Analysis of antitumor effect by antiangiogenic activity of interleukin-27

• Project/Area Number: 19590418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: SHIMIZU Motomu Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 主任研究員 (10124463)
• Co-Investigator(Kenkyū-buntansha): SHIMAMURA Mariko 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 主任研究員 (00124462) ; YOSHIMOTO Takayuki 東京医科大学, 医学部, 助教授 (80202406)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 癌 / 免疫学 / 抗腫瘍作用 / インターロイキン27 / IL-27 / 血管新生阻害 / インターロイン27 / 血管新生阻害作用

Research Abstract

本研究ではIL-6/IL-12ファミリーメンバーのIL-27による抗腫瘍作用機構について検討した。高転移性で低抗原性の悪性メラノーマB16F10にIL-27cDNAを導入した腫瘍において、IL-27は強い抗腫瘍効果を示した。IL-27の血管新生阻害を検討すると、強い阻害作用を示した。従って、IL-27の抗腫瘍作用は免疫増強ばかりではなく、血管新生阻害が重要であること示唆された。IL-27はIL-12に比べ毒性は少なく、抗腫瘍効果が同等であることから、がんの免疫療法に有望であることが期待される。

Research Products

• [Journal Article] Anti-proliferative activity of IL-27 on melanoma. (2008)
  • Author(s): T. Yoshimoto, N. Morishima, I. Mizoguchi, M. Shimizu, H. Nagai, S. Oniki, M. Oka, C. Nishigori, J. Mizuguchi
  • Journal Title: J. Immunol. 180 Pages: 6527-6535
  • Peer Reviewed
• [Journal Article] SAR oriented novel discovery of substituted phenylpropanoic acid-PPAR pan agonist with 4-adamantylphenyl group as a hydrophobic tail part. (2008)
  • Author(s): J. Kasuga, D. Yamasaki, K. Ogura, M. Shimizu, M. Sato, M. Makishima, T. Doi, Y. Hashimoto, H. Miyachi
  • Journal Title: Bioorg. Med. Chem. Lett. 18 Pages: 1110-1115
  • Peer Reviewed
• [Journal Article] Anti-proliferative activity of IL-27 on melanoma (2008)
  • Author(s): T. Yoshimoto, N. Morishima, I. Mizoguchi, M. Shimizu, H. Nagai, S. Oniki, M. Oka, C. Nishigori, J. Mizuguchi,
  • Journal Title: J.Immunol. 180 Pages: 6527-6535
  • Peer Reviewed
• [Journal Article] SAR oriented novel discovery of substituted phenylpropanoic acid-PPAR panagonist with 4-adamantylphenyl group as a hydrophobic tail part. (2008)
  • Author(s): J. Kasuga, D. Yamasaki, K. Ogura, M. Shimizu M. Sato, M. Makishima, T. Doi, Y. Hashimoto, H. Miyachi
  • Journal Title: Bioorg.Med.Chem.Lett. 18 Pages: 1110-1115
  • Peer Reviewed
• [Journal Article] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. (2007)
  • Author(s): S. Lee, C. Shinji, K. Ogura, M. Shimizu, S. Maeda, M. Sato, M. Yoshida, Y. Hashimoto, H. Miyachi
  • Journal Title: Bioorg. Med. Chem. Lett. 17 Pages: 4895-4900
  • Peer Reviewed
• [Journal Article] 正電荷ポリマーによる乳癌細胞に対する遺伝子導入の基礎研究. 査読有 (2007)
  • Author(s): 武田泰隆、榮光子、善本隆之、森本純司、清水本武、柳衛広宣
  • Journal Title: 乳癌基礎研究 16 Pages: 43-49
  • Peer Reviewed
• [Journal Article] IL-27の血管新生抑制作用 (2007)
  • Author(s): 清水本武, 島村眞里子, 善本隆之
  • Journal Title: 臨床免疫 47 Pages: 298-302
• [Journal Article] Design,synthesis,and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase(HDAC)inhibitors (2007)
  • Author(s): S. Lee, C. Shinji, K. Ogura, M. Shimizu, S. Maeda, M. Sato, M. Yoshida, Y. Hashimoto, Miyachi, H
  • Journal Title: Bioorg.Med.Chem.Lett. 17 Pages: 4895-4900
  • Peer Reviewed
• [Journal Article] IL-27の血管新生抑制作用 (2007)
  • Author(s): 清水 本武, 島村 眞理子, 善本 隆之
  • Journal Title: 臨床免疫 47 Pages: 298-302
• [Journal Article] 正電荷ポリマーによる乳癌細胞に対する遺伝子導入の基礎研究 (2007)
  • Author(s): 武田 泰隆, 栄 光子, 善本 隆之, 森本 純司, 清水 本武, 柳衛 広宣
  • Journal Title: 乳癌基礎研究 16 Pages: 43-49
  • Peer Reviewed
• [Presentation] Analysis of in vivo antitumor activity of IL-27 against melanoma. (2008)
  • Author(s): Shimizu, M., Mizuguchi, J, Yoshimoto, T.
  • Organizer: The 38^<th> Annual Meeting of the Japanese society for immunology.
  • Place of Presentation: Kyoto
• [Presentation] Analysis of antitumor activity of IL-2. (2008)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Nishito, Y., Takeda, Y., Mizuguchi, J, Yoshimoto, T.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Comprehensive gene expression analysis of melanoma B16 cells that Hgs expression level changed metastasis activity. (2008)
  • Author(s): Ogura, K., Kawashima, I., Ishikawa, Y-I., Sato, M., Shimizu, M.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines. (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Nishitho, Y., Miyachi H.
  • Organizer: 67th Annual Meeting of the Japanese cancer association.
  • Place of Presentation: Nagoya
• [Presentation] Effects of Hgs on metastasis ability of mouse melanoma B16 cells. (2008)
  • Author(s): Ogura, K., Kawashima, I., Sato, M., Shimizu, M.
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] TIPP-703, A peroxisome proliferator-activated receptor pan agonist, induces a G1-phase arrest in human pancreatic carcinoma cell lines. (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Miyachi H.
  • Organizer: The 33rd FEBS Congress - 11th IUBMB Conference "Biochemistry of Cell Regulation"
  • Place of Presentation: Athens (Greece)
• [Presentation] 正電荷ポリマーを用いたFasリガンド(FasL)遺伝子導入による乳癌遺伝子治療に向けた基礎的研究 (2008)
  • Author(s): 武田泰隆, 榮 光子, 善本隆之, 森本純司, 清水本武, 柳衛宏宣, 螺良愛朗
  • Organizer: 第18回乳癌基礎研究会
  • Place of Presentation: 福島
• [Presentation] Analysis of antitumor activity of IL-27 (2008)
  • Author(s): Shimizu, M., Sato, M., Ogura, K. Nishito, Y., Takeda, Y., Mizuguchi, J, Yoshimoto, T
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya, Nagoya Congress Center
• [Presentation] Analysis of in vivo antitumor activity of IL-27 against melanoma (2008)
  • Author(s): Shimizu. M., Mizuguchi, J, Yoshimoto, T
  • Organizer: The 38^<th> Annual Meeting of the Japanese society for immunology
  • Place of Presentation: Kyoto, Kyoto International Conference Center
• [Presentation] Effects of Hgs on metastasis ability of mouse melanoma B16 cells (2008)
  • Author(s): Ogura, K., Kawashima, I., Sato, M., Shimizu. M.
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] TIPP-703, A peroxisome proliferator-activated receptor pan agonist, induces a G1-phase arrest in human pancreatic carcinoma cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu. M.
  • Organizer: The 33rd FEBS Congress-11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu. M., Nishitho, Y., Miyachi H
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya, Nagoya Congress Center
• [Presentation] Comprehensive gene expression analysis of melanoma B16 cells that Hgs expression level changed metastasis activity (2008)
  • Author(s): Ogura, K., Kawashima, I., Ishikawa, Y-I., Sato, M., Shimizu. M
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya, Nagoya Congress Center
• [Presentation] Hgs高発現および抑制マウスメラノーマB16細胞の遺伝子発現プロファイリング (2007)
  • Author(s): 小倉潔, 佐藤眞友美, 清水本武
  • Organizer: 第30回日本分子生物学会年会・第80回生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] Role of chemokines in antitumor activity of Fas ligand (CD95L)-expressing tumor. (2007)
  • Author(s): Shimizu, M., Mizuguchi, J., Yoshimoto, T.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Role of macrophages and neutrophils in antitumor activity of Fas ligand (CD95L)-expressing tumor. (2007)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Takeda, Y., Mizuguchi, J, Yoshimoto, T.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] Effects of RNA Interference of GEF-1/Hgs on Metastasis of Mouse Melanoma B16 cells. (2007)
  • Author(s): Ogura, K., Horiguchi, S., Sato, M., Shimizu, M.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] Novel PPAR α, γ dual agonists induce a G1-phase arrest in pancreatic cancer cells. (2007)
  • Author(s): Sato, M., Ogura, K., Shimizu, M., Kunimasa, K., Ohta, T., Kaji, K., Miyachi, H.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] L-carnosine, an endogenous bioactive dipeptide inhibits angiogenesis and tumor metastasis. (2007)
  • Author(s): Shimamura, M., Ashino, H., Shimizu, M., Yamamoto, Y., Minamikawa-Tachino, R., Takahashi, S.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] Role of macrophages and neutrophils in antitumor activity of Fas lig and (CD95L)-expressing tumor (2007)
  • Author(s): Shimizu. M., Sato, M., Ogura, K. Takeda, Y., Mizuguchi J., Yoshimoto
  • Organizer: The 66^<th>Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Effects of RNA Interference of GEF-1/Hgs on Metastasis of Mouse Melanoma B16 cells (2007)
  • Author(s): Ogura, K., Horiguchi, S., Sato, M., Shimizu, M.
  • Organizer: The 66^<th>Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Novel PPAR α,γ dual agonists induce a Gl-phase arrest in pancreatic cancer cells (2007)
  • Author(s): Sato, M., Ogura, K., Shimizu. M., Kunimasa, K., Ohta, T., Kaji, K., Miyachi, H
  • Organizer: The 66^<th>Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] L-carnosine,an endogenous bioactive dipeptide inhibits angiogenesis and tumor metastasis (2007)
  • Author(s): Shunamura, M., Ashino, H., Shimizu, M., Yamamoto, Y., Minamikawa-Tachino, R., Takahashi, S
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Role of chemokines in antitumor activity of Fas ligand (CD95L)-expressing tumor (2007)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Takeda, Y., Mizuguchi, J., Yoshimoto
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Remarks]
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• [Remarks]
  • URL: http://www.rinshoken.or.jp/database/shimizu.pdf