Elucidation of the roles of tumor necrosis factor and chemokines in inflammation-associated carcinogenesis

• Project/Area Number: 19390112
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kanazawa University
• Principal Investigator: MUKAIDA Naofumi Kanazawa University, がん研究所, 教授 (30182067)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2007: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
• Keywords: 腫瘍 / 炎症 / 転移 / 遺伝子欠損マウス / 腫瘍壊死因子 / ケモカイン / 大腸がん / 炎症性腸疾患 / サイクロオキゲナーゼ / 肺転移 / マトリックスメタロプロテナーゼ / 肝細胞増殖因子 / βカテニン / アゾキシメタン / デキストラ硫酸塩

Research Abstract

腫瘍壊死因子・ケモカインの、がんの発症から進展過程における役割を、マウス・モデルにて解析した。その結果、慢性腸炎に伴う大腸がんの発症と進展過程において大腸局所で産生される腫瘍壊死因子が、肺転移モデルにおいては肺局所で産生されるケモカインであるCCL3が、それぞれ重要な役割を果たしていることが明らかとした。これらの結果は、腫瘍壊死因子・ケモカインががんの発症・進展過程において重要な役割を果たしていることを示唆している。

Research Products

• [Journal Article] Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy against hepatocellular carcinoma by M1 macrophage activation (2008)
  • Author(s): Tsuchiyama T, Nakamoto Y, Sakai Y, Mukaida N, and Kaneko S.
  • Journal Title: Cancer Sci 99(10) Pages: 2075-2082
  • NAID: 10024012389
  • Peer Reviewed
• [Journal Article] CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fiborblasts, and promotes angiogenesis in murine lung metastasis process (2008)
  • Author(s): Wu Y, Li Y-Y, Matsushima K, Baba T, and Mukaida N.
  • Journal Title: J Immunol 181(9) Pages: 6384-6393
  • NAID: 10026960956
  • Peer Reviewed
• [Journal Article] Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1-and 5-dependent manner in mice (2008)
  • Author(s): Iida N, Nakamoto Y, Baba T, Kakinoki K, LiY-Y, Wu Y, Matsushima K, Kaneko S, and Mukaida N.
  • Journal Title: J Leukocyte Biol 84(4) Pages: 1001-1010
  • NAID: 120000997200
  • Peer Reviewed
• [Journal Article] Essential involvement of CX3CR1-mediated signals in the bactericidal host defense during septic peritonitis (2008)
  • Author(s): Ishida Y, Hayashi T, Goto T, Kimura A, Akimoto S, Mukaida N, and Kondo T.
  • Journal Title: J Immunol 181(6) Pages: 4208-4218
  • Peer Reviewed
• [Journal Article] Protective roles of the fractalkine/CX3CL1-CX3CR1 interactions in alkali-induced corneal neovascularization through enhanced anti-angiogenic factor expression (2008)
  • Author(s): Lu P, Li L, Kuno K, Wu Y, Baba T, Li Y-Y, Zhang X,and Mukaida N.
  • Journal Title: J Immunol 180(6) Pages: 4283-4291
  • Peer Reviewed
• [Journal Article] Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis (2008)
  • Author(s): Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, Oshima and M, Fujii C, Mukaida N.
  • Journal Title: J Clin Invest 118(2) Pages: 560-570
  • NAID: 120006996024
  • Peer Reviewed
• [Journal Article] Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice (2008)
  • Author(s): Sawanobori Y, Ueha S, Kurachi M, Shimaoka T, Talmadge JE, Abe J, Shono Y, Kitabatake M, Kakimi K, Mukaida N, and Matsushima K.
  • Journal Title: Blood 111(12) Pages: 5457-5466
  • Peer Reviewed
• [Journal Article] Protective roles of the fractalkine/CX3CLl-CX3CRl interactions in alkali-induced corneal neovascularization through enhanced anti-angiogenic factor expression. (2008)
  • Author(s): Lu P, Li L, Kuno K, Wu Y, Baba T, Li Y-Y, Zhang X, Mukaida N.
  • Journal Title: Journal of Immunology 180 Pages: 4283-4291
  • Peer Reviewed
• [Journal Article] Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice. (2008)
  • Author(s): Iida N, Nakamoto Y, Baba T, Kakinoki K., Li Y-Y, Wu Y, Matsushima K, Kaneko S, Mukaida N.
  • Journal Title: Journal of Leukocyte Biology 84 Pages: 1001-1010
  • NAID: 120000997200
  • Peer Reviewed
• [Journal Article] CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fiborblasts, and promotes angiogenesis in murine lung metastasis process. (2008)
  • Author(s): Wu Y, Li Y-Y, Matsushima K, Baba T, Mukaida N.
  • Journal Title: Journal of Immunology 181 Pages: 6384-6393
  • NAID: 10026960956
  • Peer Reviewed
• [Journal Article] Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chroniccolitis (2008)
  • Author(s): Popivanova BK, Kitamura K, WuY, Kondo T, Kagaya T, Kaneko S, Oshima M, Fujii C, and Mukaida N
  • Journal Title: Joumal of Clinical Investigation 118(2) Pages: 560-570
  • Peer Reviewed
• [Journal Article] Essential involvement of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration (2007)
  • Author(s): Ishida Y, Kimura A, Kondo T, Hayashi T, Ueno M, Takakura N, Matsushima and K, Mukaida N.
  • Journal Title: Am J Pathol 170 Pages: 843-854
  • Peer Reviewed
• [Journal Article] IFN-γ protects cerulein-induced acute pancreatitis by repressing NF-κB activation (2007)
  • Author(s): Hayashi T, Ishida Y, Kimura A, Iwakura Y, Mukaida N, Kondo T.
  • Journal Title: J Immunol 178 Pages: 7385-7394
  • Peer Reviewed
• [Journal Article] Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant protein-1 against hepatocellular carcinoma (2007)
  • Author(s): Tsuchiyama T, Nakamoto Y, Sakai Y, Marukawa Y, Kitahara M, Mukaida N, and Kaneko S.
  • Journal Title: J Immunol 178(1) Pages: 574-583
  • NAID: 120000813306
  • Peer Reviewed
• [Journal Article] Intrahepatic interleukin-8 production during disease progression of chronic hepatitis C (2007)
  • Author(s): Tachibana Y, Nakamoto Y, Mukaida N, Kaneko S
  • Journal Title: Cancer Lett 251 Pages: 36-42
  • Peer Reviewed
• [Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma ; clinical safety (2007)
  • Author(s): Nakamoto Y, Mizukoshi E, Tsuji H, Sakai Y, Kitahara M, Arai K, Yamashita T, Yokoyama K, Mukaida N, Matsushima K, Matsui O, and Kaneko S
  • Journal Title: Clin Exp Immunol 147(2) Pages: 296-305
  • Peer Reviewed
• [Journal Article] Essential involvement of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration. (2007)
  • Author(s): Ishida Y, Kimura A, Kondo T, Hayashi T, Ueno M, Takakura N, Matsushima K, and Mukaida N.
  • Journal Title: American Journal of Pathology 170 Pages: 843-854
  • Peer Reviewed
• [Journal Article] IFN-γ protects cerulein-induced acute pancreatitis by repressing NF-kB activation. (2007)
  • Author(s): Hayashi T, Ishida Y, Kimura A, Iwakura Y, Mukaida N, & Kondo T
  • Journal Title: Joumal of lmmunology 178 Pages: 7385-7394
  • Peer Reviewed
• [Presentation] Pathogenic roles of the CX3CL1-CX3CR1 ineractions in dextran sodium sulfate-induced acute colitis in mice (2008)
  • Author(s): Kostadinova F, Popivanova and BK, Mukaida N.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Role of a chemokine receptor, CCR2, in azoxymethane/dextran sulfate sodium-induced colon carcinogenesis in mice (2008)
  • Author(s): Popivanova BK, Kostadinova F, and Mukaida N.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] The roles of chemokine receptors, CCR2 and CX3CR1, in arthritis in IL-1-deficient mice (2008)
  • Author(s): Fujii H, Baba T, Hamano R, Kawano M, and Mukaida N
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Thymic Spirα+ dendritic cells induce central tolerance against bloodstream antigens (2008)
  • Author(s): Baba T, Wu Y, and Mukaida N.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] 抗サイトカイン療法の可能性。未来医療ワークショップ:難治性癌への新しい取り組み(招待講演) (2008)
  • Author(s): 向田直史
  • Organizer: 第45回日本婦人科腫瘍学会
  • Place of Presentation: 金沢
  • Year and Date: 2008-11-22
• [Presentation] Possible opposite roles of CCR2 and CX3CR1 macrophages in neovascularization. (International Session 6 : Chemokine, Cytokine and Cancer) (2008)
  • Author(s): Lu P and Mukaida N.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Role of a chemokine receptor, CCR2, in azoxymehtane/dextran sodium sulfate-induced colon carcinogenesis in mice.(英語ワークショップ演題) (2008)
  • Author(s): 向田直史
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Prevention of azoxymethane/dextran sodium sulfate-induced colon carcinogenesis by CCR2 blockade (2008)
  • Author(s): Mukaida N, Kostadinova FI, and Popivanova BK.
  • Organizer: 7^<th> Joint Conference of the International Cytokine Society and the International Society of Interferon and Cytokine Research
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2008-10-15
• [Presentation] Distinctive f eature and role of the thymic Sirpα+ dendritic cells in the central tolerance (2008)
  • Author(s): Baba T, and Mukaida N
  • Organizer: 10^<th> International Symposium on Dendritic Cells
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2008-10-03
• [Presentation] 腫瘍壊死因子(TNF)阻害剤の、炎症関連大腸がんに対する治療効果 (2008)
  • Author(s): 向田直史
  • Organizer: 第12回がん分子標的治療研究会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-26
• [Presentation] Prevention of azoymethane/dextran sodium sulfate-Induced colon carcinogenesis by CCR2 blockade. (2008)
  • Author(s): Mukaida N, Kostadinova FI, Popivanova BK
  • Organizer: 7^<th> Joint Conference of the International Cytokine Society and the International Society for Interferonand Cytokine Research.
  • Place of Presentation: Montreal, Canada
• [Presentation] Fractalkine receptor/CX3CR1-deficiency enhanced alkali-induced corneal nevascularization with reduced infiltration of anti-angiogenic factor expressing-macrophages (2007)
  • Author(s): Lu P, Li L, Kuno K, Wu Y, Li Y-Y, Murphy PM, Zhang X, and Mukaida N.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Essential contribution of the CCL3-CCR5 axis in lung metastasis process (2007)
  • Author(s): Wu Y, Lu P, Li Y-Y, and Mukaida N.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Reversal of chronic colitis-associated colon carcinoma progression by tumor necrosis factor blockade. (Oral presentation) (2007)
  • Author(s): Mukaida N, and Popivanova BK.
  • Organizer: 15^<th> Annual Meeting of the International Cytokine Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2007-10-28
• [Presentation] 自殺遺伝子治療による腫瘍免疫成立におけるCCケモカイン受容体1および5の役割の検討 (2007)
  • Author(s): 飯田宗穂、中本安成、柿木嘉平太、金子周一、向田直史
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Alleviation of chronic colitis-associated colon carcinoma progression by tumor necrosis factor blockade. (英語ワークショップ演題) (2007)
  • Author(s): 向田直史、Popivanova BK.
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Induction of specific tumor immunity by suicide gene therapy in CC chemokine receptor (CCR)1- or CCR5-dependent manner (2007)
  • Author(s): 飯田宗穂、中本安成、柿木嘉平太、金子周一、向田直史
  • Organizer: 第11回基盤的癌免疫研究会総会
  • Place of Presentation: 東京。
  • Year and Date: 2007-07-11
• [Presentation] マウスの肺転移過程におけるケモカインCCL3 とそのレセプターの役割の解析。(ワークショップ演題) (2007)
  • Author(s): 向田直史、呉俣
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山
  • Year and Date: 2007-07-09
• [Presentation] 内胚葉由来臓器がんにおけるセリン/スレオニンキナーゼPim-3の発現と役割。(ワークショップ演題) (2007)
  • Author(s): 向田直史
  • Organizer: 第11回がん分子標的治療研究会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-05
• [Presentation] Alleviation of chronic colitis-associated colon carcinoma progression by tumor necrosis factor blockade. (Poster Award) (2007)
  • Author(s): Popivanova BK and Mukaida N.
  • Organizer: 16^<th> International Symposium on Molecular Cell Biology of Macrophage 2007
  • Place of Presentation: Shizuoka, Japan
  • Year and Date: 2007-06-14
• [Presentation] Reversal of chronic colitis-associated colon carcinoma progression by tumor necrosis factor blockade. (2007)
  • Author(s): Mukaida N and Popivanova BK
  • Organizer: 15th Annual Meeting of the International Cytokine Society. (Oral Presentation)
  • Place of Presentation: San Francisco, USA.
• [Presentation] Alleviation of chronic colitis-associated colon carcinoma progression by tumor necrosis factor blockade. (2007)
  • Author(s): 向田 直史、Popivanova BK.
  • Organizer: 第66回日本癌学会総会(英語ワークショップ演題)
  • Place of Presentation: 横浜
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/bunsiseitai/JapContent.html
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/bunsiseitai/JapContent.html
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/bunsiseitai/JapContent.html