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2013 Fiscal Year Final Research Report

Development of a new miRNA delivery system for targeting cancer stem cells

Research Project

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Project/Area Number 23659626
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionTokyo Medical University

Principal Investigator

UEDA Shinobu  東京医科大学, 医学部, 助手 (00521874)

Co-Investigator(Kenkyū-buntansha) KURODA Masahiko  東京医科大学, 医学部, 教授 (80251304)
TAKANASHI Masakatsu  東京医科大学, 医学部, 講師 (80312007)
OHNO Shinichiro  東京医科大学, 医学部, 助教 (90513680)
Co-Investigator(Renkei-kenkyūsha) TSUCHIDA Akihiko  東京医科大学, 医学部, 教授 (50207396)
Project Period (FY) 2011 – 2013
Keywords乳がん / miRNA / エキソソーム
Research Abstract

It is known to dysregulation of microRNAs contribution to the development and progression of cancers. MiRNAs in serum correlate with the cancer, cardiovascular disorders and the various types of diseases. In addition, extracellular miRNAs have been detected in exosomes isolated from numerous body fluids including serum. In this study, we examined whether exosomes were a new useful tools for gene delivery in a model of cancer. Modified exosomes with the GE11 peptide that binds to EGFR including let-7a were prepared (let-7a/GE11 exosomes). let-7a/GE11 exosomes were intravenously injected into Rag2-/- mice transplanted breast cancer cells (HCC-70). After four injections, let-7a/GE11 exosomes markedly suppressed tumor growth. These results suggest that exosomes may provide an effective miRNA delivery system for cancer therapy.

  • Research Products

    (41 results)

All 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results) Presentation (16 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Adult-specific systemic over-expression reveals novel in vivo effects of the soluble forms of ActRIIA, ActRIIB and BMPRII2013

    • Author(s)
      Yamawaki K, Ueda S, Okada T, Oshima T, Kakitani M, Kato T, Tomizuka K
    • Journal Title

      PLoS One

      Volume: 8(10) Pages: e78076

    • DOI

      10.1371/journal.pone.0078076.

    • Peer Reviewed
  • [Journal Article] Significant modulation of the hepatic proteome induced by exposure to low temperature in Xenopus laevis2013

    • Author(s)
      Nagasawa K, Tanizaki Y, Okui T, Watarai A, Ueda S, Kato T
    • Journal Title

      Biology Open

      Volume: 2(10) Pages: 1057-69

    • DOI

      10.1242/bio.20136106.

    • Peer Reviewed
  • [Journal Article] Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells2013

    • Author(s)
      Nishi H, Kuroda M, Isaka K
    • Journal Title

      Oncol Rep

      Volume: 30(2) Pages: 751-6

    • DOI

      10.3892/or.2013.2527.

    • Peer Reviewed
  • [Journal Article] GKR6-deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance2013

    • Author(s)
      Nakaya M, Tajima M, Kosako H, Nakaya T, Hashimoto A, Watari K, Nishihara H, Ohba M, Komiya S, Tani N, Nishida M, Taniguchi H, Sato Y, Matsumoto M, Tsuda M, Kuroda M, Inoue K, and Kurose H
    • Journal Title

      Nature Communications

      Volume: 4 Pages: 1532

    • DOI

      10.1038/ncomms2540.

    • Peer Reviewed
  • [Journal Article] The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis2013

    • Author(s)
      Murakami Y, Tamori A, Itami S, Tanahashi T, Toyoda H, Tanaka M, Wu W, Brojigin N, Kaneoka Y, Maeda A, Kumada T, Kawada N, Kubo S and Kuroda M
    • Journal Title

      BMC Cancer.(Section : Genetics, genomics and epigenetics)

      Volume: 13 Pages: 99

    • DOI

      10.1186/1471-2407-13-99.

    • Peer Reviewed
  • [Journal Article] Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells2013

    • Author(s)
      Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M
    • Journal Title

      Molecular Therapy

      Volume: 21(1) Pages: 185-191

    • DOI

      10.1038/mt.2012.180.

    • Peer Reviewed
  • [Journal Article] Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes2013

    • Author(s)
      Katsuda T, Tsuchiya R, Kosaka N,Yoshioka Y, Takagaki K, Oki K, Takeshita F, Sakai Y, Kuroda M, Ochiya T
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 3 Pages: 1197

    • DOI

      10.1038/srep01197

    • Peer Reviewed
  • [Journal Article] An adaptor protein complex of FRS2beta and CIN85/CD2AP provides a novel mechanism for ErbB2/HER2 protein downregulation2013

    • Author(s)
      Minegishi Y, Shibagaki Y, Mizutani A, Fujita K, Tezuka T, Kinoshita M, Kuroda M, Hattori S, Gotoh N
    • Journal Title

      Cancer Science

      Volume: 104(3) Pages: 345-52

    • DOI

      10.1111/cas.12086.

    • Peer Reviewed
  • [Journal Article] Roles of exosomes and microvesicles in disease pathogenesis2013

    • Author(s)
      Ohno S, Ishikawa A, Kuroda M
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 65(3) Pages: 398-401

    • DOI

      10.1016/j.addr.2012.07.019.

  • [Journal Article] Leukemia cell to endothelial cell communication via exosomal miRNAs2012

    • Author(s)
      Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH
    • Journal Title

      Oncogene

      Volume: 32(22) Pages: 2747-55

    • DOI

      10.1038/onc.2012.295

    • Peer Reviewed
  • [Journal Article] TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis regulator PAI-1 in human myxoid liposarcoma2012

    • Author(s)
      Borjigin N, Ohno S, Wu W, Tanaka M, Suzuki R, Fujita K, Takanashi M, Oikawa K, Goto T, Motoi T, Kosaka T, Yamamoto K, Kuroda M
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 427(2) Pages: 355-60

    • DOI

      10.1016/j.bbrc.2012.09.063.

    • Peer Reviewed
  • [Journal Article] Drug-resistant colon cancer stem cells are Lgr5-negative and are capable of tumor reconstitution progressing through a Lgr5-positive state2012

    • Author(s)
      Kobayashi S, Yamada-Okabe H, Suzuki M, Natori O, Kato A, Matsubara K, Chen YJ, Yamazaki M, Funahashi S, Yoshida K, Hashimoto E, Watanabe Y, Mutoh H, Ashihara M, Kato C, Watanabe T, Yoshikubo T, Tamaoki N, Ochiya T, Kuroda M, Levine AJ, and Yamazaki T
    • Journal Title

      Stem cell

      Volume: 30(12) Pages: 2631-44

    • DOI

      10.1002/stem.1257.

    • Peer Reviewed
  • [Journal Article] Efficacy of a Novel Class of RNA Interference Therapeutic Agents2012

    • Author(s)
      Hamasaki T, Suzuki H, Shirohzu H, Matsumoto T, D'Alessandro-Gabazza CN, Gil-Bernabe P, Boveda-Ruiz D, Naito M, Kobayashi T, Toda M, Mizutani T, Taguchi O, Morser J, Eguchi Y, Kuroda M, Ochiya T, Hayashi H, Gabazza EC, Ohgi T
    • Journal Title

      PLoS One

      Volume: 7(8) Pages: e42655

    • DOI

      10.1371/journal.pone.0042655.

    • Peer Reviewed
  • [Journal Article] Isolation of miRNAs that target EGFR mRNA in human lung cancer2012

    • Author(s)
      Yamaguchi G, Takanashi M, Tanaka M, Fujita K, Ohira T, Kuroda M, Ikeda N
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420(2) Pages: 411-6

    • DOI

      10.1016/j.bbrc.2012.03.008.

    • Peer Reviewed
  • [Journal Article] Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen2012

    • Author(s)
      Xu M, Takanashi M, Oikawa K, Nishi H, Isaka K, Yoshimoto T, Ohyashiki J, Kuroda M
    • Journal Title

      Cancer Sci

      Volume: 103(4) Pages: 821-7

    • DOI

      10.1111/j.1349-7006.2012.02221.x.

    • Peer Reviewed
  • [Journal Article] Mitotic figure recognition : agreement among pathologists and computerized detector2012

    • Author(s)
      Malon C, Brachtel E, Cosatto E, Graf HP, Kurata A, Kuroda M, Meyer JS, Saito A, Wu S, Yagi Y
    • Journal Title

      Anal Cell Pathol (Amst)

      Volume: 35(2) Pages: 97-100

    • DOI

      10.3233/ACP-2011-0029.

    • Peer Reviewed
  • [Journal Article] miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer2011

    • Author(s)
      Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, Ueda S, Takanashi M, Kuroda M
    • Journal Title

      Cancer Sci

      Volume: 102(12) Pages: 2264-71

    • DOI

      10.1111/j.1349-7006.2011.02081.x

    • Peer Reviewed
  • [Journal Article] Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production2011

    • Author(s)
      Xu M, Morishima N, Mizoguchi I, Chiba Y, Fujita K, Kuroda M, Iwakura Y, Cua DJ, Yasutomo K, Mizuguchi J, Yoshimoto T
    • Journal Title

      Eur J Immunol

      Volume: 41(10) Pages: 2828-39

    • DOI

      10.1002/eji.201141291

    • Peer Reviewed
  • [Journal Article] Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C2011

    • Author(s)
      Onomoto K, Morimoto S, Kawaguchi T, Toyoda H, Tanaka M, Kuroda M, Uno K, Kumada T, Matsuda F, Shimotohno K, Fujita T, Murakami Y
    • Journal Title

      PLoS One

      Volume: 6(5) Pages: e19799

    • DOI

      10.1371/journal.pone.0019799.

    • Peer Reviewed
  • [Journal Article] Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma2011

    • Author(s)
      Ohyashiki K, Umezu T, Yoshizawa S, Ito Y, Ohyashiki M, Kawashima H, Tanaka M, Kuroda M, Ohyashiki JH
    • Journal Title

      PLoS One

      Volume: 6(2) Pages: e16408

    • DOI

      10.1371/journal.pone.0016408.

    • Peer Reviewed
  • [Journal Article] The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families2011

    • Author(s)
      Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, Kosaka N, Ochiya T, Shimotohno K
    • Journal Title

      PLoS One

      Volume: 6(1) Pages: e16081

    • DOI

      10.1371/journal.pone.0016081.

    • Peer Reviewed
  • [Presentation] 新規のlipid conjugate RNA を用いたがん治療法の開発2013

    • Author(s)
      黒田雅彦、高梨正勝、須藤カツ子
    • Organizer
      第72回日本癌学会総会
    • Year and Date
      20131003-05
  • [Presentation] microRNA の病理研究・治療への応用2013

    • Author(s)
      黒田雅彦、村上善基、上田しのぶ、藤田浩司
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      20130606-08
  • [Presentation] 新規核酸を用いた血管新生網膜症に対する分子標的治療法の開発2013

    • Author(s)
      高梨正勝、須藤カツ子、松永芳径、石川章夫、大木忠明、濱崎智洋、後藤浩、黒田雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      20130606-08
  • [Presentation] 前立腺癌におけるmicroRNA-200c の発現解析2013

    • Author(s)
      山田正俊、大野慎一郎、藤田浩司、倉田厚、黒田雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      20130606-08
  • [Presentation] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells2013

    • Author(s)
      Ohno S, Takanashi M, Ohgi T, Mizutani T, Murakami Y, Kuroda M
    • Organizer
      Keystone Symposia Conference - Noncoding RNAs in Development and Cancer(A7)
    • Place of Presentation
      Vancouver, British Columbia, CANADA
    • Year and Date
      20130120-25
  • [Presentation] マウスに経口投与したエクソソームの生体内での安定性と分布2012

    • Author(s)
      髙梨 正勝、須藤 カツ子、大野 慎一郎、上田 しのぶ、石川 章夫、黒田 雅彦
    • Organizer
      第71回日 本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 大腸癌発生における形態異常とmiRNA2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 血管新生網膜症に対する分子標的治療法を目指した核酸薬の開発2012

    • Author(s)
      髙梨 正勝、須藤 カツ子、松永 芳径、大木 忠明、濱崎 智洋、谷口 維紹、仲矢 丈雄、臼井 嘉彦、後藤 浩、黒田 雅彦
    • Organizer
      第32回日本眼薬理学会
    • Place of Presentation
      滋賀
    • Year and Date
      20120915-16
  • [Presentation] EGFR リガンド発現エクソソームを用いた新規ドラッグデリバリーシステムの開発2012

    • Author(s)
      大野 慎一郎、上田 しのぶ、石川 章夫、松山 永久、藤田 浩司、高梨 正勝、黒田雅彦
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      20120426-28
  • [Presentation] Selective target delivery of miRNA using EGF expressing exosomes2012

    • Author(s)
      Ohno S, Takanashi M, Ueda S, Ohgi T, Mizutani T, Kuroda M
    • Organizer
      Keystone symposia Nucleic Acid Therapeutics : From Base Pairs to Bedsides (A2)
    • Place of Presentation
      Santa Fe, New Mexico
    • Year and Date
      20120110-15
  • [Presentation] Delivery of miRNA to the EGFR-expressed tumor by systemic injection of target exosomes2012

    • Author(s)
      Ohno S, Takanashi M, Sudo K, Mizutani T, Ochiya T, Kuroda M
    • Organizer
      International Society for the EGFR-extracellular Vesicled (ISEV)
    • Place of Presentation
      Gothenburg, Sweden
    • Year and Date
      2012-04-18
  • [Presentation] Delivery of antitumor molecules to the EGFR expressing cancer using EGF expressing exosomes2011

    • Author(s)
      大野 慎一郎、上田 しのぶ、石川 章夫、藤田 浩司、高梨 正勝、黒田 雅彦
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20111213-16
  • [Presentation] 乳がん幹細胞の維持に関与する microRNA の探索2011

    • Author(s)
      上田 しのぶ、高梨正勝、黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] リガンド修飾エクソソームによるEGFreceptor 発現細胞を標的としたドラッグデリバリーシステムの開発2011

    • Author(s)
      大野 慎一郎、上田 しのぶ、石川 章夫、松山永久、高梨 正勝、黒田 雅彦
    • Organizer
      第70回日 本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] CD63-GFP を発現したエクソソームのマウス生体内での安定性と分布について2011

    • Author(s)
      高梨 正勝、須藤 カツ子、大野 慎一郎、上田 しのぶ、石川 章夫、黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] 人工型exosome の生体内分布と安定性についての研究2011

    • Author(s)
      高梨 正勝、須藤 カツ子、大野 慎一郎、上田 しのぶ、石川章夫、黒田 雅彦
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      20110428-30
  • [Book] 新たなドラッグデリバリーシステムとしてのエクソソーム.細胞工学2013

    • Author(s)
      大野慎一郎、髙梨 正勝、黒田 雅彦
    • Total Pages
      53-56
    • Publisher
      秀潤社, vol.32 No.1
  • [Book] 臨床・創薬利用が見えてきたmicroRNA.遺伝子医学MOOK232012

    • Author(s)
      落谷孝広/監修、黒田雅彦・尾崎充彦/編集
    • Publisher
      メディカルドゥ
  • [Book] 次世代に向けた核酸医薬品の新技術 -RNA 干渉法を用いた分子標的核酸医薬の開発.化学第67巻第9号2012

    • Author(s)
      仲矢丈雄・黒田雅彦・大木忠明
    • Total Pages
      25-29
    • Publisher
      株式会社化学同人
  • [Remarks]

    • URL

      http://www.tokyo-med.ac.jp/molpathol/index.html

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Published: 2015-06-25  

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