Acid sphingomyelinase-derived liver macrophage inhibits growth of metastatic colon cancer in the liver.

• Project/Area Number: 26460965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Metropolitan Komagome Hospital (Clinical research laboratory)
• Principal Investigator: Yosuke Osawa 東京都立駒込病院(臨床研究室), 肝臓内科, 医長 (60447787)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 転移性肝腫瘍 / 肝線維化 / スフィンゴ脂質 / βカテニンシグナル / 原発性肝腫瘍 / スフィンゴ脂質シグナル / Wnt/βカテニンシグナル / 酸性スフィンゴミエリナーゼ / マクロファージ

Outline of Final Research Achievements

Sphingolipids regulate carcinogenesis and proliferation, survival, and apoptosis of cancer cells.In this study, the involvement of ASM in liver metastasis of colon cancer was examined. ASM in the liver inhibits tumor growth through cytotoxic macrophage. Thus, targeting ASM may represent a new therapeutic strategy for treating liver metastasis of colon cancer.

Research Products

• [Journal Article] Selective inhibitor of Wnt/β-catenin/CBP signaling ameliorates hepatitis C virus-induced liver fibrosis in mouse model (2017)
  • Author(s): Yuko Tokunaga, Yosuke Osawa, Takahiro Ohtsuki, Yukiko Hayashi, Kenzaburo Yamaji, Daisuke Yamane, Mitsuko Hara, Keisuke Munekata, Kyoko Tsukiyama-Kohara, Tsunekazu Hishima, Soichi Kojima, Kiminori Kimura, and *Michinori Kohara
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 325-325
  • DOI: 10.1038/s41598-017-00282-w
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of Cyclic Adenosine Monophosphate (cAMP)-response Element-binding Protein (CREB)- binding Protein (CBP)/β-Catenin Reduces Liver Fibrosis in Mice. (2015)
  • Author(s): Osawa Y, Oboki K, Imamura J, Kojika E, Hayashi Y, Hishima T, Saibara T, Shibasaki F, Kohara M, Kimura K
  • Journal Title: EBioMedicine Volume: 2 Issue: 11 Pages: 1751-8
  • DOI: 10.1016/j.ebiom.2015.10.010
  • Peer Reviewed / Open Access
• [Journal Article] Blockade of Indoleamine 2,3-Dioxygenase Reduces Mortality from Peritonitis and Sepsis in Mice by Regulating Functions of CD11b+ Peritoneal Cells. (2014)
  • Author(s): Hoshi M, Osawa Y ら
  • Journal Title: Infect Immun Volume: 82 Pages: 4487-4495
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] マウス肝線維化におけるWnt/β-cateninシグナルの関与 (2016)
  • Author(s): 大澤陽介 今村潤 木村公則
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-05-19
• [Presentation] マウス肝線維化におけるWnt/β-cateninシグナルの関与 (2016)
  • Author(s): 大澤陽介 今村潤 木村公則
  • Organizer: 第１２０回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] Inhibition of CBP/β-catenin reduces liver fibrosis in mice. (2016)
  • Author(s): Osawa Y, Imamura J, Kimura K
  • Organizer: Asian Pacific Association for the Study of the Liver (APASL)
  • Place of Presentation: Tokyo.
  • Year and Date: 2016-02-22
  • Int'l Joint Research
• [Presentation] マウス肝線維化におけるWnt/β-cateninシグナルの関与 (2015)
  • Author(s): 大澤陽介 今村潤 木村公則
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-22
• [Presentation] 胆管結紮誘導性慢性肝障害モデルにおけるKupffer細胞とTNF-αの役割 (2014)
  • Author(s): 大澤陽介
  • Organizer: 第28回肝類洞壁細胞研究会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-12-13
• [Presentation] 胆管結紮誘導性慢性肝障害モデルにおけるKupffer細胞とTNF-alphaの役割 (2014)
  • Author(s): 大澤陽介
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-30
• [Presentation] 大腸癌細胞由来転移性肝腫瘍の増殖における酸性スフィンゴミエリナーゼの役割 (2014)
  • Author(s): 大澤陽介
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-23