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Effects of FGF2 on the leukemia microenvironment in the bone marrow

Research Project

Project/Area Number 23591382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionAichi Medical University (2012-2013)
Nagoya University (2011)

Principal Investigator

NAKAYAMA Takayuki  愛知医科大学, 医学部, 講師 (00456659)

Co-Investigator(Renkei-kenkyūsha) NAOE Tomoki  名古屋医療センター, 血液内科, 院長 (50217634)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血液腫瘍学 / 血液悪性腫瘍幹細胞 / ニッチェ / 血液学 / 腫瘍微小環境 / ケモカイン / 白血病ニッチェ
Research Abstract

We examined effects of FGF2 on interaction between leukemia cells and its microenvironment. Significantly fewer AML cells were recovered from cocultures with murine stromal monolayers treated with FGF2 than from control. FGF2 also facilitate the sensitivity of CML cells toward imatinib in the coculture. Accordingly, AML cells in cell cycle quiescent are less in FGF2-treated monolayers than control. We next treated human AML mouse model with Ara-C in combination w/wo FGF2. BM sections from FGF2-treated mice displayed thickened bone trabeculae and an increased number of leukemia cells compared to control. FGF2 did not help leukemia cells survive from Ara-C in the spleen. These observations suggest that the endosteal region consisting of osteoblasts is important for leukemia cells to survive from chemotherapy, and that FGF2 favors leukemia cell in the BM via promoting osteoblast functions.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 2 results) Presentation (10 results)

  • [Journal Article] Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions2014

    • Author(s)
      Satoshi Nishiwaki, Takayuki Nakayama, Makoto Murata, Tetsuya Nishida, Seitaro Terakura, Shigeki Saito, Tomonori Kato, Hiroki Mizuno, Nobuhiko Imahashi, Aika Seto, Yukiyasu Ozawa, Koichi Miyamura, Masafumi Ito, Kyosuke Takeshita, Hidefumi Kato, Shinya Toyokuni, Keisuke Nagao, Ryuzo Ueda, and Tomoki Naoe
    • Journal Title

      PLOS one

      Volume: 9(5) Issue: 5 Pages: e96252-e96252

    • DOI

      10.1371/journal.pone.0096252

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recovery of flow-mediated vasodilatation after repetitive measurements is involved in early vascular impairment: comparison with indices of vascular tone.2014

    • Author(s)
      Inaba H, Takeshita K, Uchida Y, Hayashi M, Okumura T, Hirashiki A, Yoshikawa D, Ishii H, Yamamoto K, Nakayama T, Hirayama M, Matsumoto H, Matsushita T, Murohara T
    • Journal Title

      PLOS one

      Volume: 9(1) Issue: 1 Pages: 1-9

    • DOI

      10.1371/journal.pone.0083977

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell therapy using adipose-derived mesenchymal stromal cells : current status and perspectives2013

    • Author(s)
      Nakayama T, and Kato H
    • Journal Title

      Japanese Journal of Transfusion and Cell Therapy

      Volume: 59(3) Pages: 450-456

    • NAID

      10031185432

    • URL

      https://www.jstage.jst.go.jp/article/jjtc/59/3/59_450/_article/-char/ja/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib2012

    • Author(s)
      水野 紘樹
    • Journal Title

      Leukemia

      Volume: 26 Issue: 10 Pages: 2269-2269

    • DOI

      10.1038/leu.2012.81

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis.2012

    • Author(s)
      Nishiwaki S
    • Journal Title

      Int J Hematol.

      Volume: 96(3) Issue: 3 Pages: 295-300

    • DOI

      10.1007/s12185-012-1140-8

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation : macrophage-targeted steroid therapy2012

    • Author(s)
      西脇聡史
    • Journal Title

      International Journal of Hematology

      Volume: (Epub ahead of print) Issue: 4 Pages: 428-33

    • DOI

      10.1007/s12185-012-1023-z

    • NAID

      10030632677

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stress Augments Insulin Resistance and Prothrombotic State : Role of Visceral Adipose-Derived Monocyte Chemoattractant Protein-12012

    • Author(s)
      Uchida Y
    • Journal Title

      Diabetes

      Volume: (In press) Issue: 6 Pages: 1552-61

    • DOI

      10.2337/db11-0828

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells stably transduced with a dominant-negative inhibitor of CCL2 greatly attenuate bleomycine-induced lung damage2011

    • Author(s)
      斎藤繁紀
    • Journal Title

      The American Journal of Pathology

      Volume: 179 Issue: 3 Pages: 1088-1094

    • DOI

      10.1016/j.ajpath.2011.05.027

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin-induced angiogenesis and arteriogenesis is mediated by Notchl in a murine hindlimb ischemia model without induction of VEGF2011

    • Author(s)
      Kikuchi R
    • Journal Title

      Lab Invest

      Volume: 91 Issue: 5 Pages: 691-703

    • DOI

      10.1038/labinvest.2011.5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful fertility management of a patient with factor V deficiency: planned transfusion of fresh frozen plasma under infertility treatment2011

    • Author(s)
      Iwase A, Matsushita T
    • Journal Title

      Fertil Steril

      Volume: 95(6) Issue: 6 Pages: 2124.e5-2124.e7

    • DOI

      10.1016/j.fertnstert.2011.01.011

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells stably transduced with a dominant negative inhibitor of CCL2 greatly attenuate bleomycin-induced lung damage.2011

    • Author(s)
      Saito S, Nakayama T*, Hashimoto N, Miyata Y, Egashira K, Nakao N, Nishiwaki S, Hasegawa M, Hasegawa Y, Naoe T
    • Journal Title

      Am J Pathol.

      Volume: 179 Pages: 1088-94

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin-induced angiogenesis and arteriogenesis is mediated by Notch1 in a murine hindlimb ischemia model without induction of VEGF.2011

    • Author(s)
      Kikuchi R, Takeshita K, Uchida Y, Kondo M, Cheng XW, Nakayama T, Yamamoto K, Matsushita T, Liao JK, Murohara T
    • Journal Title

      Lab Invest.

      Volume: 91 Pages: 691-703

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful fertility management of a patient with factor V deficiency: planned transfusion of fresh frozen plasma under infertility treatment.2011

    • Author(s)
      Iwase A, Goto M, Manabe S, Hirokawa W, Kobayashi H, Nakahara T, Takikawa S, Kotani T, Sumigama S, Tsuda H, Nakayama T, Suzuki N, Matsushita T, Kikkawa F.
    • Journal Title

      Fertil Steril.

      Volume: 95

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-12014

    • Author(s)
      Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M, Cheng XW, Egashira K, Matsushita T, Nakamura H, Murohara T.
    • Organizer
      Keystone symposia
    • Place of Presentation
      BC, Canada
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mesenchymal stem cells stably transduced with a dominant negative inhibitor of CCL2 greatly attenuate bleomycin-induced lung damage2013

    • Author(s)
      Nakayama T, Saito S, Naoe T
    • Organizer
      第61回日本輸血・細胞療法学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Stress augments insulin resistance and prothrombotic state : role of visceral adipose-derived CCL22013

    • Author(s)
      Uchida Y, Takeshita K, Nakayama T.
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] The effectiveness of macrophage-targeted therapy by dexamethasone palmitate for refractory GVHD2012

    • Author(s)
      Nishiwaki S, Nakayama T, Naoe T.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib2012

    • Author(s)
      Nakayama T, Mizuno H, Naoe T
    • Organizer
      第34回日本血栓止血学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] The effectiveness of macrophage-targeted therapy by dexamethasone palmitate for refractory GVHD2012

    • Author(s)
      Takayuki Nakayama, Satoshi Nishiwaki, Makoto Murata, Tetsuya Nishida, Seitaro Terakura, Shigeki Saito, Tomoki Naoe et al.
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Efficacy and safety of adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis.2012

    • Author(s)
      Takayuki Nakayama
    • Organizer
      The 60th Annual Meeting of the Japanese Society of Transfusison Medicine and Cell therapy
    • Place of Presentation
      Fukushima, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib.2012

    • Author(s)
      Takayuki Nakayama
    • Organizer
      The 34th Annual Meeting of the Japanese Society of Thrombosis and Hemostasis
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] 造血支持を目的としたヒト脂肪組織由来間葉系幹細胞の有効性、安全性の検討2011

    • Author(s)
      中山享之、中尾典彦、直江知樹
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib

    • Author(s)
      Nakayama T, Mizuno H, Naoe T
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Vancouver, BC, Canada
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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