda J, Mizutani A, Kasai T, Murakami H, Hamada H, Salomon DS, Mikuni K, Seno Y, Mandai T, Seno M

    J Microencapsul   33 ( 2 )   172 - 182   2016年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3109/02652048.2016.1144815

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  • Release of siRNA from Liposomes Induced by Curcumin

    Kazuyo Fujita,Yoshie Hiramatsu ,Hideki Minematsu,Masaharu Somiya,Shun'ichi Kuroda,Masaharu Seno*,Shuji Hinuma

    Journal of Nanotechnology   2016   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2016/7051523

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  • A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm). 査読

    Calle AS, Nair N, Oo AK, Prieto-Vila M, Koga M, Khayrani AC, Hussein M, Hurley L, Vaidyanath A, Seno A, Iwasaki Y, Calle M, Kasai T, Seno M.

    American Journal of Cancer Research   6 ( 12 )   2799 - 2815   2016年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • iPSC-derived cancer stem cells provide a model of tumor vasculature 査読

    Marta Prieto-Vila,Ting Yan,Anna Sanchez Calle,Neha Nair,Laura Hurley,Tomonari Kasai,Hiroki Kakuta,Junko Masuda,Hiroshi Murakami,Akifumi Mizutani,Masaharu Seno

    American Journal of Cancer Research   6 ( 9 )   1906 - 1921   2016年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis. 査読

    Sugii Y, Kasai T, Ikeda M, Vaidyanath A, Kumon K, Mizutani A, Seno A, Tokutaka H, Kudoh T, Seno M

    Biomark Cancer   8   17 - 23   2016年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4137/BIC.S33542

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  • Synthesis, Biological Evaluation, Docking and QSAR Studies of Some Novel Naphthalimide Dithiocarbamate Analogs as Antitumor and Anti-Inflammatory Agents. 査読

    Zahra MH, Osman AMA, Agwa H, Nair N, Calle AS, Hurley L, Farag D, Kasai T, Seno M, Zahran M

    Medicinal Chemistry (Los Angeles)   6 ( 12 )   694 - 703   2016年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 第3節 iPS細胞を用いたがん幹細胞モデル作成のポイントとその評価, 「次世代のがん治療薬・診断のための研究開発~免疫療法・遺伝子治療・がん幹細胞~、第13章 がん幹細胞を標的とした治療薬研究」

    技術情報協会   348 - 353   2016年

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  • 球面自己組織化マップを用いたキナーゼパネルアセイデータのクラスタリング 査読

    工藤孝幸, 妹尾昌治

    CCISJ Bulletin   34 ( 1 )   2 - 5   2016年

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    担当区分:責任著者  

    DOI: 10.11546/cicsj.34.2

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  • がんモデル動物を用いた悪性度の違いによる全身免疫能変化の解析

    増田 潤子, 高山 英次, 佐藤 あやの, 守本 祐司, 本庶 仁子, 石塚 俊晶, 徳野 慎一, 青笹 季文, 光吉 俊二, 重廣 司, 前野 成実, 村上 宏, 笠井 智成, 水谷 昭文, Vaidyanath Arun, 妹尾 彬正, 川木 晴美, 神谷 真子[水野], 近藤 信夫, 一瀬 雅夫, 一戸 辰夫, 妹尾 昌治

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [1P1079] - [1P1079]   2015年12月

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    担当区分:責任著者   記述言語:日本語   出版者・発行元:(公社)日本生化学会  

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  • 鉄コントロールによる新規がん幹細胞治療 査読

    二宮 卓之, 大原 利章, 勝部 亮一, 賀島 肇, 加藤 卓也, 野間 和広, 田澤 大, 香川 俊輔, 水谷 昭文, 笠井 智成, 妹尾 昌治, 藤原 俊義

    日本癌学会総会記事   74回   IS4 - 6   2015年10月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Dextran sodium sulfate-induced colitis in dendritic cell deletion mice 査読

    Junko Masuda, Atsuhi Kitani, Ivan Fuss, Masaharu Seno, Warren Strober

    CANCER RESEARCH   75   2015年8月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-4296

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  • Derivation of a model of cancer stem cell from human induced pluripotent stem cells 査読

    Tomonari Kasai, Kenta Hoshikawa, Shuto Takejiri, Masashi Ikeda, Kazuki Kumon, Anna Sanchez Calle, Arun Vaidyanath, Akifumi Mizutani, Chen Ling, Masaharu Seno

    CANCER RESEARCH   75   2015年8月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-LB-144

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  • Iron control is a novel therapeutic target of cancer stem cells

    Takayuki Ninomiya, Toshiaki Ohara, Hajime Kashima, Ryoichi Katsube, Kazuhiro Noma, Yasuko Tomono, Akifumi Mizutani, Tomonari Kasai, Masaharu Seno, Shinji Kuroda, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuhiro Shirakawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

    CANCER RESEARCH   75   2015年8月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-4243

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  • Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress.

    Ishii H, Kamikawa S, Hirohata S, Mizutani A, Abe K, Seno M, Oohashi T, Ninomiya Y

    Acta Med Okayama   69 ( 3 )   145 - 153   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18926/AMO/53521

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  • Insight into Cancer Stem Cell Niche; Lessons from Cancer Stem Cell Models Generated In Vitro.

    Biology in Stem Cell Niche, Part of the series Stem Cell Biology and Regenerative Medicine   211 - 226   2015年

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  • Spherical Self-Organizing Map Detects MYBL 1 As Candidate Gene for Triple-Negative Breast Cancer. 査読

    Ikeda M, Kumon K, Omoto K, Sugii Y, Mizutani A, Vaidyanath A, Kudoh T, Kasai T, Masuda S, Seno M

    Neurosci Biomed Eng   3 ( 2 )   94 - 101   2015年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Bacteria: Prospective Savior in Battle against Cancer 査読

    Neha Nair, Tomonari Kasai, Masaharu Seno

    ANTICANCER RESEARCH   34 ( 11 )   6289 - 6296   2014年11月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Conventional anticancer therapies such as chemotherapy are losing their sheen in the battle against cancer. Therefore, strategies for treatment of cancer need to be constantly modified to fulfill the growing demands of alternative therapies. Several viral and non-viral vectors have been exploited for anticancer gene therapy. But over the years bacteria have been proven to be an important candidate for successful evasion of cancer. They serve as invaluable source of tumor-specific anticancer genes, toxins, polysaccharides for synthesis of nanodrugs and gene-delivery vectors. The current review assesses the role of important bacterial groups in different spheres of anti-cancer research.

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche 査読

    Akifumi Mizutani, Shuichi Matsuda, Ting Yan, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Tomonari Kasai, Junko Masuda, Takyuki Kudoh, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-3026

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  • Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived exosomes/microvesicles 査読

    Yan Ting, Junko Masuda, Akifumi Mizutani, Ling Chen, Tsukasa Shigehiro, Shuichi Matsuda, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Mary J. C. Hendrix, Luigi Strizzi, David S. Salomon, Li Fu, Masaharu Seno

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-3016

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  • Anti-cancer activity of immunoliposomes encapsulated effective amount of glycosylated paclitaxel with novel loading strategy 査読

    Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    担当区分:責任著者   記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-4461

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  • Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation. 査読

    Shigehiro T, Kasai T, Murakami M, Sekhar SC, Tominaga Y, Okada M, Kudoh T, Mizutani A, Murakami H, Salomon DS, Mikuni K, Mandai T, Hamada H, Seno M.

    PLoS One   9 ( 9 )   e107976   2014年9月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0107976

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  • 鉄コントロールによるがん幹細胞の新規治療法(Iron control is a potent novel therapeutic for cancer stem cells) 査読

    二宮 卓之, 大原 利章, 浦野 真一, 勝部 亮一, 野間 和広, 田澤 大, 香川 俊輔, 水谷 昭文, 笠井 智成, 妹尾 昌治, 藤原 俊義

    日本癌学会総会記事   73回   P - 1187   2014年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs. 査読

    Int Immunopharmacol   21 ( 2 )   283 - 292   2014年8月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.intimp2014.05.007

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche. 査読

    Matsuda S, Yan T, Mizutani A, Sota T, Hiramoto Y, Prieto-Vila M, Chen L, Satoh A, Kudoh T, Kasai T, Murakami H, Fu L, Salomon DS, Seno M.

    Int J Cancer   135 ( 1 )   27 - 36   2014年7月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A Cancer Stem Cell Model: An Insight into the Conversion of Induced Pluripotent Stem Cells to Cancer Stem-Like Cells 査読

    Akifumi Mizutani, Ling Chen, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Li Fu, Masaharu Seno

    Cancer Stem Cells   79 - 87   2014年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Wiley Blackwell  

    Appropriate model cell lines recapitulating cancer stem cell (CSC) properties would accelerate not only investigation of cancer stem cells but also development of new clinical cancer therapy by establishing a screening system for anti-cancer stem cell agents. In this chapter, the authors introduce their recent work and others to generate cells with cancer stem cell properties in vitro. They also discuss the concept of cancer stem cells with results obtained from originally established cancer stem-like cells. Finally, they describe future applications of the model to basic and clinical studies. In the field of regeneration therapy, the pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising sources of differentiated cells for transplantation. Interestingly, these cancer stem-like cells were not required to be introduced with the genes for cell surface markers that are commonly used to characterize and isolate cancer stem cells.

    DOI: 10.1002/9781118356203.ch6

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  • The new proposal of the calculation for the significance degree by once SOM learning - Using iris, gene, and Tof-SIMS data 査読

    M. Oyabu, H. Tokutaka, M. Ohkita, M. Seno, M. Ohki

    2014 Joint 7th International Conference on Soft Computing and Intelligent Systems, SCIS 2014 and 15th International Symposium on Advanced Intelligent Systems, ISIS 2014   1114 - 1119   2014年2月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:Institute of Electrical and Electronics Engineers Inc.  

    The significance degree of each component was calculated only by once SOM learning where the Spherical Self-Organizing-Map (SSOM) was used for the demonstration. The method can also be used by the usual planar SOM. In the method, kinds of specimens of the data are inserted in each column as each specimen. The method is first demonstrated using the iris data.

    DOI: 10.1109/SCIS-ISIS.2014.7044648

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  • Development of 111In-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging.

    Ogawa M, Umeda IO, Kosugi M, Kawai A, Hamaya Y, Takashima M, Yin H, Kudoh T, Seno M, Magata Y.

    J Nucl Med.   55 ( 1 )   115 - 120   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2967/jnumed.113.123158

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  • Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles. 査読

    Yan T, Mizutani A, Chen L, Takaki M, Hiramoto Y, Matsuda S, Shigehiro T, Kasai T, Kudoh T, Murakami H, Masuda J, Hendrix MJ, Strizzi L, Salomon DS, Fu L, Seno M.

    J Cancer   5 ( 7 )   572 - 584   2014年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.7150/jca.8865

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  • Cancer stem cells converted from pluripotent stem cells and the cancerous niche. 査読

    Kasai T, Chen L, Mizutani A, Kudoh T, Murakami H, Fu L, Seno M

    Journal of Stem cells & regenerative medicine   10 ( 1 )   2 - 7   2014年

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  • Mouse induced pluripotent stem cell microenvironment generates epithelial-mesenchymal transition in mouse Lewis lung cancer cells. 査読

    Chen L, Mizutani A, Kasai T, Yan T, Jin G, Vaidyanath A, El-Aarag BY, Liu Y, Kudoh T, Salomon DS, Fu L, Seno M.

    Am J Cancer Res.   4 ( 1 )   80 - U92   2014年

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells.

    El-Aarag BY, Kasai T, Zahran MA, Zakhary NI, Shigehiro T, Sekhar SC, Agwa HS, Mizutani A, Murakami H, Kakuta H, Seno M.

    Biomed Res Int.   152659   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1155/2014/152659

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  • Mutual dependence between cancer stem cells and their progenies: the niche created by the progenies is sustaining cancer stem cells.

    Cancer Cell & Microenvironment   1 ( 4 )   141 - 144   2014年

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  • Cytokine expression in human dermal fibroblasts stimulated with eosinophil cationic protein measured by protein array.

    Sato T, Soga Y, Yamaguchi T, Meguro M, Maeda H, Tada J, Otani T, Seno M, Takashiba S.

    Asian Pac J Allergy Immunol   31 ( 4 )   271 - 276   2013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: 10.12932/AP0287.31.4.2013

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  • High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor.

    Auf G, Jabouille A, Delugin M, Guérit S, Pineau R, North S, Platonova N, Maitre M, Favereaux A, Vajkoczy P, Seno M, Bikfalvi A, Minchenko D, Minchenko O, Moenner M

    BMC Cancer.   13   13 - 597   2013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: 10.1186/1471-2407-13-597

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  • Development of an Epidermal Growth Factor Derivative with EGFR Blocking Activity 査読

    Clara Panosa, Francesc Tebar, Montserrat Ferrer-Batalle, Humphrey Fonge, Masaharu Seno, Raymond M. Reilly, Anna Massaguer, Rafael De Llorens

    PLOS ONE   8 ( 7 )   2013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)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    The members of the epidermal growth factor (EGF)/ErbB family are prime targets for cancer therapy. However, the therapeutic efficiency of the existing anti-ErbB agents is limited. Thus, identifying new molecules that inactivate the ErbB receptors through novel strategies is an important goal on cancer research. In this study we have developed a shorter form of human EGF (EGFt) with a truncated C-terminal as a novel EGFR inhibitor. EGFt was designed based on the superimposition of the three-dimensional structures of EGF and the Potato Carboxypeptidase Inhibitor (PCI), an EGFR blocker previously described by our group. The peptide was produced in E. coli with a high yield of the correctly folded peptide. EGFt showed specificity and high affinity for EGFR but induced poor EGFR homodimerization and phosphorylation. Interestingly, EGFt promoted EGFR internalization and translocation to the cell nucleus although it did not stimulate the cell growth. In addition, EGFt competed with EGFR native ligands, inhibiting the proliferation of cancer cells. These data indicate that EGFt may be a potential EGFR blocker for cancer therapy. In addition, the lack of EGFR-mediated growth-stimulatory activity makes EGFt an excellent delivery agent to target toxins to tumours over-expressing EGFR.

    DOI: 10.1371/journal.pone.0069325

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  • Nano-micrometer-architectural acidic silica prepared from iron oxide of Leptothrix ochracea origin. 査読

    Hashimoto H, Itadani A, Kudoh T, Fukui S, Kuroda Y, Seno M, Kusano Y, Ikeda Y, Benino Y, Nanba T, Nakanishi M, Fujii T, Takada J.

    ACS Appl Mater Interfaces   12 ( 5 )   518 - 523   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • A novel remote loading method with solubility gradient to encapsulate effevtive amount of taxanes into liposomes.

    Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

    CANCER RESEARCH   73 ( 8 )   2013年4月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2013-LB-8

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  • マウスiPS細胞から作るがん幹細胞モデル

    笠井智成, 陳 凌, 工藤孝幸, 水谷昭文, 妹尾昌治

    細胞工学   32 ( 3 )   330 - 337   2013年

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  • Chemo-enzymatic Synthesis of Propionyl-ester-linked Taxol-monosaccharide Conjugate and its Drug Delivery System Using Hybrid-Bio-nanocapsules Targeting Brain Glioma Cells. 国際誌

    Hiroki Hamada, Kei Shimoda, Masaharu Seno

    Clinical medicine insights. Women's health   6   71 - 5   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Taxol is recognized as one of the most potent anticancer agents used in the treatment of breast and ovarian cancers, which are common cancers in women. To overcome its shortcomings, that is, its low water-solubility that reduces drug loading capacity of DDS carriers when incorporating taxol, chemo-enzymatic synthesis of ester-linked taxol-glucose conjugate, i.e., 7-propionyltaxol 2″-O-α-D-glucoside, as a water soluble taxol prodrug was achieved by using a-glucosidase as a glucosylation catalyst. The water-solubility of 7-propionyltaxol 2″-O-α-D-glucoside (25 mM) was 63 fold higher than that of taxol (0.4 mM). The pre-S1 peptide which displays on the surface of bio-nanocapsules, which are nanoparticles composed of the hepatitis B virus surface antigen, was replaced with the antibody affinity motif of protein A. Conjugation of such bio-nanocapsules with anti-human epidermal growth factor receptor antibody gave hybrid bio-nanocapsules. The hybrid bio-nanocapsules were effective for delivering 7-propionyltaxol 2″-O-α-D-glucoside to human brain glioma cells. 7-Propionyltaxol 2″-O-α-D-glucoside was effectively hydrolyzed to give taxol in 95% by human glioma cells. The drug loading capacity of hybrid bio-nanocapsules incorporating 7-propionyltaxol 2″-O-α-D-glucoside was 120 times higher than that incorporating taxol itself.

    DOI: 10.4137/CMWH.S8213

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  • Development and characterization of cancer stem cell model from mouse iPS cells

    Ling Chen, Shuichi Matsuda, Tomonari Kasai, Yuh Sugii, Masashi Okada, Koichi Igarashi, Ayano Satoh, Takayuki Kudoh, Takayuki Kudoh, Li Fu, Masaharu Seno

    CANCER RESEARCH   72   2012年4月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-418

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  • Preparation and evaluation of glycosylated paclitaxel loaded in tastuzumab-immunoliposome

    Masaharu Murakami, Tomonari Kasai, Masashi Okada, Katsuhiko Mikuni, Naoyoshi Egashira, Masaharu Seno, Hiroki Hamada

    CANCER RESEARCH   72   2012年4月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-5700

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  • Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-monosaccharide conjugate and its drug delivery system using hepatitis B virus envelope L bio-nanocapsules. 国際誌

    Kei Shimoda, Manabu Hamada, Masaharu Seno, Tadakatsu Mandai, Hiroki Hamada

    Biochemistry insights   5   11 - 5   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-glucose conjugate, ie, 7-glycolyltaxol 2″-O-α-D-glucoside, was achieved by using α-glucosidase as a biocatalyst. The water-solubility of 7-glycolyltaxol 2″-O-α-D-glucoside (21 μM) was 53 fold higher than that of taxol. The hepatitis B virus envelope L particles (bio-nanocapsules) are effective for delivering 7-glycolyltaxol 2″-O-α-D-glucoside to human hepatocellular carcinoma NuE cells.

    DOI: 10.4137/BCI.S9824

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  • Extracellular Matrix Modulates Insulin Production During Differentiation of AR42J Cells:

    Hamamoto, Kohei; Yamada, Satoko; Hara, Akemi; et al.

    Journal of Cellular Biochemistry   112 ( 1 )   318 - 329   2011年1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/jcb.22930

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  • Construction of a high-efficiency multi-site-directed mutagenesis.

    Tan H, Li Y, Chen L, Kasai T, Seno M

    African J Biotechnol   10 ( 3 )   449 - 452   2011年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Generation of Cancer Stem Cell Model from Mouse iPS Cells.

    A. Mizutani, S-I. Matsuda, T. Kasai, T. Kudoh, L. Chen, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   22   2011年

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    記述言語:英語   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Analysis of endothelium mimicry by the CSC-like cells derived from iPS cells.

    S-I. Matsuda, A. Mizutani, T. Kasai, A. Satoh, T. Kudoh, L. Chen, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   22   2011年

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    記述言語:英語   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Optimization of Bacterial Plasmid Transformation Using Nanomaterials Based on the Yoshida Effect

    Tan H, Fu L, Seno M

    International Journal of Molecular Sciences   11 ( 12 )   4962 - 4973   2010年12月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms11124962

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  • First Report of Cucumber mosaic virus in Sweet Cherry in the People's Republic of China

    Tan H, Li S, Du X, Seno M

    Plant Disease   94 ( 11 )   1378 - 1378   2010年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1094/PDIS-07-10-0549

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  • Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells.

    Hirai M, Minematsu H, Hiramatsu Y, Kitagawa H, Otani T, Iwashita S, Kudoh T, Chen L, Li Y, Okada M, Salomon DS, Igarashi K, Chikuma M, Seno M.

    International Journal of Pharmaceutics   391 ( 1-2 )   274 - 283   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: 10.1016/j.ijpharm.2010.02.030

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  • E-selectin targeting to visualize tumorsin vivo.

    Hirai M, Hiramatsu Y, Iwashita S, Otani T, Chen L, Li YG, Okada M, Oie K, Igarashi K, Wakita H, Seno M.

    Contrast Media & Molecular Imaging   5 ( 2 )   70 - 77   2010年3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/cmmi.367

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  • Production of biologically active IgG hinge-tag soluble epidermal growth factor receptors (ErbB).

    Otani T, Hashizume T, Nagaoka T, Fukuda T, Tang CK, Salomon DS, Seno M.

    Biotechnology Letters   32 ( 3 )   361 - 366   2010年3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/s10529-009-0160-9

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  • Administration of Conophylline and Betacellulin-delta4 Increases the beta-cell Mass in Neonal Streptozotocin-treated Rats.

    Kodera T, Yamada S, Yamamoto Y, Hara A, Tanaka Y, *Seno M, Umezawa K, Takei I, Kojima I.

    Endocrine Journal   56 ( 6 )   799 - 806   2009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: 10.1507/endocrj.K09E-158

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  • Delivery of sodium borocaptate to glioma cells using immunoliposome conjugated with anti-EGFR antibodies by ZZ-His

    Feng B, Tomizawa K, Michiue H, Miyatake S, Han XJ, Fujimura A, *Seno M, Kirihata M, Matsui H.

    Biomaterials   30 ( 9 )   1746 - 1755   2009年3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.biomaterials.2008.12.010

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  • Human eosinophil cationic protein enhances stress fiber formation in Balb/c 3T3 fibroblasts and differentiation of rat neonatal cardiomyocytes.

    Fukuda T, Iwata M, Kitazoe M, Maeda T, Salomon D, Hirohata S, Tanizawa K, Kuroda S, *Seno M.

    Growth Factors   27 ( 4 )   228 - 236   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/08977190902987149

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  • Spherical self-organizing map as a helpful tool to identify category-specific cell surface markers.

    Tuoya, Sugii Y, Satoh H, Yu D, Matsuura Y, Tokutaka H, *Seno M.

    Biochemical and Biophysical Research Communications   376 ( 2 )   414 - 418   2008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.bbrc.2008.09.010

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  • Intracellular Delivery of Glutathione S-Transferase-fused Proteins into Mammalian Cells by Polyethylenimine-Glutathione Conjugates.

    Murata H, Futami J, Kitazoe M, Yonehara T, Nakanishi H, Kosaka M, Tada H, Sakaguchi M, Yagi Y,* Seno M, Huh NH, Yamada H.

    Journal of Biochemistry   144 ( 4 )   447 - 455   2008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: 10.1093/jb/mvn087

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  • Smad2 functions as a co-activator of canonical Wnt/beta-catenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300.

    Hirota M, Watanabe K, Hamada S, Sun Y, Strizzi L, Mancino M, Nagaoka T, Gonzales M, *Seno M, Bianco C, Salomon DS.

    Cellular Signalling   20 ( 9 )   1632 - 1641   2008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.cellsig.2008.05.003

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  • Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice.

    Yamamoto Y, Yamada S, Kodera T, Hara A, Motoyoshi K, Tanaka Y, Nagaoka T, *SenoM, Kojima I.

    Growth Factors   26 ( 4 )   173 - 179   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/08977190802136854

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  • Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2.

    Hashizume T, Fukuda T, Nagaoka T, Tada H, Yamada H, Watanabe K, Salomon DS, *Seno M.

    Cell Biology International   32 ( 7 )   814 - 826   2008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: 10.1016/j.cellbi.2008.03.012

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  • A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1.

    Nagaoka T, Fukuda T, Hashizume T, Nishiyama T, Tada H, Yamada H, Salomon DS, Yamada S, Kojima I, *Seno M.

    Journal of Molecular Biology   380 ( 1 )   83 - 94   2008年6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.jmb.2008.03.054

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  • A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4.

    Hisanaga E, Park KY, Yamada S, Hashimoto H, Takeuchi T, Mori M,* Seno M, Umezawa K, Takei I, Kojima I.

    Endocrine Journal   55 ( 3 )   535 - 543   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1507/endocrj.K07E-173

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  • Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation.

    Bokui N, Otani T, Igarashi K, Kaku J, Oda M, Nagaoka T, *Seno M, Tatematsu K, Okajima T, Matsuzaki T, Ting K, Tanizawa K, Kuroda S.

    Febs Letters   582 ( 2 )   365 - 371   2008年1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.febslet.2007.12.006

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  • Morphological and Microstructural Study of Iron Oxide Microtubes formed by Iron Oxidizing Bacteria, Leptothrix ochracea

    H. Hashimoto, H. Asaoka, J. Takada, T. Fujii, M. Nakanishi, S. Yokoyama, R. Murakami, Y. Kusano, Y. Ikeda, M. Seno

    Global Roadmap of Ceramics - ICC2 Proceedings   6-P-011-1-6-P-011-4   2008年

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  • Growth factor induction of Cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration.

    Watanabe K, Bianco C, Strizzi L, Hamada S, Mancino M, Bailly V, Mo W, Wen D, Miatkowski K, Gonzales M, Sanicola M, *Seno M, Salomon DS.

    J Biol Chem   282 ( 43 )   31643 - 31655   2007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: 10.1074/jbc.M702713200

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  • Development of bionanocapsules targeting brain tumors.

    Tsutsui Y, Tomizawa K, Nagita M, Michiue H, Nishiki T, Ohmori I, Seno M, Matsui H.

    J Control Release.   122 ( 2 )   159 - 164   2007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.jconrel.2007.06.019

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  • 'Crystal lattice engineering,' an approach to engineer protein crystal contacts by creating intermolecular symmetry: Crystallization and structure determination of a mutant human RNase 1 with a hydrophobic interface of leucines.

    Yamada H, Tamada T, Kosaka M, Miyata K, Fujiki S, Tano M, Moriya M, Yamanishi M, Honjo E, Tada H, Ino T, Yamaguchi H, Futami J, *Seno M, Nomoto T, Hirata T, Yoshimura M, Kuroki R.

    Protein Sci.   16 ( 7 )   1389 - 1397   2007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: 10.1110/ps.072851407

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  • Conophylline and Betacellulin-delta4: an Effective Combination of Differentiation Factors for Pancreatic beta Cells. 査読

    Kitamura RI, Ogata T, Tanaka Y, Motoyoshi K, *Seno M, Takei I, Umezawa K, Kojima I.

    Endocr J.   54 ( 2 )   255 - 264   2007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)  

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  • Gene therapy of liver tumors with human liver-specific nanoparticles (vol 14, pg 74, 2007)

    M. Ueda, Y. Iwasaki, T. Yamada, A. Kondo, M. Seno, K. Tanizawa, S. Kuroda, M. Sakamoto, M. Kitajima

    CANCER GENE THERAPY   14 ( 4 )   440 - 440   2007年4月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    DOI: 10.1038/sj.cgt.7701031

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  • AR42J細胞の分化に対する細胞外基質の影響

    濱本 耕平, 山田 聡子, 山本 頼綱, 小寺 力, 原 朱美, 妹尾 昌治, 小島 至

    糖尿病   50 ( Suppl.1 )   S - 349   2007年4月

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    記述言語:日本語   出版者・発行元:(一社)日本糖尿病学会  

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  • Characterization of bio-nanocapsule as a transfer vector targeting human hepatocyte carcinoma by disulfide linkage modification.

    Nagaoka T, Fukuda T, Yoshida S, Nishimura H, Yu D, Kuroda S, Tanizawa K, Kondo A, Ueda M, Yamada H, Tada H, *Seno M.

    J Control Release.   118 ( 3 )   348 - 356   2007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: 10.1016/j.jconrel.2006.12.020

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  • 脳腫瘍を標的としたバイオナノカプセルの開発

    筒井 佑美, 富澤 一仁, 西木 禎一, 大守 伊織, 名木田 真奈, 妹尾 昌治, 松井 秀樹

    日本生理学雑誌   69 ( 3 )   125 - 125   2007年3月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • Characteristics of hollow microtubes consisting of amorphous iron oxide nanoparticles produced by iron oxidizing bacteria, Leptothrix ochracea

    H. Hashimoto, S. Yokoyama, H. Asaoka, Y. Kusano, Y. Ikeda, *M. Seno, J. Takada, , T. Fujii, M. Nakanishi and R. Murakami,

    Journal of Magnetism and Magnetic Materials   310 ( 2 )   2405 - 2407   2007年3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.jmmm.2006.10.793

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  • Gene therapy of liver tumors with human liver-specific nanoparticles.

    Iwasaki Y, Ueda M, Yamada T, Kondo A, *Seno M, Tanizawa K, Kuroda S, Sakamoto M, Kitajima M.

    Cancer Gene Ther.   14 ( 1 )   74 - 81   2007年1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/sj.cgt.7700990

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  • 心筋症治療薬の開発シーズ:好酸球由来塩基性タンパク質

    妹尾昌治

    ちゅうごく産業創造センター会報   No.74, p40-41.   2007年

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  • Conophylline and betacellulin delta 4 promote differentiation of pancreatic cells both in vitro and in vivo

    Tsutomu Kodera, Takeki Ogata, Yoritsuna Yamamoto, Kazuo Umezawa, Masaharu Seno, Yuji Tanaka, Itaru Kojima, Yasuhiro Watanabe

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   80P - 80P   2007年

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • バイオナノキャリアの開発とがん遺伝子治療への応用

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    バイオテクノロジージャーナル   7 ( 1 )   41 - 47   2007年

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  • Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties.

    Yagi H, Ueda M, Jinno H, Aiura K, Mikami S, Tada H, *Seno M, Yamada H, Kitajima M.

    Cancer Sci.   97 ( 12 )   1315 - 1320   2006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: 10.1111/j.1349-7006.2006.00336.x

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  • Secretory production system of bionanocapsules using a stably transfected insect cell line.

    Shishido T, Muraoka M, Ueda M, *Seno M, Tanizawa K, Kuroda S, Fukuda H, Kondo, A.

    Appl Microbiol Biotechnol.   73 ( 3 )   505 - 511   2006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: 10.1007/s00253-006-0486-3

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  • Hydrogen peroxide and endothelin-1 are novel activators of betacellulin ectodomain shedding.

    Sanderson MP, Abbott CA, Tada H, *Seno M, Dempsey PJ, Dunbar AJ.

    J Cell Biochem.   99 ( 2 )   609 - 623   2006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: 10.1002/jcb.20968

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  • FGF挿入型のヒト組み替えbFGF-RNaseを用いた腫瘍増殖抑制効果の検討

    八木 洋, 上田 政和, 神野 浩光, 相浦 浩一, 妹尾 昌治, 多田 宏子, 山田 秀徳, 北島 政樹

    日本癌治療学会誌   41 ( 2 )   697 - 697   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • FGF挿入型のヒト組み替えbFGF-RNaseを用いた腫瘍増殖抑制効果の検討

    八木 洋, 上田 政和, 神野 浩光, 相浦 浩一, 妹尾 昌治, 多田 宏子, 山田 秀徳, 北島 政樹

    外科と代謝・栄養   40 ( 3 )   132 - 132   2006年6月

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    記述言語:日本語   出版者・発行元:日本外科代謝栄養学会  

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  • Denatured and Reversibly Cationized p53 Readily Enters Cells and Simultaneously Folds to the Functional Protein in the Cells.

    Murata H, Sakaguchi M, Futami J, Kitazoe M, Maeda T, Doura H, Kosaka M, Tada, H, *Seno M, Huh NH, Yamada H.

    Biochemistry.   45 ( 19 )   6124 - 6132   2006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: 10.1021/bi052642a

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  • Mechanisms of the growth-inhibitory effect of the RNase-EGF fused protein against EGFR-overexpressing cells.

    Hoshimoto S, Ueda M, Jinno H, Kitajima M, Futami J, *Seno M.

    Anticancer Res.   26 ( 2A )   857 - 863   2006年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Engineered bio-nanocapsules, the selective vector for drug delivery system

    DW Yu, T Fukuda, Tuoya, S Kuroda, K Tanizawa, A Kondo, M Ueda, T Yamada, H Tada, M Seno

    IUBMB LIFE   58 ( 1 )   1 - 6   2006年1月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS INC  

    The bio-nanocapsule (BNC) is our concept of artificial hollow nanoparticles that have been designed and produced through biotechnological procedures. We proposed an empty virus-like particle, which consists of a recombinant L envelope protein of hepatitis B virus (HBV) and a lipid derived from the host cell, as an engineered BNC. Although this BNC was first developed as an immunogen of hepatitis B vaccine, the pre-S1 region in N-terminus of L envelope protein confers hepatocyte specific infectivity of HBV on the BNC. This recombinant BNC is now being developed as a novel platform of drug delivery system (DDS) vector for selective delivery.

    DOI: 10.1080/15216540500484368

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  • Separation of Dual Affinity of Betacellulin to ErbB Receptors

    T. Nagaoka, H. Tada, H. Yamada, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   17   2006年

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    記述言語:英語   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • 中空バイオナノ粒子を用いたDDSの開発とその産業化

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    Drug Delivery System   21 ( 4 )   435 - 443   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2745/dds.21.435

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  • Betacellulin-delta4, a novel differentiation factor for pancreatic beta-cells, ameliorates glucose intolerance in streptozotocin-treated rats.

    Ogata T, Dunbar AJ, Yamamoto Y, Tanaka Y, *Seno M, Kojima I.

    Endocrinology.   146 ( 11 )   4673 - 4681   2005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: 10.1210/en.2005-0456

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  • Identification of cell surface marker candidates on SV-T2 cells using DNA microarray on DLC-coated glass.

    Tuoya, Hirayama K, Nagaoka T, Yu D, Fukuda T, Tada H, Yamada H, *Seno M

    Biochem Biophys Res Commun.   334 ( 1 )   263 - 268   2005年8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.bbrc.2005.06.083

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  • 細胞および組織特異的遺伝子導入を可能にするバイオナノカプセル

    山田 忠範, 妹尾 昌治, 上田 政和, 近藤 昭彦, 谷澤 克行, 黒田 俊一

    生物工学会誌   83・8・380-383   2005年8月

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    記述言語:日本語  

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  • Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1.

    Hayashida T, Ueda M, Aiura K, Tada H, Onizuka M,*Seno M, Yamada H, Kitajima M.

    Protein Eng Des Sel.   18 ( 7 )   321 - 327   2005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: 10.1093/protein/gzi040

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  • The specific delivery of proteins to human liver cells by engineered bio-nanocapsules.

    Yu D, Amano C, Fukuda T, Yamada T, Kuroda S, Tanizawa K, Kondo A, Ueda M, Yamada H, Tada H, *Seno M

    FEBS J.   272 ( 14 )   3651 - 3660   2005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: 10.1111/j.1742-4658.2005.04790.x

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  • Protein transduction assisted by polyethylenimine-cationized carrier proteins.

    Kitazoe M, Murata H, Futami J, Maeda T, Sakaguchi M, Miyazaki M, Kosaka M, Tada H, *Seno M, Huh NH, Namba M, Nishikawa M, Maeda Y, Yamada H.

    J Biochem (Tokyo).   137 ( 6 )   693 - 701   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/jb/mvi081

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  • Intracellular delivery of proteins into mammalian living cells by polyethyleneimine-cationization.

    Futami J, Kitazoe M, Maeda T, Nukui E, Sakaguchi M, Kosaka J, Miyazaki M, Kosaka M, H Tada, *Seno M, Sasaki J, Hhuh N, Namba M, Yamada H.

    J Biosci Bioeng.   99 ( 2 )   95 - 103   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1263/jbb.99.95

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  • Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells.

    Yamada S, Terada K, Ueno Y, Sugiyama T, *Seno M, Kojima I.

    Cell Transplant.   14 ( 9 )   647 - 653   2005年

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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.ssc.2005.01.003

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  • 革新的なナノキャリア:中空バイオナノ粒子によるピンポイントDDS

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    バイオインダストリー   22 ( 5 )   22 - 27   2005年

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  • Conophylline and betacellulin-delta 4: An effective combination to induce differentiation of pancreatic beta cells

    RI Kitamura, T Ogata, Y Tanaka, MH Seno, Takei, I, K Umezawa, Kojima, I

    DIABETES   54 ( 2 )   A393 - A393   2005年

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

    DOI: 10.1507/endocrj.K06-199

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  • 中空バイオナノ粒子を用いたピンポイントDDSの開発

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治

    Chemical Engineering   50 ( 5 )   351 - 356   2005年

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  • 昆虫細胞を用いたバイオナノ粒子の効率的生産

    宍戸 卓矢, 村岡 優, 上田 政和, 妹尾 昌治, 多田 宏子, 谷澤 克行, 黒田 俊一, 福田 秀樹, 近藤 昭彦

    化学工学会 研究発表講演要旨集   2005   327 - 327   2005年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2005.0.327.0

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  • Characterization of cell surface marker proteins in SV-T2 cells

    Y Tuo, K Hirayama, T Nagaoka, H Tada, H Yamada, M Seno

    MOLECULAR BIOLOGY OF THE CELL   15   324A - 325A   2004年11月

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    記述言語:英語   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice.

    Strizzi L, Bianco C, Normanno N, *Seno M, Wechselberger C, Wallace-Jones B, Khan NI, Hirota M, Sun Y, Sanicola M, Salomon DS.

    J Cell Physiol.   201 ( 2 )   266 - 276   2004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: 10.1002/jcp.20062

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  • Insertional-fusion of basic fibroblast growth factor endowed ribonuclease 1 with enhanced cytotoxicity by steric blockade of inhibitor interaction.

    Tada H, Onizuka M, Muraki K, Masuzawa W, Futami J, Kosaka M, *Seno M, Yamada H.

    FEBS Lett.   568 ( 1-3 )   39 - 43   2004年6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.febslet.2004.05.007

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  • Reversal of streptozotocin-induced hyperglycemia by transplantation of pseudoislets consisting of beta cells derived from ductal cells.

    Ogata T, Park KY, *Seno M, Kojima I.

    Endocr J.   51 ( 3 )   381 - 386   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1507/endocrj.51.381

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  • Activin A and betacellulin: effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats.

    Li L, Yi Z, *Seno M, Kojima I.

    Diabetes   53 ( 3 )   608 - 615   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2337/diabetes.53.3.608

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  • Novel tissue and cell type-specific gene/drug delivery system using surface engineered hepatitis B virus nano-particles

    Tadanori Yamada, Masakazu Ueda, Masaharu Seno, Akihiko Kondo, Katsuyuki Tanizawa, Shun'ichi Kuroda

    Current Drug Targets - Infectious Disorders   4 ( 2 )   163 - 167   2004年

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    記述言語:英語  

    The hepatitis B virus (HBV) surface antigen (HBsAg) L particle is a hollow nano-scale particle. HBsAg L particles have many properties that make them useful for in vivo gene transfer vectors and drug delivery systems. Gene therapy so far has required the in vivo pinpoint delivery of genetic materials into the target organs and cells. Gene transfer by HBsAg L particles might be an attractive method, since their tropism is the same as that of HBV. The HBsAg L particles are able to deliver therapeutic payloads with high specificity to human hepatocytes. In addition, the specificity of L particle can be altered by displaying various cell-binding molecules on the surface. Our results indicate that the L particle is suitable for a cell- and tissue-specific gene/drug transfer vector. In this review, we discuss HBsAg L particles as a gene/drug transfer vector and its potential for the treatment of infectious diseases. © 2004 Bentham Science Publishers Ltd.

    DOI: 10.2174/1568005043341037

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  • 中空バイオナノ粒子が拓く新しい医療技術

    黒田俊一, 山田忠範, 妹尾昌治, 近藤昭彦, 上田政和, 谷澤克行

    化学工業   vol.55, no.12, pp.936-942   2004年

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  • Pinpoint drug delivery system using hollow bio-nanoparticles 査読

    T Yamada, M Seno, A Kondo, M Ueda, K Tanizawa, S Kuroda

    KOBUNSHI RONBUNSHU   61 ( 12 )   606 - 612   2004年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC POLYMER SCIENCE JAPAN  

    Hepatitis B virus envelope L proteins produced in yeast cells form hollow nanoparticles (L particles, average diameter 220 nm) displaying human liver-specific receptor. Recently, the L particles were found to incorporate genes, proteins, and drugs, and act as an efficient pinpoint delivery system to human liver-derived tissues in xenograft models. By substituting the epidermal growth factor (EGF) for human liver-specific receptor, the mutated L particles showed the affinity to the EGF receptor, not to human liver. Other similar HBV envelope proteins, e.g., M and S particles, have already been commercialized for hepatitis B vaccine, strongly suggesting the safety of L particles in human. These results indicate that the hollow bio-nanoparticles are a promising candidate for the next-generation platform of DDS, especially that related to gene therapy.

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  • Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to beta-cells in streptozotocin-treated mice

    Li L, *Seno M, Yamada H, Kojima I

    Am J Physiol Endocrinol Metab   285 ( 3 )   E577 - E583   2003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: 10.1152/ajpendo.00120.2003

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  • Nanoparticles for the delivery of genes and drugs to human hepatocytes

    Yamada T, Iwasaki Y, Tada H, Iwabuki H, Chuah MK, VandenDriessche T, FukudaH, Kondo A, Ueda M, *Seno M, Tanizawa K, Kuroda S

    Nat Biotechnol   21 ( 8 )   885 - 890   2003年8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/nbt843

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  • US venture capital for biotechnology 査読

    MD Dibner, M Trull, M Howell

    NATURE BIOTECHNOLOGY   21 ( 6 )   613 - 617   2003年6月

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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 PUBLISHING GROUP  

    DOI: 10.1038/nbt0603-613

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  • The cytotoxicity of a conjugate composed of human epidermal growth factor and eosinophil cationic protein.

    Jinno H, Ueda M, Ozawa S, Ikeda T, Kitajima M, Maeda T, *Seno M.

    Anticancer Res.   22 ( 6C )   4141 - 4145   2002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)  

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  • RNase 3 (ECP) Is an Extraordinarily Stable Protein among Human Pancreatic-Type RNases.

    Maeda T, Mahara K, Kitazoe M, Futami J, Takidani A, Kosaka M, Tada H, *Seno M, Yamada H.

    J. Biochem. (Tokyo).   132 ( 5 )   737 - 742   2002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)  

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  • 上皮増殖因子を用いたターゲッテイング療法の検討

    神野 浩光, 上田 政和, 池田 正, 北島 政樹, 妹尾 昌治

    日本癌治療学会誌   37 ( 2 )   373 - 373   2002年9月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Optimum modification for the highest cytotoxicity of cationized ribonuclease.

    Futami J, Nukui E, Maeda T, Kosaka M, Tada H, Seno M, Yamada H.

    J. Biochem. (Tokyo).   132 ( 2 )   223 - 228   2002年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Solution structure of betacellulin, a new member of EGF-family ligands.

    Miura K, Doura H, Aizawa T, Tada H, *Seno M, Yamada H, Kawano K.

    Biochem. Biophys. Res. Commun.   294 ( 5 )   1040 - 1046   2002年6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/S0006-291X(02)00585-5

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  • Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin.

    Kojima H, Nakamura T, Fujita Y, Kishi A, Fujimiya M, Yamada S, Kudo M, Nishio Y, Maegawa H, Haneda M, Yasuda H, Kojima I, *Seno M, Wong NC, Kikkawa R, Kashiwagi A.

    Diabetes   51 ( 5 )   1398 - 1408   2002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)  

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  • Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells.

    Bianco C, Adkins HB, Wechselberger C, *Seno M, Normanno N, De Luca A, Sun Y, Khan N, Kenney N, Ebert A, Williams KP, Sanicola M, Salomon DS.

    Mol.Cell Biol.   22 ( 8 )   2586 - 2597   2002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: 10.1128/MCB.22.8.2586-2597.2002

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  • EGFRを分子標的としたRNase-EGF recombinantタンパクの殺細胞効果

    星本 相淳, 上田 政和, 神野 浩光, 相浦 浩一, 渡辺 靖夫, 北島 政樹, 二見 淳一郎, 妹尾 昌治

    日本外科学会雑誌   103 ( 臨増 )   532 - 532   2002年3月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • Detection and localization of Cripto-1 binding in mouse mammary epithelial cells and in the mouse mammary gland using an immunoglobulin-cripto-1 fusion protein.

    Bianco C, Normanno N, De Luca A, Maiello MR, Wechselberger C, Sun Y, Khan N, Adkins H, Sanicola M, Vonderhaar B, Cohen B, *Seno M, Salomon D.

    J. Cell Physiol.   190 ( 1 )   74 - 82   2002年1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/jcp.10037

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  • Growth inhibition of mammalian cells by eosinophil cationic protein.

    Maeda T, Kitazoe M, Tada H, de Llorens R, Salomon DS, Ueda M, Yamada H, *Seno M.

    Eur. J. Biochem.   269 ( 1 )   307 - 316   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.0014-2956.2001.02653.x

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  • Human betacellulin structure modeled from other members of EGF family 査読

    Inés López-Torrejón, Enrique Querol, Francesc Avilés, Masaharu Seno, Rafael de Llorens, Baldomero Oliva

    Journal of Molecular Modeling   8 ( 4 )   131 - 144   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have modeled betacellulin (BTC) to gain insight into the structural elements that can explain its properties. The epidermal growth factor (EGF) signal transduction pathway, a significant mediator of several cell functions, is based on four closely related tyrosine kinase receptors. The ErbB receptors are transmembrane glycoproteins and signal transduction is initiated by ligand binding that induces receptor homo- or heterodimerization to form a complex containing two molecules of ligand and two molecules of receptor. The EGF family of ligands can be divided into three groups based on their ability to bind and activate distinct ErbB receptor homo- and heterodimers. Each member of the group formed by BTC, heparin binding EGF (HB-EGF) and epiregulin (EP) can interact with both the EGF receptor (EGFR) and heregulin receptors (ErbB-3 and ErbB-4), and are hence called "bispecific" ligands. BTC and EP also present the distinctive feature that they activate all possible heterodimeric ErbB receptors. BTC has Been modeled with the program MODELLER, using human EGF, human transforming growth factor alpha (hTGFα), human HB-EGF and human heregulin one alpha (hHRG-1α) as templates. The structure of the model as well as that of the templates were optimized and a simulation of 100 ps was run for all. The main structural properties of the model and the templates were compared and in conclusion the hBTC conformation was closely similar to that of hTGFα.

    DOI: 10.1007/s00894-002-0072-2

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  • 細胞増殖因子ベータセルリン -膵臓再生と糖尿病研究へのニューマテリアル-

    妹尾昌治

    和光純薬時報   70(3): 6-8.   2002年

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  • Promotion of beta-cell regeneration by betacellulin in ninety percent-pancreatectomized rats.

    Li L, *Seno M, Yamada H, Kojima I.

    Endocrinology   142 ( 12 )   5379 - 5385   2001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: 10.1210/en.142.12.5379

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  • Preparation of potent cytotoxic ribonucleases by cationization: enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups.

    Futami J, Maeda T, Kitazoe M, Nukui E, Tada H, *Seno M, Kosaka M, Yamada H.

    Biochemistry   40 ( 25 )   7518 - 7524   2001年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/bi010248g

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  • Physicochemical and immunological characterization of hepatitis B virus envelope particles exclusively consisting of the entire L (pre-S1+pre-S2+S) protein.

    Yamada T, Iwabuki H, Kanno T, Tanaka H, Kawai T, Fukuda H, Kondo A, *Seno M, Tanizawa K, Kuroda S.

    Vaccine.   19 ( 23-24 )   3154 - 3163   2001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: 10.1016/S0264-410X(01)00017-2

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  • Three-dimensional structure of human RNase 1DeltaN7 at 1.9 A resolution.

    Pous J, Mallorqui-Fernandez G, Peracaula R, Terzyan SS, Futami J, Tada H, Yamada H, Seno M, de Llorens R, Gomis-Ruth FX, Coll M.

    Acta Crystallogr D Biol Crystallogr.   57   498 - 505   2001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: 10.1107/S0907444901001147

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  • Expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in rat testes

    Mori H, Nomura T, *Seno M, Miki Y, Kimura T, Kogami T, Sasaki J

    Acta Histochemica et Cytochemica   34 ( 1 )   25 - 30   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • ベータセルリン:細胞増殖分化因子を応用した再生医療への試み

    妹尾昌治

    ハイテクインフォメーション   134号14-21   2001年

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  • The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer

    DS Salomon, C Bianco, AD Ebert, NI Khan, M De Santis, N Normanno, C Wechselberger, M Seno, K Williams, M Sanicola, S Foley, W Gullick, G Persico

    ENDOCRINE-RELATED CANCER   7 ( 4 )   199 - 226   2000年12月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-l) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (UR) asymmetry, In zebrafish, there is strong genetic evidence that oep functions as an obligatory cc-factor for the correct signaling of a transforming growth factor-beta (TGF beta)-related gene, nodal, during gastrulation and during UR asymmetry development. Expression of Cr-l and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-l expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-l is expressed at a low level in several different tissues including the mammary gland, In the mammary gland, expression of Cr-l in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-l protein can be detected in human milk. Overexpression of Cr-l in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-l-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta -catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-e. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of p-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

    DOI: 10.1677/erc.0.0070199

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  • 上皮増殖因子受容体(EGFR)過剰発現癌に対する生理活性物質を用いた低免疫原性ターゲッテイング療法の開発

    神野 浩光, 上田 政和, 菊池 潔, 池田 正, 北島 政樹, 二見 淳一郎, 妹尾 昌治

    日本外科学会雑誌   101 ( 臨増 )   411 - 411   2000年3月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • Processing and juxtacrine activity of membrane

    ., Igarashi,K., *Seno, M., Yamada, H.

    J. Cell. Biochem.   72 ( 3 )   423 - 434   1999年3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/(SICI)1097-4644(19990301)72:3<423::AID-JCB11>3.0.CO;2-P

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  • The three dimensional structure of human RNase4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity.

    Terzyn, S.S., Peracaula, R., de Llorens, R., Tsushima, Y., Yamada, H., *Seno, M., Gomis-Ruth, F. X. and Coll, M.

    J. Mol. Biol.   285 ( 1 )   205 - 214   1999年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1006/jmbi.1998.2288

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  • 新しい臓器特異的癌関連遺伝子のクローニングと癌遺伝子産物を分子標的とした治療法の開発

    上田 政和, 菊池 潔, 板野 理, プサラス・キリヤコス, 北島 政樹, 妹尾 昌治

    日本癌治療学会誌   33 ( 3 )   355 - 355   1998年8月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Identification of the genes associated with differentiation of AR42J cells into insulin-secreting cells

    H Mashima, J Takeda, M Seno, H Yamada, Kojima, I

    DIABETES   47   A176 - A176   1998年5月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

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  • Molecular targeting for activated T cell by recombinant human RNase and IL-2.

    M Ueda, K Psarras, M Tanabe, T Yamamura, M Kitajima, M Seno, S Komatsu

    GASTROENTEROLOGY   114 ( 4 )   A1186 - A1186   1998年4月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO  

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  • Characterization of the betacellulin receptor in pancreatic AR42J-B20 cells

    N Ishiyama, M Kanzaki, M Furukawa, J Miyagawa, T Hanafusa, M Seno, H Yamada, Kobayashi, I, Kojima, I

    DIABETOLOGIA   40   91 - 91   1997年6月

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    記述言語:英語   出版者・発行元:SPRINGER VERLAG  

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  • Genes expressed during the differentiation of AR42J cells into insulin-secreting

    H Mashima, J Takeda, M Seno, H Yamada, Kojima, I

    DIABETES   46   1378 - 1378   1997年5月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

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  • Molecular Targeting for Epidermal Growth Factor Receptor Expressed on Breast Cancer Cells by Human Fusion Protein 査読

    Ueda M, Psarras K, Jinno H, Ikeda T, Enomoto K, Kitajima M, Futami J, Yamada H, Seno M

    Breast Cancer   4 ( 4 )   253 - 255   1997年

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    掲載種別:研究論文(国際会議プロシーディングス)  

    DOI: 10.1007/BF02966516

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▼全件表示

書籍等出版物

  • 次世代のがん治療薬・診断のための研究開発~免疫療法・遺伝子治療・がん幹細胞~、第13章 がん幹細胞を標的とした治療薬研究 iPS細胞を用いたがん幹細胞モデル作成のポイントとその評価

    2016年 

     詳細を見る

  • 遺伝子・組織・生物活性化合物のクラスタリング

    海文堂出版  2015年 

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  • Insight into Cancer Stem Cell Niche; Lessons from Cancer Stem Cell Models Generated In Vitro. In: Biology in Stem Cell Niche (Ed: Kursad Turksen)

    Humana Press  2015年 

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  • がん幹細胞から考えるがんの正体 —クローン説に基づく治療薬/治療法からのパラダイムシフト

    化学同人社  2014年 

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  • マウスiPS細胞から作るがん幹細胞モデル

    羊土社  2013年 

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  • Exploring the mechanism for biological evolution: DNA methyltransferase is the pushing power of DNA and protein evolution.

    Lambert Academic Publishing  2011年 

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  • Self Organizing Maps - Applications and Novel Algorithm Design

    InTech  2011年 

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  • 中空バイオナノ粒子を用いるピンポイントDDSおよび遺伝子導入法

    シーエムシー出版(東京)  2009年 

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  • Pinpoint DDS and gene transduction using hollow bio-nanoparticle

    2009年 

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  • 自己組織化マップとそのツール

    シュプリンガー・ジャパン  2008年 

     詳細を見る

  • Chapter 11 Protein Sequence Analysis; in “Bioinformatics – a practical approach- ed.Shui Qing Ye, (Mathematical and Computational Biology Series)”

    Chapman & Hall/CRC  2007年 

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  • 自己組織化マップとその応用

    シュプリンガー・ジャパン  2007年 

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  • Bioinformatics - a practical approach -

    Chapman & Hall/CRC  2007年 

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  • ナノパーティクル・テクノロジー

    日刊工業新聞社(東京)  2003年 

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  • 「中空バイオナノ粒子を 用いるピンポイントDDSおよび遺伝子導入法」ナノバイオテクノロジー最前線

    シ ーエムシー出版(東京)  2003年 

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  • 生物工学系テキストシリーズ「バイオ機器分析入門」

    講談社サイエンティフィク  2000年 

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  • FGF-7(KGF)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • 線維芽細胞成長因子ファミリーFGF

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-1(酸性線維芽細胞成長因子,aFGF)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-2(塩基性線維芽細胞成長因子,bFGF)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-3(int-2遺伝子産物)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-4(hst-1/kFGF遺伝子産物)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-5

    タンパク質化学第8巻「成長因子I」広川書店 

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  • FGF-6(hst-2遺伝子産物)

    タンパク質化学第8巻「成長因子I」広川書店 

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  • 生物工学系テキストシリーズ「バイオ機能分析入門」、「第2章 クロマトグラフィー」

    講談社サイエンティフィク 

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▼全件表示

MISC

  • Development of Paclitaxel Glycoside Liposomes Conjugated with Anti-CD44 Antibody Targeting Ovarian Cancer Cells

    Apriliana C. Khayrani, Hafizah Mahmud, Tomonari Kasai, Tsukasa Shigehiro, Aung Ko Ko Oo, Juan Du, Md. Jahangir Alam, Koji Hara, Hiroki Hamada, Yuhki Seno, Said M. Afify, Tadakatsu Mandai, Masaharu Seno

    CANCER SCIENCE   109   1097 - 1097   2018年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. 査読 国際誌

    Ono K, Eguchi T, Sogawa C, Calderwood SK, Futagawa J, Kasai T, Seno M, Okamoto K, Sasaki A, Kozaki KI

    Journal of Cellular Biochemistry   119 ( 9 )   7350 - 7362   2018年9月

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    記述言語:英語  

    DOI: 10.1002/jcb.27039

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  • Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment. 査読 国際誌

    Oo AKK, Calle AS, Nair N, Mahmud H, Vaidyanath A, Yamauchi J, Khayrani AC, Du J, Alam MJ, Seno A, Mizutani A, Murakami H, Iwasaki Y, Chen L, Kasai T, Seno M

    Translational Oncology   11 ( 3 )   653 - 663   2018年6月

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  • Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide. 査読 国際誌

    Masuda J, Shigehiro T, Matsumoto T, Satoh A, Mizutani A, Umemura C, Saito S, Kijihira M, Takayama E, Seno A, Murakami H, Seno M

    International Journal of Molecular Sciences   19 ( 4 )   2018年4月

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    記述言語:英語  

    DOI: 10.3390/ijms19041261

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  • Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. 査読 国際誌

    Mahmud H, Kasai T, Khayrani AC, Asakura M, Oo AKK, Du J, Vaidyanath A, El-Ghlban S, Mizutani A, Seno A, Murakami H, Masuda J, Seno M

    International Journal of Molecular Sciences   19 ( 3 )   2018年2月

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    記述言語:英語  

    DOI: 10.3390/ijms19030659

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  • Iron depletion is a novel therapeutic strategy to target cancer stem cells. 査読 国際誌

    Takayuki Ninomiya, Toshiaki Ohara, Kazuhiro Noma, Yuki Katsura, Ryoichi Katsube, Hajime Kashima, Takuya Kato, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Ling Chen, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

    Oncotarget   8 ( 58 )   98405 - 98416   2017年11月

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    記述言語:英語  

    Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4. In contrast, iron depletion by the iron chelators deferasirox and deferoxamine suppressed the proliferation of miPS-LLCcm cells and the expression of stemness markers. In an allograft model, deferasirox inhibited the growth of miPS-LLCcm implants, which was associated with decreased expression of Nanog and Sox2. Altogether, iron appears to be crucial for the proliferation and maintenance of stemness of CSCs, and iron depletion may be a novel therapeutic strategy to target CSCs.

    DOI: 10.18632/oncotarget.21846

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  • Practical liposomal formulation for taxanes with polyethoxylated castor oil and ethanol with complete encapsulation efficiency and high loading efficiency 査読 国際誌

    Tsukasa Shigehiro, Junko Masuda, Shoki Saito, Apriliana, C. Khayrani, Kazumasa Jinno, Akimasa Seno, Arun Vaidyanath, Akifumi Mizutani, Tomonari Kasai, Hiroshi Murakami, Ayano Satoh, Tetsuya Ito, Hiroki Hamada, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno

    Nanomaterials   7 ( 10 )   1391 - 1398   2017年9月

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    記述言語:英語  

    DOI: 10.3390/nano7100290

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  • Synthesis and assembly of Hepatitis B virus envelope protein-derived particles in Escherichia coli 査読 国際誌

    Hao Li, Keisuke Onbe, Qiushi Liu, Masumi Iijima, Kenji Tatematsu, Masaharu Seno, Hiroko Tada, Shun’ ichi Kuroda

    Biochemical and Biophysical Research Communications   490 ( 2 )   155 - 160   2017年8月

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  • A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment 査読 国際誌

    Neha Nair,Anna Sanchez Calle,Maram, Hussein Zahra,Marta Prieto-Vila,Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno

    Scientific Reports   7 ( 1 )   6838 - 6838   2017年7月

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  • Tumor growth limited to subcutaneous site vs tumor growth in pulmonary site exhibit differential effects on systemic immunities 査読 国際誌

    Junko Masuda, Eiji Takayama, Warren Strober, Ayano Satoh, Yuji Morimoto, Yasuko Honjo, Tatsuo Ichinohe, Shin Ichi Tokuno, Toshiaki Ishizuka, Takahiro Nakata, Akifumi Mizutani, Naoki Umemura, Atsushi Kitani, Ivan J. Fuss, Tsukasa Shigehiro, Harumi Kawaki, Masako Mizuno-Kamiya, Nobuo Kondoh, Masaharu Seno

    Oncology Reports   38 ( 1 )   449 - 455   2017年7月

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    記述言語:英語  

    DOI: 10.3892/or.2017.5646

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  • Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2.

    El-Aarag B, Kasai T, Masuda J, Agwa H, Zahran M, Seno M.

    Biomedicine & Pharmacotherapy   85   549 - 555   2017年1月

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  • Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2

    Bishoy El-Aarag ,Tomonari Kasai*,Junko Masuda*,Hussein Agwa ,Magdy Zahran ,Masaharu Seno*

    Biomedicine and Pharmacotherapy, Biomedicine, Revue europeenne d'etudes cliniques et biologiques. European journal of clinical and biological research, Revue francaise d'etudes cliniques et biologiques, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   85   549 - 555   2017年1月

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    担当区分:筆頭著者   記述言語:英語  

    DOI: 10.1016/j.biopha.2016.11.063

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  • Hyaluronic Acid Mediated Enrichment of CD44 Expressing Glioblastoma Stem Cells in U251MG Xenograft Mouse Model.

    Vaidyanath A, Mahmud HB, Khayrani AC, Oo AK, Seno A, Asakura A, Kasai T, Seno M

    Journal of Stem Cell Research and Therapy   2017年

  • Immunoliposomes: Recent Progress of Liposomal Drug Delivery System Coupled with Antibodies. in “Liposomes: Historical, Clinical and Molecular Perspectives

    Shigehiro T, Seno, M

    Liposomes Historical,Clinical and Molecular Perspectives   189 - 209   2017年

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  • 腫瘍を標的とした抗体提示リポソームの開発と製剤化

    妹尾昌治, 重廣司

    DDS先端技術の製剤への応用開発   249 - 262   2017年

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  • Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting

    Junko Masuda, Hiroshi Kawamoto, Warren Strober, Eiji Takayama, Akifumi Mizutani, Hiroshi Murakami, Tomokatsu Ikawa, Atsushi Kitani, Narumi Maeno, Tsukasa Shigehiro, Ayano Satoh, Akimasa Seno, Vaidyanath Arun, Tomonari Kasai, Ivan J. Fuss, Yoshimoto Katsura, Masaharu Seno

    APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY   180 ( 8 )   1559 - 1573   2016年12月

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    記述言語:英語   出版者・発行元:HUMANA PRESS INC  

    Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Kruppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.

    DOI: 10.1007/s12010-016-2187-4

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  • Meibomian gland dysfunction model in hairless mice bred under special diet limiting lipid content

    Hideki Miyake, Tomoko Oda, Osamu Katsuta, Masaharu Seno, Masatsugu Nakamura

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   57 ( 12 )   2016年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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  • Characterization of gene expression patterns among artificially developed cancer stem cells using spherical self-organizing map

    Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno

    Cancer Informatics   15   163 - 178   2016年8月

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    記述言語:英語   出版者・発行元:Libertas Academica Ltd.  

    We performed gene expression microarray analysis coupled with spherical self-organizing map (sSOM) for artificially developed cancer stem cells (CSCs). The CSCs were developed from human induced pluripotent stem cells (hiPSCs) with the conditioned media of cancer cell lines, whereas the CSCs were induced from primary cell culture of human cancer tissues with defined factors (OCT3/4, SOX2, and KLF4). These cells commonly expressed human embryonic stem cell (hESC)/hiPSC-specific genes (POU5F1, SOX2, NANOG, LIN28, and SALL4) at a level equivalent to those of control hiPSC 201B7. The sSOM with unsupervised method demonstrated that the CSCs could be divided into three groups based on their culture conditions and original cancer tissues. Furthermore, with supervised method, sSOM nominated TMED9, RNASE1, NGFR, ST3GAL1, TNS4, BTG2, SLC16A3, CD177, CES1, GDF15, STMN2, FAM20A, NPPB, CD99, MYL7, PRSS23, AHNAK, and LOC152573 genes commonly upregulating among the CSCs compared to hiPSC, suggesting the gene signature of the CSCs.

    DOI: 10.4137/CIN.S39839

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  • Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells

    Neha Nair, Arun Vaidyanath, Kenta Hoshikawa, Anna Sanchez Calle, Tomonari Kasai, Masaharu Seno

    CANCER RESEARCH   76   2016年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-LB-278

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  • The significance of c-Kit protooncogene in iCSC-derived PDAC model

    Anna Sanchez Calle, Kenta Hoshikawa, Neha Nair, Marta Prieto-Vila, Arun Vaidyanath, Tomonari Kasai, Masaharu Seno

    CANCER RESEARCH   76   2016年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-1725

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  • Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content

    Hideki Miyake, Tomoko Oda, Osamu Katsuta, Masaharu Seno, Masatsugu Nakamura

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   57 ( 7 )   3268 - 3275   2016年6月

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    記述言語:英語   出版者・発行元:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

    PURPOSE. A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD).
    MEHODS. Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model.
    RESULTS. After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis.
    CONCLUSIONS. We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.

    DOI: 10.1167/iovs.16-19227

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  • Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses

    Masashi Okada, Zhen-Wu Mei, Md. Imran Hossain, Li Wang, Taihei Tominaga, Takeshi Takebayashi, Masaharu Murakami, Mizuki Yasuda, Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Ibrahim El Tantawy El Sayed, Shingo Dan, Takao Yamori, Masaharu Seno, Tsutomu Inokuchi

    MEDICINAL CHEMISTRY RESEARCH   25 ( 5 )   879 - 892   2016年5月

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    記述言語:英語   出版者・発行元:SPRINGER BIRKHAUSER  

    A plant-derived neocryptolepine core, the 5-Me-indolo[2,3-b]quinoline skeleton, was emblazoned with substituents at C11 and C2 and then tested against various cancer cell lines to find potent anticancer agents. In the in vitro antiproliferative activity assay against the breast cancer MDA-MB-453 cell line, the attachment of alkylamino substituents at C11 of the 5-Me-indolo[2,3-b]quinoline induced improved activities. Specifically, 11-(3-aminopropylamino) and 11-(4-aminobutylamino) derivatives indicated the highest activity and selectivity against MDA-MB-453 (IC50 = 0.3-0.5 mu M) and also exhibited a higher cytotoxicity against the colon adenocarcinoma (WiDr) and ovarian cancer (SKOv3) cell lines. A synergistic effect by attachment of substituents at C2 was favorably observed with an electron-donating group, such as CH3O, and unfavorably observed with an electron-withdrawing one, such as F and CF3. Further modification of the terminal free amino group of the lariat attachment at C11 into the corresponding acylamides and 2,3-dihydrobenzo[e][1,3]thiazin-4-ones was not effective for the antiproliferative activity. The computer-assisted database analysis, COMPARE, suggested that 14e and 13b have a mode of action similar to actinomycin D and 13c has a mode of actions similar to vindesine sulfate or aclarubicin hydrochloride. However, the new compounds may have other unique mode of actions since the correlation coefficients (r) were in relatively low levels.

    DOI: 10.1007/s00044-016-1508-z

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  • Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient

    Tsukasa Shigehiro, Wenjia Zhai, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Tomonari Kasai, Hiroshi Murakami, Hiroki Hamada, David S. Salomon, Katsuhiko Mikuni, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno

    JOURNAL OF MICROENCAPSULATION   33 ( 2 )   172 - 182   2016年2月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Docetaxel comprises one of the most effective anti-cancer drugs despite of serious side effects. Liposomes encapsulation is practically feasible to deliver the drug. However, due to the significant hydrophobicity, docetaxel will be integrated into the lipid bilayer resulting in poor encapsulation capacity. Here, we evaluated a remote loading strategy using a solubility gradient made between the two solvents for 7-glucosyloxyacetyldocetaxel, which has enhanced water solubility of docetaxel with a coupled glucose moiety. Therefore, 7-glucosyloxyacetyldocetaxel was more effectively encapsulated into liposomes with 71.0% of encapsulation efficiency than docetaxel. While 7-glucosyloxyacetyldocetaxel exhibited 90.9% of tubulin stabilisation activity of docetaxel, 7-glucosyloxyacetyldocetaxel encapsulated in liposomes significantly inhibited the growth of tumour in vivo with side effects less than unencapsulated drug. Collectively, the encapsulation of 7-glucosyloxyacetyldocetaxel into liposomes by remote loading under the solubility gradient is considered to be a promising application to prepare practical drug delivery system.

    DOI: 10.3109/02652048.2016.1144815

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  • Release of siRNA from Liposomes Induced by Curcumin

    Kazuyo Fujita, Yoshie Hiramatsu, Hideki Minematsu, Masaharu Somiya, Shun'ichi Kuroda, Masaharu Seno, Shuji Hinuma

    Journal of Nanotechnology   2016   2016年

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    記述言語:英語   出版者・発行元:Hindawi Limited  

    Liposomes are a potential carrier of small interfering RNA (siRNA) for drug delivery systems (DDS). In this study, we searched for a molecule capable of controlling the release of siRNA from a certain type of liposomes and found that curcumin could induce the release of siRNA from the liposomes encapsulating siRNA within 30 min. However, the release of siRNA from the liposomes by curcumin showed a unique dose-response (i.e., bell-shaped curve) with a maximal induction at around 60 μg/ml of curcumin. Liposomal lipid compositions and temperatures influenced the efficiency in the release of siRNA induced by curcumin. About 10% of curcumin at a 60 μg/ml dose was incorporated into the liposomes within 30 min under our experimental conditions. Our results suggest a possibility that curcumin is useful in controlling the permeability of liposomes carrying large molecules like siRNA.

    DOI: 10.1155/2016/7051523

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  • A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

    Sugii Y, Kasai T, Ikeda M, Vaidyanath A, Kumon K, Mizutani A, Seno A, Tokutaka H, Kudoh T, Seno M

    Biomark Cancer   8   17 - 23   2016年

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  • iPSC-derived cancer stem cells provide a model of tumor vasculature

    Marta Prieto-Vila, Ting Yan, Anna Sanchez Calle, Neha Nair, Laura Hurley, Tomonari Kasai, Hiroki Kakuta, Junko Masuda, Hiroshi Murakami, Akifumi Mizutani, Masaharu Seno

    AMERICAN JOURNAL OF CANCER RESEARCH   6 ( 9 )   1906 - 1921   2016年

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    記述言語:英語   出版者・発行元:E-CENTURY PUBLISHING CORP  

    To grow beyond a size of approximately 1-2 mm(3), tumor cells activate many processes to develop blood vasculature. Growing evidences indicate that the formation of the tumor vascular network is very complex, and is not restricted to angiogenesis. Cancer cell-derived tumor vasculatures have been recently described. Among them, endothelial differentiation of tumor cells have been directly related to cancer stem cells, which are cells within a tumor that possess the capacity to self-renew, and to exhibit multipotential heterogeneous lineages of cancer cells. Vasculogenic mimicry has been described to be formed by cancer cells expressing stemness markers. Thus, cancer stem cells have been proposed to contribute to vasculogenic mimicry, though its relation is yet to be clarified. Here, we analyzed the tumor vasculature by using a model of mouse cancer stem cells, miPS-LLCcm cells, which we have previously established from mouse induced pluripotent stem cells and we introduced the DsRed gene in miPS-LLCcm to trace them in vivo. Various features of vasculature were evaluated in ovo, in vitro, and in vivo. The tumors formed in allograft nude mice exhibited angiogenesis in chick chorioallantoic membrane assay. In those tumors, along with penetrated host endothelial vessels, we detected endothelial differentiation from cancer stem cells and formation of vasculogenic mimicry. The angiogenic factors such as VEGF-A and FGF2 were expressed predominantly in the cancer stem cells subpopulation of miPS-LLCcm cells. Our results suggested that cancer stem cells play key roles in not only the recruitment of host endothelial vessels into tumor, but also in maturation of endothelial linage of cancer stem cell's progenies. Furthermore, the undifferentiated subpopulation of the miPS-LLCcm participates directly in the vasculogenic mimicry formation. Collectively, we show that miPS-LLCcm cells have advantages to further study tumor vasculature and to develop novel targeting strategies in the future.

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  • A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm)

    Anna Sanchez Calle, Neha Nair, Aung KoKo Oo, Marta Prieto-Vila, Megumi Koga, Apriliana Cahya Khayrani, Maram Hussein, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Yoshiaki Iwasaki, Malu Calle, Tomonari Kasai, Masaharu Seno

    AMERICAN JOURNAL OF CANCER RESEARCH   6 ( 12 )   2799 - 2815   2016年

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    記述言語:英語   出版者・発行元:E-CENTURY PUBLISHING CORP  

    Pancreatic ductal adenocarcinoma (PDAC) is the most representative form of pancreatic cancers. PDAC solid tumours are constituted of heterogeneous populations of cells including cancer stem cells (CSCs), differentiated cancer cells, desmoplastic stroma and immune cells. The identification and consequent isolation of pancreatic CSCs facilitated the generation of genetically engineered murine models. Nonetheless, the current models may not be representative for the spontaneous tumour occurrence. In the present study, we show the generation of a novel pancreatic iPSC-converted cancer stem cell lines (CSCcm) as a cutting-edge model for the study of PDAC. The CSCcm lines were achieved only by the influence of pancreatic cancer cell lines conditioned medium and were not subjected to any genetic manipulation. The xenografts tumours from CSCcm lines displayed histopathological features of ADM, PanIN and PDAC lesions. Further molecular characterization from RNA-sequencing analysis highlighted primary culture cell lines (1st CSCcm) as potential candidates to represent the pancreatic CSCs and indicated the establishment of the pancreatic cancer molecular pattern in their subsequent progenies 2nd CSCcm and 3rd CSCcm. In addition, preliminary RNA-seq SNPs analysis showed that the distinct CSCcm lines did not harbour single point mutations for the oncogene Kras codon 12 or 13. Therefore, PDAC-CSCcm model may provide new insights about the actual occurrence of the pancreatic cancer leading to develop different approaches to target CSCs and abrogate the progression of this fatidic disease.

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  • Synthesis, Biological Evaluation, Docking and QSAR Studies of Some Novel Naphthalimide Dithiocarbamate Analogs as Antitumor and Anti-Inflammatory Agents.

    Zahra MH, Osman AMA, Agwa H, Nair N, Calle AS, Hurley L, Farag D, Kasai T, Seno M, Zahran M

    Medicinal Chemistry (Los Angeles)   6 ( 12 )   694 - 703   2016年

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  • 球面自己組織化マップを用いたキナーゼパネルアセイデータのクラスタリング

    工藤孝幸, 妹尾昌治

    CCISJ Bulletin   34 ( 1 )   2 - 5   2016年

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  • 第3節 iPS細胞を用いたがん幹細胞モデル作成のポイントとその評価, 「次世代のがん治療薬・診断のための研究開発~免疫療法・遺伝子治療・がん幹細胞~、第13章 がん幹細胞を標的とした治療薬研究」

    技術情報協会   348 - 353   2016年

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  • がんモデル動物を用いた悪性度の違いによる全身免疫能変化の解析

    増田 潤子, 高山 英次, 佐藤 あやの, 守本 祐司, 本庶 仁子, 石塚 俊晶, 徳野 慎一, 青笹 季文, 光吉 俊二, 重廣 司, 前野 成実, 村上 宏, 笠井 智成, 水谷 昭文, Vaidyanath Arun, 妹尾 彬正, 川木 晴美, 神谷 真子[水野], 近藤 信夫, 一瀬 雅夫, 一戸 辰夫, 妹尾 昌治

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [1P1079] - [1P1079]   2015年12月

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    記述言語:日本語   出版者・発行元:(公社)日本生化学会  

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  • Derivation of a model of cancer stem cell from human induced pluripotent stem cells

    Tomonari Kasai, Kenta Hoshikawa, Shuto Takejiri, Masashi Ikeda, Kazuki Kumon, Anna Sanchez Calle, Arun Vaidyanath, Akifumi Mizutani, Chen Ling, Masaharu Seno

    CANCER RESEARCH   75   2015年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-LB-144

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  • Iron control is a novel therapeutic target of cancer stem cells

    Takayuki Ninomiya, Toshiaki Ohara, Hajime Kashima, Ryoichi Katsube, Kazuhiro Noma, Yasuko Tomono, Akifumi Mizutani, Tomonari Kasai, Masaharu Seno, Shinji Kuroda, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuhiro Shirakawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

    CANCER RESEARCH   75   2015年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2015-4243

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  • Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress.

    Ishii H, Kamikawa S, Hirohata S, Mizutani A, Abe K, Seno M, Oohashi T, Ninomiya Y

    Acta Med Okayama   69 ( 3 )   145 - 153   2015年6月

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  • Spherical Self-Organizing Map Detects MYBL 1 As Candidate Gene for Triple-Negative Breast Cancer.

    Ikeda M, Kumon K, Omoto K, Sugii Y, Mizutani A, Vaidyanath A, Kudoh T, Kasai T, Masuda S, Seno M

    Neurosci Biomed Eng   3 ( 2 )   94 - 101   2015年

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  • Insight into Cancer Stem Cell Niche; Lessons from Cancer Stem Cell Models Generated In Vitro.

    Biology in Stem Cell Niche, Part of the series Stem Cell Biology and Regenerative Medicine   211 - 226   2015年

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  • Bacteria: Prospective Savior in Battle against Cancer

    Neha Nair, Tomonari Kasai, Masaharu Seno

    ANTICANCER RESEARCH   34 ( 11 )   6289 - 6296   2014年11月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Conventional anticancer therapies such as chemotherapy are losing their sheen in the battle against cancer. Therefore, strategies for treatment of cancer need to be constantly modified to fulfill the growing demands of alternative therapies. Several viral and non-viral vectors have been exploited for anticancer gene therapy. But over the years bacteria have been proven to be an important candidate for successful evasion of cancer. They serve as invaluable source of tumor-specific anticancer genes, toxins, polysaccharides for synthesis of nanodrugs and gene-delivery vectors. The current review assesses the role of important bacterial groups in different spheres of anti-cancer research.

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  • Anti-cancer activity of immunoliposomes encapsulated effective amount of glycosylated paclitaxel with novel loading strategy

    Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

    CANCER RESEARCH   74 ( 19 )   2014年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-4461

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  • Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation

    Tsukasa Shigehiro, Tomonari Kasai, Masaharu Murakami, Sreeja C. Sekhar, Yuki Tominaga, Masashi Okada, Takayuki Kudoh, Akifumi Mizutani, Hiroshi Murakami, David S. Salomon, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

    PLOS ONE   9 ( 9 )   e107976   2014年9月

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    記述言語:英語   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.

    DOI: 10.1371/journal.pone.0107976

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  • In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs

    Bishoy Y. A. El-Aarag, Tomonari Kasai, Magdy A. H. Zahran, Nadia I. Zakhary, Tsukasa Shigehiro, Sreeja C. Sekhar, Hussein S. Agwa, Akifumi Mizutani, Hiroshi Murakami, Hiroki Kakuta, Masaharu Seno

    INTERNATIONAL IMMUNOPHARMACOLOGY   21 ( 2 )   283 - 292   2014年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-alpha, VEGF(165), and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 625-100 mu M. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-alpha, VEGF(165), and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as antitumor and anti-angiogenic agents. (C) 2014 The Authors. Published by Elsevier B.V.

    DOI: 10.1016/j.intimp2014.05.007

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche

    Shuichi Matsuda, Ting Yan, Akifumi Mizutani, Tatsuyuki Sota, Yuki Hiramoto, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Takayuki Kudoh, Tomonari Kasai, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

    INTERNATIONAL JOURNAL OF CANCER   135 ( 1 )   27 - 36   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The self-renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs.

    DOI: 10.1002/ijc.28648

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  • Cancer stem cells maintain a hierarchy of differentiation by creating their niche

    Shuichi Matsuda, Ting Yan, Akifumi Mizutani, Tatsuyuki Sota, Yuki Hiramoto, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Takayuki Kudoh, Tomonari Kasai, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

    INTERNATIONAL JOURNAL OF CANCER   135 ( 1 )   27 - 36   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The self-renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS-LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS-LLCcm cells were autonomously balanced with stem-like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self-renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS-LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs.

    DOI: 10.1002/ijc.28648

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  • A Cancer Stem Cell Model: An Insight into the Conversion of Induced Pluripotent Stem Cells to Cancer Stem-Like Cells

    Akifumi Mizutani, Ling Chen, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Li Fu, Masaharu Seno

    Cancer Stem Cells   79 - 87   2014年4月

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    記述言語:英語   出版者・発行元:Wiley Blackwell  

    Appropriate model cell lines recapitulating cancer stem cell (CSC) properties would accelerate not only investigation of cancer stem cells but also development of new clinical cancer therapy by establishing a screening system for anti-cancer stem cell agents. In this chapter, the authors introduce their recent work and others to generate cells with cancer stem cell properties in vitro. They also discuss the concept of cancer stem cells with results obtained from originally established cancer stem-like cells. Finally, they describe future applications of the model to basic and clinical studies. In the field of regeneration therapy, the pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising sources of differentiated cells for transplantation. Interestingly, these cancer stem-like cells were not required to be introduced with the genes for cell surface markers that are commonly used to characterize and isolate cancer stem cells.

    DOI: 10.1002/9781118356203.ch6

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  • Development of In-111-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging

    Mikako Ogawa, Izumi O. Umeda, Mutsumi Kosugi, Ayumi Kawai, Yuka Hamaya, Misato Takashima, Hongxia Yin, Takayuki Kudoh, Masaharu Seno, Yasuhiro Magata

    JOURNAL OF NUCLEAR MEDICINE   55 ( 1 )   115 - 120   2014年1月

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    記述言語:英語   出版者・発行元:SOC NUCLEAR MEDICINE INC  

    Macrophage infiltration is a common characteristic feature of atherosclerotic-vulnerable plaques. Macrophages recognize phosphatidylserine (PS) exposed on the surface of apoptotic cells, which triggers the engulfment of the apoptotic cells by macrophages through phagocytosis. In this study, we prepared radiolabeled PS liposomes for detection of vulnerable plaques. Methods: PS liposomes were prepared by lipid film hydration. Phosphatidylcholine (PC) liposomes were prepared as controls. Liposomes (100 or 200 nm) were generated by an extruder to produce PS100, PS200, PC100, and PC200 liposomes. These were then radiolabeled by encapsulating In-111-nitrilotriacetic acid using an active-loading method. In-111 liposomes were incubated with cultured macrophages for 2 h, and the uptake level was measured. For biodistribution studies, the In-111 liposomes were injected intravenously into ddY mice. In addition, the In-111 liposomes were injected into apolipoprotein E-deficient (apoE-/-) mice, and the aortas were harvested for autoradiography and oil red O staining. For SPECT imaging, In-111 liposomes were injected intravenously into Watanabe heritable hyperlipidemic rabbits and scanned 48 h after injection. Results: The radiochemical yields were greater than 95% for all the prepared In-111 liposomes. The level of in vitro uptake by macrophages was 60.5, 14.7, 32.0, and 14.4 percentage injected dose per milligram of protein for In-111-PS100, In-111-PC100, In-111-PS200, and In-111-PC200, respectively. In biodistribution studies, high spleen uptake was seen with PC liposomes. Liver uptake was high for all liposomes but was lowest with In-111-PS200. The blood half-lives were 3.2, 22.0, 3.6, and 7.4 min for In-111-PS100, In-111-PC100, In-111-PS200, and In-111-PC200, respectively. The distribution of In-111-labeled PS liposomes into atherosclerotic regions determined by autoradiography was well matched with the results of oil red O staining in apoE-/- mice. The target-to-nontarget ratios were 2.62, 2.23, 3.27, and 2.51 for In-111-PS100, In-111-PC100, In-111-PS200, and In-111-PC200, respectively. The aorta was successfully visualized by SPECT at 48 h after In-111-labeled PS liposome injection; however, high liver uptake was also observed. Discussion: From the in vitro uptake study, it has been demonstrated that macrophage targeting was accomplished by PS modification. Also, an atherosclerotic region was successfully detected by In-111-PS200 in apoE-/- mice and Watanabe heritable hyperlipidemic rabbits in vivo. Liposome modification to obtain slower blood clearance and lower liver uptake would be required to improve the SPECT images.

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  • Chlorotoxin-Fc Fusion Inhibits Release of MMP-2 from Pancreatic Cancer Cells

    Samah El-Ghlban, Tomonari Kasai, Tsukasa Shigehiro, Hong Xia Yin, Sreeja Sekhar, Mikiko Ida, Anna Sanchez, Akifumi Mizutani, Takayuki Kudoh, Hiroshi Murakami, Masaharu Seno

    BIOMED RESEARCH INTERNATIONAL   152659   2014年

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    記述言語:英語   出版者・発行元:HINDAWI PUBLISHING CORPORATION  

    Chlorotoxin (CTX) is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc). The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1) in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ), the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer.

    DOI: 10.1155/2014/152659

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  • Mouse induced pluripotent stem cell microenvironment generates epithelial-mesenchymal transition in mouse Lewis lung cancer cells

    Ling Chen, Akifumi Mizutani, Tomonari Kasai, Ting Yan, Guoliang Jin, Arun Vaidyanath, Bishoy Y. A. El-Aarag, Yixin Liu, Takayuki Kudoh, David S. Salomon, Li Fu, Masaharu Seno

    AMERICAN JOURNAL OF CANCER RESEARCH   4 ( 1 )   80 - U92   2014年

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    記述言語:英語   出版者・発行元:E-CENTURY PUBLISHING CORP  

    Induced pluripotent stem (iPS) cells may be a powerful tool in regenerative medicine, but their potential tumorigenicity is a significant challenge for the clinical use of iPS cells. Previously, we succeeded in converting miPS cells into cancer stem cells (CSCs) under the conditions of tumor microenvironment. Both stem cells and tumor cells are profoundly influenced by bi-directional communication with their respective microenvironment, which dictates cell fate determination and behavior. The microenvironment derived from iPS cells has not been well studied. In this paper, we have investigated the effects of secreted factors from Nanog-mouse iPS (miPS) cells on mouse Lewis lung cancer (LLC) cells that are found in the conditioned media. The results demonstrated that miPS cells secrete factors that can convert the epithelia phenotype of LLC cells to a mesenchymal phenotype, and that can promote tumorigenisity, migration and invasion. Furthermore, LLC cells that have been exposed to miPS conditioned medium became resistant to apoptosis. These various biological effects suggest that the miPS microenvironment contain factors that can promote an epithelial-mesenchymal transition (EMT) through an active Snail-MMP axis or by suppressing differentiation in LLC cells.

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  • Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles

    Ting Yan, Akifumi Mizutani, Ling Chen, Mai Takaki, Yuki Hiramoto, Shuichi Matsuda, Tsukasa Shigehiro, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Junko Masuda, Mary J. C. Hendrix, Luigi Strizzi, David S. Salomon, Li Fu, Masaharu Seno

    JOURNAL OF CANCER   5 ( 7 )   572 - 584   2014年

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    記述言語:英語   出版者・発行元:IVYSPRING INT PUBL  

    Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.

    DOI: 10.7150/jca.8865

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  • Mutual dependence between cancer stem cells and their progenies: the niche created by the progenies is sustaining cancer stem cells.

    Cancer Cell & Microenvironment   1 ( 4 )   141 - 144   2014年

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  • Cancer stem cells converted from pluripotent stem cells and the cancerous niche.

    Kasai T, Chen L, Mizutani A, Kudoh T, Murakami H, Fu L, Seno M

    Journal of Stem cells & regenerative medicine   10 ( 1 )   2 - 7   2014年

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  • High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor.

    Auf G, Jabouille A, Delugin M, Guérit S, Pineau R, North S, Platonova N, Maitre M, Favereaux A, Vajkoczy P, Seno M, Bikfalvi A, Minchenko D, Minchenko O, Moenner M

    BMC Cancer.   13   13 - 597   2013年12月

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  • Cytokine expression in human dermal fibroblasts stimulated with eosinophil cationic protein measured by protein array

    Takamaro Sato, Yoshihiko Soga, Tomoko Yamaguchi, Michio Meguro, Hiroshi Maeda, Joji Tada, Takayuki Otani, Masaharu Seno, Shogo Takashiba

    ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY   31 ( 4 )   271 - 276   2013年12月

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    記述言語:英語   出版者・発行元:ALLERGY IMMUNOL SOC THAILAND,  

    Background: Eosinophil cationic protein (ECP) was reported previously to be involved in allergic inflammation with cytotoxic activity. On the other hand, recent studies showed that ECP did not induce cell death but inhibited the growth of cancer-derived cells. Our previous study indicated that human ECP enhanced differentiation of rat neonatal cardiomyocytes and stress fiber formation in Balb/c 3T3 mouse fibroblasts, while the effects of human ECP on human fibroblasts are unknown.
    Objective: The present study was performed to determine the effects of human ECP on cytokine expression in human fibroblasts by protein array.
    Methods: The effects of recombinant human ECP (rhECP) on normal human dermal fibroblasts (NHDF) were examined by assaying cell growth. Furthermore, cytokine expression of NHDF stimulated by ECP, which could influence cell growth, was evaluated by protein array.
    Results: ECP was not cytotoxic but enhanced the growth of NHDF. The peak rhECP concentration that enhanced the cell counts by 1.56-fold was 100 ng/mL, which was significantly different from cultures without ECP stimulation (ANOVA/ Scheffe's test, P &lt; 0.05). Array analyses indicated that ciliary neurotrophic factor (CNTF), neutrophil-activating peptide (NAP)-2, and neurotrophin (NT)-3 were significantly upregulated in NHDF stimulated with 100 ng/mL ECP compared to those without stimulation.
    Conclusion: ECP is not cytotoxic but enhances the growth of NHDF. CNTF, NAP-2, and NT-3 were suggested to be involved in enhancing the growth of NHDF. These findings will contribute to determination of the role of ECP in allergic inflammation.

    DOI: 10.12932/AP0287.31.4.2013

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  • Steering target selectivity and potency by fragment-based de novo drug design.

    Rodrigues T, Kudoh T, Roudnicky F, Lim YF, Lin YC, Koch CP, Seno M, Detmar M, Schneider G.

    Angew Chem Int Ed Engl   52 ( 38 )   10006 - 10009   2013年9月

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  • Steering Target Selectivity and Potency by Fragment-Based De Novo Drug Design

    Tiago Rodrigues, Takayuki Kudoh, Filip Roudnicky, Yi Fan Lim, Yen-Chu Lin, Christian P. Koch, Masaharu Seno, Michael Detmar, Gisbert Schneider

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   52 ( 38 )   10006 - 10009   2013年9月

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    記述言語:英語   出版者・発行元:WILEY-V C H VERLAG GMBH  

    DOI: 10.1002/anie.201304847

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  • Nano-micrometer-architectural acidic silica prepared from iron oxide of leptothrix ochracea origin

    Hideki Hashimoto, Atsushi Itadani, Takayuki Kudoh, Satoshi Fukui, Yasushige Kuroda, Masaharu Seno, Yoshihiro Kusano, Yasunori Ikeda, Yasuhiko Benino, Tokuro Nanba, Makoto Nakanishi, Tatsuo Fujii, Jun Takada

    ACS Applied Materials and Interfaces   5 ( 11 )   5194 - 5200   2013年6月

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    記述言語:英語  

    We prepared nano-micrometer-architectural acidic silica from a natural amorphous iron oxide with structural silicon which is a product of the iron-oxidizing bacterium Leptothrix ochracea. The starting material was heat-treated at 500 C in a H2 gas flow leading to segregation of α-Fe crystalline particles and then dissolved in 1 M hydrochloric acid to remove the α-Fe particles, giving a gray-colored precipitate. It was determined to be amorphous silica containing some amount of iron (Si/Fe = ∼60). The amorphous silica maintains the nano-microstructure of the starting material - ∼1-μm-diameter micrometer-tubules consisting of inner globular and outer fibrillar structures several tens of nanometer in size - and has many large pores which are most probably formed as a result of segregation of the α-Fe particles on the micrometer-tubule wall. The smallest particle size of the amorphous silica is ∼10 nm, and it has a large surface area of 550 m2/g with micropores (0.7 nm). By using pyridine vapor as a probe molecule to evaluate the active sites in the amorphous silica, we found that it has relatively strong Brønsted and Lewis acidic centers that do not desorb pyridine, even upon evacuation at 400 C. The acidity of this new silica material was confirmed through representative two catalytic reactions: ring-opening reaction and Friedel-Crafts-type reaction, both of which are known to require acid catalysts. © 2013 American Chemical Society.

    DOI: 10.1021/am401029r

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  • Nano-micrometer-architectural acidic silica prepared from iron oxide of leptothrix ochracea origin

    Hideki Hashimoto, Atsushi Itadani, Takayuki Kudoh, Satoshi Fukui, Yasushige Kuroda, Masaharu Seno, Yoshihiro Kusano, Yasunori Ikeda, Yasuhiko Benino, Tokuro Nanba, Makoto Nakanishi, Tatsuo Fujii, Jun Takada

    ACS Applied Materials and Interfaces   5 ( 11 )   5194 - 5200   2013年6月

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    記述言語:英語  

    We prepared nano-micrometer-architectural acidic silica from a natural amorphous iron oxide with structural silicon which is a product of the iron-oxidizing bacterium Leptothrix ochracea. The starting material was heat-treated at 500 C in a H2 gas flow leading to segregation of α-Fe crystalline particles and then dissolved in 1 M hydrochloric acid to remove the α-Fe particles, giving a gray-colored precipitate. It was determined to be amorphous silica containing some amount of iron (Si/Fe = ∼60). The amorphous silica maintains the nano-microstructure of the starting material - ∼1-μm-diameter micrometer-tubules consisting of inner globular and outer fibrillar structures several tens of nanometer in size - and has many large pores which are most probably formed as a result of segregation of the α-Fe particles on the micrometer-tubule wall. The smallest particle size of the amorphous silica is ∼10 nm, and it has a large surface area of 550 m2/g with micropores (0.7 nm). By using pyridine vapor as a probe molecule to evaluate the active sites in the amorphous silica, we found that it has relatively strong Brønsted and Lewis acidic centers that do not desorb pyridine, even upon evacuation at 400 C. The acidity of this new silica material was confirmed through representative two catalytic reactions: ring-opening reaction and Friedel-Crafts-type reaction, both of which are known to require acid catalysts. © 2013 American Chemical Society.

    DOI: 10.1021/am401029r

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  • Eosinophil cationic protein enhances stabilization of β-catenin during cardiomyocyte differentiation in P19CL6 embryonal carcinoma cells.

    Jin G, Mizutani A, Fukuda T, Otani T, Yan T, Prieto Vila M, Murakami H, Kudoh T, Hirohata S, Kasai T, Salomon DS, Seno M

    Mol Biol Rep.   40 ( 4 )   3165 - 3171   2013年4月

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  • Eosinophil cationic protein enhances stabilization of beta-catenin during cardiomyocyte differentiation in P19CL6 embryonal carcinoma cells

    Guoliang Jin, Akifumi Mizutani, Takayuki Fukuda, Takayuki Otani, Ting Yan, Marta Prieto Vila, Hiroshi Murakami, Takayuki Kudoh, Satoshi Hirohata, Tomonari Kasai, David S. Salomon, Masaharu Seno

    MOLECULAR BIOLOGY REPORTS   40 ( 4 )   3165 - 3171   2013年4月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Prior to gastrulation, the Wnt signaling pathway through stabilized beta-catenin enhances the differentiation of mouse ES cell into cardiomyocytes. We have recently shown that cardiomyocyte differentiation is enhanced by eosinophil cationic protein (ECP) through accelerated expression of marker genes of early cardiac differentiation. Furthermore, ECP enhanced the expression of Wnt3a in P19CL6 cells which were stimulated to differentiate into cardiomyocytes by DMSO. Following these findings, we evaluated in this study the potential of ECP to activate the Wnt/beta-catenin signaling pathway during cardiomyocyte differentiation. Analysis by real time qPCR revealed that ECP increased the expression of Frizzled genes such as Frizzled-1, -2, -4 and -10 in P19CL6 cells in the presence of DMSO. The increased expression of those Wnt receptors was found to inhibit the phosphorylation of beta-catenin resulting in the stabilization and translocation of beta-catenin into the nucleus of P19CL6 cells during the early stages of cardiomyocyte differentiation. When assessed for beta-catenin/TCF transcriptional activity with a TCF-luciferase (TOP/FOP) assay, ECP enhanced luciferase activity in P19CL6 cells during 48 h after transfection with TOP/FOP flash reporter in a stoichiometric manner. Collectively, this suggests that ECP can activate a canonical Wnt/beta-catenin signaling pathway by enhancing the stabilization of beta-catenin during cardiomyocyte differentiation.

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  • A novel remote loading method with solubility gradient to encapsulate effevtive amount of taxanes into liposomes.

    Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

    CANCER RESEARCH   73 ( 8 )   2013年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2013-LB-8

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  • 再生医療薬としての心筋分化促進因子ECP (特集 ライフイノベーションの未来戦略)

    水谷 昭文, 笠井 智成, 妹尾 昌治

    化學工業   64 ( 4 )   249 - 253   2013年4月

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    記述言語:日本語   出版者・発行元:小峰工業出版  

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  • Acidic Amorphous Silica Prepared from Iron Oxide of Bacterial Origin

    Hideki Hashimoto, Atsushi Itadani, Takayuki Kudoh, Yasushige Kuroda, Masaharu Seno, Yoshihiro Kusano, Yasunori Ikeda, Makoto Nakanishi, Tatsuo Fujii, Jun Takada

    ACS APPLIED MATERIALS & INTERFACES   5 ( 3 )   518 - 523   2013年2月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    Microporous and mesoporous silica derived from biogenous iron oxide is an attractive catalyst for various organic reactions. Biogenous iron oxide contains structural silicon, and amorphous silica remains after iron oxide is dissolved in concentrated hydrochloric acid. The amorphous silica containing slight amounts of iron (Si/Fe = similar to 150) is composed of similar to 6-nm-diameter granular particles. The amorphous silica has a large surface area of 540 m(2)/g with micropores (1.4 nm) and mesopores (&lt;3 nm). By using pyridine vapor as a probe molecule to evaluate the active sites in the amorphous silica, it was found that this material has strong Bronsted and Lewis acid sites. When the catalytic performance of this material was evaluated for reactions including the ring opening of epoxides and Friedel Crafts-type alkylations, which are known to be catalyzed by acid catalysts, this material showed yields higher than those obtained with common silica materials.

    DOI: 10.1021/am302837p

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  • Acidic amorphous silica prepared from iron oxide of bacterial origin.

    Hashimoto H, Itadani A, Kudoh T, Kuroda Y, Seno M, Kusano Y, Ikeda Y, Nakanishi M, Fujii T, Takada J.

    ACS Appl Mater Interfaces   5 ( 3 )   518 - 523   2013年2月

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  • Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors.

    Nagaoka T, Karasawa H, Turbyville T, Rangel MC, Castro NP, Gonzales M, Baker A, Seno M, Lockett S, Greer YE, Rubin JS, Salomon DS, Bianco C

    Cellular signalling   25 ( 1 )   178 - 189   2013年1月

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  • Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors

    Tadahiro Nagaoka, Hideaki Karasawa, Thomas Turbyville, Maria-Cristina Rangel, Nadia P. Castro, Monica Gonzales, Alyson Baker, Masaharu Seno, Stephen Lockett, Yoshimi E. Greer, Jeffrey S. Rubin, David S. Salomon, Caterina Bianco

    Cellular Signalling   25 ( 1 )   178 - 189   2013年1月

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    記述言語:英語  

    Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells. © 2012.

    DOI: 10.1016/j.cellsig.2012.09.024

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  • マウスiPS細胞から作るがん幹細胞モデル

    笠井智成, 陳 凌, 工藤孝幸, 水谷昭文, 妹尾昌治

    細胞工学   32 ( 3 )   330 - 337   2013年

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  • Theranostic protein targeting ErbB2 for bioluminescence imaging and therapy for cancer. 国際誌

    Xiao-Jian Han, Ling-Fei Sun, Yuki Nishiyama, Bin Feng, Hiroyuki Michiue, Masaharu Seno, Hideki Matsui, Kazuhito Tomizawa

    PloS one   8 ( 9 )   e75288   2013年

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    記述言語:英語  

    A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.

    DOI: 10.1371/journal.pone.0075288

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  • Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells

    Sreeja C. Sekhar, Tomonari Kasai, Ayano Satoh, Tsukasa Shigehiro, Akifumi Mizutani, Hiroshi Murakami, Bishoy Y. A. El-Aarag, David S. Salomon, Anna Massaguer, Rafael de Llorens, Masaharu Seno

    JOURNAL OF CANCER   4 ( 5 )   391 - 401   2013年

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    記述言語:英語   出版者・発行元:IVYSPRING INT PUBL  

    The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment.

    DOI: 10.7150/jca.6470

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  • Identification of caveolin-1 as a potential causative factor in the generation of trastuzumab resistance in breast cancer cells.

    Sekhar SC, Kasai T, Satoh A, Shigehiro T, Mizutani A, Murakami H, El-Aarag BY, Salomon DS, Massaguer A, de Llorens R, Seno M.

    J Cancer   4 ( 5 )   391 - 401   2013年

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  • Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer. 国際誌

    Han XJ, Sun LF, Nishiyama Y, Feng B, Michiue H, Seno M, Matsui H, Tomizawa K.

    PLoS One.   8 ( 9 )   e75288 - e75288   2013年

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  • Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway.

    Growth Factors   30 ( 5 )   344 - 355   2012年10月

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  • Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway

    Guoliang Jin, Akifumi Mizutani, Takayuki Fukuda, Ling Chen, Keisuke Nakanishi, Ting Yan, Takayuki Kudoh, Satoshi Hirohata, Tomonari Kasai, Hiroshi Murakami, David S. Salomon, Masaharu Seno

    GROWTH FACTORS   30 ( 5 )   344 - 355   2012年10月

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    We investigated the functional role of eosinophil cationic protein (ECP) in regulating cardiomyogenesis using mouse P19CL6 embryonic carcinoma cells. ECP was confirmed to accelerate the cardiomyocyte differentiation of P19CL6 cells by enhancing the rate and area size of beating of cardiomyocyte and by facilitating the expression of cardiomyocyte-specific genes, such as GATA4 and alpha-MHC. Since cardiomyocyte differentiation in vivo is considered to follow mesoderm induction, the induction of Brachyury, a marker of mesoderm, was assessed. Brachyury expression was found to be enhanced after the addition of ECP. This enhancement was due to the stimulation of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation by ECP. In this context, treatment with SU5402, an inhibitor of fibroblast growth factor (FGF) receptor 1, suppressed Brachyury expression, phosphorylation of ERK1/2, and cardiomyocyte differentiation induced by ECP. We concluded that ECP might induce mesoderm differentiation through FGF signaling pathway and enhance subsequent cardiomyocyte differentiation in concert with dimethyl sulfoxide in P19CL6 cells. ECP may be a novel factor for cardiomyocyte differentiation, which should be very useful to prepare adequate numbers of cardiomyocytes for therapeutic cell transplantation.

    DOI: 10.3109/08977194.2012.709852

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  • A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells

    Ling Chen, Tomonari Kasai, Yueguang Li, Yuh Sugii, Guoliang Jin, Masashi Okada, Arun Vaidyanath, Akifumi Mizutani, Ayano Satoh, Takayuki Kudoh, Mary J. C. Hendrix, David S. Salomon, Li Fu, Masaharu Seno

    PLOS ONE   7 ( 4 )   e33544   2012年4月

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    記述言語:英語   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5'-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.

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  • Preparation and evaluation of glycosylated paclitaxel loaded in tastuzumab-immunoliposome

    Masaharu Murakami, Tomonari Kasai, Masashi Okada, Katsuhiko Mikuni, Naoyoshi Egashira, Masaharu Seno, Hiroki Hamada

    CANCER RESEARCH   72   2012年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-5700

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  • Development and characterization of cancer stem cell model from mouse iPS cells

    Ling Chen, Shuichi Matsuda, Tomonari Kasai, Yuh Sugii, Masashi Okada, Koichi Igarashi, Ayano Satoh, Takayuki Kudoh, Takayuki Kudoh, Li Fu, Masaharu Seno

    CANCER RESEARCH   72   2012年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-418

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  • The Conformational Polymorphism of the Green Fluorescent Protein

    Molecular Biology   46 ( 1 )   142 - 148   2012年2月

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  • The Conformational Polymorphism of the Green Fluorescent Protein

    Haidong Tan, Yueguang Li, Ling Chen, Takayuki Kudoh, Tomonari Kasai, Masaharu Seno

    MOLECULAR BIOLOGY   46 ( 1 )   142 - 148   2012年2月

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    記述言語:英語   出版者・発行元:MAIK NAUKA/INTERPERIODICA/SPRINGER  

    Green fluorescent protein (GFPuv) has been widely used as a reporter fused to individual targeting sequences. However, its state in liquid and its effect on other proteins are still unclear. The conformational polymorphisms of glutathione-S-transferase-green fluorescent protein (GST-GFPuv), GFPuv and GST were analyzed by native polyacrylamide gel, indicating that GST was in many different states while GFPuv and GST-GFPuv were only in four and two slightly different states. Four different circular dichroism spectra were obtained from the GFPuv polymorphisms. The single molecular behavior of GST-GFPuv and GFPuv was also characterized by MALDI-TOF MS. Thus, we demonstrated that: (1) there might be four different structural polymorphisms for the native GFPuv; (2) GFPuv could reduce its partner's polymorphism as a fusion protein. Although GFPuv had many merits as a reporter, its unreliability was found in the study. DOI: 10.1134/S0026893311060045

    DOI: 10.1134/S0026893311060045

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  • Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis.

    Kasai T, Nakamura K, Vaidyanath A, Chen L, Sekhar S, El-Ghlban S, Okada M, Mizutani A, Kudoh T, Murakami H, Seno M

    J Drug Deliv.   2012   975763   2012年

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  • A model of cancer stem cells derived from mouse induced pluripotent stem cells.

    PLoS One   7 ( 4 )   e33544   2012年

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    記述言語:英語  

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  • Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis.

    2012   975763   2012年

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  • Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand

    Arun Vaidyanath, Toshihiro Hashizume, Tadahiro Nagaoka, Nao Takeyasu, Hitomi Satoh, Ling Chen, Jiyou Wang, Tomonari Kasai, Takayuki Kudoh, Ayano Satoh, Li Fu, Masaharu Seno

    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE   15 ( 11 )   2525 - 2538   2011年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

    DOI: 10.1111/j.1582-4934.2011.01277.x

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  • Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand

    Vaidyanath, Arun; Hashizume, Toshihiro; Nagaoka, Tadahiro; et al.

    Journal of Cellular and Molecular Medicine   15 ( 11 )   2525 - 2538   2011年11月

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  • Construction of a high-efficiency multi-site-directed mutagenesis

    Haidong Tan, Yueguang Li, Ling Chen, Tomonari Kasai, Masaharu Seno

    AFRICAN JOURNAL OF BIOTECHNOLOGY   10 ( 3 )   449 - 452   2011年1月

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    記述言語:英語   出版者・発行元:ACADEMIC JOURNALS  

    Although site-directed mutagenesis has been used in many fields, it still has low rate of success and high cost because of low-yield target products. A modified method for multi-site-directed mutagenesis was developed with shifted primer design and cold-start polymerase chain reaction (PCR). The developed method was successfully applied to hexapeptide gene synthesis and recombinant enterokinase gene modification in the plasmids pET41a and pET24b-EK. The efficiency was pronounced at a 1:10 molar ratio of 7-base mutant products to 705-bp fragment products as control. Even in a 10-base substitution mutagenic PCR, a 1:50 molar ratio of mutant products to 705-bp fragment products was reached. Meanwhile, the quality of mutants was proved through the transformation efficiency and sequencing. This method was beneficial to prepare high-quality multibase mutagenesis and also implied that large-scale multibase mutagenesis was feasible, efficient, economical, and productive.

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  • Extracellular Matrix Modulates Insulin Production During Differentiation of AR42J Cells: Functional Role of Pax6 Transcription Factor

    Kohei Hamamoto, Satoko Yamada, Akemi Hara, Tsutomu Kodera, Masaharu Seno, Itaru Kojima

    JOURNAL OF CELLULAR BIOCHEMISTRY   112 ( 1 )   318 - 329   2011年1月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Extracellular matrix (ECM) modulates differentiation of pancreatic beta-cells during development. However, the mechanism by which ECM proteins modulate differentiation is not totally clear. We investigated the effect of ECM proteins on differentiation beta-cells in vitro. We investigated the effect of basement membrane ECM on differentiation of AR42J cells and rat ductal cells. First, we examined the effect of reconstituted basement membrane, Matrigel on differentiation of AR42J cells induced by activin and betacellulin. Matrigel augmented insulin production and increased the expression of GLUT2, SUR1, and glucokinase. Among various transcription factors investigated, Matrigel markedly upregulated the expression of Pax6. When Pax6 was overexpressed in cells treated with activin and betacellulin, the expression of insulin was upregulated. Conversely, knockdown of Pax6 significantly reduced the insulin expression in cells cultured on Matrigel. The effects of Matrigel on insulin-production and induction of Pax6 were reproduced partially by laminin-1, a major component of Matrigel, and inhibited by anti-integrin-beta 1 antibody. Matrigel also enhanced the activation of p38 mitogen-activated kinase induced by activin and betacellulin, which was inhibited by anti-beta 1 antibody. Finally, the effect of Matrigel on differentiation was reproduced in rat cultured ductal cells, and Matrigel also increased the expression of Pax6. These results indicate that basement membrane ECM augments differentiation of pancreatic progenitor cells to insulin-secreting cells by upregulating the expression of Pax6. J. Cell. Biochem. 112: 318329, 2011. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/jcb.22930

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  • Clustering Genes, Tissues, Cells and Bioactive Chemicals by Sphere SOM

    Self Organizing Maps-applications and novel algorithm design   15 ( 11 )   371 - 386   2011年

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  • Clustering Genes, Tissues, Cells and Bioactive Chemicals by Sphere SOM

    15 ( 11 )   371 - 386   2011年

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  • Generation of Cancer Stem Cell Model from Mouse iPS Cells.

    A. Mizutani, S-I. Matsuda, T. Kasai, T. Kudoh, L. Chen, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   22   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Analysis of endothelium mimicry by the CSC-like cells derived from iPS cells.

    S-I. Matsuda, A. Mizutani, T. Kasai, A. Satoh, T. Kudoh, L. Chen, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   22   2011年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Optimization of Bacterial Plasmid Transformation Using Nanomaterials Based on the Yoshida Effect

    Haidong Tan, Li Fu, Masaharu Seno

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   11 ( 12 )   4962 - 4973   2010年12月

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    記述言語:英語   出版者・発行元:MDPI AG  

    With the help of sepiolite, a unique method for transforming DNA into bacteria, based on the Yoshida effect, has been developed recently. However, we confronted many problems when this newest method was tried. Only a few transformants could be obtained even when 100 ng of plasmid pET15b was used, and a successful result seemed difficult to repeat. To address this problem, we optimized the operating method and could achieve about 15,000 transformants using the same amount of plasmid, which could match the efficiency gained using the calcium chloride transformation method. Meanwhile, the results could also be reproduced well. In the same way, carbon nanotubes were used to attain more than 15,000 transformants in the same situation. Therefore, the transformation method could be extended to other nanomaterials. Meanwhile, compared with the mechanism previously reported, we verified quite a different principle for the mechanism responsible for such a transformation. In sum, this unique transformation can be developed to become the third widely-used transformation method in laboratories in addition to the chemical method and electroporation.

    DOI: 10.3390/ijms11124962

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  • First Report of Cucumber mosaic virus in Sweet Cherry in the People&apos;s Republic of China

    H. D. Tan, S. Y. Li, X. F. Du, M. Seno

    PLANT DISEASE   94 ( 11 )   1378 - 1378   2010年11月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)   出版者・発行元:AMER PHYTOPATHOLOGICAL SOC  

    DOI: 10.1094/PDIS-07-10-0549

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  • Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells

    M. Hirai, H. Minematsu, Y. Hiramatsu, H. Kitagawa, T. Otani, S. Iwashita, T. Kudoh, L. Chen, Y. Li, M. Okada, D. S. Salomon, K. Igarashi, M. Chikuma, M. Seno

    INTERNATIONAL JOURNAL OF PHARMACEUTICS   391 ( 1-2 )   274 - 283   2010年5月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects.
    High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis-diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of COOP. We further conjugated the CDDP-Lip with Sialyl Lewis(X) (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis(X) enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues. (C) 2010 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ijpharm.2010.02.030

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  • E-selectin targeting to visualize tumors in vivo

    Masahiko Hirai, Yoshie Hiramatsu, Shinki Iwashita, Takayuki Otani, Ling Chen, Yue-guang Li, Masashi Okada, Kazunori Oie, Koich Igarashi, Hideaki Wakita, Masaharu Seno

    CONTRAST MEDIA & MOLECULAR IMAGING   5 ( 2 )   70 - 77   2010年3月

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    記述言語:英語   出版者・発行元:JOHN WILEY & SONS LTD  

    Generally angiogenic factors induce the expression of E-selectin in vascular endothelial cells in the tumors. In this study, we employed an anti-E-selectin monoclonal antibody to target tumors in vivo and evaluated an optical imaging reagent to visualize tumor regions. The anti-E-selectin antibody was conjugated on the surface of liposomes, which encapsulated the near-infrared fluorescent substances Cy3 or Cy5.5. The liposomes efficiently recognized human umbilical vein endothelial cells only when E-selectin was induced by angiogenic factors such as TNF-alpha in vitro. Cy5.5 encapsulated into liposomes that were conjugated with an anti-E-selectin antibody successfully visualized Ehrlich ascites tumor cells when transplanted into mice. Thus, E-selectin targeting with liposomes containing a near-infrared fluorescent dye was found effective in visualizing tumors in vivo. This strategy should be extremely useful as a method to identify sentinel lymphatic nodes and angiogenic tumors as well as use for drug delivery to tumor cells. Copyright (C) 2010 John Wiley & Sons, Ltd.

    DOI: 10.1002/cmmi.367

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  • Production of biologically active IgG hinge-tag soluble epidermal growth factor receptors (ErbB)

    Takayuki Otani, Toshihiro Hashizume, Tadahiro Nagaoka, Tomoko Fukuda, Careen K. Tang, David S. Salomon, Masaharu Seno

    BIOTECHNOLOGY LETTERS   32 ( 3 )   361 - 366   2010年3月

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    記述言語:英語   出版者・発行元:SPRINGER  

    The extracellular domains (ECD) of epidermal growth factor receptors, ErbB1, 2, 3 and 4, were designed as soluble dimeric forms. Each ECD was fused to a short hinge region derived from IgG, such that the stable dimer could be formed with disulfide bridges. This hinge-tagged design minimized the molecular weight to approximately 50% of the conventional Fc-fusion design without an Fc domain of IgG. The refolded dimers could be easily analyzed and characterized by SDS-PAGE. Hinge-tagged soluble ErbBs demonstrated significant affinity for betacellulin and heregulin. The IgG hinge-tag should be a simple method to design soluble dimers that would be useful for high throughput screening of ligands, antagonists or derivatives.

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  • Administration of Conophylline and Betacellulin-delta 4 Increases the beta-cell Mass in Neonatal Streptozotocin-treated Rats

    Tsutomu Kodera, Satoko Yamada, Yoritsuna Yamamoto, Akemi Hara, Yuji Tanaka, Masaharu Seno, Kazuo Umezawa, Izumi Takei, Itaru Kojima

    ENDOCRINE JOURNAL   56 ( 6 )   799 - 806   2009年9月

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    記述言語:英語   出版者・発行元:JAPAN ENDOCRINE SOC  

    The present study was conducted to examine the effect of administration of conophylline (CnP) and betacellulin delta 4 (BTC delta 4) on the beta-cell mass in neonatal streptozotocin-treated rats (neonatal STZ rats). STZ (100 mu g/g) was injected into neonatal rats, and then CnP (2 mu g/g) and/or BTC delta 4 (200 pmol/g) were administered to neonatal STZ rats for 1 week. The plasma glucose concentration was monitored, and an intraperitoneal glucose tolerance test (ipGTT) was performed on day 8 and at 8 weeks after the STZ injection. In neonatal STZ rats treated with control solution (S group), the plasma glucose concentration increased for several days after the STZ injection, returned to nearly normal levels, and then increased gradually after six weeks of age. Eight weeks after the STZ-injection, the plasma glucose concentration was increased significantly compared to that of normal rats. The glucose response to ipGTT was significantly reduced in neonatal STZ rats treated with CnP (CnP group), BTC delta 4 (delta 4 group) and CnP+BTC delta 4 (CnP+delta 4 group). The beta-cell mass and the insulin content of the pancreas were significantly increased in the CnP group and delta 4 group. The effect of CnP+delta 4 was greater than ;that of CnP alone or BTC delta 4 alone. CnP+BTC delta 4 significantly increased the number of PDX-1-positive ductal cells and the number of insulin/BrdU double-positive ductal cells. These results indicate the efficacy of CnP and BTC delta 4 in increasing the beta-cells mass of neonatal STZ-treated rats.

    DOI: 10.1507/endocrj.K09E-158

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  • Delivery of sodium borocaptate to glioma cells using immunoliposome conjugated with anti-EGFR antibodies by ZZ-His

    Bin Feng, Kazuhito Tomizawa, Hiroyuki Michiue, Shin-ichi Miyatake, Xiao-Jian Han, Atsushi Fujimura, Masaharu Seno, Mitsunori Kirihata, Hideki Matsui

    BIOMATERIALS   30 ( 9 )   1746 - 1755   2009年3月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    Nanoparticles are effective of delivering cargo into cells. Here, sodium borocaptate (BSH) was encapsulated in liposomes composed of nickel lipid, and anti-epidermal growth factor receptor (EGFR) antibodies were conjugated to the liposomes using the antibody affinity motif of protein A (ZZ) as an adaptor (immunoliposomes). The immunoliposomes were used to deliver BSH into EGFR-overexpressing glioma cells. Immunohistochemical analysis using an anti-BSH monoclonal antibody revealed that BSH was delivered effectively into the cells but not into EGFR-deficient glioma or primary astrocytes. In an animal model of brain tumors, both the liposomes and the BSH were only observed in the tumor. Moreover, the efficiency of (10)B&apos;s delivery into glioma cells was confirmed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) both in vitro and in vivo. The results suggest that this system utilizing immunoliposomes provides an effective means of delivering (10)B into glioma cells in boron neutron capture therapy (BNCT). (C) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2008.12.010

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  • Human eosinophil cationic protein enhances stress fiber formation in Balb/c 3T3 fibroblasts and differentiation of rat neonatal cardiomyocytes

    Takayuki Fukuda, Miki Iwata, Midori Kitazoe, Takashi Maeda, David Salomon, Satoshi Hirohata, Katsuyuki Tanizawa, Shun&apos;ichi Kuroda, Masaharu Seno

    GROWTH FACTORS   27 ( 4 )   228 - 236   2009年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    We found that eosinophil cationic protein (ECP) stimulated the growth of mouse Balb/c 3T3 fibroblasts. ECP-treated 3T3 cells were more flattened and exhibited enhanced stress fiber formation. The enhancement of cytoskeleton after addition of recombinant ECP appeared stable and was able to inhibit disassembly of actin filaments that was induced by fibroblast growth factor-2. The ROCK inhibitor, Y-27632, abrogated this enhancement on stress fiber formation that was induced by ECP indicating the involvement of Rho/ROCK signaling pathway. The effect of ECP was assessed on the differentiation of primary cardiomyocytes derived from rat neonatal heart since the development of actin filaments is significantly related with organization of stress fibers. As the result, both beating rate and the expression of cardiac muscle specific markers such as atrial natriuretic factor were enhanced in the presence of ECP. Thus ECP may also function as a cardiomyocyte differentiation factor.

    DOI: 10.1080/08977190902987149

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  • Spherical self-organizing map as a helpful tool to identify category-specific cell surface markers

    Tuoya, Yuh Sugii, Hitomi Satoh, Dongwei Yu, Yasaburo Matsuura, Heizo Tokutaka, Masaharu Seno

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   376 ( 2 )   414 - 418   2008年11月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We analyzed gene expression profiles of five tumor cell lines (NB2a, NB41A3, C1300N18, BC3H1, and Neuro2a) derived from a category of nervous system using our originally developed cell surface marker DNA microarray in order to search for tumor-specific cell surface markers common to these cells. To visualize the expression patterns and to extract candidate genes of interest based on the expression profiles of several cell lines, we employed the clustering procedure of spherical self-organizing-map. As the result, three candidates of tumor-specific cell surface markers were picked up when the expression profiles were compared with that from normal brain tissue. RT-qPCR showed the expression of these genes was higher in tumor cells than in normal brain. Here we demonstrated the spherical self-organizing-map analysis should be useful to identify the candidates of cell surface markers common and specific to the group of cells or tissues of interest. (C) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2008.09.010

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  • Intracellular delivery of glutathione S-transferase-fused proteins into mammalian cells by polyethylenimine-glutathione conjugates

    Hitoshi Murata, Junichiro Futami, Midori Kitazoe, Takayuki Yonehara, Hidetaka Nakanishi, Megumi Kosaka, Hiroko Tada, Masakiyo Sakaguchi, Yasuyuki Yagi, Masaharu Seno, Nam-ho Huh, Hidenori Yamada

    JOURNAL OF BIOCHEMISTRY   144 ( 4 )   447 - 455   2008年10月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    The glutathione S-transferase (GST)-fused protein expression system has been extensively used to generate a large quantity of proteins and has served for functional analysis in vitro. In this study, we developed a novel approach for the efficient intracellular delivery of GST-fused proteins into living cells to expand their usefulness up to in vivo use. Since protein cationization techniques are powerful strategies for efficient intracellular uptake by adsorptive-mediated endocytosis, GST-fused proteins were cationized by forming a complex with a polycationic polyethylenimine (PEI)-glutathione conjugate. On screening of protein transduction, optimized PEI-glutathione conjugate for protein transduction was characterized by a partly oligomerized mixture of PEI with average molecular masses of 600 (PEI600) modified with multiple glutathiones, which could have sufficient avidity for GST. Furthermore, enhanced endosomal escape of transduced GST-fused proteins was observed when they were delivered with a glutathione-conjugated PEI600 derivative possessing a hydroxybutenyl moiety. These results were confirmed by both intracellular confocal imaging of GST-fused green fluorescent protein and activation of an endogenous growth signal transduction pathway by a GST-fused constitutively active mutant of a kinase protein. These PEI-glutathione conjugates seem to be convenient molecular tools for protein transduction of widely used GST-fused proteins.

    DOI: 10.1093/jb/mvn087

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  • Smad2 functions as a co-activator of canonical Wnt/beta-catenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300

    Morihisa Hirota, Kazuhide Watanabe, Shin Hamada, Youping Sun, Luigi Strizzi, Mario Mancino, Tadahiro Nagaoka, Monica Gonzales, Masaharu Seno, Caterina Bianco, David S. Salomon

    CELLULAR SIGNALLING   20 ( 9 )   1632 - 1641   2008年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE INC  

    Both canonical Wnt/beta-catenin and TGF beta/Smad signaling pathways coordinately regulate pattern formation during embryogenesis as well as tumor progression. Evidence of cross-talk between these two pathways has been reported. Here we demonstrated that the Activin-like kinase 4 (Alk4)/Smad2 pathway facilitates the transcriptional activity of the oncogenic Wnt/beta-catenin/Tcf4 pathway through a novel Smad4-independent mechanism. Upon activation, Smad2 physically interacted with Tcf4, beta-catenin and the co-activator p300 to enhance transcriptional activity of beta-catenin/Tcf4 through the histone acetyltransferase activity of p300. Transactivation by Smad2 was independent of a Smad-binding element (SBE) and Smad4. Indeed, the enhancement of beta-catenin/Tcf4 transcriptional activity by activated Smad2 was negatively regulated by the presence of Smad4. Moreover, a tumor-derived missense mutant of Smad2, lacking the ability to bind to Smad4 was still able to enhance the Tcf4 transcriptional reporter in the presence of p-catenin and Tcf4. Our findings suggest that Smad2 may function as an activator of canonical Wnt/beta-catenin/Tcf4 signaling through a SBE/Smad4-independent pathway. Published by Elsevier Inc.

    DOI: 10.1016/j.cellsig.2008.05.003

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  • Characteristics of hollow microtubes consisting of amorphous iron oxide nanoparticles produced by iron oxidizing bacteria, Leptothrix ochracea (vol 310, pg 2405, 2007)

    H. Hashimoto, S. Yokoyama, H. Asaoka, Y. Kusano, Y. Ikeda, M. Seno, J. Takada, T. Fujii, M. Nakanishi, R. Murakami

    JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS   320 ( 18 )   2310 - 2310   2008年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    DOI: 10.1016/j.jmmm.2008.01.046

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  • Reversal of streptozotocin-induced hyperglycemia by continuous supply of betacellulin in mice

    Yoritsuna Yamamoto, Satoko Yamada, Tsutomu Kodera, Akemi Hara, Kazuo Motoyoshi, Yuji Tanaka, Tadahiro Nagaoka, Masaharu Seno, Itaru Kojima

    GROWTH FACTORS   26 ( 4 )   173 - 179   2008年8月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Previous studies have shown the efficacy of betacellulin (BTC) to promote P-cell regeneration. Because of its short half-life, however, the effect of BTC may have been underestimated. This study was conducted to assess the effect of continuous administration of BTC on P-cell regeneration. Adenovirus vectors encoding proBTC (Ad-proBTC) and mature BTC (Ad-mBTC) were prepared, and the efficacy of secretion of BTC was compared in AML12 hepatocytes. When AML12 cells were infected with Ad-proBTC or Ad-mBTC, cells infected with Ad-mBTC secreted considerably larger amount of BTC. We then infused Ad-mBTC into the mouse tail vein. Expression of BTC was detected in the liver for at least 21 days, and serum BTC was maintained at approximately 1 ng/ml for 7 days. When Ad-mBTC was infused immediately after administration of STZ (170 mg/kg), elevation of the plasma glucose induced by STZ was markedly inhibited, and the plasma glucose concentration remained at less than 200 mg/dl for 21 days. The insulin content and the P-cell mass were significantly increased in Ad-mBTC-infused mice. These results indicate that continuous administration of BTC is quite effective in promoting regeneration of P-cells.

    DOI: 10.1080/08977190802136854

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  • Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2

    Toshihiro Hashizume, Takayuki Fukuda, Tadahiro Nagaoka, Hiroko Tada, Hidenori Yamada, Kazuhide Watanabe, David S. Salomon, Masaharu Seno

    CELL BIOLOGY INTERNATIONAL   32 ( 7 )   814 - 826   2008年7月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    ErbB2, which is a member of the epidermal growth factor (erbB) receptor family, is frequently overexpressed in breast and ovarian cancers. Antibody and small molecule anti-tyrosine kinase inhibitors have been developed for targeted therapies for cancers overexpressing erbB2. Internalization and downregulation of erbB2, which is induced by a ligand, may be important for efficacious therapeutic effects. However, ligand-dependent erbB2 internalization has not been well characterized. Here we investigated the internalization of erbB2 in SKBr3 and SKOv3 cells, both overexpressing erbB2, using an EC-1 peptide fused to eGFP (EC-eGFP), which specifically binds to erbB2. ErbB2 was internalized in SKOv3 cells when the cells were treated with EC-eGFP. The accumulation of endosomal erbB2 was EC-eGFP dependent, which colocalized with transferrin implying endocytosis via clathrin-coated pits. In contrast, internalization of erbB2 was not observed in SKBr3 cells. As a result, two different mechanisms, which are cell type dependent for the internalization of erbB2, are proposed. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.cellbi.2008.03.012

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  • A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1

    Tadahiro Nagaoka, Takayuki Fukuda, Toshihiro Hlashizume, Tomoko Nishiyama, Hiroko Tada, Hidenori Yamada, David S. Salomon, Satoko Yamada, Itaru Kojima, Masaharu Seno

    JOURNAL OF MOLECULAR BIOLOGY   380 ( 1 )   83 - 94   2008年6月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    Betacellulin (BTC) is one of the members of the epidermal growth factor (EGF) ligand family of ErbB receptor tyrosine kinases. It is a differentiation factor as well as a potent mitogen. BTC promotes the differentiation of pancreatic acinar-derived AR42J cells into insulin-producing cells. It independently and preferentially binds to two type I tyrosine kinase receptors, the EGF receptor (ErbB1) and ErbB4. However, the physiochemical characteristics of BTC that are responsible for its preferential binding to these two receptors have not been fully defined. In this study, to investigate the essential amino acid residues of BTC for binding to the two receptors, we introduced point mutations into the EGF domain of BTC employing error-prone PCR. The receptor binding abilities of 190 mutants expressed in Escherichia coli were assessed by enzyme immunoassay. Replacement of the glutamic acid residue at position 88 with a lysine residue in BTC was found to produce a significant loss of affinity for binding to ErbB1, while the affinity of binding to ErbB4 was unchanged. In addition, the mutant of BTC-E/88/K showed less growth-promoting activity on BALB/c 3T3 cells compared with that of the wild-type BTC protein. Interestingly, the BTC mutant protein promoted differentiation of pancreatic acinar AR42J cells at a high frequency into insulin-producing cells compared with AR42J cells that were treated with wild-type BTC protein. These results indicate the possibility of designing BTC mutants, which have an activity of inducing differentiation only, without facilitating growth promotion. (C) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jmb.2008.03.054

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  • A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4

    Etsuko Hisanaga, Kee-Yong Park, Satoko Yamada, Hiromi Hashimoto, Toshlyukj Takeuchi, Masatomo Mori, Masaharu Seno, Kazuo Umezawa, Izumi Takei, Itaru Kojima

    ENDOCRINE JOURNAL   55 ( 3 )   535 - 543   2008年6月

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    記述言語:英語   出版者・発行元:JAPAN ENDOCRINE SOC  

    The present study was conducted to establish a method to induce differentiation of bone marrow (MB)-derived mesenchymal cells into insulin-producing cells. When mouse BM-derived mesenchymal cells were cultured for 60 days in medium containing 10% fetal calf serum and 25 mM glucose, they expressed insulin. Addition of activin A and betacellulin (BTC) accelerated differentiation, and immunoreactive insulin was detected 14 days after the treatment. Insulin-containing secretory granules were observed in differentiated cells by electron microscopy. Treatment of BM-derived mesenchymal cells with conophylline (CnP) and BTC-delta4 further accelerated differentiation, and mRNA for insulin was detected 5 to 7 days after the treatment. Mesencymal cells treated with CnP and BTC-delta4 responded to a high concentration of glucose and secreted mature insulin. When these cells were transplanted into streptozotocin-treated mice, they markedly reduced the plasma glucose concentration, and the effect continued for at least 4 weeks. These results indicate an efficacy of the combination of CnP and BTC-delta4 in inducing differentiation of BM-derived mesenchymal cells into insulin-producing cells.

    DOI: 10.1507/endocrj.K07E-173

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  • Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

    Nobuyuki Bokui, Takayuki Otani, Koichi Igarashi, Junichiro Kaku, Mitsuo Oda, Tadahiro Nagaoka, Masaharu Seno, Kenji Taternatsu, Toshihide Okajima, Takashi Matsuzaki, Kang Ting, Katsuyuki Tanizawa, Shunichi Kuroda

    FEBS LETTERS   582 ( 2 )   365 - 371   2008年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2007.12.006

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  • Transient cell proliferation with polyethylenimine-cationized N-terminal domain of simian virus 40 large T-antigen

    Hitoshi Murata, Junichiro Futami, Midori Kitazoe, Megumi Kosaka, Hiroko Tada, Masaharu Seno, Hidenori Yamada

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   105 ( 1 )   34 - 38   2008年1月

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    記述言語:英語   出版者・発行元:SOC BIOSCIENCE BIOENGINEERING JAPAN  

    Polyethylenimine (PEI) cationization is a powerful strategy for protein transduction into cells. In this study, we attempted the artificial regulation of cell proliferation by protein transduction of the N-terminal domain (1-132 amino acids) of the simian virus 40 large T-antigen (SVLT-N), which inactivates retinoblastoma family proteins but not p53. To deliver SVLT-N into cells, we employed an indirect cationization method by forming a complex of biotynylated SVLT-N through disulfide bonds (biotin-SS-SVLT-N) and PEI-cationized avidin (PEI600-avidin). Using this complex, SVLT-N was transduced into the nucleus of confluent and quiescent Balb/c 3T3 cells and was found to be complexed with a cellular target protein, pRb. Furthermore, SVLT-N transduction induced cell proliferation in spite of confluent conditions. Because SVLT-N thus transduced into cells gradually degraded and was not detectable after a 4-d incubation, transiently transformed cells were obtained by this method. These results suggest that oncogene protein transduction technology has great potential for in vitro regulation of cell proliferation.

    DOI: 10.1263/jbb.105.34

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  • Morphological and Microstructural Study of Iron Oxide Microtubes formed by Iron Oxidizing Bacteria, Leptothrix ochracea

    H. Hashimoto, H. Asaoka, J. Takada, T. Fujii, M. Nakanishi, S. Yokoyama, R. Murakami, Y. Kusano, Y. Ikeda, M. Seno

    Global Roadmap of Ceramics - ICC2 Proceedings   6-P-011-1-6-P-011-4   2008年

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  • Growth factor induction of cripto-1 shedding by glycosylphosphatidylinositol-phospholipase D and enhancement of endothelial cell migration

    Kazuhide Watanabe, Caterina Bianco, Luigi Strizzi, Shin Hamada, Mario Mancino, Veronique Bailly, Wenjun Mo, Dingyi Wen, Konrad Miatkowski, Monica Gonzales, Michele Sanicola, Masaharu Seno, David S. Salomon

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 43 )   31643 - 31655   2007年10月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Cripto-1 (CR-1) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that has been shown to play an important role in embryogenesis and cellular transformation. CR-1 is reported to function as a membrane-bound co-receptor and as a soluble ligand. Although a number of studies implicate the role of CR-1 as a soluble ligand in tumor progression, it is unclear how transition from the membrane-bound to the soluble form is physiologically regulated and whether differences in biological activity exist between these forms. Here, we demonstrate that CR-1 protein is secreted from tumor cells into the conditioned medium after treatment with serum, epidermal growth factor, or lysophosphatidic acid, and this soluble form of CR-1 exhibits the ability to promote endothelial cell migration as a paracrine chemoattractant. On the other hand, membranebound CR-1 can stimulate endothelial cell sprouting through direct cell-cell interaction. Shedding of CR-1 occurs at the GPI-anchorage site by the activity of GPI-phospholipase D (GPIPLD), because CR-1 shedding was suppressed by siRNA knockdown of GPI-PLD and enhanced by overexpression of GPI-PLD. These findings describe a novel molecular mechanism of CR-1 shedding, which may contribute to endothelial cell migration and possibly tumor angiogenesis.

    DOI: 10.1074/jbc.M702713200

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  • Development of bionanocapsules targeting brain tumors

    Yumi Tsutsui, Kazuhito Tomizawa, Mana Nagita, Hiroyuki Michiue, Tei-ichi Nishiki, Iori Ohmori, Masaharu Seno, Hideki Matsui

    JOURNAL OF CONTROLLED RELEASE   122 ( 2 )   159 - 164   2007年9月

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    記述言語:英語   出版者・発行元:ELSEVIER  

    Bionanocapsules (BNCs) are hollow nanoparticles that are composed of L protein (the hepatitis B virus surface antigen) and show specific affinity for human hepatocytes. The pre-S1 peptide displayed on the surface of BNCs is the specific ligand for binding to the receptor on human hepatocytes. Therefore, BNCs are not delivered to other tissues, such as the brain. The aim of the present study was to develop a novel drug delivery system (DIDS) targeting brain tumors using BNCs that selectively targeted brain tumors. Epidermal growth factor receptor (EGFR), especially a constitutively active genomic sequence deletion variant of EGFR (EGFRvIII), is overexpressed in human glioblastoma. In the present study, we replaced the pre-S1 peptide with the antibody affinity motif of protein A and made hybrid BNCs conjugated with anti-human EGFR antibody recognizing EGFRvIII. The hybrid BNCs were efficiently delivered to glioma cells but not normal glial cells. Moreover, we confirmed the specific delivery of the hybrid BNCs to brain tumors in an in vivo brain tumor model. These results suggest that this new approach using BNCs is a promising system for brain tumor-targeted drug delivery. (C) 2007 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jconrel.2007.06.019

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  • 'Crystal lattice engineering,' an approach to engineer protein crystal contacts by creating intermolecular symmetry: Crystallization and structure determination of a mutant human RNase 1 with a hydrophobic interface of leucines

    Hidenori Yamada, Taro Tamada, Megumi Kosaka, Kohei Miyata, Shinya Fujiki, Masaru Tano, Masayuki Moriya, Mamoru Yamanishi, Eijiro Honjo, Hiroko Tada, Takeshi Ino, Hiroshi Yamaguchi, Junichiro Futami, Masaharu Seno, Takashi Nomoto, Tomoko Hirata, Motonobu Yoshimura, Ryota Kuroki

    PROTEIN SCIENCE   16 ( 7 )   1389 - 1397   2007年7月

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    記述言語:英語   出版者・発行元:COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT  

    A protein crystal lattice consists of surface contact regions, where the interactions of specific groups play a key role in stabilizing the regular arrangement of the protein molecules. In an attempt to control protein incorporation in a crystal lattice, a leucine zipper-like hydrophobic interface (comprising four leucine residues) was introduced into a helical region (helix 2) of the human pancreatic ribonuclease 1 (RNase 1) that was predicted to form a suitable crystallization interface. Although crystallization of wild-type RNase 1 has not yet been reported, the RNase 1 mutant having four leucines (4L-RNase 1) was successfully crystallized under several different conditions. The crystal structures were subsequently determined by Xray crystallography by molecular replacement using the structure of bovine RNase A. The overall structure of 4L-RNase 1 is quite similar to that of the bovine RNase A, and the introduced leucine residues formed the designed crystal interface. To characterize the role of the introduced leucine residues in crystallization of RNase 1 further, the number of leucines was reduced to three or two (3L-and 2L-RNase 1, respectively). Both mutants crystallized and a similar hydrophobic interface as in 4L-RNase 1 was observed. A related approach to engineer crystal contacts at helix 3 of RNase 1 (N4L- RNase 1) was also evaluated. N4L- RNase 1 also successfully crystallized and formed the expected hydrophobic packing interface. These results suggest that appropriate introduction of a leucine zipper-like hydrophobic interface can promote intermolecular symmetry for more efficient protein crystallization in crystal lattice engineering efforts.

    DOI: 10.1110/ps.072851407

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  • Characterization of bio-nanocapsule as a transfer vector targeting human hepatocyte carcinoma by disulfide linkage modification

    Tadahiro Nagaoka, Takayuki Fukuda, Shinnosuke Yoshida, Hirohito Nishimura, Dongwei Yu, Shun'ichi Kuroda, Katsuyuki Tanizawa, Akhko Kondo, Masakazu Ueda, Hidenori Yamada, Hiroko Tada, Masaharu Seno

    JOURNAL OF CONTROLLED RELEASE   118 ( 3 )   348 - 356   2007年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The bio-nanocapsules (BNCs) composed of the recombinant envelope L-protein of hepatitis B virus constitute efficient delivery vectors specifically targeting human hepatocytes. Here, we have tried to enhance the stability of the BNCs because the L-proteins in the BNCs were aggregated due to random disulfide bridging when stored for a long period at 4 degrees C. The envelope protein contains fourteen cysteine residues in the S domain. Aggregation of the envelope proteins might be avoided if unessential cysteine residues are replaced or removed because the irreversible alkylation of the free sulfhydryl group protects against the aggregation and enhances the efficiency of encapsulation. In this study, the possibility of reducing the number of cysteine residues in the S domain to enhance the stability of the BNCs was assessed. The replacement of each cysteine residue by site-directed mutation showed that nine of fourteen cysteine residues were not essential to obtaining BNCs secreted into the culture media. Furthermore, upon evaluating the combination of these mutations, it was found that eight residues of replacement were acceptable. The mutant BNCs with replaced eight cysteine residues were not only more resistant against trypsin, but also more effective in transducing genes into human hepatoma-derived HepG2 cells than the original type BNC. Thus, we demonstrated that the minimized number of cysteine residues in the S domain could enhance the stability of the BNCs. (c) 2006 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jconrel.2006.12.020

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  • AR42J細胞の分化に対する細胞外基質の影響

    濱本 耕平, 山田 聡子, 山本 頼綱, 小寺 力, 原 朱美, 妹尾 昌治, 小島 至

    糖尿病   50 ( Suppl.1 )   S - 349   2007年4月

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    記述言語:日本語   出版者・発行元:(一社)日本糖尿病学会  

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  • Gene therapy of liver tumors with human liver-specific nanoparticles (vol 14, pg 74, 2007)

    M. Ueda, Y. Iwasaki, T. Yamada, A. Kondo, M. Seno, K. Tanizawa, S. Kuroda, M. Sakamoto, M. Kitajima

    CANCER GENE THERAPY   14 ( 4 )   440 - 440   2007年4月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    DOI: 10.1038/sj.cgt.7701031

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  • Characteristics of hollow microtubes consisting of amorphous iron oxide nanoparticles produced by iron oxidizing bacteria, Leptothrix ochracea

    H. Hashimoto, S. Yokoyama, H. Asaoka, Y. Kusano, Y. Ikeda, M. Seno, J. Takada, T. Fujii, M. Nakanishi, R. Murakami

    JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS   310 ( 2 )   2405 - 2407   2007年3月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Some features of characteristic iron oxide sheaths which the iron oxidizing bacteria Leptothrix ochracea ( L. oceracea) formed were studied in order to make clear their morphology microstructure, chemical composition, and crystal structure through scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), and X-ray diffraction (XRD). Each sheath was a hollow tube with average outer and inner diameters of 1.1 and 1.4 m, respectively. Their length ranged from 10 to 200 mu m and the aspect ratio was 10-200. Each sheath was constructed by very small particles with a diameter of less than 100 nm. The hollow sheaths were mainly composed of Fe and O with small amounts of Si and P. The chemical composition analyzed by EDX was roughly Fe: Si: P = 80: 15: 5 with the exception of O. XRD measurement revealed that crystal structures of the sheath were similar to that of 2-line ferrihydrite. The sheath showed spin-glass-like magnetic properties. (c) 2006 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jmmm.2006.10.793

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  • 脳腫瘍を標的としたバイオナノカプセルの開発

    筒井 佑美, 富澤 一仁, 西木 禎一, 大守 伊織, 名木田 真奈, 妹尾 昌治, 松井 秀樹

    日本生理学雑誌   69 ( 3 )   125 - 125   2007年3月

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    記述言語:日本語   出版者・発行元:(一社)日本生理学会  

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  • Gene therapy of liver tumors with human liver-specific nanoparticles

    Y. Iwasaki, M. Ueda, T. Yamada, A. Kondo, M. Seno, K. Tanizawa, S. Kuroda, M. Sakamoto, M. Kitajima

    CANCER GENE THERAPY   14 ( 1 )   74 - 81   2007年1月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    The development of safe and efficient liver-specific gene delivery approaches offers new perspectives for the treatment of liver disease, in particular, liver cancer. We evaluated the therapeutic potential of hepatotropic nanoparticles for gene therapy of liver tumor. These nanoparticles do not contain a viral genome and display the hepatitis B virus L antigen, which is essential to confer hepatic specificity. It has not been shown whether a therapeutic effect could be obtained using L nanoparticles in a human liver tumor xenograft model. Rats bearing human hepatic ( NuE) and non-hepatic tumors were injected with L nanoparticles containing a green fluorescent protein ( GFP) expression plasmid. GFP expression was observed only in NuE-derived tumors but not in the non-hepatic tumor. The potential for treatment of liver tumors was analyzed using L nanoparticles containing the herpes simplex virus thymidine kinase gene, in conjunction with ganciclovir pro-drug administration. The growth of NuE-derived tumors in L particle-injected rats was significantly suppressed, but not of the non-hepatic tumor control. In summary, this is the first demonstration that nanoparticles could be used for delivery of therapeutic genes with anti-tumor activity into human liver tumors. This intravenous delivery system may be one of the major advantages as compared to many other viral vector systems.

    DOI: 10.1038/sj.cgt.7700990

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  • 心筋症治療薬の開発シーズ:好酸球由来塩基性タンパク質

    妹尾昌治

    ちゅうごく産業創造センター会報   No.74, p40-41.   2007年

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  • バイオナノキャリアの開発とがん遺伝子治療への応用

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    バイオテクノロジージャーナル   7 ( 1 )   41 - 47   2007年

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  • Conophylline and betacellulin delta 4 promote differentiation of pancreatic cells both in vitro and in vivo

    Tsutomu Kodera, Takeki Ogata, Yoritsuna Yamamoto, Kazuo Umezawa, Masaharu Seno, Yuji Tanaka, Itaru Kojima, Yasuhiro Watanabe

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   80P - 80P   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties

    Hiroshi Yagi, Masakazu Ueda, Hiromitsu Jinno, Koichi Aiura, Shuji Mikami, Hiroko Tada, Masaharu Seno, Hidenori Yamada, Masaki Kitajima

    CANCER SCIENCE   97 ( 12 )   1315 - 1320   2006年12月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P &lt; 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent.

    DOI: 10.1111/j.1349-7006.2006.00336.x

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  • Secretory production system of bionanocapsules using a stably transfected insect cell line

    Takuya Shishido, Masaru Muraoka, Masakazu Ueda, Masaharu Seno, Katsuyuki Tanizawa, Shun'ichi Kuroda, Hideki Fukuda, Akihiko Kondo

    APPLIED MICROBIOLOGY AND BIOTECHNOLOGY   73 ( 3 )   505 - 511   2006年12月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Bionanocapsules (BNCs) are hollow nanoscale particles composed of L protein of the hepatitis B virus surface antigen that represent specific affinity for human hepatocytes. BNCs can transfer genes and drugs into human hepatocytes efficiently and specifically. BNC can be expressed in yeast cells. In this study, we developed a new L particle production system using a stably transfected insect cell line. For this purpose, we established a host vector system using the Trichoplusia ni insect cell line. L particles were efficiently secreted by the overexpression of the L protein, which was fused to the secretion signal peptide. The concentration of L particles was reached approximately 1.7 mu g/ml in 5 days during cultivation in a serum-free medium without antibiotic selective pressure. The production of L particles was maintained for at least 75 days. The secretory production of L particles facilitated their easy purification by chromatography. Furthermore, it was demonstrated that purified L particles can transfect only human hepatocytes. Therefore, an insect cell expression system is an attractive tool for the production of BNC.

    DOI: 10.1007/s00253-006-0486-3

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  • Hydrogen peroxide and endothelin-1 are novel activators of betacellulin ectodomain shedding

    Michael P. Sanderson, Catherine A. Abbott, Hiroko Tada, Masaharu Seno, Peter J. Dempsey, Andrew J. Dunbar

    JOURNAL OF CELLULAR BIOCHEMISTRY   99 ( 2 )   609 - 623   2006年10月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    The betacellulin precursor (pro-BTC) is a novel substrate for ADAM10-mediated ectodomain shedding. In this report, we investigated the ability of novel physiologically relevant stimuli, including G-protein coupled receptor (GPCR) agonists and reactive oxygen species (ROS), to stimulate pro-BTC shedding. We found that in breast adenocarcinoma MCF7 cells overexpressing pro-BTC, hydrogen peroxide (H2O2) was a powerful stimulator of ectodomain shedding. The stimulation of pro-BTC shedding by H2O2 was blocked by the broad-spectrum metalloprotease inhibitor TAPI-0 but was still functional in ADAM17 (TACE)-deficient stomach epithelial cells indicating the involvement of a distinct metalloprotease. H2O2-induced pro-BTC shedding was blocked by co-culturing cells in the anti-oxidant N-acetyl-L-cysteine but was unaffected by culture in calcium-deficient media. By contrast, calcium ionophore, which is a previously characterized activator of pro-BTC shedding, was sensitive to calcium depletion but was unaffected by co-culture with the anti-oxidant, identifying a clear distinction between these stimuli. We found that in vascular smooth muscle cells overexpressing pro-BTC, the GPCR agonist endothelin-1 (ET-1) was a strong inducer of ectodomain shedding. This was blocked by a metalloprotease inhibitor and by overexpression of catalytically inactive E385AADAM10. However, overexpression of wild-type ADAM10 or ADAM17 led to an increase in ET-1-induced pro-BTC shedding providing evidence for an involvement of both enzymes in this process. This study identifies ROS and ET-1 as two novel inducers of pro-BTC shedding and lends support to the notion of activated shedding occurring under the control of physiologically relevant stimuli. J. Cell. Biochem. 99: 609-623, 2006. (c) 2006 Wiley-Liss, Inc.

    DOI: 10.1002/jcb.20968

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  • Denatured and reversibly cationized p53 readily enters cells and simultaneously folds to the functional protein in the cells

    H Murata, M Sakaguchi, J Futami, M Kitazoe, T Maeda, H Doura, M Kosaka, H Tada, M Seno, N Huh, H Yamada

    BIOCHEMISTRY   45 ( 19 )   6124 - 6132   2006年5月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    Cationization is a powerful strategy for internalizing a protein into living cells. On the other hand, a reversibly cationized denatured protein through disulfide bonds is not only soluble in water but also able to fold to the native conformation in vitro. When these advantages in cationization were combined, we developed a novel method to deliver a denatured protein into cells and simultaneously let it fold to express its function within cells. This "in-cell folding" method enhances the utility of recombinant proteins expressed in Escherichia coli as inclusion bodies; that is, the recombinant proteins in inclusion bodies are solubilized by reversible cationization through cysteine residues by disulfide bonds with aminopropyl methanethiosulfonate or pyridyldithiopropionylpolyethylenimine and then incubated with cells without an in vitro folding procedure. As a model protein, we investigated human tumor-suppressor p53. Treatment of p53-null Saos-2 cells with reversibly cationized p53 revealed that all events examined as indications of the activation of p53 in cells, such as reduction of disulfide bonds followed by tetramer formation, localization into the nucleus, induction of p53 target genes, and induction of apoptosis of cells, occurred. These results suggest that reversible cationization of a denatured protein through cysteine residues is an alternative method for delivery of a functional protein into cells. This method would be very useful when a native folded protein is not readily available.

    DOI: 10.1021/bi052642a

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  • Mechanisms of the growth-inhibitory effect of the RNase-EGF fused protein against EGFR-overexpressing cells

    S Hoshimoto, M Ueda, H Jinno, M Kitajima, J Futami, M Seno

    ANTICANCER RESEARCH   26 ( 2A )   857 - 863   2006年3月

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    記述言語:英語   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: We previously showed the usefulness of a fused protein of human pancreatic ribonuclease1 (hRNase1) with human epidermal growth factor (hEGF) for molecular targeting of EGF receptor (EGFR)-overexpressing cells. In this study, the mechanisms underlying the inhibition of cell growth by RNase-EGF fused proteins was confirmed. Materials and Methods: Des. 1-7 hRNase1 was genetically fused to hEGF. The fused proteins were expressed and isolated from Escherichia coli. The internalization of hRNase1-hEGF was confirmed by confocal fluorescence microscopy. The growth-inhibitory effect of the fused proteins was evaluated by MTT assay. Results: FITC-labelled hRNase1-hEGF was internalized into EGFR-overexpressing A431 cells. The internalization was not observed in A 431 cells pre-treated with hEGF and EGFR-deficient H69 cells. The growth-inhibitory effect of des.1-7 hRNase1-hEGF against A431 cells was statistically significantly more pronounced than that of hRNase1-hEGF. Conclusion: RNase-EGF fused proteins are internalized through EGFR and inhibit cell growth by exerting their ribonucleolytic activity in the cytosol.

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  • Engineered bio-nanocapsules, the selective vector for drug delivery system

    DW Yu, T Fukuda, Tuoya, S Kuroda, K Tanizawa, A Kondo, M Ueda, T Yamada, H Tada, M Seno

    IUBMB LIFE   58 ( 1 )   1 - 6   2006年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:TAYLOR & FRANCIS INC  

    The bio-nanocapsule (BNC) is our concept of artificial hollow nanoparticles that have been designed and produced through biotechnological procedures. We proposed an empty virus-like particle, which consists of a recombinant L envelope protein of hepatitis B virus (HBV) and a lipid derived from the host cell, as an engineered BNC. Although this BNC was first developed as an immunogen of hepatitis B vaccine, the pre-S1 region in N-terminus of L envelope protein confers hepatocyte specific infectivity of HBV on the BNC. This recombinant BNC is now being developed as a novel platform of drug delivery system (DDS) vector for selective delivery.

    DOI: 10.1080/15216540500484368

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  • 中空バイオナノ粒子を用いたDDSの開発とその産業化

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    Drug Delivery System   21 ( 4 )   435 - 443   2006年

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    記述言語:英語  

    DOI: 10.2745/dds.21.435

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  • Separation of Dual Affinity of Betacellulin to ErbB Receptors

    T. Nagaoka, H. Tada, H. Yamada, M. Seno

    MOLECULAR BIOLOGY OF THE CELL   17   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Betacellulin-delta 4, a novel differentiation factor for pancreatic beta-cells, ameliorates glucose intolerance in streptozotocin-treated rats

    T Ogata, AJ Dunbar, Y Yamamoto, Y Tanaka, M Seno, Kojima, I

    ENDOCRINOLOGY   146 ( 11 )   4673 - 4681   2005年11月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    We previously described a novel alternatively spliced mRNA transcript of the betacellulin (BTC) gene. This splice isoform, termed BTC-delta 4, lacks the C-loop of the epidermal growth factor motif and the transmembrane domain as a result of exon 4 'skipping'. In this study, we expressed BTC-delta 4 recombinantly to explore its biological function. When BTC-delta 4 was expressed in COS-7 cells, it was secreted largely into the culture medium, in contrast to BTC. Unlike BTC, highly purified recombinant BTC-delta 4 produced in Escherichia coli failed to bind or induce tyrosine phosphorylation of either ErbB1 or ErbB4, nor did it antagonize the binding of BTC to these receptors. Consistent with this, BTC-delta 4 failed to stimulate DNA synthesis in Balb/c 3T3 and INS-1 cells. However, BTC-delta 4 induced differentiation of pancreatic beta-cells; BTC-delta 4 converted AR42J cells to insulin-producing cells. When recombinant BTC-delta 4 was administered to streptozotocin-treated neonatal rats, it reduced the plasma glucose concentration and improved glucose tolerance. Importantly, BTC-delta 4 significantly increased the insulin content, the beta-cell mass, and the numbers of islet-like cell clusters and PDX-1-positive ductal cells. Thus, BTC-delta 4 is a secreted protein that stimulates differentiation of beta-cells in vitro and in vivo in an apparent ErbB1- and ErbB4- independent manner. The mechanism by which BTC-delta 4 exerts this action on beta-cells remains to be defined but presumably involves an, as yet, unidentified unique receptor.

    DOI: 10.1210/en.2005-0456

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  • Identification of cell surface marker candidates on SV-T2 cells using DNA microarray on DLC-coated glass

    Tuoya, K Hirayama, T Nagaoka, DW Yu, T Fukuda, H Tada, H Yamada, M Seno

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   334 ( 1 )   263 - 268   2005年8月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We analyzed gene expression profiles of normal mouse fibroblast BALB/c 3T3 cells and its SV40 transformant SV-T2 cells using our originally developed cell surface marker DNA microarray, which is prepared on a diamond-like carbon-coated glass. As a result, CD62L and IL-6 receptor alpha gene expressions were upregulated in SV-T2 and were thought to be candidates for cell surface markers of the cells. The result of microarray analysis was validated by real-time quantitative PCR, immunohistochemistry and biological assays. These data show that our cell surface marker DNA microarray should be useful in finding the candidates of cell type-specific surface markers. (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2005.06.083

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  • 細胞および組織特異的遺伝子導入を可能にするバイオナノカプセル

    山田 忠範, 妹尾 昌治, 上田 政和, 近藤 昭彦, 谷澤 克行, 黒田 俊一

    生物工学会誌   83・8・380-383   2005年8月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1

    T Hayashida, M Ueda, K Aiura, H Tada, M Onizuka, M Seno, H Yamada, M Kitajima

    PROTEIN ENGINEERING DESIGN & SELECTION   18 ( 7 )   321 - 327   2005年7月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    Human pancreatic ribonuclease-1 (RNase1) does not exhibit its cytotoxicity unless it is artificially internalized into the cytosol. Furthermore, once it encounters the cytosolic RNase inhibitor (RI), the activity of RNase1 is seriously reduced. To achieve the cellular targeting of RNase1 and the blocking of RI binding simultaneously, the basic fibroblast growth factor (bFGF) sequence was inserted into RNase1 at the RI binding site using a gene fusion technique. The effect of this fusion protein, CL-RFN89, on the angiogenesis, which was accelerated by FGF-FGF receptor interaction, was investigated. It was shown by using fluorescein-labeled CL-RFN89, that the binding to human umbilical vein endothelial cells (HUVECs) was dependent on the existence of the FGF receptors. In addition, CL-RFN89 inhibited the cellular growth of HUVECs in vitro and also inhibited the tube formation, using a three-dimensional tube formation assay. Furthermore, this fusion protein was shown to prevent in vivo tumor cell-induced angiogenesis, using the mouse dorsal air sac assay. These results demonstrated that CL-RFN89 inhibits angiogenesis in vitro and in vivo and that it can be expected to be a potent antiangiogenic agent.

    DOI: 10.1093/protein/gzi040

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  • The specific delivery of proteins to human liver cells by engineered bio-nanocapsules

    DW Yu, C Amano, T Fukuda, T Yamada, S Kuroda, K Tanizawa, A Kondo, M Ueda, H Yamada, H Tada, M Seno

    FEBS JOURNAL   272 ( 14 )   3651 - 3660   2005年7月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    A bio-nanocapsule (BNC), composed of the surface antigen (sAg) of the hepatitis B virus, is an efficient nanomachine with which to accomplish the liver-specific delivery of genes and drugs. Approximately 110 molecules of sAg are associated to form a BNC particle with an average diameter of 130 nm. The L protein is an sAg peptide composed mainly of preS and S regions. The preS region, with specific affinity for human hepatocytes, is localized in the N-terminus. The S region following the preS has two transmembrane regions responsible for the formation of particles. In this study, the fusion of emerald green fluorescent protein (EGFP) at the C-terminus of the S region was designed to deliver proteins to human hepatocytes. Truncation of the C-terminus of the S region was required to obtain sufficient expression levels in Cos7 cells. The nanoparticles that were produced delivered EGFP to human hepatoma cells, displaying the EGFP moiety outside, or enclosing it inside. However, only a single orientation characterizes the particle, so that either type of L fusion particle could be effectively and independently separated by an antibody affinity column. The dual C-terminal topologies of the L fusion particles designed in this study could be applied to various proteins for the C-terminal moiety of the L fusion proteins, depending on the character of the proteins, such as cytoplasmic proteins, as well as cytokines or ligands to cell surface receptors. We suggest that this fusion design is the most efficient way to prepare a BNC that delivers proteins to specific cells or tissues.

    DOI: 10.1111/j.1742-4658.2005.04790.x

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  • Protein transduction assisted by polyethylenimine-cationized carrier proteins

    M Kitazoe, H Murata, J Futami, T Maeda, M Sakaguchi, M Miyazaki, M Kosaka, H Tada, M Seno, N Huh, M Namba, M Nishikawa, Y Maeda, H Yamada

    JOURNAL OF BIOCHEMISTRY   137 ( 6 )   693 - 701   2005年6月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    Previously, we have reported that cationized-proteins covalently modified with polyethylenimine (PEI) (direct PEI-cationization) efficiently enter cells and function in the cytosol [Futami et al. (2005) J. Biosci. Bioeng. 99,95-1031. However, it may be more convenient if a protein could be delivered into cells just by mixing the protein with a PEI-cationized carrier protein having a specific affinity (indirect PEI-cationization). Thus, we prepared PEI-cationized avidin (PEI-avidin), streptavidin (PEI-streptavidin), and protein G (PEI-protein G), and examined whether they could deliver biotinylated proteins and antibodies into living cells. PEI-avidin (and/or PEI-streptavidin) carried biotinylated GFPs into various mammalian cells very efficiently. A GFP variant containing a nuclear localization signal was found to arrive even in the nucleus. The addition of a biotinylated RNase A derivative mixed with PEI-streptavidin to a culture medium of 3T3-SV-40 cells resulted in remarkable cell growth inhibition, suggesting that the biotinylated RNase A derivative entered cells and digested intracellular RNA molecules. Furthermore, the addition of a fluorescein-labeled antiS100C (beta-actin binding protein) antibody mixed with PEI-protein G to human fibroblasts resulted in the appearance of a fluorescence image of actin-like filamentous structures in the cells. These results indicate that indirect PEI-cationization using non-covalent interaction is as effective as the direct PEI-cationization for the transduction of proteins into living cells and for expression of their functions in the cytosol. Thus, PEI-cationized proteins having a specific affinity for certain molecules such as PEI-streptavidin, PEI-avidin and PEI-protein G are concluded to be widely applicable protein transduction carrier molecules.

    DOI: 10.1093/jb/mvi081

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  • Conophylline and betacellulin-delta 4: An effective combination to induce differentiation of pancreatic beta cells

    RI Kitamura, T Ogata, Y Tanaka, MH Seno, Takei, I, K Umezawa, Kojima, I

    DIABETES   54 ( 2 )   A393 - A393   2005年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER DIABETES ASSOC  

    DOI: 10.1507/endocrj.K06-199

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  • Intracellular delivery of proteins into mammalian living cells by polyethylenimine-cationization

    Junichiro Futami, Midori Kitazoe, Takashi Maeda, Emiko Nukui, Masakiyo Sakaguchi, Jun Kosaka, Masahiro Miyazaki, Megumi Kosaka, Hiroko Tada, Masaharu Seno, Junzo Sasaki, Nam-Hu Huh, Masayoshi Namba, Hidenori Yamada

    Journal of Bioscience and Bioengineering   99 ( 2 )   95 - 103   2005年

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    記述言語:英語   出版者・発行元:Society of Fermentation and Bioengineering  

    In the post-genomic era, there is pressing need for development of protein manipulation methodology to analyze functions of proteins in living cells. For this purpose, techniques to deliver functional proteins into living cells are currently being evaluated as alternative approaches to the introduction of transcriptionally active DNA. Here, we describe a novel method for efficient protein transduction into living cells in which a protein is simply cationized with polyethylenimine (PEI) by limited chemical conjugation. PEI-cationized proteins appear to adhere to the cell surface by ionic charge interaction and then internalize into cells in a receptor- and transporter-independent fashion. Since PEI is an organic macromolecule with a high cationic-charge density, limited coupling with PEI results in endowment of sufficient cationic charge to proteins without causing serious decline in their fundamental functions. A number of PEI-cationized proteins, such as ribonuclease (RNase), green fluorescent protein (GFP) and immunoglobulin (IgG), efficiently entered cells and functioned in the cytosol. Our results suggest that protein cationization techniques using PEI will be useful for the development of protein transduction technology. © 2005, The Society for Biotechnology.

    DOI: 10.1263/jbb.99.95

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  • Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells

    S Yamada, K Terada, Y Ueno, T Sugiyama, M Seno, Kojima, I

    CELL TRANSPLANTATION   14 ( 9 )   647 - 653   2005年

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    記述言語:英語   出版者・発行元:COGNIZANT COMMUNICATION CORP  

    To apply cell transplantation for treatment of diabetes mellitus, a sufficient number of beta-cell sources are required. In the present study, we examined whether an epithelial cell line obtained from normal adult rat liver, namely hepatic stem-like (HSL) cells, which can be converted to both hepatocytes and billiary epithelial cells, could be a potential beta-cell source. The growth speed of HSL cells was rapid and these cells were easily expanded in vitro. Bipotential hepatic stem cells, HSL cells, also expressed PGP9.5, which is expressed in neurons, beta-cells, and progenitor cells of the pancreatic endocrine cells as well. Sodium butyrate induced morphological changes in HSL cells and converted them into flattened cells with large cytoplasm. When HSL cells were incubated with a combination of 5 mM sodium butyrate and I nM betacellulin, most of the cells were converted into morphologically neuron-like cells. RT-PCR analysis revealed that a series of transcriptional factors involved in differentiation of pancreatic endocrine cells was induced by the treatment with sodium butyrate and betacellulin. mRNAs for insulin, pancreatic polypeptide, and somatostatin were also observed. Immunoreactive pancreatic polypeptide, somatostatin, and insulin were detected in sodium butyrate and betacellulin-treated HSL cells. In conclusion, HSL cells obtained from adult normal liver also have the potential to differentiate into pancreatic endocrine cells in vitro. HSL cells may be one of the potential beta-cell sources for cell transplant therapy for insulin-dependent diabetes.

    DOI: 10.1016/j.ssc.2005.01.003

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  • 革新的なナノキャリア:中空バイオナノ粒子によるピンポイントDDS

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    バイオインダストリー   22 ( 5 )   22 - 27   2005年

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  • 中空バイオナノ粒子を用いたピンポイントDDSの開発

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治

    Chemical Engineering   50 ( 5 )   351 - 356   2005年

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  • Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-cripto-1 transgenic mice

    L Strizzi, C Bianco, N Normanno, M Seno, C Wechselberger, B Wallace-Jones, NI Khan, M Hirota, YP Sun, M Sanicola, DS Salomon

    JOURNAL OF CELLULAR PHYSIOLOGY   201 ( 2 )   266 - 276   2004年11月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    Epithelial-mesenchymal transition (EMT) facilitates migration and invasion of epithelial tumor cells. Cripto-1 (CR-1), a member of the epidermal growth factor-CFC protein family increases migration of cells in vitro. Here the expression of molecular markers and signaling molecules characteristic of EMT were assessed in mammary gland hyperplasias and tumors from mice expressing the human CR-1 transgene by the MMTV promoter (MMTV-CR-1) and in mouse mammary epithelial cell line HC-11 overexpressing CR-1 (HC-11/CR-1). Western blot analysis showed decreased expression of E-cadherin in MMTV-CR-1 tumors and in HC-11/CR-1 cells. The expression of N-cadherin, vimentin, cyclin-D1, and of the zinc-finger transcription factor, snail, was increased in MMTV-CR-1 tumors. Increased snail mRNA was also found in HC-11/CR-1 cells. Expression of phosphorylated (N-c-Src, P-focal adhesion kinase (FAK), P-Akt, P-glycogen synthease kinase 30 (GSK-3beta), dephosphorylated (DP)-beta-catenin, and various integrins such as, alpha 3, alpha v, beta 1, beta 3, and beta 4 was also increased in MMTV-CR-1 tumors. Immunohistochemistry showed positive staining for vimentin, N-cadherin, cyclin-D1, smooth muscle actin, fibronectin, snail, and beta-catenin in MMTV-CR-1 tumor sections. HC-11/CR-1 cells treated with the c-Src inhibitor PP2 reduced the expression of P-c-Src and of P-FAK, P-Akt, P-GSK-3beta, DP-beta-catenin all known to be activated by c-Src. Migration of HC-1I/CR-1 cells was also reduced by PP2 treatment. These results suggest that CR-1 may play a significant role in promoting the increased expression of markers and signaling molecules associated with EMT. (C) 2004 Wiley-Liss, Inc.

    DOI: 10.1002/jcp.20062

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  • Characterization of cell surface marker proteins in SV-T2 cells

    Y Tuo, K Hirayama, T Nagaoka, H Tada, H Yamada, M Seno

    MOLECULAR BIOLOGY OF THE CELL   15   324A - 325A   2004年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CELL BIOLOGY  

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  • Insertional-fusion of basic fibroblast growth factor endowed ribonuclease 1 with enhanced cytotoxicity by steric blockade of inhibitor interaction

    H Tada, M Onizuka, K Muraki, W Masuzawa, J Futami, M Kosaka, M Seno, H Yamada

    FEBS LETTERS   568 ( 1-3 )   39 - 43   2004年6月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Basic fibroblast growth factor (bFGF) was inserted in the middle of human ribonuclease 1 (RNase1) sequence at an RNase inhibitor (RI)-binding site (Gly89) by a new gene fusion technique, insertional-fusion. The resultant insertional-fusion protein (CL-RFN89) was active both as bFGF and as RNase. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI-binding caused by fused bFGF domain. As a result, CL-RFN89 showed stronger growth inhibition on B16/BL6 melanoma cells than an RI-sensitive tandem fusion protein. Thus, the insertional-fusion technique increases accessible positions for gene fusion on RNase, resulting in construction of a potent cytotoxic RNase. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2004.05.007

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  • Reversal of streptozotocin-incluced hyperglycemia by transplantation of pseudoislets consisting of beta cells derived from ductal cells

    T Ogata, KY Park, M Seno, Kojima, I

    ENDOCRINE JOURNAL   51 ( 3 )   381 - 386   2004年6月

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    記述言語:英語   出版者・発行元:JAPAN ENDOCRINE SOCIETY  

    The present study was conducted in an attempt to treat streptozotocin (STZ)-induced hyperglycemia by transplanting beta cells derived from pancreatic ductal cells. Ductal cells obtained from neonatal rats were cultured in vitro. Approximately 70% of the cells were converted to insulin-secreting cells by incubating with betacellulin and activin A. Differentiated cells responded to a depolarizing concentration of potassium, tolbutamide and a high concentration of glucose, and insulin secretion increased by 2.5-, 2.3- and 1.6-fotd, respectively. We then prepared pseudoislets using the differentiated cells, which exhibited greatly improved glucose-responsiveness, with a high concentration of glucose inducing a 3-fold increase in insulin secretion. We transplanted these pseudoislets into the portal vein of STZ-treated nude mice. Before transplantation, the plasma glucose concentration was above 400 mg/dl, and after transplantation it was markedly reduced, the effect of which persisted for two weeks. These results indicate that STZ-induced hyperglycemia can be treated by transplanting pseudoislets consisting of 0 cells derived from ductal cells.

    DOI: 10.1507/endocrj.51.381

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  • Activin A and betacellulin - Effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats

    L Li, ZH Yi, M Seno, Kojima, I

    DIABETES   53 ( 3 )   608 - 615   2004年3月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

    Activin A and betacellulin (BTC) are thought to regulate differentiation of pancreatic beta-cells during development and regeneration of beta-cells in adults. In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic beta-cells. One-dayold Sprague-Dawley rats were injected with STZ (85 mug/g) and then administered for 7 days with activin A and/or BTC. Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading. The pancreatic insulin content and beta-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months. Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting beta-cells, ductal cells, and 8-cells. The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC. In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased. These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic beta-cells and improved glucose metabollism. in adults.

    DOI: 10.2337/diabetes.53.3.608

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  • 中空バイオナノ粒子を用いたピンポイントドラッグデリバリーシステム

    山田忠範, 妹尾昌治, 近藤昭彦, 上田政和, 谷澤克行, 黒田俊一

    高分子論文集、Japanese Jouranal of Polymer Science and Technology   61 ( 12 )   606 - 612   2004年

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    記述言語:日本語  

    DOI: 10.1295/koron.61.606

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  • Novel tissue and cell type-specific gene/drug delivery system using surface engineered hepatitis B virus nano-particles

    Tadanori Yamada, Masakazu Ueda, Masaharu Seno, Akihiko Kondo, Katsuyuki Tanizawa, Shun'ichi Kuroda

    Current Drug Targets - Infectious Disorders   4 ( 2 )   163 - 167   2004年

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    The hepatitis B virus (HBV) surface antigen (HBsAg) L particle is a hollow nano-scale particle. HBsAg L particles have many properties that make them useful for in vivo gene transfer vectors and drug delivery systems. Gene therapy so far has required the in vivo pinpoint delivery of genetic materials into the target organs and cells. Gene transfer by HBsAg L particles might be an attractive method, since their tropism is the same as that of HBV. The HBsAg L particles are able to deliver therapeutic payloads with high specificity to human hepatocytes. In addition, the specificity of L particle can be altered by displaying various cell-binding molecules on the surface. Our results indicate that the L particle is suitable for a cell- and tissue-specific gene/drug transfer vector. In this review, we discuss HBsAg L particles as a gene/drug transfer vector and its potential for the treatment of infectious diseases. © 2004 Bentham Science Publishers Ltd.

    DOI: 10.2174/1568005043341037

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  • 中空バイオナノ粒子が拓く新しい医療技術

    黒田俊一, 山田忠範, 妹尾昌治, 近藤昭彦, 上田政和, 谷澤克行

    化学工業   vol.55, no.12, pp.936-942   2004年

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  • Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to beta-cells in streptozotocin-treated mice

    L Li, M Seno, H Yamada, Kojima, I

    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM   285 ( 3 )   E577 - E583   2003年9月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Beta-cellulin (BTC) induces differentiation of pancreatic beta-cells and promotes regeneration of beta-cells in experimental diabetes. The present study was conducted to determine if BTC improved glucose metabolism in severe diabetes induced by a high dose of streptozotocin (STZ) in mice. Male ICR mice were injected with 200 mug/g ip STZ, and various doses of BTC were administered daily for 14 days. The plasma glucose concentration increased to a level of &gt;500 mg/dl in STZ-injected mice. BTC (0.2 mug/g) significantly reduced the plasma glucose concentration, but a higher concentration was ineffective. The effect of BTC was marked by day 4 but became smaller on day 6 or later. The plasma insulin concentration and the insulin content were significantly higher in mice treated with 0.1 and 0.2 mug/g BTC. BTC treatment significantly increased the number of beta-cells in each islet as well as the number of insulin-positive islets. Within islets, the numbers of 5-bromo-2-deoxyuridine/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells were significantly increased by BTC. These results indicate that BTC improved hyperglycemia induced by a high dose of STZ by promoting neoformation of beta-cells, mainly from somatostatin-positive islet cells.

    DOI: 10.1152/ajpendo.00120.2003

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  • Nanoparticles for the delivery of genes and drugs to human hepatocytes

    T Yamada, Y Iwasaki, H Tada, H Iwabuki, MKL Chuah, T VandenDriessche, H Fukuda, A Kondo, M Ueda, M Seno, K Tanizawa, S Kuroda

    NATURE BIOTECHNOLOGY   21 ( 8 )   885 - 890   2003年8月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    Hepatitis B virus envelope L particles form hollow nanoparticles displaying a peptide that is indispensable for liver-specific infection by hepatitis B virus in humans. Here we demonstrate the use of L particles for the efficient and specific transfer of a gene or drug into human hepatocytes both in culture and in a mouse xenograft model. In this model, intravenous injection of L particles carrying the gene for green fluorescent protein (GFP) or a fluorescent dye resulted in observable fluorescence only in human hepatocellular carcinomas but not in other human carcinomas or in mouse tissues. When the gene encoding human clotting factor IX was transferred into the xenograft model using L particles, factor IX was produced at levels relevant to the treatment of hemophilia B. The yeast-derived L particle is free of viral genomes, highly specific to human liver cells and able to accommodate drugs as well as genes. These advantages should facilitate targeted delivery of genes and drugs to the human liver.

    DOI: 10.1038/nbt843

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  • バイオナノ 粒子を用いる遺伝子・薬剤のピンポイントドラッグデリバリーシステム

    妹尾昌治, 黒田俊一, 近藤昭彦, 多田宏子, 谷澤克行, 上田政和

    バイ オインダストリー   20(4):54-64   2003年

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  • 「中空バイオナノ粒子に よるピンポイントドラッグデリバリーシステム」

    近藤昭彦, 黒田俊一, 谷澤克行, 妹尾昌治, 上田政和

    化学工学   67巻12号 649-714頁   2003年

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  • The cytotoxicity of a conjugate composed of human epidermal growth factor and eosinophil cationic protein

    H Jinno, M Ueda, S Ozawa, T Ikeda, M Kitajima, T Maeda, M Seno

    ANTICANCER RESEARCH   22 ( 6C )   4141 - 4145   2002年11月

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    記述言語:英語   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: Conventional targeted therapy with foreign proteins is highly immunogenic. In this study, we developed targeted therapy composed of human endogenous proteins and evaluated its efficacy in vitro. Materials and Methods: Human epidermal growth factor (EGF) was chemically linked to human eosinophil cationic protein (ECP). The cytotoxicity of the EGF-ECP conjugate was evaluated by MTT assay. Results: The conjugate showed dose-dependent cytotoxicity on EGF receptor (EGFR)-overexpressing BT-20 cells with an IC50 of 1.5 x 10(-7) M, whereas the IC50 of ECP alone was almost 10(-4) M, The conjugate had no detectable cytotoxicity against EGF receptor- deficient H69 cells. Excess EGF protected BT-20 cells from the cytotoxicity of the conjugate. Comparing the cytotoxicity and the level of EGFR expression, the cytotoxicity of the conjugate was positively correlated with the level of EGFR expression of each cell line. Conclusion: Conjugates composed solely of human proteins might be useful with less immunogenicity and less toxicity than the conventional immunotoxins for targeted therapy.

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  • RNase 3 (ECP) is an extraordinarily stable protein among human pancreatic-type RNases

    T Maeda, K Mahara, M Kitazoe, J Futami, A Takidani, M Kosaka, H Tada, M Seno, H Yamada

    JOURNAL OF BIOCHEMISTRY   132 ( 5 )   737 - 742   2002年11月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    There have been some attempts to develop immunotoxins utilizing human RNase as a cytotoxic domain of antitumor agents. We have recently shown that only human RNase 3 (eosinophil cationic protein, ECP) among five human pancreatic-type RNases excels in binding to the cell surface and has a growth inhibition effect on several cancer cell lines, even though the RNase activity of RNase 3 is completely inhibited by the ubiquitously expressed cytosolic RNase inhibitor. This phenomenon may be explained by that RNase 3 is very stable against proteolytic degradation because RNase 3 internalized through endocytosis could have a longer life time in the cytosol, resulting in the accumulation of enough of it to exceed the concentration of RNase inhibitor, which allows the degradation of cytosolic RNA molecules. Thus, we compared the stabilities of human pancreatic-type RNases (RNases 1-5) and bovine RNase A by means of guanidium chloride-induced denaturation experiments based on the assumption of a two-state transition for unfolding. It was demonstrated that RNase 3 is extraordinarily stabler than either RNase A or the other human RNases (by more than 25 kJ/mol). Thus, our data suggest that in addition to its specific affinity for certain cancer cell lines, the stability of RNase 3 contributes to its unique cytotoxic effect and that it is important to stabilize a human RNase moiety through protein engineering for the design of human RNase-based immunotoxins.

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  • Optimum modification for the highest cytotoxicity of cationized ribonuclease

    J Futami, E Nukui, T Maeda, M Kosaka, H Tada, M Seno, H Yamada

    JOURNAL OF BIOCHEMISTRY   132 ( 2 )   223 - 228   2002年8月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    Cationization of a protein is considered to be a powerful strategy for internalizing a functional protein into cells. Cationized proteins appear to adsorb to the cell surface by electrostatic interactions, then enter the cell in a receptor- and transporter-independent fashion. Thus, in principle, all cell types appear to take up cationized proteins. Since ribonucleases (RNases) have a latent cytotoxic potential, cationized RNases could be useful cancer chemotherapeutics. In this study, we investigated the effect of the degree of cationization on the cytotoxicity of RNase A by modifying carboxyl groups with ethylenediamine. We found that there is an optimum degree of modification for cytotoxicity, in which 5 to 7 out of 11 carboxyl groups in RNase A are modified, toward MCF-7 and 3T3-SV-40 cells. More interestingly, the cytotoxicity of cationized RNase As correlates well with the value of [RNase activity] x [estimated concentration of RNase free from RNase inhibitor], mimicking the practical enzymatic activity of cationized RNase As in cytosol. The results indicate that cationization of a protein to an optimum level is important for maintaining protein function in the cytosol. Sophisticated protein cationization techniques will help to advance protein transduction technology.

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  • Solution structure of betacellulin, a new member of EGF-family ligands

    K Miura, H Doura, T Aizawa, H Tada, M Seno, H Yamada, K Kawano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   294 ( 5 )   1040 - 1046   2002年6月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The solution structure of the EGF-like domain of betacellulin (BTCe), a newly discovered member of the epidermal growth factor (EGF) family, has been determined using two-dimensional nuclear magnetic resonance spectroscopy. This is the first report to identify the solution structure of the EGF-family ligand monomers that interact with both ErbB-1 and ErbB-4. The solution structure of BTCe was calculated using 538 NMR-derived restraints. The overall structure of BTCe was stabilized by three disulfide bonds, a hydrophobic core, and 23 hydrogen bonds. It appears that BTCe is comprised of five beta-strands and one short 3(10) helical turn. The secondary structural elements of BTCe are basically similar to those of the other EGF-family proteins, except that several significant variations of the structural properties were found. It is suggested that the structural variations between BTCe and the other EGF-family ligands may affect the specific receptor-recognition properties of EGF-family ligands. (C) 2002 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0006-291X(02)00585-5

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  • Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin

    H Kojima, T Nakamura, Y Fujita, A Kishi, M Fujimiya, S Yamada, M Kudo, Y Nishio, H Maegawa, M Haneda, H Yasuda, Kojima, I, M Seno, NCW Wong, R Kikkawa, A Kashiwagi

    DIABETES   51 ( 5 )   1398 - 1408   2002年5月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

    Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. Although these cells produced multiple enteroendocrine hormones, they did not produce insulin. Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. By examining the mechanism of differentiation in BYK cells, we found that another transcription factor, islet factor 1 (Isl-1) was newly expressed with the disappearance of Pax-6 expression in those cells after exposure to betacellulin. These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. Furthermore, implantation of the Isl-YK-14 cells into diabetic rats reduced the animals' plasma glucose levels; glucose levels dropped from 19.4 to 16.9 mmol/l 1 day after the injection of cells. As expected, the plasma insulin concentrations were 2.7 times higher in the diabetic rats injected with Isl-YK-14 cells compared to in controls. In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1.

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  • Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial cells

    C Bianco, HB Adkins, C Wechselberger, M Seno, N Normanno, A De Luca, YP Sun, N Khan, N Kenney, A Ebert, KP Williams, M Sanicola, DS Salomon

    MOLECULAR AND CELLULAR BIOLOGY   22 ( 8 )   2586 - 2597   2002年4月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor beta family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.

    DOI: 10.1128/MCB.22.8.2586-2597.2002

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  • Growth inhibition of mammalian cells by eosinophil cationic protein

    T Maeda, M Kitazoe, H Tada, R de Llorens, DS Salomon, M Ueda, H Yamada, M Seno

    EUROPEAN JOURNAL OF BIOCHEMISTRY   269 ( 1 )   307 - 316   2002年1月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Eosinophil cationic protein (ECP), one of the major components of basic granules of eosinophils, is cytotoxic to tracheal epithelium. However, the extent of this effect on other cell types has not been evaluated in vitro. In this study, we evaluated the effect of ECP on 13 mammalian cell lines. ECP inhibited the growth of several cell lines including those derived from carcinoma and leukemia in a dose-dependent manner. The IC50 values on A431 cells, MDA-MB-453 cells, HL-60 cells and K562 cells were estimated to be approximate to1-5 muM. ECP significantly suppressed the size of colonies of A431 cells, and decreased K562 cells in G(1)/G(0) phase. However, there was little evidence that ECP killed cells in either cell line. These effects of ECP were not enhanced by extending its N-terminus. Rhodamine B isothiocyanate-labeled ECP started to bind to A431 cells after 0.5 h and accumulated for up to 24 h, indicating that specific affinity for the cell surface may be important. ne affinity of ECP for heparin was assessed and found to be reduced when tryptophan residues, one of which is located at a position in the catalytic subsite of ribonuclease in ECP, were modified. The growth-inhibitory effect was also attenuated by this modification. These results suggest that growth inhibition by ECP is dependent on cell type and is cytostatic.

    DOI: 10.1046/j.0014-2956.2001.02653.x

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  • Detection and localization of Cripto-1 binding in mouse mammary epithelial cells and in the mouse mammary gland using an immunoglobulin-Cripto-1 fusion protein

    C Bianco, N Normanno, A De Luca, MR Maiello, C Wechselberger, Y Sun, N Khan, H Adkins, M Sanicola, B Vonderhaar, B Cohen, M Seno, D Salomon

    JOURNAL OF CELLULAR PHYSIOLOGY   190 ( 1 )   74 - 82   2002年1月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    Human Cripto-1 (CR-1), a member of the epidermal growth factor-CFC (EGF-CFC) family of peptides, is expressed in the developing mouse mammary gland and can modulate mammary epithelial cell migration, branching morphogenesis and milk protein expression in vitro. In order to screen for a CR-1 receptor and to identify potential CR-1 target tissues, we constructed a fusion protein comprising the EGF-like domain of CR-1 and the Fc domain of a human IgG1. The recombinant CR-1 fusion protein (CR-1-Fc) was biologically active as it was able to activate the ras/raf/mitogen activated protein kinase (MAPK) pathway and to inhibit transcription of the milk protein P-casein in NMuMG and HC-11 mouse mammary epithelial cells. By using immunocytochemistry and by an in situ enzyme-linked immunosorbent assay (ELISA), CR-1-Fc was found to specifically bind to NMuMG and HC-11 cells. Finally, immunohistochemical analysis using CR-1-Fc showed a specific localization of CR-1 binding to tissue sections from mouse mammary gland. In particular, more than 60% of the epithelial cells were intensely stained with the CR-1-Fc fusion protein in the lactating mouse mammary gland, whereas approximately 25% of the mammary epithelial cells were stained in the gland from pregnant mouse. Since expression of mouse cripto-1 (Cr-1) in the pregnant and lactating mouse mammary gland as well as its presence in milk has been previously demonstrated, these data strongly suggest that an autocrine pathway involving Cr-1 and its putative receptor is operating in the mouse mammary gland during pregnancy and lactation. Published 2002 Wiley-Liss, Inc.(dagger)

    DOI: 10.1002/jcp.10037

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  • 細胞増殖因子ベータセルリン -膵臓再生と糖尿病研究へのニューマテリアル-

    妹尾昌治

    和光純薬時報   70(3): 6-8.   2002年

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  • Human betacellulin structure modeled from other members of EGF family.

    Lopez-Torrejon I, Querol E, Aviles FX, *Seno M, De Llorens R, Oliva B.

    J. Mol. Model.   8 ( 4 )   131 - 144   2002年

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  • Promotion of beta-cell regeneration by betacellulin in ninety percent-pancreatectomized rats

    L Li, M Seno, H Yamada, Kojima, I

    ENDOCRINOLOGY   142 ( 12 )   5379 - 5385   2001年12月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Betacellulin is thought to promote growth and differentiation of pancreatic beta -cells. We investigated the effect of betacellulin on regeneration of pancreatic beta -cells in 90%-pancreatectomized rats. Ninety percent pancreatectomy was performed in male Wistar rats and betacellulin (0.5 mug/g body weight) or saline was administered daily for 10 d starting immediately after pancreatectomy. In pancreatectomized rats, the morning-fed plasma glucose was significantly lower and the plasma insulin concentration was significantly higher in betacellulin-treated rats than those in control rats for up to 4 wk. Thirty days after pancreatectomy, a glucose tolerance test was performed. Betacellulin reduced the plasma glucose response to ip glucose loading. In control rats, the plasma insulin concentration was significantly lower and did not respond to glucose. In contrast, the plasma insulin concentration increased slightly but significantly in betacellulin-treated rats. Thirty days after pancreatectomy, the beta -cell mass was greater and the insulin content was significantly higher in betacellulin-treated rats than those in control rats. The numbers of islet cell-like cluster and bromodeoxy uridine/insulin double-positive cells in both islet cell-like cluster and islets were significantly higher in betacellulin-treated rats. These results indicate that administration of betacellulin improves glucose metabolism by promoting beta -cell regeneration in 90%-pancreatectomized rats.

    DOI: 10.1210/en.142.12.5379

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  • Preparation of potent cytotoxic ribonucleases by cationization: Enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups

    J Futami, T Maeda, M Kitazoe, E Nukui, H Tada, M Seno, M Kosaka, H Yamada

    BIOCHEMISTRY   40 ( 25 )   7518 - 7524   2001年6月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    Carboxyl groups of bovine RNase A were amidated with ethylenediamine (to convert negative charges of carboxylate anions to positive ones), 2-aminoethanol (to eliminate negative charges), and taurine (to keep negative charges), respectively, by a carbodiimide reaction. Human RNase 1 was also modified with ethylenediamine. Surprisingly, the modified RNases were all cytotoxic toward 3T3-SV-40 cells despite their decreased ribonucleolytic activity. However, their enzymatic activity was not completely eliminated by the presence of excess cytosolic RNase inhibitor (RI). As for native RNase A and RNase 1 which were not cytotoxic, they were completely inactivated by RI. More interestingly, within the cytotoxic RNase derivatives. cytotoxicity correlated well with the net positive charge. RNase 1 and RNase A modified with ethylenediamine were more cytotoxic than naturally occurring cytotoxic bovine seminal RNase. An experiment using the fluorescence-labeled RNase derivatives indicated that the more cationic RNases were more efficiently adsorbed to the cells. Thus, it is suggested that the modification of carboxyl groups could change complementarity of RNase to RI and as a result endow RNase cytotoxicity and that cationization enhances the efficiency of cellular uptake of RNase so as to strengthen its cytotoxicity. The finding that an extracellular human enzyme such as RNase 1 could be effectively internalized into the cell by cationization suggests that cationization is a simple strategy for efficient delivery of a protein into cells and may open the way of the development of new therapeutics.

    DOI: 10.1021/bi010248g

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  • Three-dimensional structure of human RNase 1 Delta N7 at 1.9 angstrom resolution

    J Pous, G Mallorqui-Fernandez, R Peracaula, SS Terzyan, J Futami, H Tada, H Yamada, M Seno, R de Llorens, FX Gomis-Ruth, M Coll

    ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY   57   498 - 505   2001年4月

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    記述言語:英語   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    Human pancreatic ribonuclease 1 (RNase 1) is considered to be the human counterpart of bovine pancreatic RNase A. Truncation of seven amino-acid residues from the aminoterminal sequence resulted in RNase 1 Delta N7, which has a reduced ribonucleolytic activity and a lower affinity for the human placental RNase inhibitor (PRI). This RNase 1 variant has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data to 1.9 Angstrom resolution. The molecule displays the alpha + beta folding topology typical of members of the RNase A superfamily. The main distinct features found in RNase 1 Delta N7 are basically located in three loops affecting the fitting of the enzyme to the active site of subtilisin and the shape of the B2 subsite. These changes, taken with the lack of the catalytically active residue Lys7, may explain the reduced affinity of RNase 1 Delta N7 for PRI and the low ribonucleolytic activity of the protein when compared with the native enzyme.

    DOI: 10.1107/S0907444901001147

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  • Physicochemical and immunological characterization of hepatitis B virus envelope particles exclusively consisting of the entire L (pre-S1+pre-S2+S) protein

    T Yamada, H Iwabuki, T Kanno, H Tanaka, T Kawai, H Fukuda, A Kondo, M Seno, K Tanizawa, S Kuroda

    VACCINE   19 ( 23-24 )   3154 - 3163   2001年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    The hepatitis B virus (HBV) envelope (env) protein is composed of three regions: the 108- or 119-residue pre-Si region involved in the direct interaction with hepatocytes. the 55-residue pre-SZ region associated with the polymerized albumin-mediated interaction, and the major 226-residue S protein region. Thus, to improve the immunogenic potency of conventional HE vaccines, development of a new vaccine containing the entire pre-Si region in addition to pre-S2 and S is desired. We previously reported the efficient production of the HBV env L (pre-S1 + pre-S2 + S) protein in the recombinant yeast cells [J Biol Chem 267 (1992) 1953]. In this study, the HBV env L protein produced as nano-particles in yeast has been purified and characterized. By equilibrium sedimentation. an average molecular weight of L particle was estimated to be approximately 6.3 x 10(6), indicating that about 110 molecules of L proteins are assembled into an L particle. By atomic force microscopy in a moist atmosphere. the L particles were observed as large spherical particles with a diameter of 50-500 nm. The L particles were stable on short-time heating at a high temperature and long-time storage at a low temperature but rather unstable on repeated freezing and thawing and treatment with dithiothreitol. When immunized in mice. L particles elicited efficiently and simultaneously the anti-g, anti-pre-S2, and anti-pre-Si antibodies. The ED50 values in mice for the anti-S and anti-pre-S2 antibodies were similar to those elicited by the M (pre-S2 + S) particles. Furthermore. the anti-pre-Si rabbit antibodies were found to recognize various segments of the pre-Si region, including the pre-Si (21-47) segment. These results show the high ability of L particles to induce all antibodies against HBV env proteins, hence promising the future application of L particles for the next generation HE vaccine. (C) 2001 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0264-410X(01)00017-2

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  • ベータセルリン:細胞増殖分化因子を応用した再生医療への試み

    妹尾昌治

    ハイテクインフォメーション   134号14-21   2001年

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  • Expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in rat testes

    H Mori, T Nomura, M Seno, Y Miki, T Kimura, T Kogami, J Sasaki

    ACTA HISTOCHEMICA ET CYTOCHEMICA   34 ( 1 )   25 - 30   2001年

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    記述言語:英語   出版者・発行元:JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY  

    We investigated the expression of reactive oxygen species (ROS)-related enzyme mRNA to clarify the role of ROS in reproduction. In the present study, we investigated the expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in rat testes by in situ hybridization. To prepare digoxigenin-labeled probes, we obtained 5 ' -phosphorylated oligonucleotides containing sense and antisense sequences (93-mer) with EcoR I or Hind III restriction sites as protruding cohesive ends (total 99-mer). Then, both oligonucleotides were annealed and cloned into a pGEM4Z vector. The resultant plasmid DNA was linearized with EcoR I or Hind III and used as a template for the synthesis of labeled sense or antisense riboprobes.
    PHGPx mRNA was expressed stage-specifically during spermatogenesis in adult rats. It was not expressed during spermatogonia, but its expression first appeared in stage VII pachytene spermatocytes, became evident in stage VIII pachytene spermatocytes and increased gradually until becoming diplotene spermatocytes. It decreased slightly during the metaphase of meiosis, and then gradually increased as the spermatids differentiated. The expression was marked in spermatids between steps 7 and 12, and the maximum expression was observed in step 9-10 spermatids. Expression was diminished completely in step 18 spermatids. These results suggest that PHGPx plays an essential role in spermatogenesis.

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  • The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer

    DS Salomon, C Bianco, AD Ebert, NI Khan, M De Santis, N Normanno, C Wechselberger, M Seno, K Williams, M Sanicola, S Foley, W Gullick, G Persico

    ENDOCRINE-RELATED CANCER   7 ( 4 )   199 - 226   2000年12月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:SOC ENDOCRINOLOGY  

    The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-l) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (UR) asymmetry, In zebrafish, there is strong genetic evidence that oep functions as an obligatory cc-factor for the correct signaling of a transforming growth factor-beta (TGF beta)-related gene, nodal, during gastrulation and during UR asymmetry development. Expression of Cr-l and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-l expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-l is expressed at a low level in several different tissues including the mammary gland, In the mammary gland, expression of Cr-l in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-l protein can be detected in human milk. Overexpression of Cr-l in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-l-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta -catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-e. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of p-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

    DOI: 10.1677/erc.0.0070199

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  • Stabilization of human RNase 1 by introduction of a disulfide bond between residues 4 and 118

    J Futami, H Tada, M Seno, S Ishikami, H Yamada

    JOURNAL OF BIOCHEMISTRY   128 ( 2 )   245 - 250   2000年8月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    In order to stabilize human RNase 1 by introduction of an intramolecular cross-link, a mutant protein (4-118CL RNase 1), in which Arg4 and Val118 are replaced with cysteine residues and linked by a disulfide bond, was designed and expressed in Escherichia coli as inclusion bodies. The 4-118CL RNase 1 that refolded under redox conditions was a monomer without free SH groups and retained 11% of the activity of the wild-type recombinant RNase 1, indicating that the mutant enzyme was correctly folded with the formation of an additional disulfide bond between Cys4 and Cys118, From guanidium chloride denaturation experiments based on the assumption of a two-state transition for unfolding, it was demonstrated that the introduction of the present cross-link increased the thermodynamic stability of RNase 1 by 2.0 kcal/mol. This value was lower than that, 5.4 kcal/mol, theoretically calculated from the reduction of chain entropy of the unfolded state due to the introduction of the cross-link. These results suggest that the present cross-link also destabilized the folded state of RNase 1 by 3.4 kcal/mol. Along with the increase in the thermodynamic stability, the stability of RNase 1 against trypsin digestion was also significantly increased by the introduction of this cross-link. It is likely, although not proven, that stabilized human RNases are favorable for clinical use, because human RNase-based immunotoxins should have long half-lives as to proteolytic degradation after endocytosis.

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  • Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 Å resolution

    Goretti Mallorquí-Fernández, Joan Pous, Rosa Peracaula, Joan Aymamí, Takashi Maeda, Hiroko Tada, Hidenori Yamada, Masaharu Seno, Rafael De Llorens, F.Xavier Gomis-Rüth, Miquel Coll

    Journal of Molecular Biology   300 ( 5 )   1297 - 1307   2000年7月

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    記述言語:英語   出版者・発行元:Academic Press  

    Eosinophil cationic protein (ECP
    RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1.75 Å resolution. The molecule displays the α + β folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption. (C) 2000 Academic Press.

    DOI: 10.1006/jmbi.2000.3939

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  • Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 Å resolution

    Goretti Mallorquí-Fernández, Joan Pous, Rosa Peracaula, Joan Aymamí, Takashi Maeda, Hiroko Tada, Hidenori Yamada, Masaharu Seno, Rafael De Llorens, F.Xavier Gomis-Rüth, Miquel Coll

    Journal of Molecular Biology   300 ( 5 )   1297 - 1307   2000年7月

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    記述言語:英語   出版者・発行元:Academic Press  

    Eosinophil cationic protein (ECP
    RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1.75 Å resolution. The molecule displays the α + β folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption. (C) 2000 Academic Press.

    DOI: 10.1006/jmbi.2000.3939

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  • Three-dimensional crystal structure of human eosinophil cationic protein (RNase3) at 1.75 A resolution..

    Mallorqui-Fernandez G, Pous J, Peracaula R, Aymami J, Maeda T, Tada H, Yamada H, *Seno M, de Llorens R, Gomis-Ruth FX, Coll M.

    J Mol Biol.   300 ( 5 )   1297 - 1307   2000年7月

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  • Molecular cloning and expression of rat betacellulin cDNA

    Hiroko Tada, Masaharu Seno, Hidenori Yamada, Reiko Sasada, Koichi Igarashi

    Biochimica et Biophysica Acta - Gene Structure and Expression   1492 ( 1 )   285 - 288   2000年6月

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    記述言語:英語  

    The cDNA encoding an entire open reading frame of rat betacellulin has been cloned from rat kidney. Expression of this cDNA in COS7 cells showed a significant amount of mitogenic activity in the culture media. Western blotting of the cell lysates suggested that the membrane-anchored precursor was cleaved to release its ectodomain very efficiently. Copyright (C) 2000.

    DOI: 10.1016/S0167-4781(00)00106-8

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  • Molecular cloning and expression of rat betacellulin cDNA

    Hiroko Tada, Masaharu Seno, Hidenori Yamada, Reiko Sasada, Koichi Igarashi

    Biochimica et Biophysica Acta - Gene Structure and Expression   1492 ( 1 )   285 - 288   2000年6月

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    記述言語:英語  

    The cDNA encoding an entire open reading frame of rat betacellulin has been cloned from rat kidney. Expression of this cDNA in COS7 cells showed a significant amount of mitogenic activity in the culture media. Western blotting of the cell lysates suggested that the membrane-anchored precursor was cleaved to release its ectodomain very efficiently. Copyright (C) 2000.

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  • Molecular cloning and expression of rat betacellulin cDNA

    Tada H, *Seno M, Yamada H, Sasada R, Igarashi K

    Biochim Biophys Acta.   1492 ( 1 )   285 - 288   2000年6月

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  • Targeting activated lymphocytes with an entirely human immunotoxin analogue: human pancreatic RNase1-human IL-2 fusion.

    Psarras K, Ueda M, Tanabe M, Kitajima M, Aiso S, Komatsu S, *Seno M.

    Cytokine.   12 ( 6 )   786 - 790   2000年6月

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  • Stabilization of human RNase 1 by introduction of a disulfide bond between residues 4 and 118.

    Futami J, Tada H, *Seno M, Ishikami S, Yamada H.

    J Biochem (Tokyo)   128 ( 2 )   245   2000年4月

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  • Convenient and Efficient In Vitro Folding of Disulfide-Containing Globular Protein from Crude Bacterial Inclusion Bodies

    Futami J, Tsushima Y, Tada H, *Seno M, Yamada H.

    J Biochem (Tokyo).   127 ( 3 )   435   2000年4月

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  • Convenient and Efficient In Vitro Folding of Disulfide-Containing Globular Protein from Crude Bacterial Inclusion Bodies.

    Futami J, Tsushima Y, Tada H, *Seno M, Yamada H.

    J Biochem (Tokyo)   127 ( 3 )   435   2000年4月

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  • Stabilization of human RNase 1 by introduction of a disulfide bond between residues 4 and 118.

    Futami J, Tada H, *Seno M, Ishikami S, Yamada H.

    J Biochem (Tokyo).   128 ( 2 )   245   2000年4月

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  • Convenient and efficient in vitro folding of disulfide-containing globular protein from crude bacterial inclusion bodies

    J Futami, Y Tsushima, H Tada, M Seno, H Yamada

    JOURNAL OF BIOCHEMISTRY   127 ( 3 )   435 - 441   2000年3月

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    記述言語:英語   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    We investigated how the folding yield of disulfide-containing globular proteins having positive net charges from crude bacterial inclusion bodies was affected by additives in the folding buffer. In screening folding conditions for human ribonucleases and its derivative, we found that addition of salt (about 0.4 M) to a folding buffer increased the folding yield. This suggested that electrostatic interaction between polyanionic impurities such as nucleic acids and cationic unfolded protein led to the formation of aggregates under the low-salt conditions. Since inclusion bodies were found to contain nucleic acids regardless of the electrostatic nature of the expressed protein, the electrostatic interaction between phosphate moieties of nucleic acids and basic amino acid residues of a denatured protein may be large enough to cause aggregation, and therefore the addition of salt in a folding buffer may generally be useful for promotion of protein folding from crude inclusion bodies. We further systematically investigated additives such as glycerol, guanidium chloride, and urea that are known to act as chemical chaperons, and found that these additives, together with salt, synergistically improved folding yield. This study, suggesting that the addition of salt into the folding buffer is one of the crucial points to be considered, may pave the way for a systematic investigation of the folding conditions of disulfide-containing foreign proteins from crude bacterial inclusion bodies.

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  • Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells

    M. L. De Santis, I. Martinez-Lacaci, C. Bianco, M. Seno, B. Wallace-Jones, N. Kim, A. Ebert, C. Wechselberger, D. S. Salomon

    Cell Death and Differentiation   7 ( 2 )   189 - 196   2000年

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    記述言語:英語   出版者・発行元:Nature Publishing Group  

    Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit β-casein and whey acidic protein expression in mouse mammary epithelial cells. The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bis-benzimide stained nuclei, TUNEL assay and cell death ELISA. Apoptosis could be observed after 2 days of exposure of confluent HC-11 cells to CR-1 in the absence of the survival factors EGF and insulin, with maximum apoptosis occurring at 3 days. A reduction in poly(ADP-ribose) polymerase (PARP) expression and an increase in β-catenin cleavage was found after 18 h of exposure to CR-1 suggesting that apoptosis was preceded by the induction of a caspase activity since the caspase inhibitor ZFAD.FMK could block the CR-1-induced reduction in PARP expression and CR-1-induced apoptosis. CR-1 was found to increase the expression of caspase-3-like protease. Although, the levels of p27(kip1) and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-x(L) became undetectable. These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-xL.

    DOI: 10.1038/sj.cdd.4400588

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  • Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells

    M. L. De Santis, I. Martinez-Lacaci, C. Bianco, M. Seno, B. Wallace-Jones, N. Kim, A. Ebert, C. Wechselberger, D. S. Salomon

    Cell Death and Differentiation   7 ( 2 )   189 - 196   2000年

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    記述言語:英語   出版者・発行元:Nature Publishing Group  

    Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit β-casein and whey acidic protein expression in mouse mammary epithelial cells. The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bis-benzimide stained nuclei, TUNEL assay and cell death ELISA. Apoptosis could be observed after 2 days of exposure of confluent HC-11 cells to CR-1 in the absence of the survival factors EGF and insulin, with maximum apoptosis occurring at 3 days. A reduction in poly(ADP-ribose) polymerase (PARP) expression and an increase in β-catenin cleavage was found after 18 h of exposure to CR-1 suggesting that apoptosis was preceded by the induction of a caspase activity since the caspase inhibitor ZFAD.FMK could block the CR-1-induced reduction in PARP expression and CR-1-induced apoptosis. CR-1 was found to increase the expression of caspase-3-like protease. Although, the levels of p27(kip1) and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-x(L) became undetectable. These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-xL.

    DOI: 10.1038/sj.cdd.4400588

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  • Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells.

    Miyagawa J, Hanafusa T, Sasada R, Yamamoto K, Igarashi K, Yamamori K, *Seno M, Tada H, Nammo T, Li M, Yamagata K, Nakajima H, Namba M, Kuwajima M, Matsuzawa Y

    Endocrine J.,   46 ( 6 )   755 - 764   1999年12月

  • Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells

    J Miyagawa, T Hanafusa, R Sasada, K Yamamoto, K Igarashi, K Yamamori, M Seno, H Tada, T Nammo, M Li, K Yamagata, H Nakajima, M Namba, M Kuwajima, Y Matsuzawa

    ENDOCRINE JOURNAL   46 ( 6 )   755 - 764   1999年12月

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    記述言語:英語   出版者・発行元:JAPAN ENDOCRINE SOCIETY  

    Betacellulin (BTC) purified from mouse beta cell tumor (beta TC-3) is a new member of the epidermal growth factor (EGF) family which can bind receptor tyrosine kinase, EGF receptor (erbB1) and erbB4. It has been demonstrated that proBTC mRNA was abundantly expressed in human pancreas tissue, and that ETC converted amylase-secreting rat acinar cell line (AR42J) into insulin-secreting cells, suggesting that ETC might be important for the growth and/or differentiation of islet cells. However, the cell type producing ETC in the pancreas has not been clarified. In this study, we examined the localization of ETC in human pancreas and islet cell tumors. Immunohistochemistry using specific antibodies to human ETC revealed that this protein was produced in alpha cells and duct cells, and probably in beta cells in normal adult pancreas. Furthermore, strong immunoreactivity to ETC was detected in primitive duct cells of the fetal pancreas, and both insulinoma and glucagonoma cells also showed positive immunoreactivity to ETC. EGF receptor (erbB1) and erbB4 were expressed mainly in islet and duct cells, and duct cells, respectively. These results demonstrate the localization of ETC and its receptors, and suggest that ETC may be one of the factors that have physiologically important roles such as growth and differentiation of islet cells in the human pancreas.

    DOI: 10.1507/endocrj.46.755

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  • Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells

    Jun Ichiro Miyagawa, Toshiaki Hanafusa, Reiko Sasada, Koji Yamamoto, Koichi Igarashi, Katsumi Yamamori, Masaharu Seno, Hiroko Tada, Takao Nammo, Ming Li, Kazuya Yamagata, Hiromu Nakajima, Mitsuyoshi Namba, Masamichi Kuwajima, Yuji Matsuzawa

    Endocrine Journal   46 ( 6 )   755 - 764   1999年12月

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    Betacellulin (BTC) purified from mouse β cell tumor (βTC-3) is a new member of the epidermal growth factor (EGF) family which can bind receptor tyrosine kinase, EGF receptor (erbB1) and erbB4. It has been demonstrated that proBTC mRNA was abundantly expressed in human pancreas tissue, and that BTC converted amylase-secreting rat acinar cell line (AR42J) into insulin- secreting cells, suggesting that BTC might be important for the growth and/or differentiation of islet cells. However, the cell type producing BTC in the pancreas has not been clarified. In this study, we examined the localization of BTC in human pancreas and islet cell tumors. Immunohistochemistry using specific antibodies to human BTC revealed that this protein was produced in a cells and duct cells, and probably in β cells in normal adult pancreas. Furthermore, strong immunoreactivity to BTC was detected in primitive duct cells of the fetal pancreas, and both insulinoma and glucagonoma cells also showed positive immunoreactivity to BTC. EGF receptor (erbB1) and erbB4 were expressed mainly in islet and duet cells, and duct cells, respectively. These results demonstrate the localization of BTC and its receptors, and suggest that BTC may be one of the factors that have physiologically important roles such as growth and differentiation of islet cells in the human pancreas.

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  • Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor

    J Futami, M Seno, M Ueda, H Tada, H Yamada

    PROTEIN ENGINEERING   12 ( 11 )   1013 - 1019   1999年11月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    Pancreatic-type RNases are considered to have cytotoxic potential due to their ability to degrade RNA molecules when they enter the cytosol. However, most of these RNases show little cytotoxicity because cells have no active uptake mechanism for these RNases and because the ubiquitous cytoplasmic RNase inhibitor is considered to play a protective role against the endocytotic leak of RNases from the outside of cells. To study the cytotoxic potential of RNase toward malignant cells targeting growth factor receptors, the C-terminus of human RNase 1 was fused to the N-terminus of human basic fibroblast growth factor (bFGF). This RNase-FGF fused protein effectively inhibited the growth of mouse melanoma cell line B16/BL6 with high levels of cell surface FGF receptor. This effect appeared to result from prolongation of the overall cell cycle rather than the killing of cells or specific arrest in a particular phase of the cell cycle. Thus, human RNase 1 fused to a ligand of cell surface molecules, such as the FGF receptor, is shown to be an effective candidate for a selective cell targeting agent with low toxic effects on normal cell types.

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  • Cripto-1 induces phosphatidylinositol 3 &apos;-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3 beta in human cervical carcinoma cells

    AD Ebert, C Wechselberger, S Frank, B Wallace-Jones, M Seno, Martinez-Lacaci, I, C Bianco, M De Santis, HK Weitzel, DS Salomon

    CANCER RESEARCH   59 ( 18 )   4502 - 4505   1999年9月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Cripto-1 (CR-1), a member of the epidermal growth factor-CFC peptide family, activates the ras/raf/mitogen-activated protein/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. In the present study, the role of CR-1 in the phosphatidylinositol 3&apos;-kinase (PI3K)/AKT (protein kinase B)/glycogen synthase kinase 3 beta (GSK-3 beta)dependent signaling pathway was evaluated in human SiHa cervical carcinoma cells. Our data demonstrate that CR-1 can enhance the tyrosine phosphorylation of the p85 regulatory subunit of PI3K and transiently induce the phosphorylation of AKT in a time- and dose-dependent manner. In addition, CR-1 was found to induce the phosphorylation of GSK-3 beta. Phosphorylation of AKT and GSK-3 beta by CR-1 can be blocked by LY294002, a specific inhibitor of PI3K;, thus leading to apoptosis. Finally, the apoptotic effect of LY294002 can be partially rescued by exogenous CR-1. In summary, our data suggest that human CR-1 may function as a survival factor through a PI3K-dependent signaling pathway involving AKT and GSK-3 beta.

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  • Cripto-1 induces phosphatidylinositol 3''-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells.

    Ebert AD, Wechselberger C, Frank S, Wallace-Jones B, *Seno M, Martinez-LacaciI, Bianco C, De Santis M, Weitzel HK, Salomon DS.

    Cancer Res.   59 ( 18 )   4502   1999年4月

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  • Inhibition of Cell Growth by a fused Protein of Human Basic Fibroblast Growth Factor.

    Futami J, *Seno M, Ueda M, Tada H, Yamada H

    Protein Engineering   12 ( 11 )   1013   1999年4月

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  • Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells.

    Ebert AD, Wechselberger C, Frank S, Wallace-Jones B, *Seno M, Martinez-LacaciI, Bianco C, De Santis M, Weitzel HK, Salomon DS.

    Cancer Res.   59 ( 18 )   4502   1999年4月

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  • Inhibition of Cell Growth by a fused Protein of Human Basic Fibroblast Growth Factor.

    Futami J, *Seno M, Ueda M, Tada H, Yamada H

    Protein Engineering   12 ( 11 )   1013   1999年4月

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  • Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor

    Caterina Bianco, Subha Kannan, Marta De Santis, Masaharu Seno, Careen K. Tang, Isabel Martinez-Lacaci, Nancy Kim, Brenda Wallace-Jones, Marc E. Lippman, Andreas D. Ebert, Christian Wechselberger, David S. Salomon

    Journal of Biological Chemistry   274 ( 13 )   8624 - 8629   1999年3月

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    記述言語:英語  

    Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor family that fails to directly bind to any of the four known erb B type 1 receptor tyrosine kinases. The present study demonstrates that CR-1 indirectly induces tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor-related receptors erb B-2 and erb B-3 in different mouse and human mammary epithelial cell lines. In addition, down-regulation of erb B-4 in NMuMG mouse mammary epithelial cells and in T47D human breast cancer cells, using an anti-orb B-4 blocking antibody or a hammerhead ribozyme vector targeted to orb B-4 mRNA, impairs the ability of CR-1 to fully activate mitogen-activated protein kinase. Finally, chemical cross- linking of 125I-CR-1 to mouse and human mammary epithelial cell membranes results in the labeling of two specific bands with a molecular weight of 130 and 60 kDa, suggesting that the CR-1 receptor represents a novel receptor structurally unrelated to any of the known type I receptor tyrosine kinases. In conclusion, these data demonstrate that CR-1, upon binding to an unknown receptor, can enhance the tyrosine kinase activity of erb B-4 and that a functional erb B-4 receptor is required for CR-1-induced MAPK activation.

    DOI: 10.1074/jbc.274.13.8624

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  • Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor.

    Bianco C, Kannan S, De Santis M, *Seno M, Tang CK, Martinez-Lacaci I, Kim N, Wallace-Jones B, Lippman ME, Ebert AD, Wechselberger C, Salomon DS

    J Biol Chem.   274 ( 13 )   8624 - 8629   1999年3月

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  • Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor

    C Bianco, S Kannan, M De Santis, M Seno, CK Tang, Martinez-Lacaci, I, N Kim, B Wallace-Jones, ME Lippman, AD Ebert, C Wechselberger, DS Salomon

    JOURNAL OF BIOLOGICAL CHEMISTRY   274 ( 13 )   8624 - 8629   1999年3月

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    記述言語:英語   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor family that fails to directly bind to any of the four known erb B type 1 receptor tyrosine kinases. The present study demonstrates that CR-1 indirectly induces tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor-related receptors erb B-2 and erb B-3 in different mouse and human mammary epithelial cell lines. In addition, downregulation of erb B-4 in NMuMG mouse mammary epithelial cells and in T47D human breast cancer cells, using an anti-erb B-4 blocking antibody or a hammerhead ribozyme vector targeted to erb B-4 mRNA, impairs the ability of CR-1 to fully activate mitogen-activated protein kinase. Finally, chemical cross-linking of I-125-CR-1 to mouse and human mammary epithelial cell membranes results in the labeling of two specific bands with a molecular weight of 130 and 60 kDa, suggesting that the CR-1 receptor represents a novel receptor structurally unrelated to any of the known type I receptor tyrosine kinases. In conclusion, these data demonstrate that CR-1, upon binding to an unknown receptor, can enhance the tyrosine kinase activity of erb B-4 and that a functional erb B-4 receptor is required for CR-1-induced MAPK activation.

    DOI: 10.1074/jbc.274.13.8624

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  • Processing and juxtacrine activity of membrane-anchored betacellulin

    H Tada, R Sasada, Y Kawaguchi, Kojima, I, WJ Gullick, DS Salomon, K Igarashi, M Seno, H Yamada

    JOURNAL OF CELLULAR BIOCHEMISTRY   72 ( 3 )   423 - 434   1999年3月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    Betacellulin (BTC) was originally isolated as a secreted growth factor from a mouse pancreatic beta-tumor cell line, whereas the cDNA sequence predicts that ETC is synthesized as a larger transmembrane protein. In the present study, we have characterized the membrane-anchored forms of BTC, using Chinese hamster ovary (CHO) cells, mouse fibroblast A9 cells, and a human breast cancer cell line MCF-7, all of which were stably transfected with human ETC cDNA. A9 and MCF-7 transfectants produced membrane-anchored ETC isoforms of 21, 25, 29, and 40 kDa on the cell surface, as well as a secreted BTC isoform. CHO transfectants secreted little ETC but accumulated the membrane-anchored isoforms. The cleavage of the membrane-anchored forms to release a secreted from of ETC was not enhanced by biological mediators such as a phorbol ester, which stimulates the cleavage of other membrane-anchored growth factors. The membrane-anchored forms of ETC expressed on the transfected cells induced the insulin production and/or promoted the growth in subclones of AR42J rat pancreatic cells. These results suggest that the membrane-anchored ETC can function as a juxtacrine factor in regulating the growth and differentiation of pancreatic endocrine cells. J. Cell. Biochem. 72.423-134, 1999. (C) 1999 Wiley-Liss, Inc.

    DOI: 10.1002/(SICI)1097-4644(19990301)72:3<423::AID-JCB11>3.0.CO;2-P

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  • Genes expressed during the differentiation of pancreatic ARA2J cells into insulin-secreting cells

    H Mashima, S Yamada, T Tajima, M Seno, H Yamada, J Takeda, Kojima, I

    DIABETES   48 ( 2 )   304 - 309   1999年2月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

    dPancreatic AR42J cells have the feature of pluripotency of the common precursor cells of the pancreas. Dexamethasone (Dx) converts them to exocrine cells, whereas activin A (Act) converts them into endocrine cells expressing pancreatic polypeptide. A combination of Act and betacellulin (BTC) converts them further into insulin-secreting cells, The present study identifies some of the genes involved in the process of differentiation that is induced by these factors, using the mRNA differential display and screening of the cDNA expression array. The expression levels of 7 genes were increased by Act alone, and a combination of Act and ETC increased the expression of 25 more genes. Of these, 16 represented known genes or homologues of genes characterized previously, Nine of the identified genes were unrelated to any other sequences in the database. An inhibitor of the mitogen-activated protein kinase pathway, PD098059, which blocks the differentiation into insulin-secreting cells, inhibited the expression of 18 of the 25 genes, suggesting that the proteins encoded by these genes are associated with the differentiation into insulin-producing cells, These include known genes encoding extracellular signaling molecules, such as parathyroid hormone-related peptide, cyloskeletal proteins, and intracellular signaling molecules. Identification and characterization of these differentially expressed genes should help to clarify the molecular mechanism of differentiation of pancreatic cells and the; gene products that enable the beta-cells to produce insulin.

    DOI: 10.2337/diabetes.48.2.304

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  • The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity

    SS Terzyan, R Peracaula, R de Llorens, Y Tsushima, H Yamada, M Seno, FX Gomis-Ruth, M Coll

    JOURNAL OF MOLECULAR BIOLOGY   285 ( 1 )   205 - 214   1999年1月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS LTD  

    The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the chi(1) = -72.49 degrees rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the =N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases. (C) 1999 Academic Press.

    DOI: 10.1006/jmbi.1998.2288

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  • Genes expressed during the differentiation of pancreatic AR42J cells into insulin-secreting cells

    Hirosato Mashima, Shirou Yamada, Tomoko Tajima, Masaharu Seno, Hidenori Yamada, Jun Takeda, Itaru Kojima

    Diabetes   48 ( 2 )   304 - 309   1999年

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    記述言語:英語   出版者・発行元:American Diabetes Association Inc.  

    Pancreatic AR42J cells have the feature of pluripotency of the common precursor cells of the pancreas. Dexamethasone (Dx) converts them to exocrine cells, whereas activin A (Act) converts them into endocrine cells expressing pancreatic polypeptide. A combination of Act and betacellulin (BTC) converts them further into insulin-secreting cells. The present study identifies some of the genes involved in the process of differentiation that is induced by these factors, using the mRNA differential display and screening of the cDNA expression array. The expression levels of 7 genes were increased by Act alone, and a combination of Act and BTC increased the expression of 25 more genes. Of these, 16 represented known genes or homologues of genes characterized previously. Nine of the identified genes were unrelated to any other sequences in the database. An inhibitor of the mitogen-activated protein kinase pathway, PD098059, which blocks the differentiation into insulin-secreting cells, inhibited the expression of 18 of the 25 genes, suggesting that the proteins encoded by these genes are associated with the differentiation into insulin-producing cells. These include known genes encoding extracellular signaling molecules, such as parathyroid hormone- related peptide, cytoskeletal proteins, and intracellular signaling molecules. Identification and characterization of these differentially expressed genes should help to clarify the molecular mechanism of differentiation of pancreatic cells and the gene products that enable the β- cells to produce insulin.

    DOI: 10.2337/diabetes.48.2.304

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  • Genes expressed during the differentiation of pancreatic AR42J cells into insulin-secreting cells.

    Mashima, H., Yamada, S., Tajima, T., *Seno, M., Yamada, H., Takeda, J. and Kojima, I.

    Diabetes   48 ( 2 )   304 - 309   1999年

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  • 新しい臓器特異的癌関連遺伝子のクローニングと癌遺伝子産物を分子標的とした治療法の開発

    上田 政和, 菊池 潔, 板野 理, プサラス・キリヤコス, 北島 政樹, 妹尾 昌治

    日本癌治療学会誌   33 ( 3 )   355 - 355   1998年8月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Identification of the genes associated with differentiation of AR42J cells into insulin-secreting cells

    H Mashima, J Takeda, M Seno, H Yamada, Kojima, I

    DIABETES   47   A176 - A176   1998年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER DIABETES ASSOC  

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  • Molecular targeting for activated T cell by recombinant human RNase and IL-2.

    M Ueda, K Psarras, M Tanabe, T Yamamura, M Kitajima, M Seno, S Komatsu

    GASTROENTEROLOGY   114 ( 4 )   A1186 - A1186   1998年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO  

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  • Multiple-labeling of oligonucleotide probes for in situ hybridization

    Junzo Sasaki, Hitoshi Yamamoto, Takako Nomura, Junko Matsuura, Masaharu Seno, Eisuke F. Sato, Masayasu Inoue

    Acta Histochemica et Cytochemica   31 ( 4 )   275 - 279   1998年

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    記述言語:英語   出版者・発行元:Japan Society of Histochemistry and Cytochemistry  

    We describe here a method to synthesize probes for in situ hybridization. This method provides more efficient incorporation of the reporter molecules such as 35S-UTP or digoxigenin-UTP into the oligonucleotide probes than other methods. Two 99-base oligonucleotides complementary to each other were obtained as purified and lyophilized products (&gt
    99%). These oligonucleotides were designed as follows. The sequence of 77 bases derived from reported cDNA sequence in the literature was flanked by the restriction sites of EcoR I and Hind III (6 bases for each) with extended random sequences of 5 bases at both ends (total 99 bases). Both oligonucleotides were then annealed and digested with EcoR I and Hind III. The gel-purified EcoR I/Hind III-cut DNA fragment was cloned into the pGEM4Z vector. The resultant plasmid DNA was linearized with EcoR I or Hind III and used as a template for the synthesis of labeled sense or antisense riboprobes. The amelogenin probes prepared by this method clearly distinguished the localized expression of mRNA when applied to in situ hybridization.

    DOI: 10.1267/ahc.31.275

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  • BALB/c 3T3 cells co-expressing FGF-2 and soluble FGF receptor acquire tumorigenicity

    Masaharu Seno, Akinori Masago, Atsushi Nishimura, Hiroko Tada, Megumi Kosaka, Reiko Sasada, Koichi Igarashi, Satimaru Seno, Hidenori Yamada

    Cytokine   10 ( 4 )   290 - 294   1998年

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    記述言語:英語   出版者・発行元:Academic Press  

    The physiological significance of the soluble fibroblast growth factor (FGF) receptors is not clear yet although they are present in blood, vitreous fluid and in the extracellular matrix of vascular endothelial cells. A hypothesis that they might help FGF-2 release from cells is very interesting because FGF-2 does not have clear secretion signal and the mechanism of the secretion of FGF-2 is still unclear. Single overexpression of FGF-2 is related neither to the secretion potential of the molecule nor to the tumorigenicity of the cells. In this report, BALB/c 3T3 cells transformed with the full length of human FGF-2 cDNA are further transformed with the cDNA coding the extracellular domain of human FGF receptor 1. The obtained transformants co-expressing FGF-2 and soluble FGF receptor are highly tumorigenic in nude mice, while the parental cells do not show any tumorigenicity. In the conditioned medium of the double-transformants, FGF-2 is immunologically detected. These results suggest that naturally produced soluble form of FGF receptor supports the release of FGF-2 from the cells and that over-expression of these two molecules leads to induce the malignant tumours in vivo.

    DOI: 10.1006/cyto.1997.0286

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  • BALB/c 3T3 cells co-expressing FGF-2 and soluble FGF receptor acquire tumorigenicity

    Masaharu Seno, Akinori Masago, Atsushi Nishimura, Hiroko Tada, Megumi Kosaka, Reiko Sasada, Koichi Igarashi, Satimaru Seno, Hidenori Yamada

    Cytokine   10 ( 4 )   290 - 294   1998年

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    記述言語:英語   出版者・発行元:Academic Press  

    The physiological significance of the soluble fibroblast growth factor (FGF) receptors is not clear yet although they are present in blood, vitreous fluid and in the extracellular matrix of vascular endothelial cells. A hypothesis that they might help FGF-2 release from cells is very interesting because FGF-2 does not have clear secretion signal and the mechanism of the secretion of FGF-2 is still unclear. Single overexpression of FGF-2 is related neither to the secretion potential of the molecule nor to the tumorigenicity of the cells. In this report, BALB/c 3T3 cells transformed with the full length of human FGF-2 cDNA are further transformed with the cDNA coding the extracellular domain of human FGF receptor 1. The obtained transformants co-expressing FGF-2 and soluble FGF receptor are highly tumorigenic in nude mice, while the parental cells do not show any tumorigenicity. In the conditioned medium of the double-transformants, FGF-2 is immunologically detected. These results suggest that naturally produced soluble form of FGF receptor supports the release of FGF-2 from the cells and that over-expression of these two molecules leads to induce the malignant tumours in vivo.

    DOI: 10.1006/cyto.1997.0286

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  • Studies on the betacellulin receptor in pancreatic AR42J cells

    N. Ishiyama, M. Kanzaki, M. Seno, H. Yamada, I. Kobayashi, I. Kojima

    Diabetologia   41 ( 6 )   623 - 628   1998年

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    記述言語:英語  

    Betacellulin is a member of the epidermal growth factor family and converts pancreatic AR42J cells into insulin-producing cells. This study was conducted to characterise the receptor for betacellulin in AR42J cells. AR42J cells expressed two classes of binding sites for radioactive iodine labelled betacellulin, with Kd values of 4.6 x 10-11 mol/l and 3.0 x 10-10 mol/l. The binding of [125I]betacellulin was inhibited by unlabelled betacellulin in a dose-dependent manner, but epidermal growth factor was 50 fold less effective than betacellulin. Affinity cross-linking showed a [125I]betacellulin-binding protein with a molecular weight of approximately 180 KDa. When this protein was immunoprecipitated with antibody against epidermal growth factor receptors ErbB-1, ErbB-2, ErbB-3 or ErbB-4, it was immunoprecipitated only by the anti-ErbB-1 antibody. When the [125I]betacellulin-labelled proteins were immunoprecipitated with a combination of the four ErbB antibodies, and the unprecipitated proteins were then immunoprecipitated with anti-phosphotyrosine antibody, a 190 KDa protein was observed. Betacellulin induced the tyrosine phosphorylation of ErbB-1, ErbB-2 and ErbB-4. Finally, while 100 pmol/l betacellulin converted all of the AR42J into insulin-producing cells in the presence of activin A, 10 nmol/l epidermal growth factor induced differentiation in only about 30% of the cells. Higher concentrations of epidermal growth factor were less effective. Neu differentiation factor in the presence or absence of epidermal growth factor was ineffective. These results indicate that betacellulin binds to ErbB-1 and possibly another protein with a molecular weight of 190 KDa. The latter betacellulin-binding protein may be involved in the differentiation-inducing activity of betacellulin.

    DOI: 10.1007/s001250050959

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  • Studies on the betacellulin receptor in pancreatic AR42J cells

    N. Ishiyama, M. Kanzaki, M. Seno, H. Yamada, I. Kobayashi, I. Kojima

    Diabetologia   41 ( 6 )   623 - 628   1998年

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    記述言語:英語  

    Betacellulin is a member of the epidermal growth factor family and converts pancreatic AR42J cells into insulin-producing cells. This study was conducted to characterise the receptor for betacellulin in AR42J cells. AR42J cells expressed two classes of binding sites for radioactive iodine labelled betacellulin, with Kd values of 4.6 x 10-11 mol/l and 3.0 x 10-10 mol/l. The binding of [125I]betacellulin was inhibited by unlabelled betacellulin in a dose-dependent manner, but epidermal growth factor was 50 fold less effective than betacellulin. Affinity cross-linking showed a [125I]betacellulin-binding protein with a molecular weight of approximately 180 KDa. When this protein was immunoprecipitated with antibody against epidermal growth factor receptors ErbB-1, ErbB-2, ErbB-3 or ErbB-4, it was immunoprecipitated only by the anti-ErbB-1 antibody. When the [125I]betacellulin-labelled proteins were immunoprecipitated with a combination of the four ErbB antibodies, and the unprecipitated proteins were then immunoprecipitated with anti-phosphotyrosine antibody, a 190 KDa protein was observed. Betacellulin induced the tyrosine phosphorylation of ErbB-1, ErbB-2 and ErbB-4. Finally, while 100 pmol/l betacellulin converted all of the AR42J into insulin-producing cells in the presence of activin A, 10 nmol/l epidermal growth factor induced differentiation in only about 30% of the cells. Higher concentrations of epidermal growth factor were less effective. Neu differentiation factor in the presence or absence of epidermal growth factor was ineffective. These results indicate that betacellulin binds to ErbB-1 and possibly another protein with a molecular weight of 190 KDa. The latter betacellulin-binding protein may be involved in the differentiation-inducing activity of betacellulin.

    DOI: 10.1007/s001250050959

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  • Multiple-labeling of oligonucleotide probes for in situ hybridization

    Junzo Sasaki, Hitoshi Yamamoto, Takako Nomura, Junko Matsuura, Masaharu Seno, Eisuke F. Sato, Masayasu Inoue

    Acta Histochemica et Cytochemica   31 ( 4 )   275 - 279   1998年

     詳細を見る

    記述言語:英語   出版者・発行元:Japan Society of Histochemistry and Cytochemistry  

    We describe here a method to synthesize probes for in situ hybridization. This method provides more efficient incorporation of the reporter molecules such as 35S-UTP or digoxigenin-UTP into the oligonucleotide probes than other methods. Two 99-base oligonucleotides complementary to each other were obtained as purified and lyophilized products (&gt
    99%). These oligonucleotides were designed as follows. The sequence of 77 bases derived from reported cDNA sequence in the literature was flanked by the restriction sites of EcoR I and Hind III (6 bases for each) with extended random sequences of 5 bases at both ends (total 99 bases). Both oligonucleotides were then annealed and digested with EcoR I and Hind III. The gel-purified EcoR I/Hind III-cut DNA fragment was cloned into the pGEM4Z vector. The resultant plasmid DNA was linearized with EcoR I or Hind III and used as a template for the synthesis of labeled sense or antisense riboprobes. The amelogenin probes prepared by this method clearly distinguished the localized expression of mRNA when applied to in situ hybridization.

    DOI: 10.1267/ahc.31.275

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  • Characterization of the betacellulin receptor in pancreatic AR42J-B20 cells

    N Ishiyama, M Kanzaki, M Furukawa, J Miyagawa, T Hanafusa, M Seno, H Yamada, Kobayashi, I, Kojima, I

    DIABETOLOGIA   40   91 - 91   1997年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER VERLAG  

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  • Genes expressed during the differentiation of AR42J cells into insulin-secreting

    H Mashima, J Takeda, M Seno, H Yamada, Kojima, I

    DIABETES   46   1378 - 1378   1997年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER DIABETES ASSOC  

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  • Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form

    M Seno, H Tada, M Kosaka, R Sasada, K Igarashi, Y Shing, J Folkman, M Ueda, H Yamada

    GROWTH FACTORS   13 ( 3-4 )   181 - 191   1996年

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    記述言語:英語   出版者・発行元:HARWOOD ACAD PUBL GMBH  

    Betacellulin (BTC) was found to be expressed mainly in human pancreas and small intestine. This finding suggests that ETC possesses some specific function distinguished from the other members of epidermal growth factor (EGF) family. To clarify this function, the released form of human ETC has been expressed in E.coli, purified, and characterized. The recombinant human ETC was produced as an inclusion body. This material was dissolved in guanidine-HCl under reducing conditions, refolded, and purified through sequential liquid chromatography. Purified ETC was electrophoresed under reducing conditions and a molecular size of 18 kDa was determined, which is the supposed size of a dimer of the peptide. However, chemical analysis failed to show a covalently linked dimer. The molecular mass of ETC analyzed by mass spectrometry revealed it to be 9 kDa, which is consistent with theoretical value for a monomer. Recombinant ETC showed growth promoting activity for mouse fibroblasts and rat aortic smooth muscle cells which was equivalent to EGF. On the other hand, ETC was found to exhibit a growth inhibitory effect on the cells overexpressing EGF receptor.

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  • Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form

    M Seno, H Tada, M Kosaka, R Sasada, K Igarashi, Y Shing, J Folkman, M Ueda, H Yamada

    GROWTH FACTORS   13 ( 3-4 )   181 - 191   1996年

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    記述言語:英語   出版者・発行元:HARWOOD ACAD PUBL GMBH  

    Betacellulin (BTC) was found to be expressed mainly in human pancreas and small intestine. This finding suggests that ETC possesses some specific function distinguished from the other members of epidermal growth factor (EGF) family. To clarify this function, the released form of human ETC has been expressed in E.coli, purified, and characterized. The recombinant human ETC was produced as an inclusion body. This material was dissolved in guanidine-HCl under reducing conditions, refolded, and purified through sequential liquid chromatography. Purified ETC was electrophoresed under reducing conditions and a molecular size of 18 kDa was determined, which is the supposed size of a dimer of the peptide. However, chemical analysis failed to show a covalently linked dimer. The molecular mass of ETC analyzed by mass spectrometry revealed it to be 9 kDa, which is consistent with theoretical value for a monomer. Recombinant ETC showed growth promoting activity for mouse fibroblasts and rat aortic smooth muscle cells which was equivalent to EGF. On the other hand, ETC was found to exhibit a growth inhibitory effect on the cells overexpressing EGF receptor.

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  • Recombinant human pancreatic ribonuclease produced in e. coli : Importance of the amino-terminal sequence

    Junichiro Futami, Masaharu Seno, Megumi Kosaka, Hiroko Tada, Satimaru Seno, Hidenori Yamada

    Biochemical and Biophysical Research Communications   216 ( 1 )   406 - 413   1995年

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    記述言語:英語  

    Human pancreatic ribonuclease I (hRNase 1) in the mature form has been produced in E.coli using T7 expression system. The recombinant hRNase 1 protein was solubilized from the inclusion bodies, refolded in glutathione redox system, and purified through chromatographic procedures by utilizing cation-exchange and reversed-phase columns. The ribonucleolytic activity of recombinant hRNase 1 was examined on yeast RNA and cytidylyl-3′,5′-adenosine revealing the distinctive ribonucleolytic activity. The activity was perfectly inhibited by human placental RNase inhibitor. Truncation of 7 amino acid residues in the amino-terminal sequence resulted in much reduction in ribonucleolytic activity and in affinity to human placental RNase inhibitor with the disintegration of secondary structures of the protein observed by circular dichroism spectra. The present study has revealed the important contribution of the amino-terminal sequence of hRNase I to the characteristics of the protein. © 1995 by Academic Press, Inc.

    DOI: 10.1006/bbrc.1995.2638

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  • An S-alkylating reagent with positive charges as an efficient solubilizer of denatured disulfide-containing proteins

    Hidenori Yamada, Masaharu Seno, Ayumi Kobayashi, Takeshi Moriyama, Megumi Kosaka, Yuji Ito, Taiji Imoto

    Journal of Biochemistry   116 ( 4 )   852 - 857   1994年

     詳細を見る

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

    A novel S-alkylating reagent, N-(3-bromopropyl)-N, N, N', N', N'-pentamethyl-1, 3-pro-panedi(ammonium bromide) (TAP2-Br) which carries two positive charges in the molecule, was prepared to increase the solubility or to decrease the hydrophobicity of cysteinecontaining denatured proteins (or peptides). S-Alkylation with TAP2-Br introduces two positive charges per cysteine residue, which will effectively shift the net charge of a protein in the positive direction. Disulfide-containing proteins, such as hen egg-white lysozyme, RNase A, BSA, and soybean trypsin inhibitor (Kunitz type), were reduced and S-alkylated with TAP2-Br to evaluate the potential of this reagent compared with other S-alkylating reagents such as monoiodoacetic acid, bromosuccinic acid and (3-bromopropyl)trimethylammonium bromide. The solubilities of these denatured proteins in the pH range of 2-10 indicated that S-alkylation with TAP2-Br effectively solubilized not only basic proteins (lysozyme and RNase) but also an acidic protein containing a fairly large number of cysteine residues (BSA). Moreover, the retentions of cysteine-containing tryptic peptides derived from lysozyme on reversed-phase HPLC were greatly reduced by S-alkylation with TAP2-Br. These results indicate that TAP2-Br is very useful to increase the solubility of some cysteine-containing denatured proteins and to decrease the hydrophobicity of peptides containing cysteine residue(s). © 1994 BY THE JOURNAL OF BIOCHEMISTRY.

    DOI: 10.1093/oxfordjournals.jbchem.a124606

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  • An S-alkylating reagent with positive charges as an efficient solubilizer of denatured disulfide-containing proteins

    Hidenori Yamada, Masaharu Seno, Ayumi Kobayashi, Takeshi Moriyama, Megumi Kosaka, Yuji Ito, Taiji Imoto

    Journal of Biochemistry   116 ( 4 )   852 - 857   1994年

     詳細を見る

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

    A novel S-alkylating reagent, N-(3-bromopropyl)-N, N, N', N', N'-pentamethyl-1, 3-pro-panedi(ammonium bromide) (TAP2-Br) which carries two positive charges in the molecule, was prepared to increase the solubility or to decrease the hydrophobicity of cysteinecontaining denatured proteins (or peptides). S-Alkylation with TAP2-Br introduces two positive charges per cysteine residue, which will effectively shift the net charge of a protein in the positive direction. Disulfide-containing proteins, such as hen egg-white lysozyme, RNase A, BSA, and soybean trypsin inhibitor (Kunitz type), were reduced and S-alkylated with TAP2-Br to evaluate the potential of this reagent compared with other S-alkylating reagents such as monoiodoacetic acid, bromosuccinic acid and (3-bromopropyl)trimethylammonium bromide. The solubilities of these denatured proteins in the pH range of 2-10 indicated that S-alkylation with TAP2-Br effectively solubilized not only basic proteins (lysozyme and RNase) but also an acidic protein containing a fairly large number of cysteine residues (BSA). Moreover, the retentions of cysteine-containing tryptic peptides derived from lysozyme on reversed-phase HPLC were greatly reduced by S-alkylation with TAP2-Br. These results indicate that TAP2-Br is very useful to increase the solubility of some cysteine-containing denatured proteins and to decrease the hydrophobicity of peptides containing cysteine residue(s). © 1994 BY THE JOURNAL OF BIOCHEMISTRY.

    DOI: 10.1093/oxfordjournals.jbchem.a124606

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  • Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody m31-15, which inhibits cell motility

    Masayuki Miyake, Masaru Koyama, Masaharu Seno, Shuichi Ikeyama

    Journal of Experimental Medicine   174 ( 6 )   1347 - 1354   1991年12月

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    記述言語:英語  

    A murine monodonal antibody (M31-15) was identified using the penetration-inhibiting assay of a human lung adenocarcinoma cell line (MAC10) and remarkably inhibited the phagokinetic tract motility of various cancer cell lines. The antigen, motility-related protein (MRP-1), recognized by M31-15, was 25- and 28-kD proteins, and M31-15 was used to isolate a cDNA clone from a human breast carcinoma cDNA library. Sequence analysis revealed that MRP-1 had strong similarity with a B cell surface antigen (CD37), a melanoma-associated antigen (ME491), the target of an antiproliferative antibody (TAPA-1), a human tumor-associated antigen (CO-029), and the Sm23 antigen of the trematode parasite Schistosoma mansoni. © 1991, Rockefeller University Press., All rights reserved.

    DOI: 10.1084/jem.174.6.1347

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  • Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody m31-15, which inhibits cell motility

    Masayuki Miyake, Masaru Koyama, Masaharu Seno, Shuichi Ikeyama

    Journal of Experimental Medicine   174 ( 6 )   1347 - 1354   1991年12月

     詳細を見る

    記述言語:英語  

    A murine monodonal antibody (M31-15) was identified using the penetration-inhibiting assay of a human lung adenocarcinoma cell line (MAC10) and remarkably inhibited the phagokinetic tract motility of various cancer cell lines. The antigen, motility-related protein (MRP-1), recognized by M31-15, was 25- and 28-kD proteins, and M31-15 was used to isolate a cDNA clone from a human breast carcinoma cDNA library. Sequence analysis revealed that MRP-1 had strong similarity with a B cell surface antigen (CD37), a melanoma-associated antigen (ME491), the target of an antiproliferative antibody (TAPA-1), a human tumor-associated antigen (CO-029), and the Sm23 antigen of the trematode parasite Schistosoma mansoni. © 1991, Rockefeller University Press., All rights reserved.

    DOI: 10.1084/jem.174.6.1347

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  • A sensitive enzyme immunoassay for human basic fibroblast growth factor

    Hiroyuki Watanabe, Akira Hori, Masaharu Seno, Yoshio Kozai, Koichi Igarashi, Yuzo Ichimori, Koichi Kondo

    Biochemical and Biophysical Research Communications   175 ( 1 )   229 - 235   1991年2月

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    記述言語:英語  

    A sensitive sandwich enzyme immunoassay for human basic fibroblast growth factor (HbFGF) was developed employing three monoclonal antibodies (MAb3H3, MAb98 and MAb52). The Fab' fragment of MAb3H3 which inhibits HbFGF biological activity was conjugated to horseradish peroxidase. A mixture of MAb52 and MAb98 was used in the solid phase. Neiter human acidic fibroblast growth factor, hst-1/KS3 product nor acid denatured HbFGF was cross-reactive in this assay system. The detection limit of this assay system was 1 pg/well. Using this assay, some tumor cell lines were revealed to produce a higher level of bFGF than a normal one. Serum samples from normal volunteers were also assayed, and immuno-reactive HbFGF could be detected in 16 out of 57 samples at range 30∼206 pg/ml. © 1991 Academic Press, Inc.

    DOI: 10.1016/S0006-291X(05)81224-0

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  • A sensitive enzyme immunoassay for human basic fibroblast growth factor

    Hiroyuki Watanabe, Akira Hori, Masaharu Seno, Yoshio Kozai, Koichi Igarashi, Yuzo Ichimori, Koichi Kondo

    Biochemical and Biophysical Research Communications   175 ( 1 )   229 - 235   1991年2月

     詳細を見る

    記述言語:英語  

    A sensitive sandwich enzyme immunoassay for human basic fibroblast growth factor (HbFGF) was developed employing three monoclonal antibodies (MAb3H3, MAb98 and MAb52). The Fab' fragment of MAb3H3 which inhibits HbFGF biological activity was conjugated to horseradish peroxidase. A mixture of MAb52 and MAb98 was used in the solid phase. Neiter human acidic fibroblast growth factor, hst-1/KS3 product nor acid denatured HbFGF was cross-reactive in this assay system. The detection limit of this assay system was 1 pg/well. Using this assay, some tumor cell lines were revealed to produce a higher level of bFGF than a normal one. Serum samples from normal volunteers were also assayed, and immuno-reactive HbFGF could be detected in 16 out of 57 samples at range 30∼206 pg/ml. © 1991 Academic Press, Inc.

    DOI: 10.1016/S0006-291X(05)81224-0

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  • EXPRESSION OF MODIFIED BFGF CDNAS IN MAMMALIAN-CELLS

    R SASADA, M SENO, T WATANABE, K IGARASHI

    FIBROBLAST GROWTH FACTOR FAMILY   638   149 - 160   1991年

     詳細を見る

    記述言語:英語   出版者・発行元:NEW YORK ACAD SCIENCES  

    DOI: 10.1111/j.1749-6632.1991.tb49025.x

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  • Mitogenic Effects of Fibroblast Growth Factors in Cultured Fibroblastsa Expression of Modified bFGF cDNAs in Mammalian Cells

    REIKO SASADA, MASAHARU SENO, TATSUYA WATANABE, KOICHI IGARASHI

    Annals of the New York Academy of Sciences   638 ( 1 )   149 - 160   1991年

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  • Carboxyl‐terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin

    Masaharu SENO, Reiko SASADA, Tsutomu KUROKAWA, Koichi IGARASHI

    European Journal of Biochemistry   188 ( 2 )   239 - 245   1990年

     詳細を見る

    記述言語:英語  

    The carboxyl‐terminal sequence of basic fibroblast growth factor (bFGF) is rich in basic amino acid residues, a common characteristic amongst fibroblast growth factors, and is considered to contribute greatly to the binding to negatively charged extracellular matrixes such as heparin. To study the relationship between the affinity for heparin and the carboxyl‐terminal structure of bFGF, amino‐ or carboxyl‐terminal truncated molecules were produced in Escherichia coli using recombinant DNA techniques. These terminally truncated bFGFs were applied to a heparin‐affinity HPLC column. Truncation of more than six amino acid residues from the carboxyl‐terminal made the bFGF produced in E. coli markedly difficult to solubilize and weakened its affinity for heparin, though bFGF having up to 46 amino acids removed showed significant stimulation of the DNA synthesis of BALB/c3T3 cells. This stimulation of the DNA synthesis was also recognized by the bFGF having 40 amino acids removed from its amino‐terminal, while the affinity of this peptide for heparin has been shown to be equal to that of the mature bFGF (146 amino acids). These results show that the affinity of bFGF for heparin depends significantly on its carboxyl‐terminal structure and that the essential part for receptor binding is present between Asp41 and Ser100. Moreover, it suggests that the Phe139Leu140Pro141, present in all members of the FGF family, contributes greatly to the stable structure of the intact molecule. Copyright © 1990, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1432-1033.1990.tb15395.x

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  • Molecular characterization of recombinant human acidic fibroblast growth factor produced in e. Coli: Comparative studies with human basic fibroblast growth factor

    Tatsuya Watanabe, Masaharu Seno, Reiko Sasada, Koichi Igarashi

    Molecular Endocrinology   4 ( 6 )   869 - 879   1990年

     詳細を見る

    記述言語:英語  

    Synthetic cDNA coding for human acidic fibroblast growth factor (haFGF) was expressed in E. coli under the control of the T7 promoter. The haFGF produced was purified extensively using heparin-Seph-arose and phenyl-Sepharose columns. The mitogenic activity of haFGF on 3T3 and endothelial cells was significantly potentiated in the presence of heparin (10-50 μg/ml), while angiogenic activity was observed on chick embryo chorioallantoic membrane without exogenously added heparin. This significant potentiation of mitogenic activity was observed specifically with haFGF, not human basic fibroblast growth factor (hbFGF). Circular dichroism spectra of haFGF was not affected by the presence of heparin. The affinity of haFGF for heparin was examined using heparin affinity HPLC and was precisely confirmed to be relatively lower than that of hbFGF. These results implied that haFGF was potentiated by heparin and that this potentiation did not involve a significant change in the conformation of the haFGF molecule. The affinity of haFGF for copper was also confirmed to be higher than that of hbFGF using a copper affinity HPLC column. In addition, under acidic conditions, haFGF appeared more stable than hbFGF and was further stabilized in the presence of heparin. © 1990 by The Endocrine Society.

    DOI: 10.1210/mend-4-6-869

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  • Molecular characterization of recombinant human acidic fibroblast growth factor produced in e. Coli: Comparative studies with human basic fibroblast growth factor

    Tatsuya Watanabe, Masaharu Seno, Reiko Sasada, Koichi Igarashi

    Molecular Endocrinology   4 ( 6 )   869 - 879   1990年

     詳細を見る

    記述言語:英語  

    Synthetic cDNA coding for human acidic fibroblast growth factor (haFGF) was expressed in E. coli under the control of the T7 promoter. The haFGF produced was purified extensively using heparin-Seph-arose and phenyl-Sepharose columns. The mitogenic activity of haFGF on 3T3 and endothelial cells was significantly potentiated in the presence of heparin (10-50 μg/ml), while angiogenic activity was observed on chick embryo chorioallantoic membrane without exogenously added heparin. This significant potentiation of mitogenic activity was observed specifically with haFGF, not human basic fibroblast growth factor (hbFGF). Circular dichroism spectra of haFGF was not affected by the presence of heparin. The affinity of haFGF for heparin was examined using heparin affinity HPLC and was precisely confirmed to be relatively lower than that of hbFGF. These results implied that haFGF was potentiated by heparin and that this potentiation did not involve a significant change in the conformation of the haFGF molecule. The affinity of haFGF for copper was also confirmed to be higher than that of hbFGF using a copper affinity HPLC column. In addition, under acidic conditions, haFGF appeared more stable than hbFGF and was further stabilized in the presence of heparin. © 1990 by The Endocrine Society.

    DOI: 10.1210/mend-4-6-869

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  • Carboxyl‐terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin

    Masaharu SENO, Reiko SASADA, Tsutomu KUROKAWA, Koichi IGARASHI

    European Journal of Biochemistry   188 ( 2 )   239 - 245   1990年

     詳細を見る

    記述言語:英語  

    The carboxyl‐terminal sequence of basic fibroblast growth factor (bFGF) is rich in basic amino acid residues, a common characteristic amongst fibroblast growth factors, and is considered to contribute greatly to the binding to negatively charged extracellular matrixes such as heparin. To study the relationship between the affinity for heparin and the carboxyl‐terminal structure of bFGF, amino‐ or carboxyl‐terminal truncated molecules were produced in Escherichia coli using recombinant DNA techniques. These terminally truncated bFGFs were applied to a heparin‐affinity HPLC column. Truncation of more than six amino acid residues from the carboxyl‐terminal made the bFGF produced in E. coli markedly difficult to solubilize and weakened its affinity for heparin, though bFGF having up to 46 amino acids removed showed significant stimulation of the DNA synthesis of BALB/c3T3 cells. This stimulation of the DNA synthesis was also recognized by the bFGF having 40 amino acids removed from its amino‐terminal, while the affinity of this peptide for heparin has been shown to be equal to that of the mature bFGF (146 amino acids). These results show that the affinity of bFGF for heparin depends significantly on its carboxyl‐terminal structure and that the essential part for receptor binding is present between Asp41 and Ser100. Moreover, it suggests that the Phe139Leu140Pro141, present in all members of the FGF family, contributes greatly to the stable structure of the intact molecule. Copyright © 1990, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1432-1033.1990.tb15395.x

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  • Synthesis of hepatitis B virus e antigen in E. coli

    Takashi Inada, Yuko Misumi, Masaharu Seno, Shuichi Kanezaki, Yasuo Shibata, Yushi Oka, Haruo Onda

    Virus Research   14 ( 1 )   27 - 47   1989年

     詳細を見る

    記述言語:英語  

    Hepatitis B virus core antigen (HBcAg) gene was deleted at some unique restriction enzyme sites, or at random, and inserted into the expression plasmids of E. coli which had the tryptophan promoter. E. coli transformants with the plasmids, synthesized materials with many kinds of antigenicity of HBcAg, HBeAg, or both HBcAg and HBeAg. HBeAg-specific material smaller than native HBeAg was produced in a stable condition. © 1989.

    DOI: 10.1016/0168-1702(89)90067-1

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  • Synthesis of hepatitis B virus e antigen in E. coli

    Takashi Inada, Yuko Misumi, Masaharu Seno, Shuichi Kanezaki, Yasuo Shibata, Yushi Oka, Haruo Onda

    Virus Research   14 ( 1 )   27 - 47   1989年

     詳細を見る

    記述言語:英語  

    Hepatitis B virus core antigen (HBcAg) gene was deleted at some unique restriction enzyme sites, or at random, and inserted into the expression plasmids of E. coli which had the tryptophan promoter. E. coli transformants with the plasmids, synthesized materials with many kinds of antigenicity of HBcAg, HBeAg, or both HBcAg and HBeAg. HBeAg-specific material smaller than native HBeAg was produced in a stable condition. © 1989.

    DOI: 10.1016/0168-1702(89)90067-1

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  • Nucleotide sequence of rat basic fibroblast growth factor cDNA

    Tsutomu Kurokawa, Masaharu Seno, Koichi Igarashi

    Nucleic Acids Research   16 ( 11 )   5201   1988年6月

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  • Nucleotide sequence of rat basic fibroblast growth factor cDNA

    Tsutomu Kurokawa, Masaharu Seno, Koichi Igarashi

    Nucleic Acids Research   16 ( 11 )   5201   1988年6月

     詳細を見る

  • Expression of cDNA encoding human basic fibroblast growth factor in E.coli

    Makoto Iwane, Tsutomu Kurokawa, Reiko Sasada, Masaharu Seno, Shizue Nakagawa, Koichi Igarashi

    Biochemical and Biophysical Research Communications   146 ( 2 )   470 - 477   1987年7月

     詳細を見る

    記述言語:英語  

    The cDNA encoding human basic fibroblast growth factor was expressed in E.coli under the control of trp promoter. Bacterially synthesized hbFGF was highly purified using a heparin affinity HPLC column. By this chromatography, hbFGF was eluted as four distinct forms, which were indistinguishable by SDS polyacrylamide gel electrophoresis, amino acid composition, and partial terminal sequence analysis. These molecules stimulated the growth of fibroblasts and endothelial cells although their specific activities varied. The angiogenesis activity of these molecules was also confirmed. © 1987.

    DOI: 10.1016/0006-291X(87)90553-5

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  • Expression of cDNA encoding human basic fibroblast growth factor in E.coli

    Makoto Iwane, Tsutomu Kurokawa, Reiko Sasada, Masaharu Seno, Shizue Nakagawa, Koichi Igarashi

    Biochemical and Biophysical Research Communications   146 ( 2 )   470 - 477   1987年7月

     詳細を見る

    記述言語:英語  

    The cDNA encoding human basic fibroblast growth factor was expressed in E.coli under the control of trp promoter. Bacterially synthesized hbFGF was highly purified using a heparin affinity HPLC column. By this chromatography, hbFGF was eluted as four distinct forms, which were indistinguishable by SDS polyacrylamide gel electrophoresis, amino acid composition, and partial terminal sequence analysis. These molecules stimulated the growth of fibroblasts and endothelial cells although their specific activities varied. The angiogenesis activity of these molecules was also confirmed. © 1987.

    DOI: 10.1016/0006-291X(87)90553-5

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  • A Hybrid Protein between IFN-γ

    FEBS lett.   199 ( 2 )   187 - 192   1986年4月

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  • A hybrid protein between IFN-γ and IL-2

    Masaharu Seno, Shuji Hinuma, Haruo Onda, Koichi Igarashi

    FEBS Letters   199 ( 2 )   187 - 192   1986年4月

     詳細を見る

    記述言語:英語  

    The complementary DNAs encoding human interferon-γ (IFN-γ) and human interleukin-2 (IL-2), two different proteins involved in the same immune system, were fused to code a hybrid protein, which was expressed in E. coli to investigate the interactions of these two proteins at the molecular level. Through immunoprecipitation analysis, this protein was revealed to be of about 31 kDa, which was expected from nucleotide sequencing, and to have the antigenicities of both IFN-γ and IL-2. The extract from bacteria expressing this hybrid protein showed at least two biological activities: an antiviral activity derived from IFN-γ and the ability to support the growth of natural killer (NK) cells derived from IL-2. Comparing the enhancement of NK cell activity of this hybrid protein with IFN-γ and IL-2, this hybrid protein appears to conserve each activity almost completely without diminishing the other. © 1986.

    DOI: 10.1016/0014-5793(86)80477-X

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  • Expression of Human Immunoglobu in ε Chain cDNA in E. coli

    Nucleic Acids Res.   11 ( 10 )   3077 - 3085   1983年5月

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  • Expression of human immunoglobulin E ε chain cDNA in E.coli

    Tsutornu Kurokawa, Masaharu Seno, Reiko Sasada, Yoshitaka Ona, Haruo Onda, Koichi Igarashi, Masakazu Kikuchi, Yukio Sugino, Tasuku Honjo

    Nucleic Acids Research   11 ( 10 )   3077 - 3085   1983年5月

     詳細を見る

    記述言語:英語  

    Using the cDNA of human 1D6DC
    chain, three expression plasmids that code directly the constant portion of the 1D6DC
    chain (C1D6DC
    l-C 1D6DC
    4, C 1D6DC
    2-C 1D6DC
    C4 and C 1D6DC
    3-C 1D6DC
    4 domains) were constructed. These 1D6DC
    chain peptides were synthesized in E. coli under the control of the trp promoter-operator. The bacterially produced peptides have the antigenicity of human 1D6DC
    chain and gave the molecular weights equal to the values calculated from the amino acid sequence of the constructed plasmids. © 1983 IRL Press Limited.

    DOI: 10.1093/nar/11.10.3077

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  • Molecular Cloning and Nucleotide Sequencing of Human Immunoglobulin ε Chain cDNA

    Nucleic Acids Res.   11 ( 3 )   719 - 726   1983年2月

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  • Molecular cloning and nucleotide sequencing of human immunoglobulin € chain cDNA

    Masaharu Seno, Tsutomu Kurokawa, Yoshitaka Ono, Haruo Onda, Reiko Sasada, Koichi Lagarshi, Masakazu Kikuchi, Yukio Sugino, Yasuyoshi Nishida, Tasuku Honjo

    Nucleic Acids Research   11 ( 3 )   719 - 726   1983年2月

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    記述言語:英語  

    DNA complementary to mRNA of human immunoglobulin E heavy chain (€ chain) isolated and purified from U266 cells has been synthesized and inserted into the PstI site of pBR322 by G-C tailing. This recombinant plasm id was used to transform E.coliXl776 to screen 1445 tetracycline resistant colonies. Nine clones (pGETl - 9) containing cDNA coding for the human e chain were recognized by colony hybridization and Southern blotting analysis with a nick-translated human IgE genome fragment. The nucleotide sequence of the longest eDNA contained in pGET2 was determined. The results indicate that the sequence of 1657 nucleotides codes for 494 amino acids covering a part of the variable region and all of the constant region of the human e chain. Most of the amino acid sequence deduced from the nucleotide sequence is in substantial agreement with that reported. Furthermore a termination codon after the -C00H terminal amino acid marks the beginning of a 3' untranslated region of 125 nucleotides with a poly A tail. Taking this into account, the structure of the human e chain mRNA, except a part of the 5' end, is conserved fairly well in the cDNA insert in pGET2. © 1983 IRL Press Limited.

    DOI: 10.1093/nar/11.3.719

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▼全件表示

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  • Cancer stem cell research using iPSCs and its Future.

    科学技術における日本とエジプトの研究交流  2017年 

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  • Cancer Stem Cell Research Using iPSCs and its Future.

    Stem cells Symposium  2017年 

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  • 多能性幹細胞からがん幹細胞を作り出す次世代のがん研究

    第18回自己組織化マップ研究会  2017年 

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  • 地域発の医工連携イノベーションの現状と展望(新大学院設置に向けて)

    メディカルイノベーション2017  2017年 

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  • iPS細胞から樹立する「がん幹細胞コレクション」と診断・治療への展望

    ライフサイエンスワールド2016  2016年 

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  • Development of novel method for risk assessment of chemical compounds in the induction of cancer stem cells from iPS cells

    ICCA-LRI and NIHS Worlshop  2016年 

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  • iPS細胞を利用するがん幹細胞研究とその将来性

    平成28年度宮城県立がんセンターセミナー  2016年 

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  • がん幹細胞モデル細胞におけるダウノルビシンによるカスパーゼ非依存アポトーシスの誘導

    第75回日本癌学会学術総会  2016年 

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  • 球面自己組織化マップを利用した人工がん幹細胞発現遺伝子解析

    第75回日本癌学会学術総会  2016年 

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  • iPS細胞を利用するがん研究用動物モデル

    BioJapan2016  2016年 

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  • Strategy for the enhancement of encapsulation effeciency in liposomal drug delivery system

    NCRM NICHE 2016  2016年 

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  • 化学物質によるがん幹細胞誘導性メカニズムの解明

    第39回日本分子生物学会年会  2016年 

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  • ヒトiPS細胞から作製するがん幹細胞モデル

    第39回日本分子生物学会年会  2016年 

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  • 胚様体形成させたiPS細胞から誘導するがん幹細胞

    第39回日本分子生物学会年会  2016年 

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  • iPS細胞由来がん幹細胞におけるカスパーゼ-CAD非依存的アポトーシス

    第39回日本分子生物学会年会  2016年 

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  • The significance of c-Kit protp-oncogene in iCSC-derived PDAC model

    米国がん学会年会2016  2016年 

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  • Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells

    米国がん学会年会2016  2016年 

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  • iPS derived CSC model with lung metastasis developed in the microenvironment of lung carcinoma

    The American Society for Cell Biology  2016年 

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  • Gab2タンパク質を介するG-CSF刺激依存の好中球分化誘導シグナル

    第39回日本分子生物学会年会  2016年 

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  • 球面自己組織化マップを用いた人工がん幹細胞遺伝子発現解析

    第39回日本分子生物学会年会  2016年 

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  • グローバル市場進出における日韓技術協力モデル

    2016日韓グローバルビジネス協力活性化フォーラム  2016年 

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  • 化学物質のがん幹細胞誘導性評価においてiPS細胞を用いる技術の開発

    日本動物実験代替法学会  2015年 

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  • iPS細胞を利用する「がん幹細胞コレクション」の樹立に向けた取り組み

    ライフサイエンスワールド2015  2015年 

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  • iPS細胞を用いたがん幹細胞モデル作成のポイントとその評価

    がん幹細胞を標的とした新しい治療薬・診断法の開発  2015年 

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  • グリコシル化パクリタキセルを内封するイムノリポソーム

    おかやまバイオアクティブ研究会 第47回シンポジウム  2015年 

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  • 多能性幹細胞から作るがん幹細胞モデル

    第74 回日本癌学会学術総会  2015年 

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  • 糖修飾ドセタキセル封入リポソームを用いたドラッグデリバリー

    第74 回日本癌学会学術総会  2015年 

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  • Acquisition of immortalization prior to malignancy during the miPS-CSC generation.

    第74 回日本癌学会学術総会  2015年 

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  • iPS細胞から解き明かす「がん幹細胞」とその治療戦略への応用

    BioJapan 2015  2015年 

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  • Cancer stem cells developed from iPS cells and prospects of application to therapy

    2nd Chang-Gung/Waters COI symposium: Metabolic Aspects of Human aging  2015年 

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  • シグナル伝達阻害剤によるがん幹細胞誘導メカニズムの解析

    第38 回日本分子生物学会年会  2015年 

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  • 肝臓がんへ分化するがん幹細胞モデルの作成

    第38 回日本分子生物学会年会  2015年 

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  • Generation of Cancer stem cells (CSC) from hiPS cells

    第8 回高度医療都市を創出する未来技術国際シンポジウム  2015年 

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  • Development of novel method to evaluate the inducibility of cancer stem cells with chemical compounds

    第8 回高度医療都市を創出する未来技術国際シンポジウム  2015年 

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  • Characterization of Cancer Stem Cell Model from Mouse Induced Pluripotent Stem Cells Treated with Conditioned Medium of Human Hepatoma Cell Lines

    第8 回高度医療都市を創出する未来技術国際シンポジウム  2015年 

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  • 乳癌と正常組織を識別する遺伝子セットの網羅的探索

    第38 回日本分子生物学会年会  2015年 

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  • がん幹細胞miPS-LLCcmが形成する微小環境によるNanogタンパク質の局在変化

    第38 回日本分子生物学会年会  2015年 

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  • G-CSF刺激依存の好中球分化誘導におけるGab2タンパク質の役割

    第38 回日本分子生物学会年会  2015年 

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  • がん幹細胞:創製およびniche解析への応用

    第38回日本分子生物学会年会  2015年 

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  • 化学物質のがん幹細胞化誘導においてiPS細胞を用いる技術の開発

    日本動物実験代替法学会  2015年 

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  • 化学物質のがん幹細胞誘導性に関するin vitroにおける簡易評価技術の開発

    日本動物実験代替法学会  2015年 

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  • iPS細胞を利用する化学物質のがん幹細胞誘導性評価技術の開発

    日本動物代替法学会 第27回大会  2014年 

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  • Tumor derived exosomes/microvesicles convert mouse induced pluripotent stem cells to cancer stem cells

    Exosomes & Single cell Analysis Summit  2014年 

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  • Tumor derived exosomes/microvesicles convert mouse iPS cells to cancer stem-like cells

    第73回 日本癌学会学術総会  2014年 

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  • ヒトiPS細胞から作るがん幹細胞

    第73回 日本癌学会学術総会  2014年 

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  • がんの全てを網羅する「がん幹細胞コレクション」計画

    Bio Japan 2014  2014年 

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  • Gab3過剰発現によるG-CSF刺激依存性の好中球分化誘導の阻害

    第37回日本分子生物学会年会  2014年 

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  • がん幹細胞ニッチにおけるがん幹細胞の自己複製制御機構の解析

    第37回日本分子生物学会年会  2014年 

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  • iPS 細胞より誘導するがん幹細胞

    Bio tech 2014 国際バイオテクノロジー展  2014年 

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  • Cancer Stem Cells maintain a hierarchy of differentiation by creating their niche

    第7回高度医療都市を創出する未来技術国際シンポジウム  2014年 

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  • Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells

    第7回高度医療都市を創出する未来技術国際シンポジウム  2014年 

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  • An effective targeted drug delivery with immunoliposomes encapsulated paclitaxel glycoside

    第7回高度医療都市を創出する未来技術国際シンポジウム  2014年 

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  • Our cancer stem cell project: past, present and future

    第7回高度医療都市を創出する未来技術国際シンポジウム  2014年 

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  • iPS細胞から作るがん幹細胞ライブラリー-抗がん剤スクリーニングプラットフォームとして-

    化学療法基盤支援活動 第3回シンポジウム  2014年 

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  • iPS細胞から作るがん幹細胞モデル

    BIO tech 2013 第12回国際バイオテクノロジー・技術会議 アカデミックフォーラム  2013年 

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  • A novel remote loading method with solubility gradient to encapsulate effective amount of taxanes into liposomes

    American Association for Cancer Research Annual Meeting 2013  2013年 

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  • An Insight into Cancer Stem Cells throught a Cancer Stem Cell Model Developed from Mouse iPSCs

    第19回チャールズハイデルベルガー国際がん研究シンポジウム  2013年 

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