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In vivo observation of stemness acquisition in differentiated cancer cells

Research Project

Project/Area Number 25670177
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionNara Medical University

Principal Investigator

KUNIYASU Hiroki  奈良県立医科大学, 医学部, 教授 (00253055)

Co-Investigator(Kenkyū-buntansha) KITADAI Yasuhiko  広島大学, 医歯薬学大学院, 准教授 (10304437)
CHIHARA Yoshitomo  奈良県立医科大学, 医学部, 講師 (40405395)
FUJIMOTO Yoshio  奈良県立医科大学, 医学部, 教授 (90192731)
Co-Investigator(Renkei-kenkyūsha) TAKAKI Miyako  奈良県立医科大学, 医学部, 特任教授 (00033358)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsがん幹細胞 / 幹細胞分化 / キネティクス / がん細胞分化・脱分化 / 多光子励起蛍光顕微鏡 / 冬眠性がん幹細胞 / 増殖性がん幹細胞 / 分化がん細胞 / 幹細胞可塑性
Outline of Final Research Achievements

Dedifferentiation or acquisition of stemness was examined in mouse cancer cells. Expression of CD133 and nucleostemin in CT26 cells showed that differentiations of dormant cancer stem (DCS) to proliferating cancer stem (PCS) and PCS to differentiated cancer cells (DCC) were found in 3.5% and 5.6%, respectively. In contrast, dedifferentiations of DCC to PCS and PCS to DCS were found in 1.7% and 1%, respectively. In in vivo observation of KT-5 cells in mouse brain showed stem-related ALP activity was disappeared in 16%, whereas appeared in 1%. These findings suggest that the dedifferentiation or acquisition of stemness might be a common phenomenon in cancer. The biological meaning and clinical importance should be examined in further studies.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (51 results)

All 2015 2014 2013 Other

All Journal Article (30 results) (of which Peer Reviewed: 30 results,  Acknowledgement Compliant: 10 results,  Open Access: 12 results) Presentation (13 results) (of which Invited: 4 results) Book (6 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] High motility group box 1 induces cancer aggressiveness and drug resistance.2015

    • Author(s)
      Ohmori H, Luo Y, Fujii K, Sasaki T, Kuniyasu H
    • Journal Title

      Annals of Clinical Pathology

      Volume: 3(1) Pages: 1042-1042

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alteration of the plasma free amino acids profiles in cancer patients is associated with dysregulated metabolism in skeletal muscle2015

    • Author(s)
      Luo Y, Yoneda J, Sasaki T, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H
    • Journal Title

      Archives of Cancer Research

      Volume: 3(1) Pages: 5-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] AKT plays a crucial role in gastric cancer.2015

    • Author(s)
      Sasaki T, Yamashita Y, Kuniyasu H
    • Journal Title

      Oncology Letters

      Volume: in press

    • NAID

      120005976143

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 18F-fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in oral squamous cell carcinoma.2015

    • Author(s)
      Shimomura H, Sasahira T, Yamanaka Y, Kurihara M, Imai Y, Tamaki S, Yamakawa N, Shirone N, Hasegawa M, Kuniyasu H, Kirita T
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 20(2) Issue: 2 Pages: 308-316

    • DOI

      10.1007/s10147-014-0711-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model2015

    • Author(s)
      Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
    • Journal Title

      J Virol

      Volume: 89 Issue: 9 Pages: 4866-4879

    • DOI

      10.1128/jvi.03676-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after transection of the gut in rodents.2015

    • Author(s)
      Goto K, Kawahara I, Kuniyasu H, Takaki M
    • Journal Title

      J Physiol Sci

      Volume: 未定 Issue: 4 Pages: 377-383

    • DOI

      10.1007/s12576-015-0377-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Update of molecular pathobiology in oral cancer: a review.2014

    • Author(s)
      Sasahira T, Kirita T, Kuniyasu H.
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 19 Issue: 3 Pages: 431-436

    • DOI

      10.1007/s10147-014-0684-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Significance of AKT in gastric cancer.2014

    • Author(s)
      Sasaki T, Kuniyasu H
    • Journal Title

      International Journal of Oncology

      Volume: 45(6) Issue: 6 Pages: 2187-2192

    • DOI

      10.3892/ijo.2014.2678

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer.2014

    • Author(s)
      Sasaki T, Ohmori H, et al
    • Journal Title

      Pathobiology

      Volume: 81 Issue: 1 Pages: 36-41

    • DOI

      10.1159/000351721

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible peripheral mechanism for taste disorder in S-1 administered rats.2014

    • Author(s)
      Aoki K, Obata K, Kurihara M, Kuniyasu H, Kirita T, Takaki M
    • Journal Title

      Int J Clin Oncol

      Volume: 19 Issue: 3 Pages: 549-556

    • DOI

      10.1007/s10147-013-0572-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer usurps skeletal muscle as an energy repository2014

    • Author(s)
      Luo Y, Ohmori H, et al
    • Journal Title

      Cancer Res

      Volume: 74 Issue: 1 Pages: 330-340

    • DOI

      10.1158/0008-5472.can-13-1052

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prox1 and FOXC2 Act as Regulators of Lymphangiogenesis and Angiogenesis in Oral Squamous Cell Carcinoma2014

    • Author(s)
      Sasahira T, Ueda N, Yamamoto K, Kurihara M, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H
    • Journal Title

      PLoS One

      Volume: 9(3) Issue: 3 Pages: e92534-e92534

    • DOI

      10.1371/journal.pone.0092534

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas2014

    • Author(s)
      Kuwada M, Kuniyasu H, et al
    • Journal Title

      BMC Res Note

      Volume: 7 Issue: 1 Pages: 203-203

    • DOI

      10.1186/1756-0500-7-203

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression.2014

    • Author(s)
      Zhou L, Luo Y, Sato S, Tanabe E, Kitayoshi M, Fujiwara R, Sasaki T, Fujii K, Ohmori H, Kuniyasu H
    • Journal Title

      Pathobiology

      Volume: 81(4) Issue: 4 Pages: 169-175

    • DOI

      10.1159/000362092

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method2014

    • Author(s)
      Shunsuke Shinmei, Kazuhiro Sentani, Tetsutaro Hayashi, Naoya Sakamoto, Keisuke Goto, Htoo Zarni Oo, Yutaka Naito, Jun Teishima, Akio Matsubara, Naohide Oue, Hiroki Kuniyasu, Wataru Yasui
    • Journal Title

      Urologic Oncology

      Volume: 32 Issue: 6 Pages: 769-778

    • DOI

      10.1016/j.urolonc.2014.03.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum CD10 is associated with liver metastasis in colorectal cancer.2014

    • Author(s)
      Sasaki T, Kuniyasu H, Luo Y, Fujiwara R, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y
    • Journal Title

      Journal of Surgical Research

      Volume: 192 Issue: 2 Pages: 390-394

    • DOI

      10.1016/j.jss.2014.05.071

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma2014

    • Author(s)
      Sasahira T, Kirita T, Yamamoto K, Ueda N, Kurihara M, Matsushima S, Bhawal UK, Bosserhoff AK, Kuniyasu H
    • Journal Title

      Eur J Cancer

      Volume: 50 Issue: 12 Pages: 2142-2151

    • DOI

      10.1016/j.ejca.2014.05.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HuD promotes progression of oral squamous cell carcinoma2014

    • Author(s)
      Sasahira T, Kurihara M, Yamamoto K, Ueda N, Nakashima C, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H
    • Journal Title

      Pathobiology

      Volume: 81 Issue: 4 Pages: 206-214

    • DOI

      10.1159/000366022

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of an anti-claudin-3 and -4 bispecific monoclonal antibody for cancer diagnosis and therapy2014

    • Author(s)
      Xiangru Li, Manami Iida, Minoru Tada, Akihiro Watari, Yumi Kawahigashi, Yuka Kimura, Taku Yamashita, Akiko Ishii-Watabe, Tadayuki Uno, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 351 Issue: 1 Pages: 206-213

    • DOI

      10.1124/jpet.114.216911

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression2014

    • Author(s)
      Zhou L, Kuniyasu H, et al.
    • Journal Title

      Pathobiology

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of PRL1 as a Novel Diagnostic and Therapeutic Target for Castration Resistant Prostate Cancer by the Escherichia Coli Ampicillin Secretion Trap (CAST) Method.2014

    • Author(s)
      Shinmei S, Kuniyasu H, et al.
    • Journal Title

      Urologic Oncology Seminar and

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple roles of angiotensin in colorectal cancer2013

    • Author(s)
      Kuniyasu H
    • Journal Title

      World J Clin Oncol

      Volume: 3 Issue: 12 Pages: 150-154

    • DOI

      10.5306/wjco.v3.i12.150

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of epidermal growth factor receptor in cancer metastasis and microenvironment.2013

    • Author(s)
      Sasaki T, Kuniyasu H
    • Journal Title

      Biomed Res Int

      Volume: 2013 Pages: 546318-546318

    • DOI

      10.1155/2013/546318

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma2013

    • Author(s)
      Sasahira T, Ueda N, Yamamoto K, Bhawal UK, Kurihara M, Kirita T, Kuniyasu H
    • Journal Title

      Clinical Experimental Metastasis

      Volume: 30(2) Issue: 2 Pages: 165-176

    • DOI

      10.1007/s10585-012-9525-x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy.2013

    • Author(s)
      Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H
    • Journal Title

      Eur J Cancer

      Volume: 49 Issue: 3 Pages: 741-751

    • DOI

      10.1016/j.ejca.2012.09.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma.2013

    • Author(s)
      Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
    • Journal Title

      Hum Pathol

      Volume: in press Issue: 6 Pages: 1098-1106

    • DOI

      10.1016/j.humpath.2012.09.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging of enteric neurogenesis in the deep tissue of mouse smallintestine. hearts of SERCA2a transgenic rats.2013

    • Author(s)
      Goto K, Obata K, Takaki M, 他
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 1 Pages: e54814-e54814

    • DOI

      10.1371/journal.pone.0054814

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma.2013

    • Author(s)
      Kurihara M, Kirita T, Sasahira T, Ohmori H, Matsushima S, Yamamoto K, Bosserhoff AK, Kuniyasu H
    • Journal Title

      Br J Cancer

      Volume: 108 Issue: 7 Pages: 1460-9

    • DOI

      10.1038/bjc.2013.27

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic markers of urothelial cancer based on DNA methylation analysis.2013

    • Author(s)
      Chihara Y, Kuniyasu H, et al.
    • Journal Title

      BMC Cancer

      Volume: 13 Issue: 1 Pages: 275-275

    • DOI

      10.1186/1471-2407-13-275

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased phosphorylation of AKT in high-risk gastric mucosa2013

    • Author(s)
      Sasaki T, Kuniyasu H, et al
    • Journal Title

      Anticancer Res

      Volume: 33 Pages: 3295-3300

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 鉄-アルミニウム新規合金素材を発熱体とする磁気温熱療法のマウス皮下腫瘍モデルを用いた検証2015

    • Author(s)
      國安弘基
    • Organizer
      第5回磁気ハイパーサーミア研究会
    • Place of Presentation
      奈良市
    • Year and Date
      2015-01-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 損傷した消化管壁内神経の再生新生2014

    • Author(s)
      高木 都、後藤 桂、川原 勲、鍋倉淳一、國安弘基
    • Organizer
      第16回日本神経消化器病学会
    • Place of Presentation
      東京都
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Claudin-4を標的とする治療の可能性2014

    • Author(s)
      國安弘基、羅 奕、千原良友、桑田真臣、北吉美沙穂、田邊絵里子、佐々木隆光、大森 斉、近藤昌夫
    • Organizer
      第29回発癌病理研究会
    • Place of Presentation
      いわき市
    • Year and Date
      2014-09-01 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] メタボリック症候群における大腸癌2014

    • Author(s)
      國安弘基
    • Organizer
      第103回日本病理学会総会ワークショップ
    • Place of Presentation
      広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 癌細胞はHMGB1を介して筋組織をエネルギー源として利用している2013

    • Author(s)
      國安弘基ほか
    • Organizer
      第28回発癌病理学会シンポジウム
    • Place of Presentation
      南城市
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規MIA gene familyであるMIA2の口腔癌における機能解析2013

    • Author(s)
      笹平智則、國安弘基ほか
    • Organizer
      第24回日本臨床口腔病理学会、若手シンポジウム「新しきパラダイムを求めて」
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report
  • [Presentation] 口腔癌におけるピルビン酸キナーゼ作用の多様性2013

    • Author(s)
      栗原都、國安弘基ほか
    • Organizer
      第24回日本消化器癌発生学会、シンポジウム「がんの代謝特性とがん生物学」
    • Place of Presentation
      金沢市
    • Related Report
      2013 Research-status Report
  • [Presentation] Effect of intermittent calorie restriction on cancer stem cells.2013

    • Author(s)
      Luo Y, Kuniyasu H, et al
    • Organizer
      103rd Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Research-status Report
  • [Presentation] HMGB1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy.2013

    • Author(s)
      Luo Y, Kuniyasu H, et al
    • Organizer
      Merinoff World Congress 2013:HMGB1
    • Place of Presentation
      New York
    • Related Report
      2013 Research-status Report
  • [Presentation] Merinoff World Congress 2013:HMGB12013

    • Author(s)
      Luo Y, Kuniyasu H et al
    • Organizer
      The 18th Japan-Korea Cancer Research Workshop
    • Place of Presentation
      Gifu
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer.2013

    • Author(s)
      Luo Y, Kuniyasu H, et al
    • Organizer
      4th JCA-AACR Special Joint Conference -The Latest Advances in Gastric Cancer Research: From Basic Science to Therapeutics-
    • Place of Presentation
      Urayasu
    • Related Report
      2013 Research-status Report
  • [Presentation] Fabrication process and magnetocaloric property of aluminum based beads dispersed ferromagnetic particles for magnetic hyperthermia cancer care2013

    • Author(s)
      Kodama K, Kuniyasu H, et al
    • Organizer
      4th TSME International Conference on Mechanical Engineering
    • Place of Presentation
      Pattaya, Chonburi
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of claudin-4–specific monoclonal antibodies and their anti-tumor activities.2013

    • Author(s)
      Iida M, Kuniyasu H, et al
    • Organizer
      24th Antibody Engineering & Therapeutics
    • Place of Presentation
      Huntington Beach, CA, USA
    • Related Report
      2013 Research-status Report
  • [Book] Current Research in Cancer 9‐Non-functioning neuroendocrine tumor of the pancreas- clinical implication.2015

    • Author(s)
      Sasaki T, Kuniyasu H
    • Total Pages
      165
    • Publisher
      Research Media, Kerala, India
    • Related Report
      2014 Annual Research Report
  • [Book] Current Research in Cancer 9‐Impact of trans fatty acids on colorectal cancer2015

    • Author(s)
      Kuniyasu H, Sasaki T, Fujii K, Ohmori H
    • Total Pages
      165
    • Publisher
      Research Media, Kerala, India
    • Related Report
      2014 Annual Research Report
  • [Book] Current Research in Cancer 8-Significance of AKT in gastric cancer2014

    • Author(s)
      Sasaki T, Yamashita Y, Kuniyasu H
    • Total Pages
      156
    • Publisher
      Research Media, Kerala, India
    • Related Report
      2014 Annual Research Report
  • [Book] Current Research in Cancer 8-Significance and the cause of alteration of the plasma free amino acids profiles in cancer2014

    • Author(s)
      Kuniyasu H, Luo Y, Yoneda J, Sasaki T, Fujii K, Ohmori H
    • Total Pages
      156
    • Publisher
      Research Media, Kerala, India
    • Related Report
      2014 Annual Research Report
  • [Book] Current Research in Cancer 72013

    • Author(s)
      Kuniyasu H, et al
    • Total Pages
      215
    • Publisher
      Research Media
    • Related Report
      2013 Research-status Report
  • [Book] Current Research in Cancer 72013

    • Author(s)
      Sasaki t, Kuniyasu H, et al
    • Total Pages
      215
    • Publisher
      Research Media
    • Related Report
      2013 Research-status Report
  • [Remarks] 奈良県立医科大学分子病理学講座

    • URL

      http://www.naramed-u.ac.jp/~molepath/

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] クラウディン(CLDN)4抗体、その抗体のフラグメント、その抗体を含む医薬組成物、CLDN4エピトープに結合する分子、及び腫瘍マーカーに関する発明2014

    • Inventor(s)
      國安弘基ほか
    • Industrial Property Rights Holder
      國安弘基ほか
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-036111
    • Filing Date
      2014-02-27
    • Related Report
      2013 Research-status Report
    • Overseas

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Published: 2014-07-25   Modified: 2019-07-29  

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