Development of Notch signaling inhibitor for hematological malignanciesq

• Project/Area Number: 19790660
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: MASUDA Shigeo Jichi Medical University, 医学部, 助教 (10396749)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 癌 / 分子標的療法 / 白血病 / 動物モデル / 薬剤反応性

Research Abstract

Notchシグナル阻害剤としてのγ-セクレターゼ阻害剤(GSI)がT-ALL(T細胞性急性リンパ性白血病)の皮下腫瘤モデルで奏功した。またGSIによる腫瘍血管への効果を観察した。同モデルで想定されるメカニズムとしては、GSIにより(1)白血病細胞内在性のNotchシグナル抑制(cell autonomousな直接的効果)のほか、(2)腫瘍間質の微小環境におけるNotchシグナル抑制(cell non-autonomousな間接的効果)が挙げられた。特に後者はNotchシグナル抑制に伴う腫瘍血管の機能破綻の可能性が示唆された。

Research Products

• [Journal Article] Notch activation induces the generation of functional natural killer cells from human cord blood CD34-positive cells devoid of interleukin-15. (2009)
  • Author(s): Haraguchi K, Suzuki T, Koyama N, Kumano K, Nakahara F, Matsumoto A, Yokoyama Y, Sakata-Yanagimoto M, Masuda S, Takahashi T, Kamijo A, Takahashi K, Takanashi M, Okuyama Y, Yasutomo K, Sakano S, Yagita H, Kurokawa M, Ogawa S, Chiba S.
  • Journal Title: J Immunol 182(10) Pages: 6188-6178
  • Peer Reviewed
• [Journal Article] ERas is expressed in primate embryonic stem cells but not related to tumorigenesis (2009)
  • Author(s): Tanaka Y, Masuda S, et.al.
  • Journal Title: Cell Transplant (in press)
  • Peer Reviewed
• [Journal Article] Notch activation induces the generation of functional natural killer cells from human cord blood CD34-positive cells devoid of interleukin-15 (2009)
  • Author(s): Haraguchi K, Masuda S, et.al.
  • Journal Title: J Immunol (in press)
  • Peer Reviewed
• [Journal Article] Co-Transplantation of MSC Improves the Engraftment of HSC after Auto-iBMT in Non-Human Primates (2008)
  • Author(s): Masuda S, Obara Y, Ageyama N, Shibata H, Ikeda T, Ueda Y, Ozawa K, Hanazono Y.
  • Journal Title: Blood 112(11)
  • Peer Reviewed
• [Journal Article] Variation in the incidence of teratomas after the transplantation of non-human primate ES cells into immunodeficient mice (2008)
  • Author(s): Kishi Y, Tanaka Y, Shibata H, Nakamura S, Takeuchi K, Masuda S, Ikeda T, Muramatsu S, Hanazono Y.
  • Journal Title: Cell Transplant. 17(9) Pages: 1095-1102
  • Peer Reviewed
• [Journal Article] Knockout Serum Replacement (KSR) has a suppressive effect on Sendai virus-mediated transduction of cynomolgus ES cells (2008)
  • Author(s): Kishi Y, Inoue M, Tanaka Y, Shibata H, Masuda S, Ikeda T, Hasegawa M, Hanazono Y.
  • Journal Title: Cloning Stem Cells 10(3) Pages: 307-312
  • Peer Reviewed
• [Journal Article] Sustained macroscopic engraftment of cynomolgus embryonic stem cells in xenogeneic large animals after in utero transplantation. (2008)
  • Author(s): Tanaka Y, Nakamura S, Shibata H, Kishi Y, Ikeda T, Masuda S, Sasaki K, Abe T, Hayashi S, Kitano Y, Nagao Y, Hanazono Y.
  • Journal Title: Stem Cells Dev. 17(2) Pages: 367-381
  • Peer Reviewed
• [Journal Article] Both Notch1 and Notch2 contribute to the regulation of melanocyte homeostasis (2008)
  • Author(s): Kumano K, Masuda S, Sata M, Saito T, Lee SY, Sakata-Yanagimoto M, Tomita T, Iwatsubo T, Natsugari H, Kurokawa M, Ogawa S, Chiba S.
  • Journal Title: Pigment Cell Melanoma Res. 21(1) Pages: 70-78
  • Peer Reviewed
• [Journal Article] Both Notch1 and Notch2 contribute to the regulation of melanocyte homeostasis (2008)
  • Author(s): Kumano K, Masuda S, et.al.
  • Journal Title: Pigment Cell Melanoma Res 21(1) Pages: 70-78
  • Peer Reviewed
• [Journal Article] Sustained macroscopic engraftment of cynomolgus embryonic stem cells in xenogeneic large animals after in utero transplantation (2008)
  • Author(s): Tanaka Y, Masuda S, et.al.
  • Journal Title: Stem Cells Dev 17(2) Pages: 367-381
  • Peer Reviewed
• [Journal Article] Knockout Serum Replacement (KSR) has a suppressive effect on Sendai virus-mediated transduction of cynomolgus ES cells (2008)
  • Author(s): Kishi Y, Masuda S, et.al.
  • Journal Title: Cloning Stem Cells 10(3) Pages: 307-312
  • Peer Reviewed
• [Journal Article] Variation in the incidence of teratomas after the transplantation of non-human primate ES cells into immunodeficient mice (2008)
  • Author(s): Kishi Y, Masuda S, et.al.
  • Journal Title: Cell Transplant 17(9) Pages: 1095-1102
  • Peer Reviewed
• [Journal Article] Co-Transplantation of MSC Improves the Engraftment of HSC after Auto-iBMT in Non-Human Primates (2008)
  • Author(s): Masuda S, Obara Y, et.al.
  • Journal Title: Blood 112(11)
• [Journal Article] Both Notch1 and Notch2 contribute to the regulation of melanocytehomeostasis. (2008)
  • Author(s): Kumano K, Masuda S, et. al.
  • Journal Title: Pigment Cell Melanoma Res. 21(1) Pages: 70-78
  • Peer Reviewed
• [Journal Article] Sustained macroscopic engraftment of cynomolgus embryonic stem cells in xenogeneic large animals after in utero transplantation. (2008)
  • Author(s): Tanaka Y, Masuda S, et. al.
  • Journal Title: Stem Cells Dev. (in press)
  • Peer Reviewed
• [Journal Article] ERas is expressed in primate embryonic stem cells but not related to tumorigenesis.
  • Author(s): Tanaka Y, Ikeda T, Kishi Y, Masuda S, Shibata H, Takeuchi K, Komura M, Iwanaka T, Muramatsu S, Kondo Y, Takahashi K, Yamanaka S, Hanazono Y.
  • Journal Title: Cell Transplant (in press)
  • Peer Reviewed
• [Presentation] Co-transplantation of MSCimproves the engraftment of HSC after auto-iBMT in non-human primates (2008)
  • Author(s): Masuda S
  • Organizer: 第50回米国血液学会総会(ASH)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-07
• [Presentation] Co-transplantation of MSC improves the engraftment of HSC after auto-iBMT in non-human primates (2008)
  • Author(s): Masuda S, et.al.
  • Organizer: Annual Meeting of American Society of Hematology
  • Place of Presentation: アメリカ合衆国(サンフランシスコ)
  • Year and Date: 2008-12-07
• [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果 (2008)
  • Author(s): 増田茂夫
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都・国立京都国際会館
  • Year and Date: 2008-10-11
• [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果 (2008)
  • Author(s): 増田茂夫、他
  • Organizer: 日本血液学会総会
  • Place of Presentation: 京都(国立京都国際会館)
  • Year and Date: 2008-10-11
• [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果 (2008)
  • Author(s): 増田茂夫
  • Organizer: 第7回自治医科大学シンポジウム
  • Place of Presentation: 栃木・自治医大
  • Year and Date: 2008-08-30
• [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果 (2008)
  • Author(s): 増田茂夫、他
  • Organizer: 自治医科大学シンポジウム
  • Place of Presentation: 栃木(自治医大)
  • Year and Date: 2008-08-30
• [Presentation] Notchシグナル亢進による白血病発症機構に基づいたin vivo抗腫瘍効果の解析 (2008)
  • Author(s): 増田茂夫
  • Organizer: 第6回幹細胞シンポジウム
  • Place of Presentation: 東京・学術総合センター
  • Year and Date: 2008-05-17
• [Presentation] Notchシグナル亢進による白血病発症機構に基づいたin vivo抗腫瘍効果の解析 (2008)
  • Author(s): 増田茂夫、他
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 東京(学術総合センター)
  • Year and Date: 2008-05-17
• [Presentation] サルの血液をもつヒツジの作製:キメラ率向上をめざして移植ルートの検討 (2008)
  • Author(s): 増田茂夫
  • Organizer: 第11回日本異種移植研究会
  • Place of Presentation: 大阪・国立循環器病センター
  • Year and Date: 2008-02-23
• [Presentation] サルの血液をもつヒツジの作製:サルの血液をもつヒツジの作製:キメラ率向上をめざして前処置法の検討 (2008)
  • Author(s): 増田茂夫
  • Organizer: 第11回日本異種移植研究会
  • Place of Presentation: 大阪・国立循環器病センター
  • Year and Date: 2008-02-23
• [Presentation] サルの血液をもつヒツジの作製:キメラ率向上をめざして移植ルートの検討 (2008)
  • Author(s): 増田茂夫、田中裕次郎
  • Organizer: 第11回 日本異種移植研究会
  • Place of Presentation: 大阪(国立循環器病センター)
  • Year and Date: 2008-02-23
• [Presentation] サルの血液をもつヒツジの作製:キメラ率向上をめざして前処置法の検討 (2008)
  • Author(s): 増田茂夫、阿部朋之
  • Organizer: 第11回 日本異種移植研究会
  • Place of Presentation: 大阪(国立循環器病センター)
  • Year and Date: 2008-02-23
• [Presentation] (2008)
  • Author(s): S Chiba, K Kumano, S Masuda
  • Organizer: 第1回The Notch and Cancer conference
  • Place of Presentation: Athens, Greece
• [Presentation] The molecular mechanism of Notch-induced transformation and therapeutic potential of its inhibitor (2008)
  • Author(s): 増田茂夫
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜・パシフィコ横浜
• [Presentation] Notch and Cancer (2008)
  • Author(s): Chiba S, Kumano K, Masuda S
  • Organizer: The Notch and Cancer conference
  • Place of Presentation: ギリシャ(アテネ)
• [Presentation] The molecular mechanism of Notch-induced transformation and therapeutic potential of its inhibitor. (2007)
  • Author(s): 増田 茂夫
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜(パシフィコ横浜)
• [Book] 分子細胞治療(「HOXB4発現レトロウイルスベクターを用いた幹細胞遺伝子治療において大型動物では高率に白血病を発症する」) (2008)
  • Author(s): 増田茂夫
  • Publisher: 先端医学社
• [Book] Medical Practice新・図解救急・応急処置ガイド (2008)
  • Author(s): 増田茂夫
  • Publisher: 文光堂
• [Book] Medical Practice新・図解救急・応急処置ガイドVol.25, 臨時増刊号(「血小板減少症」) (2008)
  • Author(s): 増田茂夫
  • Total Pages: 1132
  • Publisher: 文光堂
• [Book] 血液・腫瘍科(「Notchシグナルと腫瘍血管新生」) (2007)
  • Author(s): 増田茂夫
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://gantoku3.umin.jp/topics/masuda.html
• [Remarks]
  • URL: http://netplus.nikkei.co.jp/ssbiz/_techno/_te090414.html
• [Remarks]
  • URL: http://www.oishasan.co.jp/oisha/topics/rireki/09_02_06.html
• [Remarks] (科学研究費補助金「特定領域研究」がん研究に係わる特定領域研究ホームページ ; 「N・tchシグナル阻害剤による抗腫瘍効果(増田茂夫)」)
  • URL: http://gantoku3.umin.io/tooics/masuda.html
• [Remarks]
  • URL: http://netnlus.nikkei.co.in/ssbiz/techno/te090414.html
• [Remarks]
  • URL: http://www.oishasan.co.in/oisha/tooics/rireki/09_02_06.html
• [Remarks] 科学研究費補助金「特定領域研究」がん研究に係わる特定領域研究ホームページ;「Notchシグナル阻害剤による抗腫瘍効果(増田茂夫)」
  • URL: http://gantoku3.umin.jp/topics/masuda.html