Mechanism of inflammation-associated gastro-intestinal carcinogenesis

• Project/Area Number: 19390205
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yokohama City University (2009-2010); The Institute for Adult Diseases, Asahi Life Foundation (2007-2008)
• Principal Investigator: MAEDA Shin Yokohama City University, 医学研究科, 教授 (40415956)
• Co-Investigator(Kenkyū-buntansha): OGURA Keiji 東京大学, 医学部附属病院・消化器内科, 特任講師 (50376456) ; SHIBATA Wataru 朝日生命成人病研究所, 主任研究員 (00435819) ; YANAI Ayako 朝日生命成人病研究所, 主任研究員 (10415961)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 癌・動物 / 癌 / 炎症 / NF-κB / 発がん / 消化管 / 動物モデル / JNK

Research Abstract

NF-kB/IKK and JNK pathways are important cell signaling pathways that regulate the gene cluster associated with the inflammation, apoptosis, and cell proliferation. Therefore it is suggested that these pathways play important roles of the development or progression of carcinomas. We used the mouse models and examined those functions in the gastrointestinal cancers. Cancer development was inhibited in the knockout mouse of NF-kB/IKK and JNK in the stomach cancer model. In addition, the inflammation-associated cancer of colon was inhibited by the IKK inhibitor. In summary, NF-kB/IKK and JNK were should be important for the generation or progression of gastrointestinal cancers and will become the treatment targets.

Research Products

• [Journal Article] IkappaB kinase beta regulates gastric carcinogenesis via IL-1α expression. (2010)
  • Author(s): Sakamoto K, Hikiba Y, Nakagawa H, Hayakawa Y, Yanai A, Akanuma M, Ogura K, Yoshida H, Hirata Y, Kaestner KH, Omata M, Maeda S.
  • Journal Title: Gastroenterology 139 Pages: 226-38
• [Journal Article] Apoptosis Signal-Regulating Kinase 1 regulates colitis and colitis-associated tumorigenesis via the innate immune responses. (2010)
  • Author(s): Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Otsuka M, Ijichi H, Ikenoue T, Tateishi K, Akanuma M, Ogura K, Yoshida H, Ichijo H, Omata M, Maeda S.
  • Journal Title: Gastroenterology 138 Pages: 1055-1067
• [Journal Article] Apoptosis Signal-Regulating Kinase 1 regulates colitis and colitis-associated tumorigenesis via the innate immune responses. (2010)
  • Author(s): Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Otsuka M, Ijichi H, Ikenoue T, Tateishi K, Akanuma M, Ogura K, Yoshida H, Ichijo H, Omata M, Maeda S.
  • Journal Title: Gastroenterology Volume: 138 Pages: 1055-67
  • Peer Reviewed
• [Journal Article] IKKβ/NF-κB Activation Controls the Development of Liver Metastasis via IL-6 Expression. (2009)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Nakagawa H, Hirata Y, Hayakawa Y, Yanai A, Ogura K, Karin M, Omata M.
  • Journal Title: Hepatology 50 Pages: 1851-1860
• [Journal Article] Effectiveness of IkappaB kinase inhibitors in murine colitis-associated tumorigenesis. (2009)
  • Author(s): Hayakawa Y, Maeda S, Nakagawa H, Hikiba Y, Shibata W, Sakamoto K, Yanai A, Hirata Y, Ogura K, Muto S, Itai A, Omata M.
  • Journal Title: J Gastroenterol 44 Pages: 935-943
• [Journal Article] Constitutive NF-κB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. (2009)
  • Author(s): Sakamoto K, Maeda S, Hikiba Y, Nakagawa H, Hayakawa Y, Shibata W, Yanai A, Ogura K, Omata M.
  • Journal Title: Clin Cancer Res 15 Pages: 2248-2258
• [Journal Article] Effectiveness of IkappaB kinase inhibitors in murine colitis-associated tumorigenesis. (2009)
  • Author(s): Hayakawa Y, Maeda S, Nakagawa H, Hikiba Y, Shibata W, Sakamoto K, Yanai A, Hirata Y, Ogura K, Muto S, Itai A, Omata M.
  • Journal Title: J Gastroenterol Volume: 44 Pages: 935-943
  • Peer Reviewed
• [Journal Article] IKKβ/NF-κB Activation Controls the Development of Liver Metastasis via IL-6 Expression. (2009)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Nakagawa H, Hirata Y, Hayakawa Y, Yanai A, Ogura K, Karin M, Omata M.
  • Journal Title: Hepatology Volume: 50 Pages: 1851-60
  • Peer Reviewed
• [Journal Article] Constitutive NF-κB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth (2009)
  • Author(s): Sakamoto K, Maeda S, Hikiba Y, Nakagawa H, Hayakawa Y, Shibata Y, Yanai A, Ogura K, Omata M.
  • Journal Title: Clinical Cancer Research 15 Pages: 2248-58
  • Peer Reviewed
• [Journal Article] c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. (2008)
  • Author(s): Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M, Omata M.
  • Journal Title: Cancer Res 68 Pages: 5031-5039
• [Journal Article] Activation of IkappaB kinase and NF-kappaB is essential for Helicobacter pylori-induced chronic gastritis in Mongolian gerbils. (2008)
  • Author(s): Yanai A, Maeda S, Shibata W, Hikiba Y, Sakamoto K, Nakagawa H, Ohmae T, Hirata Y, Ogura K, Muto S, Itai A, Omata M.
  • Journal Title: Infect Immun 76 Pages: 781-787
• [Journal Article] Deletion of ASK1 attenuates acetaminophen-induced liver injury by inhibiting JNK activation (2008)
  • Author(s): Nakagawa H, Maeda S, Hikiba Y, Ohmae T, Shibata W, Yanai A, Sakamoto K, Ogura K, Noguchi T, Karin M, Ichijo H, Omata M.
  • Journal Title: Gastroenterology 135 Pages: 1311-21
  • Peer Reviewed
• [Journal Article] c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice (2008)
  • Author(s): Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M, Omata M.
  • Journal Title: Cancer Research 68 Pages: 5031-39
  • Peer Reviewed
• [Journal Article] Activation of Ikappa B kinase and NF-kappaB is essential for Helicobacter pylori-induced chronic gastritis in Mongolian gerbils (2008)
  • Author(s): Yanai A, Maeda S, Shibata W, Hikiba Y, Sakamoto K, Nakagawa H, ohmae T, Hirata Y, Ogura K, Muto S, Itai A, Omata M
  • Journal Title: Infect Immun 76 Pages: 781-7
  • Peer Reviewed
• [Journal Article] Cutting Edge : The I{kappa}B Kinase (IKK) Inhibitor, NEMO-Binding Domain Peptide, Blocks Inflammatory Injury in Murine Colitis. (2007)
  • Author(s): Shibata W, Maeda S, Hikiba Y, Yanai A, Ohmae T, Sakamoto K, Nakagawa H, Ogura K, Omata M.
  • Journal Title: J Immunol 179 Pages: 2681-2685
• [Journal Article] Essential roles of high mobility group box 1 in the development of marine colitis and colitis-associated cancer (2007)
  • Author(s): Maeda S, Hikiba Y, Shibata W, Ohmae T, Yanai A, Ogura K, Yamada S, Omata M
  • Journal Title: Siochem Biophys Res Commun 360 Pages: 394-400
  • Peer Reviewed
• [Journal Article] Cutting edge:The IkappaB kinase(IKK)inhibitor, NEMO-binding domain peptide, bloks inflammatory injury in murine colitis (2007)
  • Author(s): Shibata W, Maeda S, Hikiba Y, Yanai A, Ohmae T, Sakamoto K, Nakagawa H, Ogura K, Omata M
  • Journal Title: J Immunol 179 Pages: 2681-5
  • Peer Reviewed
• [Presentation] Omata M Requirement for IKKB in a Mouse Model of Pancreatic Ductal Adenocarcinoma (2010)
  • Author(s): Sakamoto K, Okamoto M Nakagawa H, Hirata Y, Hayakawa Y, Nakata W, Ijichi H
  • Organizer: Digestive Disease Week
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-07
• [Presentation] Masao Omata Colon cancer-derived factors activate NF-κB in myeloid cells via TLR2 to link inflammation and tumorigenesis (2009)
  • Author(s): Shin Maeda, Yohko Hikiba, Kei Sakamoto, Hayato Nakagawa, Yoku Hayakawa, Yoshihiro Hirata, Keiji Ogura
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago
  • Year and Date: 2009-05-05
• [Presentation] Colon cancer-derived factors activate NF-κB in myeloid cells via TLR2 to link inflammation and tumorigenesis (2009)
  • Author(s): Shin Maeda, Yohko Hikiba, Kei Sakamoto, Hayato Nakagawa, Yoku Hayakawa, Yoshihiro Hirata, Keiji Ogura, Masao Omata
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago
  • Year and Date: 2009-05-05
• [Presentation] c-Jun NH2-terminal kinase 1 is a criticalregulator for the development of chemical-induced gastric cancer in mice. (2008)
  • Author(s): Maeda S, Shibata W, Hikiba Y, Yanai A, Sakamotol K, Nakagawa H, Ogura K, Karin M, Omata M.
  • Organizer: Digestive Disease Week
• [Presentation] c-Jun NH2-terminal kinase 1 is a criticalregulator for the development of chemical-induced gastric cancer in mice (2008)
  • Author(s): Maeda S, Shibata W, Hikiba Y, Yanai A, Sakamoto 1 K, Nakagawa H, Ogura K, Karin M, Omata M.
  • Organizer: Digestive Disease Week
  • Place of Presentation: San Diego
• [Presentation] 消化管癌発生 (2007)
  • Author(s): 前田愼、芝田渉、小俣政男
  • Organizer: 増殖におけるC-Jun N-terminal kinaseの役割 Japan Digestive Disease Week (JDDW)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-20
• [Presentation] 消化管癌発生、増殖におけるC-Jun N-terminal kinaseの役割 (2007)
  • Author(s): 前田 愼、芝 田渉、小俣 政男
  • Organizer: Japan Digestive Disease Week(JDDW)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-20