Elucidation and regulation of abnormal growth of synovial cells from patients with rheumatoid arthritis

2008 Fiscal Year Final Research Report

• Project/Area Number: 17591054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Saitama Medical University
• Principal Investigator: KAMEDA Hideto Saitama Medical University, 医学部, 講師 (00265795)
• Project Period (FY): 2005 – 2008
• Keywords: 関節リウマチ / 滑膜細胞 / PDGF / アダプター蛋白 / 3次元培養

Research Abstract

関節リウマチ(RA)患者由来の滑膜細胞が増殖因子刺激により腫瘍様増殖を示す点に注目し、生理的条件に近いコラーゲンゲルを用いた3次元培養系を確立した。RA滑膜細胞は無刺激では球形に近い形態をとるが、増殖因子刺激によりシグナル分子の活性化とアクチン再構成を介して突起の著明な伸長を示して増殖し、それらは増殖因子受容体阻害薬イマチニブで阻害された。また、滑膜細胞の増殖はTリンパ球との共培養で促進された。以上より、RAの病態における増殖因子とリンパ球浸潤の役割、ならびにイマチニブのRA新規治療薬としての有用性が示された。

Research Products

• [Journal Article] Messenger RNA expression profile in peripheral blood cells from RA patients following treatment with an anti-TNFa monoclonal antibody (2008)
  • Author(s): Sekiguchi N, et al. (13 人中9 番目)
  • Journal Title: infliximab. Rheumatology 47 Pages: 780-788
  • Peer Reviewed
• [Journal Article] Platelet-derived growth factor as a therapeutic target for systemic autoimmune diseases. (2007)
  • Author(s): Kameda H, Suzuki M, Takeuchi T.
  • Journal Title: Drug Target Insights 2 Pages: 239-247
  • Peer Reviewed
• [Journal Article] メシル酸イマチニブの膠原病治療薬としての可能性 (2007)
  • Author(s): 亀田秀人
  • Journal Title: 日本臨床免疫学会会誌 30(3) Pages: 165-173
• [Journal Article] Development and validation of handy rheumatoid activity score with 38 joints (HRAS38) in rheumatoid arthritis patients receiving infliximab. (2006)
  • Author(s): Kameda H, et al. (9 人中1 番目)
  • Journal Title: Mod Rheumatol 16 Pages: 381-388
  • Peer Reviewed
• [Journal Article] Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like cells and phosphorylation of Gab adapter proteins activated by platelet-derived growth factor (2006)
  • Author(s): Kameda H, Ishigami H, Suzuki M, Abe T, Takeuchi T.
  • Journal Title: Clin Exp Immunol 144 Pages: 335-341
  • Peer Reviewed
• [Journal Article] Efficacy and safety of bucillamine, a d-penicillamine analogue, in patients with active rheumatoid arthritis. (2006)
  • Author(s): Sekiguchi N, Kameda H, Amano K, Takeuchi T.
  • Journal Title: Mod Rheumatol 16 Pages: 85-91
  • Peer Reviewed
• [Presentation] The comparison of efficacy and safety between etanercept (ETN) plus methotrexate (MTX) combination therapy and ETN monotherapy in MTX-refractory Japanese patients with rheumatoid arthritis: 52-week clinical results from the JESMR study. (2008)
  • Author(s): Kameda H,(11 人中1 番目)
  • Organizer: 72^<th> Annual Scientific meeting of ACR
  • Place of Presentation: San Francisco, USA.
  • Year and Date: 2008-10-01
• [Presentation] The comparison of efficacy and safety between etanercept (ETN) plus methotrexate (MTX) combination therapy and ETN monotherapy in MTX-refractory Japanese patients with rheumatoid arthritis: 24-week results from JESMR study. (2008)
  • Author(s): Kameda H, et al.(11 人中1 番目)
  • Organizer: Annual European Congress of Rheumatology (EULAR 2008)
  • Place of Presentation: パリ
  • Year and Date: 2008-06-01
• [Presentation] Morphological alteration and proliferation of synovial fibroblast-like cells in 3-demensional culture are induced by platelet-derived growth factor and inhibited by imatinib mesylate. (2007)
  • Author(s): Kameda H, Suzuki M, Ishigami H, Sakai H, Abe T, Takeuchi T.
  • Organizer: 71^<th> Annual Scientific meeting of ACR
  • Place of Presentation: Boston, USA.
  • Year and Date: 2007-11-01
• [Presentation] 関節リウマチの滑膜細胞増殖に及ぼすT 細胞の影響 (2007)
  • Author(s): 亀田秀人, 鈴木美由紀, 石上浩庸, 酒井宏哉, 安倍達, 竹内勤
  • Organizer: 第28 回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-01
• [Presentation] Proliferation of synovial fibroblast-like cells is synergistically enhanced by the infiltration of T lymphocytes and the stimulation with platelet-derived growth factor. (2006)
  • Author(s): Kameda H, Suzuki M, Ishigami H, Sakai H, Abe T, Takeuchi T.
  • Organizer: 70^<th> Annual Scientific meeting of ACR
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2006-11-01
• [Presentation] Association of the joint destruction in patients with rheumatoid arthritis (RA) by the indicators of clinical disease activity and the patient's quality of life (QOL). (2006)
  • Author(s): Nagasawa N, et al. (8 人中2 番目)
  • Organizer: The 12^<th> APLAR Congress
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2006-08-01
• [Presentation] Involvement of Gab adaptor proteins in the proliferative signaling through platelet-derived growth factor receptor in rheumatoid synovial fibroblast-like cells and their regulation by imatinib mesylate. (2005)
  • Author(s): Kameda H, Ishigami H, Suzuki M, Abe T, Takeuchi T.
  • Organizer: regulation by imatinib mesylate. Annual European Congress of Rheumatology EULAR 2005
  • Place of Presentation: ウイーン
  • Year and Date: 2005-06-01
• [Presentation] インフリキシマブ投与前後の関節リウマチ患者血清におけるGROαの発現検討 (2005)
  • Author(s): 小川祥江、他(9 人中2 番目)
  • Organizer: 第49 回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2005-04-01
• [Book] 関節リウマチ(ファーマナビゲーター COX-2 阻害薬編) (2006)
  • Author(s): 亀田秀人, 竹内勤(石黒直樹, 川合眞一, 森田育男, 山中寿 編)
  • Total Pages: 112-121
  • Publisher: メデイカルレビュー社 東京
• [Book] 多発性筋炎/皮膚筋炎(臨床免疫学 -基礎研究の進歩と最新の臨床-) (2005)
  • Author(s): 亀田秀人, 竹内勤(山本一彦 編)
  • Total Pages: 261-266
  • Publisher: 日本臨床社, 大阪
• [Book] 関節リウマチ(臨床免疫学 -基礎研究の進歩と最新の臨床-) (2005)
  • Author(s): 小池隆 亀田秀人、竹内勤(山本一彦 編)
  • Total Pages: 261-266
  • Publisher: 日本臨床社, 大阪
• [Book] 治療(治療. 膠原病の病理診断マニュアル(病理と臨床臨時増刊号))ュアル(病理と臨床臨時増刊号)) (2005)
  • Author(s): 亀田秀人、竹内勤(能勢眞人, 尾崎承一 編)
  • Total Pages: 48-52
  • Publisher: 文光堂,東京
• [Book] Lung disease in EBV infection.(Encyclopedia of Molecular mechanisms of Diseases.)
  • Author(s): Kameda H.(ed. by Michaela Bilic.)
  • Publisher: Springer, Heidelberg
  • Description: in press