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Elucidation of liver carcinogenesis mechanism by epigenetic reprogramming.

Research Project

Project/Area Number 24659593
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

SEKINE Keisuke  横浜市立大学, 医学部, 助教 (00323569)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords癌 / エピジェネティクス / リプログラミング
Research Abstract

As a result of introduction of the 4 factors to the HCC cell lines, colonies of iPS cell-like is formed after about 2 weeks. The established clones were investigated by morphological observation, gene expression analysis and the transplantation into immunodeficient mice. Expression of hepatocyte marker HNF4 in comparison with HCC cell lines were decreased. And increased expression of Sox2, undifferentiated marker, was observed. However, the expression of undifferentiated markers were lower compared with iPS cells. To verify the presence or absence of teratoma formation capability, clones were transplanted into the testes of immunodeficient mice (NOD / scid). However no teratoma formation was observed from clones that were established in this study.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (52 results)

All 2014 2013 2012 Other

All Journal Article (25 results) (of which Peer Reviewed: 24 results,  Open Access: 3 results) Presentation (27 results) (of which Invited: 2 results)

  • [Journal Article] Tropism of cancer stem cells to a specific distant organ2014

    • Author(s)
      Okuda R, Sekine K, Hisamatsu D, Ueno Y, Takebe T, Zheng YW, Taniguchi H
    • Journal Title

      In Vivo

      Volume: 28(3) Pages: 361-5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The CD133+CD44+ Precancerous Subpopulation of Oval Cells is a Therapeutic Target for Hepatocellular2014

    • Author(s)
      Zheng YW, Tsuchida T, Shimao T, Li B, Takebe T, Zhang RR, Sakurai Y, Ueno Y, Sekine K, Ishibashi N, Imajima M, Tanaka T, Taniguchi H
    • Journal Title

      Carcinoma Stem Cells Dev

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescent labeling and visualization of human induced pluripotent stem cells with the use of transcription activator-like effector nucleases.2014

    • Author(s)
      Sekine K, Takebe T, Taniguchi H.
    • Journal Title

      Transplant Proc.

      Volume: 46 Issue: 4 Pages: 1205-1207

    • DOI

      10.1016/j.transproceed.2014.02.003

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion via Simultaneous Suppression of Cdkn1a and Cdkn2a.2014

    • Author(s)
      Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H
    • Journal Title

      Hepatology

      Volume: 印刷中 Issue: 1 Pages: 323-333

    • DOI

      10.1002/hep.27046

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Engineering of human hepatic tissue with functional vascular networks2014

    • Author(s)
      Takebe T, Koike N, Sekine K, Fujiwara R, Amiya T, Zheng YW, Taniguchi H
    • Journal Title

      Organogenesis

      Volume: 10(2)(Epub ahead of print)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant.2014

    • Author(s)
      Takanori Takebe*, Ran-Ran Zhang, Hiroyuki Koike, Masaki Kimura, Emi Yoshizawa, Masahiro Enomura, Keisuke Sekine, Hideki Taniguchi*(*: Correspondence)
    • Journal Title

      Nature Protocols

      Volume: 9(2) Issue: 2 Pages: 396-409

    • DOI

      10.1038/nprot.2014.020

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The evidence of sophisticatedly heterogeneous population of human umbilical vein endothelial cells2014

    • Author(s)
      Zheng YW, Nie YZ, Tsuchida T, Zhang RR, Aoki K, Sekine K, Ogawa M, Takebe T, Ueno Y, Sakakibara H, Hirahara F, Taniguchi H
    • Journal Title

      Transplant Proc

      Volume: 46 Issue: 4 Pages: 1251-3

    • DOI

      10.1016/j.transproceed.2013.11.077

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Proliferating Human Hepatic Cells from Human Induced Pluripotent Stem Cells2014

    • Author(s)
      Zhang RR, Takebe T, Sekine K, Koike H, Zheng YW, Taniguchi H
    • Journal Title

      Transplant Proc

      Volume: 46(4) Issue: 4 Pages: 1201-4

    • DOI

      10.1016/j.transproceed.2013.12.021

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The development of humanized liver with Rag1 knockout rats.2014

    • Author(s)
      Tsuchida T, Zheng YW, Zhang RR, Takebe T, Ueno Y, Sekine K, Taniguchi H
    • Journal Title

      Transplant Proc

      Volume: 46 Issue: 4 Pages: 1191-3

    • DOI

      10.1016/j.transproceed.2013.12.026

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-resolution intravital imaging for monitoring the transplanted islets in mice.2014

    • Author(s)
      Takahashi Y, Takebe T, Enomura M, Koike N, Lee S, Nemeno JG, Sekine K, Lee JI, Taniguchi H.
    • Journal Title

      Transplant Proc.

      Volume: 46 Issue: 4 Pages: 1166-1168

    • DOI

      10.1016/j.transproceed.2013.11.089

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tropism of cancer stem cells to a specific distant organ2014

    • Author(s)
      Okuda R, Sekine K, Hisamatsu D, Ueno Y, Takebe T, Zheng YW, Taniguchi H.
    • Journal Title

      In Vivo

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The CD133+CD44+ Precancerous Subpopulation of Oval Cells is a Therapeutic Target for Hepatocellular Carcinoma2014

    • Author(s)
      Zheng YW, Tsuchida T, Shimao T, Li B, Takebe T, Zhang RR, Sakurai Y, Ueno Y, Sekine K, Ishibashi N, Imajima M, Tanaka T, Taniguchi H.
    • Journal Title

      Stem Cells Dev.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescent labeling and visualization of human induced pluripotent stem cells with the use of transcription activatore like effector nucleases2014

    • Author(s)
      Sekine K, Takebe T, Taniguchi H.
    • Journal Title

      Transplant Proc.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ring1B promotes hepatic stem/ progenitor cell expansion via simultaneous suppression of Cdkn1a and Cdkn2a.2014

    • Author(s)
      Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW,Takebe T, Isono KI, Koseki H, Taniguchi H.
    • Journal Title

      Hepatology

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering of human hepatic tissue with functional vascular networks.2014

    • Author(s)
      Takebe T, Koike N, Sekine K, Fujiwara R, Amiya T, Zheng YW, Taniguchi H.
    • Journal Title

      Organogenesis.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascularized and functional human liver from an iPSC-derived organ bud transplant.2013

    • Author(s)
      Takanori Takebe*, Keisuke Sekine, Masahiro Enomura, Hiroyuki Koike, Ran-Ran Zhang, Yasuharu Ueno, Yun-Wen Zheng, Naoto Koike, Shinsuke Aoyama, Yasuhisa Adachi, Hideki Taniguch*(*: Correspondence)
    • Journal Title

      Nature

      Volume: 499 Issue: 7459 Pages: 481-484

    • DOI

      10.1038/nature12271

    • NAID

      40020351046

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The generation of pancreatic β-cell spheroids in a simulated microgravity culture system.2013

    • Author(s)
      Tanaka H
    • Journal Title

      Biomaterials

      Volume: 34 Issue: 23 Pages: 5785-5791

    • DOI

      10.1016/j.biomaterials.2013.04.003

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control2013

    • Author(s)
      Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Naka michi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
    • Journal Title

      Endocrinology.

      Volume: 154 Issue: 3 Pages: 1008-20

    • DOI

      10.1210/en.2012-1542

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of Automated Culture System for Murine Induced Pluripotent Stem Cells2012

    • Author(s)
      Koike H
    • Journal Title

      BMC Biotechnology

      Volume: 12 Issue: 1 Pages: 81-81

    • DOI

      10.1186/1472-6750-12-81

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis2012

    • Author(s)
      Hirose, Y., Saijou, E., Sugan,o Y., Takeshita, F., Nishimura, S., Nonaka, H., Chen, Y.R., Sekine, K., Kido, T., Nakamura, T., Kato, S., Kanke, T., Nakamura, K., Nagai, R., Ochiya, T., Miyajima, A.
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 109 Issue: 11 Pages: 4263-4268

    • DOI

      10.1073/pnas.1117560109

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regenerative medicine approach as an alternative treatment to islet transplantation.2012

    • Author(s)
      Sekine K
    • Journal Title

      Transplant Proc

      Volume: 44(4) Issue: 4 Pages: 1104-1106

    • DOI

      10.1016/j.transproceed.2012.03.020

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Highly efficient generation of definitive endoderm lineage from human induced pluripotent stem cells2012

    • Author(s)
      Sekine K
    • Journal Title

      Transplant Proc

      Volume: 44(4) Issue: 4 Pages: 1127-1129

    • DOI

      10.1016/j.transproceed.2012.03.001

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Self-organization of human hepatic organoid by recapitulating organogenesis in vitro2012

    • Author(s)
      Takebe T
    • Journal Title

      Transplant Pro

      Volume: 44(4) Issue: 4 Pages: 1018-1020

    • DOI

      10.1016/j.transproceed.2012.02.007

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of functional human vascular network in vitro2012

    • Author(s)
      Takebe T
    • Journal Title

      Transplant Proc

      Volume: 44(4) Issue: 4 Pages: 1130-1133

    • DOI

      10.1016/j.transproceed.2012.03.039

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Basics and applications of stem cells in the pancreas2012

    • Author(s)
      Sekine K, Taniguchi H
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: 19 Issue: 6 Pages: 594-599

    • DOI

      10.1007/s00534-012-0545-3

    • NAID

      10031126973

    • Related Report
      2012 Research-status Report
  • [Presentation] 膵癌幹細胞の系譜解析に向けたin vitroアッセイ系の構築2014

    • Author(s)
      久松大介、奥田諒、関根圭輔、上野康晴、谷口英樹
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵癌幹細胞の系譜解析に向けたin vitroアッセイ系の構築2014

    • Author(s)
      久松大介、奥田 諒、関根圭輔、上野康晴、谷口英樹
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Pdx1陽性細胞は高い腫瘍形成能とスフィア形成能を有する癌幹細胞である2013

    • Author(s)
      奥田諒、関根圭輔、孫略、坪井康次、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      神奈川
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵幹/前駆細胞の膵癌幹細胞への形質転換プロセスの解析2013

    • Author(s)
      関根圭輔、孫略、奥田諒、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      神奈川
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト膵癌幹細胞における治療抵抗性機構の解析2013

    • Author(s)
      星野小百合、関根圭輔、孫略、中田晋、寺崎哲也、森永総一郎、宮城洋平、遠藤格、横瀬智之、倉田昌直、上野康晴、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      神奈川
    • Related Report
      2013 Final Research Report
  • [Presentation] Fluorescence visualizaiton of human induced pluripotent stem cells using transcription activator-like(TAL) effector nucleases2013

    • Author(s)
      Sekine K, Takebe T, Zhang R, Taniguchi H
    • Organizer
      The 13th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Targeted proteomic absolute quantification on transporters of human pancreatic cancer cells with gemcitabine-resistance2013

    • Author(s)
      Ueno Y, Hoshino S, Tsuchida N, Nakata S, Uchida Y, Sekine K, Zheng YW, Kurata M, Morinaga S, Miyagi Y, Yokose T, Endo I, Terasaki T, Hirano H, Taniguchi H
    • Organizer
      HUPO 12th annual world congress
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Pdx1陽性細胞は高い腫瘍形成能とスフィア形成能を有する癌幹細胞である2013

    • Author(s)
      奥田諒、関根圭輔、孫略、坪井康次、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵幹/前駆細胞の膵癌幹細胞への形質転換プロセスの解析2013

    • Author(s)
      関根圭輔、孫略、奥田諒、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト膵癌幹細胞における治療抵抗性機構の解析2013

    • Author(s)
      星野小百合、関根圭輔、孫略、中田晋、寺崎哲也、森永総一郎、宮城洋平、遠藤格、横瀬智之、倉田昌直、上野康晴、谷口英樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Targeted proteomic absolute quantification on transporters of human pancreatic cancer cells with gemcitabine-resistance.2013

    • Author(s)
      Ueno Y, Hoshino S, Tsuchida N, Nakata S, Uchida Y, Sekine K, Zheng YW, Kurata M, Morinaga S, Miyagi Y, Yokose T, Endo I, Terasaki T, Hirano H, Taniguchi H
    • Organizer
      HUPO 12th annual world congress.
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵癌幹細胞のin vitroアッセイ系の解析2012

    • Author(s)
      奥田諒、孫略、関根圭輔、松井智栄美、坪井康次、谷口英樹
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵癌モデルマウスを用いた膵癌幹細胞の細胞系譜解析2012

    • Author(s)
      孫略、奥田諒、関根圭輔、盛武敬、坪井康次、谷口英樹
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵肝/前駆細胞の膵癌幹細胞への形質転換プロセスの解析2012

    • Author(s)
      関根圭輔、孫略、奥田諒、谷口英樹
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of pancreatic stem/progenitor cells expressing PDX1 reside in the CD133 positive pancreatic duct2012

    • Author(s)
      Sekine K, Ishikawa M, Takebe T, Suzaki A, Kawashimo K, Matsui C, Taniguchi H
    • Organizer
      International Society for Stem Cell Research 10^<th> annual meeting
    • Place of Presentation
      Yokohama,Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵癌モデルマウスを用いた膵癌幹細胞の細胞系譜解析2012

    • Author(s)
      関根圭輔、孫略、奥田諒、谷口英樹
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌 (北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵肝/前駆細胞の膵癌幹細胞への形質転換プロセスの解析2012

    • Author(s)
      孫略、奥田諒、関根圭輔、盛武 敬、 坪井 康次、 谷口 英樹
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌 (北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵癌幹細胞のin vitroアッセイ系の解析2012

    • Author(s)
      奥田諒、孫略、関根圭輔、松井智栄美、坪井康次、谷口英樹
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Creation of vascularized human organ from induced pluripotent stem cells.2012

    • Author(s)
      Takebe T, Sekine K, Enomura M, Suzuki Y, Koike H, Zhang R, Koike N, Ueno Y, Zheng Y, Taniguchi H
    • Organizer
      International Society for Stem Cell Research 10th annual meeting.
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Self-renewal versus differentiation as well as the liver repopulation capability of human hepatic stem cells.2012

    • Author(s)
      Zheng Y, Li B, Zhang R, Kimura M, Tsuchida T, Takebe T, Ueno Y, Sekine K, Taniguchi H
    • Organizer
      International Society for Stem Cell Research 10th annual meeting.
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of pancreatic stem/progenitor cells expressing PDX1 reside in the CD133 positive pancreatic duct.2012

    • Author(s)
      Sekine K, Ishikawa M, Takebe T, Suzaki A, Kawashimo K, Matsui C, Taniguchi H
    • Organizer
      International Society for Stem Cell Research 10th annual meeting.
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵幹細胞を起点とした膵発癌プロセスの細胞系譜的解析2012

    • Author(s)
      関根圭輔、松井智栄美、孫略、長久紗耶佳、田中慎、武部貴則、谷口英樹
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 多能性幹細胞を用いた機能的なヒト臓器の創出2012

    • Author(s)
      武部貴則、関根圭輔、江野村允宏、小池博之、張冉冉、三橋優澄、上野康晴、鄭允文、谷口英樹
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 多能性幹細胞を用いた機能的なヒト臓器の創出2012

    • Author(s)
      武部貴則、関根圭輔、江野村允宏、小池博之、張冉冉、木村昌樹、魚返拓則、吉澤絵美、川又史佳、上野康晴、鄭允文、小池直人、谷口英樹
    • Organizer
      第39回日本臓器保存生物医学会学術集会
    • Place of Presentation
      コラッセふくしま(福島県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト微小血管網を有する膵島様組織の創出2012

    • Author(s)
      高橋禎暢、江野村允宏、武部貴則、関根圭輔、小池直人、田中寛康、谷口英樹
    • Organizer
      第39回日本臓器保存生物医学会学術集会
    • Place of Presentation
      コラッセふくしま(福島県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵幹細胞を起点とした膵発癌プロセスにおける膵癌幹細胞の細胞系譜的解析

    • Author(s)
      関根圭輔、孫略、上野康晴、谷口英樹
    • Organizer
      第22 回日本サイトメトリー学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ヒトiPSを用いたファーマコセロミクス基盤技術の開発

    • Author(s)
      谷口英樹、武部貴則、関根圭輔、青山晋輔、安達弥永
    • Organizer
      第127回日本薬理学会関東部会シンポジウム
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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