2021/10/27 更新

写真a

ムラカミ ヒロシ
村上 宏
MURAKAMI Hiroshi
所属
ヘルスシステム統合科学学域 准教授
職名
准教授
外部リンク

学位

  • 薬学博士, 薬学修士 ( 東京大学 )

研究キーワード

  • シグナル伝達

  • 血液細胞の増殖と分化

  • サイトカイン

  • proliferation

  • differentiation

  • hematology

  • 分子細胞生物学

  • Molecular cell Biology

  • cytokine

研究分野

  • ライフサイエンス / 薬系衛生、生物化学

  • ライフサイエンス / 薬理学

  • ライフサイエンス / 機能生物化学

  • ライフサイエンス / 細胞生物学

学歴

  • 東京大学   Graduate School, Division of Pharmaceutical Sciences  

    - 1985年

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  • 東京大学    

    1980年 - 1985年

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    国名: 日本国

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  • 東京大学   Faculty of Pharmaceutical Science  

    - 1980年

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  • 東京大学   薬学部   製薬化学科

    1976年 - 1980年

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    国名: 日本国

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経歴

  • - 岡山大学自然科学研究科 准教授   准教授

    2004年4月 - 現在

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  • - Associate Professor,Graduate School of Natural Science and Technology,Okayama University

    2004年

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  • 岡山大学工学部   生物機構工学部   助教授

    1996年12月 - 2004年3月

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  • Osaka Bioscience Institute   Research Scientist

    1993年3月 - 1996年11月

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  • Osaka Bioscience Institute   Research Associate

    1993年2月

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  • Rockefeller University   Laboratory of Cell Biology   Research Associate

    1987年6月 - 1993年1月

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  • St. Louis University Medical School   Department of Biochemistry   Postdoctoral fellow

    1985年6月 - 1987年5月

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▼全件表示

所属学協会

  • The Molecular Biology Society of Japan

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  • The Molecular Biology Society of Japan

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  • 日本分子生物学会

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論文

  • G‐CSF‐dependent neutrophil differentiation requires downregulation of MAPK activities through the Gab2 signaling pathway 査読 国際誌

    Xianglin Zhao, Shun‐ichiro Kawano, Junko Masuda, Hiroshi Murakami

    Cell Biology International   44 ( 9 )   1919 - 1933   2020年9月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Granulocyte colony-stimulating factor (G-CSF) stimulation of myeloid cells induced tyrosine-phosphorylation of cellular proteins. One of the tyrosine-phosphorylated proteins was found to be a scaffold protein, Grb2-associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G-CSF-dependent signaling. In Gab3-overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G-CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3-overexpressed cells continuously proliferated in the medium containing G-CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G-CSF stimulation-dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen-activated protein kinase (MAPK) activation were prolonged in the Gab3-overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G-CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3-overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G-CSF-dependent Gab2 phosphorylation and following its downregulation led the short-term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G-CSF stimulation.

    DOI: 10.1002/cbin.11398

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cbin.11398

  • Suppression effect on IFN-γ of adipose tissue-derived mesenchymal stem cells isolated from β2-microglobulin-deficient mice. 査読 国際誌

    Masuda J, Takayama E, Ichinohe T, Strober W, Mizuno-Kamiya M, Ikawa T, Kitani A, Kawaki H, Fuss I, Kawamoto H, Seno A, Vaidyanath A, Umemura N, Mizutani A, Kasai T, Honjo Y, Satoh A, Murakami H, Katsura Y, Kondoh N, Seno M

    Experimental and therapeutic medicine   16 ( 5 )   4277 - 4282   2018年11月

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    DOI: 10.3892/etm.2018.6689

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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

    Aung Ko Ko Oo, Anna Sanchez Calle, Neha Nair, Hafizah Mahmud, Arun Vaidyanath, Junya Yamauchi, Aprilliana Cahya Khayrani, Juan Du, Md Jahangir Alam, Akimasa Seno, Akifumi Mizutani, Hiroshi Murakami, Yoshiaki Iwasaki, Ling Chen, Tomonari Kasai, Masaharu Seno

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

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    記述言語:英語  

    Previously, we have succeeded in converting induced pluripotent stem cells (iPSCs) into cancer stem cells (CSCs) by treating the iPSCs with conditioned medium of Lewis lung carcinoma (LLC) cells. The converted CSCs, named miPS-LLCcm cells, exhibited the self-renewal, differentiation potential, and potential to form malignant tumors with metastasis. In this study, we further characterized miPS-LLCcm cells both in vivo and in vitro. The tumors formed by subcutaneous injection showed the structures with pathophysiological features consisting of undifferentiated and malignant phenotypes generally found in adenocarcinoma. Metastasis in the lung was also observed as nodule structures. Excising from the tumors, primary cultured cells from the tumor and the nodule showed self-renewal, differentiation potential as well as tumor forming ability, which are the essential characters of CSCs. We then characterized the epigenetic regulation occurring in the CSCs. By comparing the DNA methylation level of CG rich regions, the differentially methylated regions (DMRs) were evaluated in all stages of CSCs when compared with the parental iPSCs. In DMRs, hypomethylation was found superior to hypermethylation in the miPS-LLCcm cells and its derivatives. The hypo- and hypermethylated genes were used to nominate KEGG pathways related with CSC. As a result, several categories were defined in the KEGG pathways from which most related with cancers, significant and high expression of components was PI3K-AKT signaling pathway. Simultaneously, the AKT activation was also confirmed in the CSCs. The PI3K-Akt signaling pathway should be an important pathway for the CSCs established by the treatment with conditioned medium of LLC cells.

    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

    Junko Masuda, Tsukasa Shigehiro, Takuma Matsumoto, Ayano Satoh, Akifumi Mizutani, Chiho Umemura, Shoki Saito, Mayumi Kijihira, Eiji Takayama, Akimasa Seno, Hiroshi Murakami, Masaharu Seno

    International journal of molecular sciences   19 ( 4 )   2018年4月

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    記述言語:英語  

    T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-γ and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b⁺ and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development.

    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

    Hafizah Mahmud, Tomonari Kasai, Apriliana Cahya Khayrani, Mami Asakura, Aung Ko Ko Oo, Juan Du, Arun Vaidyanath, Samah El-Ghlban, Akifumi Mizutani, Akimasa Seno, Hiroshi Murakami, Junko Masuda, Masaharu Seno

    International journal of molecular sciences   19 ( 3 )   2018年2月

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    We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, KLF4 and Nanog, this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC50 at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100-150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics.

    DOI: 10.3390/ijms19030659

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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

    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 )   2017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)   出版者・発行元:MDPI AG  

    Taxanes including paclitaxel and docetaxel are effective anticancer agents preferably sufficient for liposomal drug delivery. However, the encapsulation of these drugs with effective amounts into conventional liposomes is difficult due to their high hydrophobicity. Therefore, an effective encapsulation strategy for liposomal taxanes has been eagerly anticipated. In this study, the mixture of polyethoxylated castor oil (Cremophor EL) and ethanol containing phosphate buffered saline termed as CEP was employed as a solvent of the inner hydrophilic core of liposomes where taxanes should be incorporated. Docetaxel-, paclitaxel-, or 7-oxacetylglycosylated paclitaxel-encapsulating liposomes were successfully prepared with almost 100% of encapsulation efficiency and 29.9, 15.4, or 29.1 mol% of loading efficiency, respectively. We then applied the docetaxel-encapsulating liposomes for targeted drug delivery. Docetaxel-encapsulating liposomes were successfully developed HER2-targeted drug delivery by coupling HER2-specific binding peptide on liposome surface. The HER2-targeting liposomes exhibited HER2-specific internalization and enhanced anticancer activity in vitro. Therefore, we propose the sophisticated preparation of liposomal taxanes using CEP as a promising formulation for effective cancer therapies.

    DOI: 10.3390/nano7100290

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

    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   掲載種別:研究論文(学術雑誌)   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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  • 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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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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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  • Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived exosomes/microvesicles 査読

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

    CANCER RESEARCH   74 ( 19 )   2014年10月

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

    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   掲載種別:研究論文(学術雑誌)   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 査読

    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   掲載種別:研究論文(学術雑誌)   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 査読

    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   掲載種別:研究論文(学術雑誌)   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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  • Chlorotoxin-Fc Fusion Inhibits Release of MMP-2 from Pancreatic Cancer Cells 査読

    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   2014   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)   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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  • Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles 査読

    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   掲載種別:研究論文(学術雑誌)   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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  • Eosinophil cationic protein enhances stabilization of β-catenin during cardiomyocyte differentiation in P19CL6 embryonal carcinoma cells. 査読

    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

    Molecular biology reports   40 ( 4 )   3165 - 3171   2013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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  • Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells 査読

    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   掲載種別:研究論文(学術雑誌)   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.

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  • Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway 査読

    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   掲載種別:研究論文(学術雑誌)   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.

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  • Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis. 査読

    Kasai T, Nakamura K, Vaidyanath A, Chen L, Sekhar S, El-Ghlban S, Okada M, Mizutani A, Kudoh T, Murakami H, Seno M

    Journal of drug delivery   2012   975763   2012年

  • Src homology 2 domain of overexpressed Lyn kinase is responsible for the acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation 査読

    N Oka, A Suzuki, T Omura, H Sakai, H Murakami

    CELL BIOLOGY INTERNATIONAL   30 ( 6 )   525 - 532   2006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:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

    We have previously shown that the overexpression of a Src family kinase, Lyn, and its kinase-negative form, LynKN, in a granulocyte progenitor cell line, GM-162M, accelerates neutrophilic nuclear lobulation when the cells are cultured in the presence of granulocyte colony-stimulating factor. In this study, we investigated the role of the Src homology 2 (SH2) and SH3 domains of Lyn in the accelerated induction of nuclear lobulation. In contrast to wild-type Lyn, the overexpression of its SH2 domain mutant did not induce the accelerated nuclear morphological changes, but the overexpressed SH3 domain mutant had the same effects as wild-type Lyn. Therefore, the SH2 domain of Lyn is responsible for the accelerated induction of neutrophilic nuclear lobulation upon G-CSF stimulation. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

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  • Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase 査読

    T Omura, H Sakai, H Murakami

    EUROPEAN JOURNAL OF BIOCHEMISTRY   269 ( 1 )   381 - 389   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)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Stimulation with granulocyte colony-stimulating factor (G-CSF) induces myeloid precursor cells to differentiate into neutrophils, and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However, the signaling pathways for neutrophil differentiation are still obscure. As the Si-c-like tyrosine kinase, Lyn, has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells, we examined its involvement in G-CSF-induced signal transduction in mammalian cells. Expression plasmids for wild-type Lyn (Lyn) and kinase-negative Lyn (LynKN) were introduced into a murine granulocyte precursor cell line, GM-162M, that can respond to G-CSF with neutrophil differentiation, and cell lines that overexpressed these molecules (GM-Lyn, GM-LynKN) were established. Upon G-CSF stimulation, both the GM-Lyn and GM-LynKN cells began to differentiate into neutrophils, showing early morphological changes within a few days, Much more rapidly than did the parental cells, which started to exhibit nuclear lobulation about 10 days after the cells were transferred to G-CSF-containing medium. However, the time course of expression of the myeloperoxidase gene, another neutrophil differentiation marker, was not affected by the overexpression of Lyn or LynKN. Therefore, in normal cells, protein interactions with Lyn, but not its kinase activity, are important for the induction of G-CSF-induced neutrophilic nuclear lobulation in mammalian granulopoiesis.

    DOI: 10.1046/j.0014-2956.2001.02661.x

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  • A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na+/H+ exchanger 査読

    M Matsumoto, Y Miyake, M Nagita, H Inoue, D Shitakubo, K Takemoto, C Ohtsuka, H Murakami, N Nakamura, H Kanazawa

    JOURNAL OF BIOCHEMISTRY   130 ( 2 )   217 - 225   2001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)   出版者・発行元:JAPANESE BIOCHEMICAL SOC  

    We surveyed proteins capable of binding to the cytoplasmic domain of Na+/H+ exchanger (NHE)1 in a rat brain cDNA library with the yeast two-hybrid system. One clone obtained coded for a protein reported previously as a human calcineurin homologous protein (CHP). Since CHP is homologous to the regulatory subunit B of calcineurin, we expected a possible interacting partner of CHP like the catalytic subunit of calcineurin (calcineurin A), and surveyed this putative partner again with the yeast two-hybrid system. A clone thus obtained coded for a kinase, which is basically the same as that reported for human DRAK2. Overexpression of the rat homologue of DRAK2 caused apoptosis-like cell death of NIH3T3 cells, which was dependent on the kinase activity, confirming the previous result for DRAK2. The purified CHP and rat DRAK2 proteins synthesized in Escherichia coli could bind in vitro. CHP and rat DRAK2 expressed in COS-7 cells were found to be localized in the Golgi apparatus and nucleus, respectively. Some of them was also found in the membrane peripheral region. When they were coexpressed in the same cells, most of CHP moved to the nucleus where rat DRAK2 is located, suggesting in vivo interaction of these proteins. However, minor but significant fractions of both proteins were also found in the membrane peripheral region. Rat DRAK2 is expressed highly in thymus, spleen, and testis, where the apoptosis plays an important role in physiology.

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  • Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H+-ATPase leads to early embryonic lethality 査読

    H Inoue, T Noumi, M Nagata, H Murakami, H Kanazawa

    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS   1413 ( 3 )   130 - 138   1999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)   出版者・発行元:ELSEVIER SCIENCE BV  

    Vacuolar H+-ATPase (V-ATPase) is responsible for acidification of intracellular compartments in eukaryotic cells. Its 16-kDa subunit (proteolipid, PL16) plays a central role in V-ATPase function? forming the principal channel via which protons are translocated. To elucidate physiological roles of V-ATPase in mammalian cell function and embryogenesis, we attempted to generate a PL16 null mutant mouse by gene-targeting. Mice heterozygous (PL16(+/-)) for the proteolipid mutation were intercrossed and their offspring were classified according to genotype. There were no homozygous (PL16(-/-)) pugs among 69 neonates examined. but a few PL16(-/-) embryos were found during the pre-implantation stages of embryonic development, up to day 3.5 post-coitum. These results suggested that PL16 (and hence V-ATPase) may play an essential role in cell proliferation and viability during early embryogenesis. PL16(+/-) mice were indistinguishable from their wild-type littermates and displayed no discernible abnormalities, although the PL16 mRNA level in PL16(+/-) mice decreased to about one-half of wild-type levels. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0005-2728(99)00096-1

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  • Expression of functional Na+/H+ antiporters of Helicobacter pylori in antiporter-deficient Echerichia coli mutants 査読

    H Inoue, T Sakurai, S Ujike, T Tsuchiya, H Murakami, H Kanazawa

    FEBS LETTERS   443 ( 1 )   11 - 16   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)   出版者・発行元:ELSEVIER SCIENCE BV  

    An open reading frame with a sequence homologous to Escherichia coli Na+/H+ antiporter A (ENhaA) was found in the total genomic sequence of Helicobacter pylori, a pathogenic bacterium of gastric inflammation, and was named HNhaA. The primary sequences and the hydropathy profiles of ENhaA and HNhaA were very homologous except for one additional region found in HNhaA. This sequence has about 40 hydrophilic amino acid residues inserted at the position next to residue 235 of ENhaA which corresponds to residue 245 of HNhaA. HNhaA was expressed in E. coli mutants deficient in Na+/H+ antiporters and complemented the salt-sensitive phenotype of the mutants, Membrane vesicles prepared from these transformants of HNhaA using mutants deficient in the antiporters had the antiporter activities. Surprisingly, the antiporter activity in the transformant membranes was high at acidic and neutral pH, while ENhaA did not function at these pHs. A hydrophilic region around residue 235 in ENhaA and the additional hydrophilic region of about 40 residues in the same region found in HNhaA might be responsible for this difference in activity by acting as putative pH sensors. (C) 1999 Federation of European Biochemical Societies.

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  • Reconstitution of F1-ATPase activity from Escherichia coli subunits α, β and subunit γ tagged with six histidine residues at the C-terminus 査読

    Atsuko Ekuni, Hikaru Watanabe, Nozomi Kuroda, Ken Sawada, Hiroshi Murakami, Hiroshi Kanazawa

    FEBS Letters   427 ( 1 )   64 - 68   1998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)  

    An engineered γ subunit of Escherichia coli F1-ATPase with extra 14 and 20 amino acid residues at the N- and C-termini (His-tag γ), respectively, was overproduced in E. coli and purified. Six histidines are included in the C-terminal extension. The reconstituted F1 containing α, β, and His-tagged γ exhibited sixty percent of the wild-type ATPase activity. The reconstituted αβHis-tag γ complex was subjected to affinity chromatography with nickel-nitrilotriacetic acid (Ni-NTA) agarose resin. ATPase activity was eluted specifically with imidazole. These results implied that the tag sequence protruded to the surface of the complex and did not seriously impair the activity. The reconstituted αβHis-tag γ complex, even after its binding to the resin, exhibited ATPase activity suggesting that the γ subunit, when fixed to a solid phase, may rotate the αβ complex. This system may provide a new approach for analysis of the rotation mechanisms in F1-ATPase.

    DOI: 10.1016/S0014-5793(98)00395-0

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  • Myeloid-specific transcriptional activation by murine myeloid zinc-finger protein 2 査読

    K Murai, H Murakami, S Nagata

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   95 ( 7 )   3461 - 3466   1998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)   出版者・発行元:NATL ACAD SCIENCES  

    Myeloid zinc finger protein 2 (MZF-2) is a zinc-finger transcription factor that is expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage, Here we examine the ability of murine MZF-2 (mMZF-2) to activate transcription. The mMZF-2 protein binds to a DNA element (MZF-binding site) through its zinc-finger domain. When the intact mMZF-2 was cotransfected with a reporter gene, it did not activate transcription. However, N-terminal deletion mutants greatly enhanced transcription specifically in myeloid cells, Furthermore, in an in vivo competition assay, the middle region of MZF-2 inhibited the mMZF-2-mediated transcription activation, These results suggest that mMZF-2 is a transcriptional factor that can specifically work in myeloid cells and can be divided into at least three functional domains, The N-terminal domain inhibits transactivation by masking the effect of the activation domain, The middle region recruits a coactivator, which is responsible for myeloid-specific transcriptional activation, The C-terminal zinc-finger domain functions as a DNA-binding domain.

    DOI: 10.1073/pnas.95.7.3461

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  • A novel form of the myeloid-specific zinc finger protein (MZF-2) 査読

    K Murai, H Murakami, S Nagata

    GENES TO CELLS   2 ( 9 )   581 - 591   1997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)   出版者・発行元:BLACKWELL SCIENCE LTD  

    Background: Myeloid cell development is controlled by tissue-specific transcription factors, Human myeloid zinc finger protein (MZF-1) is a putative transcription factor containing 13 zinc fingers, and has been suggested that it regulates the development of neutrophilic granulocytes,
    Results: Here, we have isolated the murine and human cDNAs which encode a novel form of MZF protein (MZF-2), Murine and human MZF-2 proteins consisted of 814 and 775 amino acids, respectively, and have identity of 75.3% between them, The C-terminal half of human MZF-2, carrying the zinc finger domains, was completely identical with that of human MZF-1, whereas the N-terminal half of MZF-2 was different from the corresponding region of human MZF-1, and was coded by distinct exons, MZF-2 mRNA was expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage, and down-regulated by G-CSE
    Conclusions: MZF-1 and MZF-2 mRNAs seem to be produced by the alternative use of two different transcription initiation sites, The distinct N-terminal half of MZF-2 carries two characteristic domains, a leucine-rich domain called LeR and an acidic domain, which suggests a unique function of MZF-2 in neutrophil development.

    DOI: 10.1046/j.1365-2443.1997.1430341.x

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  • Binding of NF-Y transcription factor to one of the cis-elements in the myeloperoxidase gene promoter that responds to granulocyte colony-stimulating factor 査読

    T Orita, K Shimozaki, H Murakami, S Nagata

    JOURNAL OF BIOLOGICAL CHEMISTRY   272 ( 37 )   23216 - 23223   1997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)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    The expression of the myeloperoxidase (MPO) gene is restricted to cells of the myeloid cell lineage and is induced by granulocyte colony stimulating factor (G-CSF). In this study, a series of deletion mutations was introduced in the promoter of the human MPO gene, which was then fused to the chloramphenicol acetyltransferase gene. The G-CSF-induced promoter activity was examined in mouse myeloid precursor FDC-P1 transformants that constitutively express the G-CSF receptor. A G-CSF-responsive element (GRE) in the MPO gene was found approximately 800 base pairs upstream from the transcription initiation site. When the 5'-flanking region of the human MPO gene contained this element, it yielded promoter activity in cells cultured with G-CSF but not in cells cultured with interleukin 3. Gel shift assays with the element showed that a specific nuclear factor(s) (NF/G-CSF) binds to the element. The NF/G-CSF was purified by affinity chromatography using an oligonucleotide of GRE. Protein sequence analysis of the purified NF/G-CSF indicated that NF/G-CSF is a ubiquitous transcription factor, NF-Y, which is composed of three subunits. The recombinant, NF-Y was then shown to bind to GRE in a combination of the three subunits.

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  • Jak1 plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor 査読

    K Shimoda, J Feng, H Murakami, S Nagata, D Watling, NC Rogers, GR Stark, IM Kerr, JN Ihle

    BLOOD   90 ( 2 )   597 - 604   1997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:AMER SOC HEMATOLOGY  

    The proliferation and differentiation of neutrophils is regulated by granulocyte-specific colony-stimulating factor (G-CSF). G-CSF uses a receptor of the cytokine receptor superfamily and, in common with all members of the family, induces the tyrosine phosphorylation and activation of members of the Janus protein tyrosine kinase (Jak) family. In both myeloid cells and a human fibrosarcoma cell line expressing the G-CSF receptor, G-CSF induces the tyrosine phosphorylation and activation of Jak1, Jak2, end Tyk2. In addition, G-CSF induces the tyrosine phosphorylation of the receptor and members of the signal transducers and activators of transcription (Stat) family, including Stat3, as well as Stat1 and Stat5, depending on the cells involved. Using mutant cell lines lacking various Jaks, we show here that Jak1 is critical for G-CSF-mediated Stat activation, whereas Jak2 or Tyk2 are either not required or play redundant or ancillary roles. In the absence of Jak1, G-CSF induces activation of Jak2 and Tyk2, but fails to induce receptor tyrosine phosphorylation and induces dramatically reduced levels of Stat activation. A kinase-inactive Jak2, when overexpressed in cells lacking endogenous Jak2, can suppress Jak1 activation, receptor phosphorylation, and Stat activation, suggesting competition in the receptor complex either for Jak1 binding or substrates. Because the requirement for Jak1 is very similar to that previously shown for interleukin-6-signaling, the data support the concept that the G-CSF receptor and gp130 are both structurally and functionally similar. (C) 1997 by The American Society of Hematology.

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  • Swapping between Fas and granulocyte colony-stimulating factor receptor 査読

    T Takahashi, M Tanaka, J Ogasawara, T Suda, H Murakami, S Nagata

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 29 )   17555 - 17560   1996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:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Fas belongs to the tumor necrosis factor/nerve growth factor receptor family. The Fas ligand binds to its receptor, Fas, and induces apoptosis in Fas-bearing cells. The granulocyte colony-stimulating factor receptor (G-CSFR) is a member of the hemopoietic growth factor receptor family. G-CSF induces its dimerization and regulates the proliferation and differentiation of neutrophilic granulocytes, We constructed hybrid receptors between Fas and G-CSFR and expressed them in the mouse T cell line WR19L or the mouse myeloid interleukin-3-dependent FDC-P1 cell line. The Fas ligand or an agonistic anti-Fas antibody stimulated proliferation of the FDC-P1 transformants expressing a chimera consisting of the Fas extracellular and G-CSFR cytoplasmic regions. On the other hand, G-CSF could not induce apoptosis in the transformants expressing the chimera consisting of the G-CSFR extracellular and Fas cytoplasmic regions, but these cells were killed by a polyclonal antibody against G-CSFR. These results indicated that receptors belonging to different receptor families can be functionally exchanged and confirm that a homodimer of G-CSFR can transduce the growth signal, whereas Fas must be oligomerized (probably trimerized) to transduce the apoptotic signal.

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  • DISTINCT SIGNAL-TRANSDUCTION THROUGH THE TYROSINE-CONTAINING DOMAINS OF THE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR 査読

    A YOSHIKAWA, H MURAKAMI, S NAGATA

    EMBO JOURNAL   14 ( 21 )   5288 - 5296   1995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)   出版者・発行元:OXFORD UNIV PRESS UNITED KINGDOM  

    The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.

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  • SIGNAL SEQUENCE REGION OF MITOCHONDRIAL PRECURSOR PROTEINS BINDS TO MITOCHONDRIAL IMPORT RECEPTOR 査読

    H MURAKAMI, G BLOBEL, D PAIN

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   90 ( 8 )   3358 - 3362   1993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)   出版者・発行元:NATL ACAD SCIENCES  

    An integral mitochondrial membrane protein (p32) of yeast has previously been molecularly cloned and sequenced and suggested to function as a mitochondrial import receptor. However, this protein has also been proposed to function as phosphate translocator [Guerin, B., Bukusoglu, C., Rakotomanana, F. & Wohlrab, H. (1990) J. Biol. Chem. 265, 19736-19741; Phelps, A., Schobert, C. T. & Wohlrab, H. (1991) Biochemistry 30, 248-2521. Here we have purified p32 after expression of its gene in Escherichia coli and assayed its ability to bind to various preproteins containing signal sequences for protein translocation into mitochondria, chloroplasts, or the endoplasmic reticulum. Our data suggest that p32 contains a binding site specific for the signal sequence region of mitochondrial preproteins. These data are consistent with the previous assignment of p32 as an import receptor and are discussed with regard to the apparently conflicting assignment of this protein as phosphate translocator.

    DOI: 10.1073/pnas.90.8.3358

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  • Machinery for protein import into chloroplasts and mitochondria 査読

    Pain D, Schnell DJ, Murakami H, Blobel G

    Genet Eng (N Y)   13   153 - 166   1991年

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  • IDENTIFICATION AND CHARACTERIZATION OF RECEPTORS FOR PROTEIN IMPORT INTO CHLOROPLASTS AND MITOCHONDRIA 査読

    D PAIN, H MURAKAMI, DJ SCHNELL, G BLOBEL

    INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS   27 ( 6 )   443 - 445   1990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)   出版者・発行元:COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH  

    An anti-idiotypic antibody approach was used to identify chloroplast and mitochondrial protein component(s) which interact with the corresponding signal sequence. The proteins thus identified can be operationally defined as receptor(s) for import of proteins into chloroplasts and mitochondria. The import receptor(s) was found in "contact sites" between the outer and inner membrane of chloroplast envelope or of mitochondria.

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  • IDENTIFICATION OF A RECEPTOR FOR PROTEIN IMPORT INTO MITOCHONDRIA 査読

    D PAIN, H MURAKAMI, G BLOBEL

    NATURE   347 ( 6292 )   444 - 449   1990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)   出版者・発行元:MACMILLAN MAGAZINES LTD  

    DOI: 10.1038/347444a0

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  • ISOLATION AND CHARACTERIZATION OF THE GENE FOR A YEAST MITOCHONDRIAL IMPORT RECEPTOR 査読

    H MURAKAMI, G BLOBEL, D PAIN

    NATURE   347 ( 6292 )   488 - 491   1990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)   出版者・発行元:NATURE PUBLISHING GROUP  

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  • 70-KD HEAT-SHOCK RELATED PROTEIN IS ONE OF AT LEAST 2 DISTINCT CYTOSOLIC FACTORS STIMULATING PROTEIN IMPORT INTO MITOCHONDRIA 査読

    H MURAKAMI, D PAIN, G BLOBEL

    JOURNAL OF CELL BIOLOGY   107 ( 6 )   2051 - 2057   1988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)   出版者・発行元:ROCKEFELLER UNIV PRESS  

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  • MAPPING AND DISRUPTION OF THE CYBB GENE CODING FOR CYTOCHROME-B561 IN ESCHERICHIA-COLI 査読

    YAMATO, I, H NAKAMURA, H MURAKAMI, Y ANRAKU

    FEMS MICROBIOLOGY LETTERS   56 ( 1 )   21 - 28   1988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)   出版者・発行元:ELSEVIER SCIENCE BV  

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  • NUCLEOTIDE-SEQUENCE OF THE CYBB GENE ENCODING CYTOCHROME-B561 IN ESCHERICHIA-COLI-K12 査読

    H NAKAMURA, H MURAKAMI, YAMATO, I, Y ANRAKU

    MOLECULAR & GENERAL GENETICS   212 ( 1 )   1 - 5   1988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)   出版者・発行元:SPRINGER VERLAG  

    DOI: 10.1007/BF00322437

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  • Cloning, expression, and sequence homologies of cDNA for human carbonic anhydrase II 査読

    Murakami H, Marelich GP, Grubb JH, Kyle JW, Sly WS

    Genomics   1 ( 2 )   159 - 166   1987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: 10.1016/0888-7543(87)90008-5

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  • PURIFICATION AND CHARACTERIZATION OF HUMAN SALIVARY CARBONIC-ANHYDRASE 査読

    H MURAKAMI, WS SLY

    JOURNAL OF BIOLOGICAL CHEMISTRY   262 ( 3 )   1382 - 1388   1987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)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

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  • PURIFICATION AND PROPERTIES OF A DIHEME CYTOCHROME-B561 OF THE ESCHERICHIA-COLI RESPIRATORY-CHAIN 査読

    H MURAKAMI, K KITA, Y ANRAKU

    JOURNAL OF BIOLOGICAL CHEMISTRY   261 ( 2 )   548 - 551   1986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)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

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  • THE ESCHERICHIA-COLI CYTOCHROME B556-GENE, CYBA, IS ASSIGNABLE AS SDHC IN THE SUCCINATE-DEHYDROGENASE GENE-CLUSTER 査読

    H MURAKAMI, K KITA, H OYA, Y ANRAKU

    FEMS MICROBIOLOGY LETTERS   30 ( 3 )   307 - 311   1985年

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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:ELSEVIER SCIENCE BV  

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  • QUANTITATIVE-DETERMINATION OF CYTOCHROMES IN THE AEROBIC RESPIRATORY-CHAIN OF ESCHERICHIA-COLI BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND ITS APPLICATION TO ANALYSIS OF MITOCHONDRIAL CYTOCHROMES 査読

    K KITA, H MURAKAMI, H OYA, Y ANRAKU

    BIOCHEMISTRY INTERNATIONAL   10 ( 2 )   319 - 326   1985年

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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:ACADEMIC PRESS AUST  

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  • CLONING OF CYBB, THE GENE FOR CYTOCHROME B561 OF ESCHERICHIA-COLI-K12 査読

    H MURAKAMI, K KITA, Y ANRAKU

    MOLECULAR & GENERAL GENETICS   198 ( 1 )   1 - 6   1984年

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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:SPRINGER VERLAG  

    DOI: 10.1007/BF00328692

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  • CHROMOSOMAL LOCATION OF THE ESCHERICHIA-COLI CYTOCHROME-B556 GENE, CYBA 査読

    H MURAKAMI, K KITA, H OYA, Y ANRAKU

    MOLECULAR & GENERAL GENETICS   196 ( 1 )   1 - 5   1984年

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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:SPRINGER VERLAG  

    DOI: 10.1007/BF00334084

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▼全件表示

書籍等出版物

  • ノックアウトマウス・データブック

    中山書店  1998年 

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  • Granulocyte colony-stimulating factor. The cytokine handbook, the third edition. (共著)

    Academic Press  1998年 

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MISC

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

    MizutaniA, Yan T, Vaidyanath A, Masuda J, Seno A, Kasai T, Murakami H, Seno M

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

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

    MizutaniA, Yan T, Vaidyanath A, Masuda J, Seno A, Kasai T, Murakami H, Seno M

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

  • 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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  • 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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  • A Cancer Stem Cell Model, an insight into the conversion of induced pluripotent stem cells to cancer stem-like cells.

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

    Cancer Stem Cells   61 - 77   2014年

  • 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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  • Src homology 2 domain of overexpressed Lyn kinase is responsible for the acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation. (共著)

    Naomi Oka, Akiko Suzuki, Tomomi Omura, Hiroshi Sakai, Hiroshi Murakami

    Cell Biology International   30 ( 6 )   525 - 532   2006年6月

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  • G-CSFによる好中球の分化誘導と細胞の形態変化、 好中球の核は花びら状

    村上宏

    生物工学 会誌   第82巻、第4号、161頁   2004年

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  • Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase. (共著)

    Omura, T, Sakai, H, Murakami, H

    European J. Biochem   269 ( 1 )   381 - 389   2002年1月

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  • 1999年のNobel生理学医学賞:Gunterの思い出

    村上宏

    ファルマシア   36 (1) p48   2000年

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  • Targeted disruption of the gene encoding the proteolipid subunit of mouse vacuolar H(+)-ATPase leads to early embryonic lethality. (共著)

    Inoue, H, Noumi, T, Nagata, M, Murakami, H, Kanazawa, H

    Biochim Biophys Act   1413 ( 3 )   130 - 138   1999年11月

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  • Expression of functional Na+/H+ antiporters of Helicobacter pylori in antiporter-deficient Escherichai coli mutants. (共著)

    Inoue, H, Sakurai, T, Ujike, S, Tsuchiya, T, Murakami, H, Kanazawa, H

    Febs Letters   443 ( 1 )   11 - 16   1999年1月

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  • Reconstitution of F1-ATPase activity from Escherichia coli subunits a, b and subunit g tagged with six histidine residues at the C-terminus. (共著)

    Ekuni, A, Watanabe, H, Kuroda, N, Sawada, K, Murakami, H, Kanazawa, H

    FEBS Letter   427 ( 1 )   64 - 68   1998年5月

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  • Myeloid-specific transcriptional activation by murine myeloid zink-finger protein 2. (共著)

    Murai, K, Murakami, H, Nagata, S

    Proc. Natl. Acad. Sci. USA   95 ( 7 )   3461 - 3466   1998年3月

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  • Granulocyte colony-stimulating factor.

    Murakami, H, Nagata, S

    The cytokine handbook, the third edition.   671-688   1998年

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  • A novel form of the myeloid-specific zinc finger protein (MZF-2). (共著)

    Murai, K, Murakami, H, Nagata, S

    Genes to Cells   2 ( 9 )   581 - 591   1997年9月

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  • Binding of NF-Y transcription factor to one of the cis-elements in the myeloperoxidase gene promoter that responds to granulocyte colony-stimulating factor. (共著)

    Orita, T, Shimozaki, K, Murakami, H, Nagata, S

    J. Biol. Chem.   272 ( 37 )   23216 - 23223   1997年9月

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  • Jak1 Plays an Essential Role for Receptor Phosphorylation and Stat Activation in Response to Granulocyte Colony-Stimulating Factor. (共著)

    Shimoda, K, Feng, J, Murakami, H, Nagata, S, Watling, D, Rogers, N.C, Stark, G.R, Kerr, I.M, Ihle, J.N

    Blood   90 ( 2 )   597 - 604   1997年7月

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  • Swapping between Fas and granulocyte colony-stimulating factor receptor. (共著)

    Takahashi, T, Tanaka, M, Ogasawara, J, Suda, T, Murakami, H, Nagata, S

    J. Biol. Chem.   271 ( 29 )   17555 - 17560   1996年7月

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  • 1p-YN-2 プラズマディスプレイの現状と展望(放電シンポジウム:放電・低温プラズマ)

    村上 宏

    日本物理学会講演概要集. 年会   51 ( 4 )   138 - 138   1996年3月

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    記述言語:日本語   出版者・発行元:一般社団法人日本物理学会  

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  • Functional domains of the G-CSF receptor that are required for signaling through the Jak-Stat pathway

    J Feng, A Yoshikawa, H Murakami, BA Witthuhn, S Nagata, JN Ihle

    BLOOD   86 ( 10 )   1020 - 1020   1995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 HEMATOLOGY  

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  • Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor. (共著)

    Yoshikawa, A, Murakami, H, Nagata, S

    EMBO J.   14 ( 21 )   5288 - 5296   1995年11月

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    記述言語:英語  

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  • カラープラズマディスプレー開発の現状

    村上 宏

    應用物理   63 ( 6 )   584 - 587   1994年6月

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    記述言語:日本語   出版者・発行元:応用物理学会  

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  • Signal sequence region of mitochondrial precursor proteins binds to mitochondrial import receptor. (共著)

    Murakami, H, Blobel, G, Pain, D

    Proc. Natl. Acad. Sci. USA.   90 ( 8 )   3358 - 3362   1993年4月

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  • ハイビジョン壁掛けテレビジョンの現状と動向

    村上 宏

    電子情報通信学会誌   75 ( 9 )   968 - 974   1992年9月

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    記述言語:日本語   出版者・発行元:電子情報通信学会  

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  • MITOCHONDRIAL IMPORT RECEPTOR INTERACTS WITH SIGNAL SEQUENCES SPECIFYING PROTEIN IMPORT INTO MITOCHONDRIA

    H MURAKAMI, D PAIN, G BLOBEL

    MOLECULAR BIOLOGY OF THE CELL   3   A126 - A126   1992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:AMER SOC CELL BIOLOGY  

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  • Machinery for protein import into chloroplasts and mitochondria. (共著)

    Pain, D, Schnell, D. J, Murakami, H, Blobel, G

    Genetic Engineering   13 ( 153 )   153 - 166   1991年

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  • Identification and characterization of receptors for protein import into chloroplasts and mitochondria. (共著)

    Pain, D, Murakami, H, Schnell, D. J, Blobel, G

    Indian J. Biochem. Biophys.   27 ( 6 )   443 - 445   1990年12月

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  • Isolation and characterization of the gene for a yeast mitochondrial import receptor. (共著)

    Murakami, H, Blobel, G, Pain, D

    Nature   347 ( 6292 )   488 - 491   1990年10月

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  • Identification of a receptor for protein import into mitochondria. (共著)

    Pain, D, Murakami, H, Blobel, G

    Nature   347 ( 6292 )   444 - 449   1990年10月

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  • 70-kD heat shock-related protein is one of at least two distinct cytosolic factors stimulating protein import into mitochondria. (共著)

    Murakami, H, Pain, D, Blobel, G

    J. Cell Biol.   107 ( 6 )   2051 - 2057   1988年12月

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    記述言語:英語  

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  • Nucleotide sequence of the cybB gene encoding cytochrome b561 in Escherichia coli K12. (共著)

    Nakamura, H, Murakami, H, Yamato, I, Anraku, Y

    Mol. Gen. Genet.   212 ( 1 )   1 - 5   1988年4月

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  • Purification and characterization of human salivary carbonic anhydrase. (共著)

    Murakami, H, Sly, W. S

    J. Biol. Chem.   262 ( 3 )   1382 - 1388   1987年1月

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  • Cloning, expression, and sequence homologies of cDNA for human carbonic anhydrase II. (共著)

    Murakami, H, Marelich, G. P, Grubb, J. H, Kyle, J. W, Sly, W. S

    Genomics   1 ( 2 )   159 - 166   1987年

  • Purification and Properties of a diheme cytochrome b561 of the Escherichia coli respiratory chain. (共著)

    Murakami, H, Kita, K, Anraku, Y

    J. Biol. Chem.   261 ( 2 )   548 - 551   1986年1月

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  • Quantitative determination of cytochromes in the aerobic respiratory chain of Escherichia coli by high-performance liquid chromatography and its application to analysis of mitochondrial cytochromes. (共著)

    Kita, K, Murakami, H, Oya, H, Anraku, Y

    Biochem. Int.   10 ( 2 )   319 - 326   1985年

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    記述言語:英語  

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  • Cloning of cybB, the gene for cytochrome b561 of Escherichia coli K12. (共著)

    Murakami, H, Kita, K, Anraku, Y

    Mol. Gen. Genet.   198 ( 1 )   1 - 6   1984年

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  • Chromosomal location of the Escherichia coli cytochrome b556 gene, cybA. (共著)

    Murakami, H, Kita, K, Oya, H, Anraku, Y

    Mol. Gen. Genet.   196 ( 1 )   1 - 5   1984年

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講演・口頭発表等

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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

    105th Annual Meeting of the American-Association-for-Cancer-Research (AACR)  2014年 

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  • G-CSF-dependent signal transduction pathways leading to neutrophil differentiation.

    第3回 高度医療都市を創出する未来技術国際シンポジウム 抗がん剤・抗感染症創薬のための標的分子生物探求  2010年 

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  • Lynキナーゼの過剰発現による好中球成熟過程での核の分葉化の促進

    第2回 高度医療都市を創出する未来技術国際シンポジウム  2009年 

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  • G-CSF受容体C末端近傍の酸性アミノ酸残基の増殖及び分化誘導シグナルへの関与

    第27回日本分子生物学会年会  2004年 

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  • G-CSF刺激による好中球の核の分葉化シグナルの解析

    第27回日本分子生物学会年会  2004年 

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  • GーCSF受容体C末端近傍の酸性アミノ酸残基の増殖及び分化誘導シグナルへの関与

    日本分子生物学会年会  2003年 

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  • G-CSF刺激依存のシグナル伝達におけるAktの機能解析

    日本分子生物学会年会  2003年 

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  • G-CSF刺激によるGab2及びGab3のリン酸化

    日本分子生物学会年会  2003年 

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  • G-CSF刺激による好中球の核の分葉化シグナルの解析

    日本分子生物学会年会  2003年 

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  • GーCSF刺激による Cbl のリン酸化

    日本分子生物学会年会  2002年 

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  • G-CSF刺激によるCblのリン酸化

    日本分子生物学会年会  2002年 

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  • G-CSF受容体C末端近傍の酸性アミノ酸残基の増殖および分化誘導シグナルへの関与

    日本分子生物学会年会  2002年 

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  • GーCSF受容体C末端近傍の酸性アミノ酸残基の増殖及び分化誘導シグナルへの関与

    日本分子生物学会年会  2002年 

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  • 酵母Na/H逆輸送担体遺伝子のクローン化とその解析

    第22回日本分子生物学会  2001年 

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  • G-CSFシグナル伝達における脱リン酸化酵素の機能解析

    第23回日本分子生物学会  2001年 

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  • G-CSF刺激による転写因子およびCDK阻害タンパク質の発現機構

    第23回日本分子生物学会  2001年 

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  • チロシンキナーゼLynの過剰発現によるG-CSF刺激依存の好中球分化における核の分葉の早期誘導

    第23回日本分子生物学会年会  2001年 

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  • G-CSF刺激依存により発現する好中球分化誘導に関与する遺伝子の検索

    日本分子生物学会年会  2001年 

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  • 分化誘導欠損変異型G-CSF受容体変異の単離とそのシグナル伝達経路の解析

    日本分子生物学会年会  2001年 

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  • G-CSF刺激依存の好中球分化に伴う増殖抑制機構

    第24回日本分子生物k学会年会  2001年 

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  • G-CSF刺激により発現する好中球分化誘導に関与する遺伝子の検索

    第24回日本分子生物学会  2001年 

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  • 分化誘導能欠損変異型G-CSF受容体の単離とそのシグナル伝達経路の解析

    第24回日本分子生物学会  2001年 

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  • G-CSF刺激依存の好中球分化に伴う増殖抑制機構

    日本分子生物学会年会  2001年 

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  • G-CSF刺激によるJak2のリン酸化の経時変化の解析

    第22回日本分子生物学会年会  2001年 

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  • G-CSFシグナル伝達における脱リン酸化酵素の機能解析

    第22回日本分子生物学会  2001年 

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  • G-CSF刺激による転写因子およびCDKタンパク質の発現誘導

    日本分子生物学会年会  2000年 

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  • チロシンキナーゼLynの過剰発現によるG-CSF刺激依存の好中球分化における核の分葉の早期誘導

    日本分子生物学会年会  2000年 

     詳細を見る

  • G-CSFシグナル伝達における脱リン酸化酵素の機能解析

    日本分子生物学会年会  2000年 

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  • 抗ラットCAP2抗体をもちいたCAP2の局在と機能の解析

    第22回日本分子生物学会年会  1999年 

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  • カルシニュウーリンB様タンパク質(CHP)とCHP結合タンパク質キナーゼ(CBK)の細胞内局在

    第22回日本分子生物学会年会  1999年 

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受賞

  • 生物学研究奨励賞

    2018年   両備檉園記念財団  

    村上 宏

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  • 岡山工学振興会科学技術賞

    1998年  

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    受賞国:日本国

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担当授業科目

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  • ヘルスシステム統合科学専門英語 (2021年度) 後期  - その他

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  • 分子細胞生物学 (2021年度) 前期  - 月3~4

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  • 基礎化学実験 (2021年度) 1・2学期  - 月5,月6,月7,月8

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  • 放射線安全利用工学2 (2021年度) 第2学期  - 金5,金6

  • 生化学及び演習2 (2021年度) 第3学期  - 月5,月6,木1,木2

  • 生化学2 (2021年度) 第3学期  - 月5,月6,木1,木2

  • ヘルスシステム統合科学専門英語 (2020年度) 後期  - その他

  • ヘルスシステム統合科学特別研究 (2020年度) 通年  - その他

  • 分子生物学 (2020年度) 第2学期  - 火5,火6,金3,金4

  • 分子遺伝学 (2020年度) 前期  - その他

  • 基礎化学実験 (2020年度) 1・2学期  - 月5,月6,月7,月8

  • 基礎化学実験 (2020年度) 1・2学期  - 木4,木5,木6,木7

  • 基礎化学実験 (2020年度) 1・2学期  - 月5,月6,月7,月8

  • 基礎化学実験 (2020年度) 1・2学期  - 木4,木5,木6,木7

  • 技術表現発表学 (2020年度) 後期  - その他

  • 放射線安全利用工学2 (2020年度) 第2学期  - 金5,金6

  • 教養生物学(バイオテクノロジー) (2020年度) 特別  - その他

  • 教養生物学(バイオテクノロジー) (2020年度) 第4学期  - 木3,木4

  • 生化学及び演習2 (2020年度) 第3学期  - 月5,月6,木1,木2

  • 生化学2 (2020年度) 第3学期  - 月5,月6,木1,木2

  • 遺伝子工学の新展開 (2020年度) 第3学期  - 木3,木4

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