Arima, Yoshimi

写真a

Affiliation

School of Medicine, Institute for Advanced Medical Research (Division of Gene Regulation) (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

Academic Degrees 【 Display / hide

  • 医学博士, 熊本大学大学院医学研究科

 

Papers 【 Display / hide

  • Targeting of cancer stem cells by differentiation therapy

    Arima Y., Nobusue H., Saya H.

    Cancer Science (Cancer Science)  111 ( 8 ) 2689 - 2695 2020.08

    ISSN  13479032

     View Summary

    © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Chemoresistance is a hallmark of cancer stem cells (CSCs). To develop novel therapeutic strategies that target CSCs, we established osteosarcoma-initiating (OSi) cells by introducing the c-Myc gene into bone marrow stromal cells derived from Ink4a/Arf KO mice. These OSi cells include bipotent committed cells (similar to osteochondral progenitor cells) with a high tumorigenic activity as well as tripotent cells (similar to mesenchymal stem cells) of low tumorigenicity. We recently showed that the tripotent OSi cells are highly resistant to chemotherapeutic agents, and that depolymerization of the actin cytoskeleton in these cells induces their terminal adipocyte differentiation and suppresses their tumorigenicity. We here provide an overview of modulation of actin cytoskeleton dynamics associated with terminal adipocyte differentiation in osteosarcoma as well as discuss the prospects for new therapeutic strategies that target chemoresistant CSCs by inducing their differentiation.

  • Molecular and cellular mechanisms underlying brain metastasis of breast cancer

    Hosonaga M., Saya H., Arima Y.

    Cancer and Metastasis Reviews (Cancer and Metastasis Reviews)   2020

    ISSN  01677659

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    © 2020, The Author(s). Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.

  • HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer.

    Arima Yoshimi

    Int J Mol Sci. (International Journal of Molecular Sciences)  19 ( 8 )  2018.07

    Joint Work,  ISSN  16616596

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    © 2018 by the authors. Licensee MDPI, Basel, Switzerland. Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16–36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer.

  • Tranilast inhibits the expression of genes related to epithelial-mesenchymal transition and angiogenesis in neurofibromin-deficient cells.

    Arima Yoshimi

    Sci Rep. (Scientific Reports)  8 ( 1 )  2018.04

    Joint Work

     View Summary

    © 2018 The Author(s). Neurofibromatosis type 1 (NF1) is caused by germline mutations in the NF1 gene and is characterized by café au lait spots and benign tumours known as neurofibromas. NF1 encodes the tumour suppressor protein neurofibromin, which negatively regulates the small GTPase Ras, with the constitutive activation of Ras signalling resulting from NF1 mutations being thought to underlie neurofibroma development. We previously showed that knockdown of neurofibromin triggers epithelial-mesenchymal transition (EMT) signalling and that such signalling is activated in NF1-associated neurofibromas. With the use of a cell-based drug screening assay, we have now identified the antiallergy drug tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid) as an inhibitor of EMT and found that it attenuated the expression of mesenchymal markers and angiogenesis-related genes in NF1-mutated sNF96.2 cells and in neurofibroma cells from NF1 patients. Tranilast also suppressed the proliferation of neurofibromin-deficient cells in vitro more effectively than it did that of intact cells. In addition, tranilast inhibited sNF96.2 cell migration and proliferation in vivo. Knockdown of type III collagen (COL3A1) also suppressed the proliferation of neurofibroma cells, whereas expression of COL3A1 and SOX2 was increased in tranilast-resistant cells, suggesting that COL3A1 and the transcription factor SOX2 might contribute to the development of tranilast resistance.

  • Periostin antisense oligonucleotide suppresses bleomycin-induced formation of a lung premetastatic niche for melanoma.

    Arima Yoshimi

    Cancer Sci. (Cancer Science)  109 ( 5 ) 1447 - 1454 2018.03

    Joint Work,  ISSN  13479032

     View Summary

    © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that up-regulation of periostin expression coincided with activation of myofibroblasts positive for α-smooth muscle actin. We established a lung metastasis model for B16 murine melanoma cells and showed that metastatic colonization of the lung by these cells was markedly promoted by bleomycin-induced lung fibrosis. Inhibition of periostin expression by giving an intratracheal antisense oligonucleotide targeting periostin mRNA was found to suppress bleomycin-induced lung fibrosis and thereby to attenuate metastatic colonization of the lung by melanoma cells. Our results indicate that periostin is a key player in the development of bleomycin-induced fibrosis and consequent enhancement of tumor cell colonization in the lung. Our results therefore implicate periostin as a potential target for prevention or treatment of lung metastasis.

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • Heterogeneous Tumors Composed of Epithelial-type and Mesenchymal-type Breast Cancer Cells

    Arima Yoshimi

    第77回日本癌学会学術総会, 2018

  • Intrahepatic cholangiocarcinoma and gallbladder carcinoma mouse model based on transplantation of syngeneic tumor-initiating cells

    Arima Yoshimi

    American Association for Cancer Research Annual Meeting 2018, 2018, Poster (general)

  • Enriching EpCAM+/Sca-1+ mouse bronchioalveolar stem cells to generate lung adenocarcinoma

    Arima Yoshimi

    American Association for Cancer Research Annual Meeting 2018, 2018, Poster (general)

  • Intratumor Heterogeneity and Cancer Promotion

    Arima Yoshimi

    第76回日本癌学会学術総会, 2017

  • TGF-β Signaling Mediated by Fibroblasts is Associated with the Histological Subtypes of Lung Adenocarcinoma

    Arima Yoshimi

    The IASLC 18th World Conference on Lung Cancer, 2017, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 不均一な乳がんに特異的な腫瘍抗原の同定と免疫細胞活性化メカニズムの解明

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 有馬 好美, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 乳がん組織の複雑さによって生じるがん細胞協調メカニズムの解明

    2016.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 有馬 好美, Grant-in-Aid for Scientific Research (C), Principal Investigator

Intellectual Property Rights, etc. 【 Display / hide

  • 細胞及びその使用

    Application No.: PCT/JP2018/008735  2018.03 

    Patent, Joint

  • 細胞及びその使用

    Application No.: 特願2017-042659  2017.03 

    Patent, Joint

  • 癌組織の不均一性マーカー及びその使用

    Application No.: 国際特許PCT/JP2016/069529  2016.06 

    Patent, Joint

  • 癌組織の不均一性マーカー及びその使用

    Application No.: 特願2015-133033  2016.06 

    Registration No.: 特許第6202659号(特願2017-5 0 3 9 7 1)  2017.09

    Patent, Joint

  • 月経困難症の予防及び/又は治療薬

    Application No.: 国際特許PCT/JP2010/060301  2012.01 

    Patent, Joint

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Awards 【 Display / hide

  • 第45回(2016年度)内藤記念特定研究助成金(第41回内藤コンファレンス ポスター発表者)

    2017.03

  • 2013年度 日本がん分子標的治療学会研究奨励賞

    2014.06, 上皮間葉転換(EMT)転写因子ZEBを標的とした治療法の開発

  • 第1回日本レックリングハウゼン病学会賞(Riccardi賞)

    2010.11