A novel anti-HMGB1 Ab therapy for treatment of B-cell lymphoma

• Project/Area Number: 20590539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Okayama University
• Principal Investigator: TAKAHASHI Hideo Okayama University, 大学院・医歯薬学総合研究科, 准教授 (60335627)
• Co-Investigator(Kenkyū-buntansha): NISHIBORI Masahiro 岡山大学, 大学院・医歯薬学総合研究科, 教授 (50135943) ; YOSHINO Tasashi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (70183704)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HMGB1 / RAGE / B細胞リンパ腫 / 単球・マクロファージ / 活性酸素 / 接着分子 / AGE / オータコイド / ヒト抗RAGE抗体

Research Abstract

A RAGE ligand, HMGB1, which is released from nucrei of necrotic cells and macropharges, acts as a cytokine and plays roles in immune response. HMGB1 is involved in the progression of B-cell limphoma. The progression depends on the monocyte/macropharge activation. RAGE ligands, HMGB1 and AGEs, activates monocyte/macropharge. Therefore, anti-HMGB1 Ab may inhibit the progression of B-cell limphoma.

Research Products

• [Journal Article] beta(2)-adrenoceptor stimulation inhibits advanced glycation end products-induced adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. (2010)
  • Author(s): Takahashi HK, Mori S, Liu K, Wake H, Zhang J, Liu R, Yoshino T, Nishibori, M.
  • Journal Title: Eur J Pharmacol. 627 Pages: 313-317
• [Journal Article] Advanced glycation end products enhance monocyte activation during human mixed lymphocyte reaction. (2010)
  • Author(s): Ohashi K, Takahashi HK, Mori S, Liu K, Wake H, Sadamori H, Matsuda H, Yagi T, Yoshino T, Nishibori M, Tanaka N
  • Journal Title: Clin Immunol 134 Pages: 345-353
• [Journal Article] Histamine inhibits advanced glycation end product-induced adhesion molecule expression on monocytes during human mixed lymphocyte reaction (2010)
  • Author(s): Zhang J, Takahashi HK, Liu K, Wake H, Liu R, Sadamori H, Matsuda H, Yagi T , Yoshino T, Mori S, Nishibori M
  • Journal Title: Br J Pharmacol. 160 Pages: 1378-1386
• [Journal Article] Effect of nicotine on advanced glycation end products-induced immune response in human monocytes. (2010)
  • Author(s): Takahashi HK, Liu K, Wake H, Mori S, Zhang J, Liu R, Yoshino T, Nishibori M.
  • Journal Title: J Pharmacol Exp Ther. 332 Pages: 1013-1021
• [Journal Article] Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression on monocytes, cytokine production and lymphocyte proliferation during human mixed lymphocyte reaction. (2010)
  • Author(s): Takahashi HK, Zhang J, Mori S, Liu K, Wake H, Liu R, Sadamori H, Matsuda H, Yagi T, Yoshino T, Nishibori M
  • Journal Title: J Pharmacol Exp Ther. 334 Pages: 964-972
• [Journal Article] Ciprofloxacin inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes. (2010)
  • Author(s): Mori S
  • Journal Title: Br J Pharmacol. Volume: 161 Pages: 229-240
  • Peer Reviewed
• [Journal Article] Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction. (2010)
  • Author(s): Zhang J
  • Journal Title: Br J Pharmacol. Volume: 160 Pages: 1378-1386
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression on monocytes, cytokine production, and lymphocyte proliferation during human mixed lymphocyte reaction. (2010)
  • Author(s): Takahashi HK
  • Journal Title: J Pharmacol Exp Ther. Volume: 334 Pages: 964-972
  • Peer Reviewed
• [Journal Article] High mobility group box 1 complexed with heparin induced angiogenesis in a matrigel plug assay. (2009)
  • Author(s): Wake H, Mori S, Liu K, Takahashi HK, Nishibori M
  • Journal Title: Acta Med Okayama 63 Pages: 249-262
  • NAID: 120002312983
• [Journal Article] Histidine-rich glycoprotein inhibited high mobility group box 1 in complex with heparin-induced angiogenesis in matrigel plug assay. (2009)
  • Author(s): Wake H, Mori S, Liu K, Takahashi HK, Nishibori M
  • Journal Title: Eur J Pharmacol. 623 Pages: 89-95
• [Journal Article] Establishment of in vitro binding assay of high mobility group box-1 and S100A12 to receptor for advanced glycation endproducts : heparin's effect on binding. (2009)
  • Author(s): Liu R, Mori S., Wake H, Zhang J, Liu K, Izushi Y, Takahashi HK, Peng B, Nishibori M
  • Journal Title: Acta Med Okayama 63 Pages: 203-211
  • NAID: 120002312782
• [Journal Article] Advanced glycation end products subspecies-selectively induce adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. (2009)
  • Author(s): Takahashi HK, Mori S, Wake H, Liu K, Yoshino T, Ohashi K, Tanaka N, Shikata K, Makino H, Nishibori M.
  • Journal Title: J Pharmacol Exp Ther. 330 Pages: 89-98
• [Journal Article] Histamine inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes. (2009)
  • Author(s): Wake H, Takahashi HK, Mori S, Liu K, Yoshino T, Nishibori M.
  • Journal Title: J Pharmacol Exp Ther 330 Pages: 826-833
• [Journal Article] Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression, cytokine production, and lymphocyte proliferation in human peripheral blood mononuclear cells. (2009)
  • Author(s): Takahashi HK, Liu K, Wake H, Mori S, Zhang J, Liu R, Yoshino T, Nishibori M.
  • Journal Title: J Pharmacol Exp Ther. 331 Pages: 656-670
• [Journal Article] Specific removal of monocytes from peripheral blood of septic patients by polymyxin B-immobilized filter column. (2009)
  • Author(s): Nishibori M, Takahashi HK, Katayama H, Mori S, Saito S, Iwagaki H, Tanaka N, Morita K, Ohtsuka A
  • Journal Title: Acta Med Okayama. 63 Pages: 65-69
  • NAID: 120002312427
• [Journal Article] Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression, cytokine production, and lymphocyte proliferation in human peripheral blood mononuclear cells. (2009)
  • Author(s): Takahashi HK
  • Journal Title: J Pharmacol Exp Ther. 331 Pages: 656-670
  • Peer Reviewed
• [Journal Article] Histamine inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes. (2009)
  • Author(s): Wake H
  • Journal Title: J Pharmacol Exp Ther. 330 Pages: 826-830
  • Peer Reviewed
• [Journal Article] Advanced glycation end products subspecies-selectively induce adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. (2009)
  • Author(s): Takahashi HK
  • Journal Title: J Pharmacol Exp Ther. 330 Pages: 89-98
  • Peer Reviewed
• [Journal Article] Stimulation of adenosine A2A receptor inhibits LPS-induced expression of intercellular adhesion molecule 1 and production of TNF-alpha in human peripheral blood mononuclear cells (2008)
  • Author(s): Haraano R
  • Journal Title: Shock 29 Pages: 154-159
  • Peer Reviewed
• [Journal Article] Effects of HMGB1 on ischemia-reperfusion injury in the rat heart. (2008)
  • Author(s): Oozawa S
  • Journal Title: Circ J. 72 Pages: 1178-1184
  • Peer Reviewed
• [Presentation] Prostaglandins E2 inhibits advanced glycation end products-induced activation of human monocytes (2010)
  • Author(s): Takahashi HK
  • Organizer: 第16回国際薬理学会
  • Place of Presentation: コペンハーゲン
  • Year and Date: 2010-07-22
• [Presentation] AGE-2とAGE-3誘導性のヒト単球の活性化に対するプロスタグランディンE2の効果 (2010)
  • Author(s): 高橋英夫
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-03-17
• [Presentation] Advanced glycation end products induce adhesion molecule expression and cytokine production in human PBMC (2010)
  • Author(s): 高橋英夫, 劉克約, 和氣秀徳, 森秀治, 西堀正洋
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
• [Presentation] Prostaglandins E_2 inhibits advanced glycation end products-induced activation of human monocytes (2010)
  • Author(s): 高橋英夫, 劉克約, 和氣秀徳, 森秀治, 西堀正洋
  • Organizer: 第16回国際薬理学会
  • Place of Presentation: コペンハーゲン
• [Presentation] AGE-2とAGE-3誘導性のヒト単球の活性化に対するプロスタグランディンE2の効果 (2010)
  • Author(s): 高橋英夫, 劉克約, 和氣秀徳, 森秀治, 西堀正洋
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] AGEサブタイプのヒト末梢血単核球への効果の解析 (2009)
  • Author(s): 高橋 英夫
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-18
• [Presentation] (2009)
  • Author(s): 高橋英夫, 森秀治, 劉克約, 和氣秀徳, 西堀正洋
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Patent(Industrial Property Rights)] 外傷性神経障害治療剤 (2010)
  • Inventor(s): 西堀正洋、森秀治、高橋英夫、和氣秀徳、劉克約、伊達勲、大熊佑、友野靖子
  • Industrial Property Rights Holder: 西堀正洋、森秀治、高橋英夫、和氣秀徳、劉克約、伊達勲、大熊佑、友野靖子
  • Industrial Property Number: 2010-214019
  • Filing Date: 2010-12-23
• [Patent(Industrial Property Rights)] RAGEとAGEの結合抑制剤のスクリーニング方法 (2010)
  • Inventor(s): 西堀正洋、森秀治、高橋英夫、和氣秀徳、劉克約
  • Industrial Property Rights Holder: 西堀正洋、森秀治、高橋英夫、和氣秀徳、劉克約
  • Industrial Property Number: 2010-214019
  • Filing Date: 2010-09-24
• [Patent(Industrial Property Rights)] RAGEとAGEの結合抑制剤のスクリーニング方法 (2010)
  • Inventor(s): 高橋英夫
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 2010-214019
  • Filing Date: 2010-09-24
• [Patent(Industrial Property Rights)] アテローム動脈硬化抑制剤 (2009)
  • Inventor(s): 西堀正洋,高橋英夫,森秀治,劉克約,友野靖子,ベイカーメディカルリサーチインスティチュート
  • Industrial Property Rights Holder: 西堀正洋,高橋英夫,森秀治,劉克約,友野靖子,ベイカーメディカルリサーチインスティチュート
  • Industrial Property Number: 2009-223472
  • Filing Date: 2009-09-28