癌幹細胞を標的とする腫瘍根絶技術の新構築の総括班

2014 Fiscal Year Annual Research Report

• Project Area: Development of Novel Treatment Strategies Targeting Cancer Stem Cells
• Project/Area Number: 22130001
• Research Institution: Kyushu University
• Principal Investigator: 赤司 浩一 九州大学, 医学(系)研究科(研究院), 教授 (80380385)
• Co-Investigator(Kenkyū-buntansha): 後藤 典子 金沢大学, がん進展制御研究所, 教授 (10251448) ; 北林 一生 独立行政法人国立がん研究センター, その他部局等, その他 (20261175) ; 田中 真二 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30253420) ; 田賀 哲也 東京医科歯科大学, 難治疾患研究所, 教授 (40192629) ; 須田 年生 慶應義塾大学, 医学部, 教授 (60118453) ; 千葉 滋 筑波大学, 医学医療系, 教授 (60212049) ; 佐谷 秀行 慶應義塾大学, 医学部, 教授 (80264282) ; 中山 敬一 九州大学, 生体防御医学研究所, 教授 (80291508)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 癌幹細胞 / 幹細胞ニッチ / 分子標的治療

Outline of Annual Research Achievements

総括班では、各計画研究と公募研究の有機的連携を促すためのハブ機能に重点を置いて、領域全体の方向性確認を目的としたミーティングの開催、webページを通した情報発信に取り組んできた。
平成26年度の主な取り組みとしては、(1)領域ホームページの充実と研究成果の公開、(2)第8回総括班会議の開催（平成26年5月29日、福岡）、(4)第9回総括班会議の開催（平成26年11月20-21日、福岡）、(5)領域内での共有可能な研究資源の構築などである 。2回の総括班会議において領域内連携の強化を図り、共同研究の実績も上がってきた。計画研究間での共同研究推進のみならず公募研究との連携に力を入れた。また、ハードとソフト両面において研究資源を共有するシステムをもちいることで、高い生産性を維持することができきた。具体的には、(1)癌幹細胞可視化技術（東京医科歯科大学）の共有、(2)遺伝子発現プロファイリングデータの共有（東京大学医科学研究所）、(3)次世代免疫不全マウスをもちいた異種移植技術の共有（九州大学）、(4)タンパク質量分析および修飾解析技術の共有（国立がん研究センター）などが特に有効に機能した。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Prognostic role of Child-Pugh score 5 and 6 in hepatocellular carcinoma patients who underwent curative hepatic resection. (2015)
  • Author(s): Okajima C, Arii S, Tanaka S, Matsumura S, Ban D, Ochiai T, Irie T, Kudo A, Nakamura N, Tanabe M.
  • Journal Title: Am J Surg. Volume: 209 Pages: 199-205
  • DOI: 10.1016/j.amjsurg.2014.03.009.
  • Peer Reviewed
• [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. (2014)
  • Author(s): Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
  • Journal Title: Immunity Volume: 41 Pages: 402-13
  • DOI: 10.1016/j.immuni.2014.08.005.
  • Peer Reviewed
• [Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. (2014)
  • Author(s): Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
  • Journal Title: Exp. Hematol. Volume: 42 Pages: 955-65
  • DOI: 10.1016/j.exphem.2014.07.267.
  • Peer Reviewed
• [Journal Article] The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment. (2014)
  • Author(s): Iwamoto C, Takenaka K, Urata S, Yamauchi T, Shima T, Kuriyama T, Daitoku S, Saito Y, Miyamoto T, Iwasaki H, Kitabayashi I, Itoh K, Kishimoto J, Kohda D, Matozaki T, Akashi K.
  • Journal Title: Exp. Hematol. Volume: 42 Pages: 163-71
  • DOI: 10.1016/j.exphem.2013.11.005.
  • Peer Reviewed
• [Journal Article] Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. (2014)
  • Author(s): Nobusue H, Onishi N, Shimizu T, Sugihara E, Oki Y, Sumikawa Y, Chiyoda T, Akashi K, *Saya H and Kano K
  • Journal Title: Nat Commun. Volume: 5 Pages: 3368
  • DOI: 10.1038/ncomms4368.
  • Peer Reviewed
• [Journal Article] IGF2 preserves osteosarcoma cell survival by creating an autophagic state of dormancy that protects cells against chemotherapeutic stress. (2014)
  • Author(s): Shimizu T, Sugihara E, Yamaguchi-Iwai S, Tamaki S, Koyama Y, Kamel W, Ueki A, Ishikawa T, Chiyoda T, Osuka S, Onishi N, Ikeda H, Kamei J, Matsuo K, Fukuchi Y, Nagai T, Toguchida J, Toyama Y, Muto A and Saya H.
  • Journal Title: Cancer Res. Volume: 74 Pages: 6531-41
  • DOI: 10.1158/0008-5472.CAN-14-0914
  • Peer Reviewed
• [Journal Article] p57 regulates T-cell development and prevents lymphomagenesis by balancing p53 activity and pre-TCR signaling. (2014)
  • Author(s): Matsumoto, A., Takeishi, S., Nakayama, K. I.
  • Journal Title: Blood Volume: 123 Pages: 3429-39
  • DOI: 10.1182/blood-2013-10-532390.
  • Peer Reviewed
• [Journal Article] HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism. (2014)
  • Author(s): Yamauchi, T., Nishiyama, M., Moroishi, T., Yumimoto, K., Nakayama, K. I.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 16430-41
  • DOI: 10.1074/jbc.M113.541490.
  • Peer Reviewed
• [Journal Article] The nuclear export signal (NES) within CALM is necessary for CALM-AF10-induced leukemia. (2014)
  • Author(s): Suzuki M, Yamagata K, Shino M, Aikawa Y, Akashi K, Watanabe T, Kitabayashi I.
  • Journal Title: Cancer Sci. Volume: 105 Pages: 315-23
  • DOI: 10.1111/cas.12347.
  • Peer Reviewed
• [Journal Article] Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion. (2014)
  • Author(s): Shima H, Yamagata K, Aikawa Y, Shino M, Koseki H, Shimada H, Kitabayashi I.
  • Journal Title: Int. J. Hematol. Volume: 99 Pages: 21-31
  • DOI: 10.1007/s12185-013-1466-x.
  • Peer Reviewed
• [Journal Article] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. (2014)
  • Author(s): Hasegawa S, Eguchi H, Nagano H, Konno M, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Nishida N, Koseki J, Nishimura T, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
  • Journal Title: Br. J. Cancer Volume: 111 Pages: 1572-80
  • DOI: 10.1038/bjc.2014.454.
  • Peer Reviewed
• [Journal Article] Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma. (2014)
  • Author(s): Kohsaka S, Hinohara K, Wang L, Nishimura T, Urushido M, Yachi K, Tsuda M, Tanino M, Kimura T, Nishihara H, Gotoh N, Tanaka S.
  • Journal Title: Neuro Oncol. Volume: 16 Pages: 960-70
  • DOI: NA
  • Peer Reviewed
• [Journal Article] Frs2α and Shp2 signal independently of Gab to mediate FGF signaling in lens development. (2014)
  • Author(s): Li H, Tao C, Cai Z, Hertzler-Schaefer K, Collins TN, Wang F, Feng GS, Gotoh N, Zhang X.
  • Journal Title: J Cell Sci. Volume: 127 Pages: 571-82
  • DOI: 10.1242/jcs.134478.
  • Peer Reviewed
• [Journal Article] Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin. (2014)
  • Author(s): Nakamura-Ishizu A, Takubo K, Fujioka M, Suda T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 454 Pages: 353-7
  • DOI: NA
  • Peer Reviewed
• [Journal Article] Neurons limit angiogenesis by titrating VEGF in retina. (2014)
  • Author(s): Okabe K, Kobayashi S, Yamada T, Kurihara T, Tai-Nagara I, Miyamoto T, Mukouyama YS, Sato TN, Suda T, Ema M, Kubota Y.
  • Journal Title: Cell Volume: 159 Pages: 584-96
  • DOI: 10.1016/j.cell.2014.09.025.
  • Peer Reviewed
• [Journal Article] Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling. (2014)
  • Author(s): Kobayashi I, Kobayashi-Sun J, Kim AD, Pouget C, Fujita N, Suda T, Traver D.
  • Journal Title: Nature Volume: 512 Pages: 319-23
  • DOI: 10.1038/nature13623.
  • Peer Reviewed
• [Journal Article] The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. (2014)
  • Author(s): Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T.
  • Journal Title: Blood Volume: 123 Pages: 2540-9
  • DOI: 10.1182/blood-2013-07-517847.
  • Peer Reviewed
• [Journal Article] Alcohol consumption and recurrence of non-B or non-C hepatocellular carcinoma after hepatectomy: a propensity score analysis. (2014)
  • Author(s): Kudo A, Tanaka S, Ban D, Matsumura S, Irie T, Ochiai T, Nakamura N, Arii S, Tanabe M.
  • Journal Title: J Gastroenterol. Volume: 49 Pages: 1352-61
  • DOI: 10.1007/s00535-013-0899-6.
  • Peer Reviewed
• [Journal Article] Sox17-mediated maintenance of fetal intra-aortic hematopoietic cell clusters. (2014)
  • Author(s): Nobuhisa I, Osawa M, Uemura M, Kishikawa Y, Anani M, Harada K, Takagi H, Saito K, Kanai-Azuma M, Kanai Y, Iwama A, Taga T.
  • Journal Title: Mol Cell Biol. Volume: 34 Pages: 1976-90
  • DOI: 10.1128/MCB.01485-13.
  • Peer Reviewed
• [Journal Article] A growth-promoting signaling component cyclin D1 in neural stem cells has antiastrogliogenic function to execute self-renewal. (2014)
  • Author(s): Bizen N, Inoue T, Shimizu T, Tabu K, Kagawa T, Taga T.
  • Journal Title: Stem Cells. Volume: 32 Pages: 1602-15
  • DOI: 10.1002/stem.1613.
  • Peer Reviewed
• [Presentation] TIM-3 Signaling and Human Myeloid Leukemia Stem Cell Development (2015)
  • Author(s): Koichi Akashi
  • Organizer: KEYSTONE SYMPOSIA
  • Place of Presentation: Keystone, Colorado USA
  • Year and Date: 2015-02-26
• [Presentation] 白血病幹細胞研究のすゝめ (2014)
  • Author(s): 赤司 浩一
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-02
• [Presentation] 造血器腫瘍幹細胞 (2014)
  • Author(s): 赤司 浩一
  • Organizer: 第101回近畿血液学地方会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-28
• [Presentation] TIM-3, as a Target for Eradication of Cancer Stem Cells (2014)
  • Author(s): Koichi Akashi
  • Organizer: The Uehara Memorial Foundation Symposium
  • Place of Presentation: 東京
  • Year and Date: 2014-06-17
• [Presentation] 造血器腫瘍幹細胞 (2014)
  • Author(s): 赤司 浩一
  • Organizer: 第3回日本血液学会東海地方会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-04-26
• [Presentation] Cancer Stem Cell (2014)
  • Author(s): 赤司 浩一
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24
• [Remarks] 新学術領域研究「癌幹細胞を標的とする腫瘍根絶技術の新構築」
  • URL: http://www.cancer-stem-cell.com