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

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 関節リウマチ / 滑膜細胞 / PDGF / アダプター蛋白 / 3次元培養 / イマチニブ

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] Messenger RNA expression profile in peripheral blood cells from RA patients following treatment with an anti-TNFα monoclonal antibody, infliximab. (2008)
  • Author(s): Sekiguchi N, Kawauchi S, Furuya T, Inaba N, Matsuda K, Ando S, Ogasawara M, Aburatani H, Kameda H, Amano K, Abe T, Ito S, Takeuchi T.
  • Journal Title: Rheumatology 47 Pages: 780-788
  • Peer Reviewed
• [Journal Article] Retrospective study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan : one -year clinical outcome (RECONFIRM -2). (2008)
  • Author(s): Tanaka Y, Takeuchi T, Inoue E, Saito K, Sekiguchi N, Sato E, Nawata M, Kameda H, Iwata S, Amano K, Yamanaka H.
  • Journal Title: Mod Rheumatol 18 Pages: 146-152
  • Peer Reviewed
• [Journal Article] Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis manag ement group in Japan : One -year outcome of joint destuction (REC0NFIRM-2J). (2008)
  • Author(s): Takeuchi T, Yamanaka H, Inoue E, Nagasawa H, Nawata M, Ikari K, Saito K, Sekiguchi N, Sato E, Kameda H, Iwata S, Mochizuki T, Amano K, Tanaka Y.
  • Journal Title: Mod Rheumatol 18 Pages: 447-454
  • 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
  • NAID: 10019552860
• [Journal Article] Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis. (2007)
  • Author(s): Kameda H, Okuyama A, Tamaru J-I, Itoyama S, Iizuka A, Takeuchi T.
  • Journal Title: Clin Rheumatol 26 Pages: 1585-1589
• [Journal Article] Retrospective study on the notable efficacy and related factors of inflixmab therapy in a rheumatoid arthritis management group in Japan(RECONFIRM). (2007)
  • Author(s): Yamanaka H, Tanaka Y, Sekiguchi N, Inoue E, Saito K, Kameda H, Iikuni N, Nawata M, Amano K, Shinozaki M, Takeuchii T.
  • Journal Title: Mod Rheumatol 17 Pages: 28-32
• [Journal Article] Prospective study of low-dose cyclosporne A in patients with refractory lupus nephritis. (2007)
  • Author(s): Ogawa H, Kameda H, Nagasawa H, Sekiguch N, Takei H, Tsuzaka K, Amano K, Takeuchi T.
  • Journal Title: Mod Rheumatol 17 Pages: 92-97
• [Journal Article] Clinical significance of elevated serum levels of matrix metalloproteinase-3 and C-reactive protein in patients with rheumatoid arthritis. (2007)
  • Author(s): Nagasawa H, Kameda H, Amano K, Takeuchi T.
  • Journal Title: APLARJ Rheumatol 10 Pages: 295-299
• [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
  • NAID: 10020584521
  • 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
  • NAID: 10017479089
  • 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 Hideto
  • Journal Title: Clin Exp Immunol 144 Pages: 335-341
• [Journal Article] Efficacy and safety of bucillamine, a d-penicillamine analogue, in patients with active rheumatoid arthritis. (2006)
  • Author(s): Sekiguchi Naoya
  • Journal Title: Mod Rheumatol 16 Pages: 85-91
• [Journal Article] Impact of TNF inhibitors on rheumatoid arthritis. (2006)
  • Author(s): Takeuchi Tsutomu
  • Journal Title: Inflammation and Regeneration 26 Pages: 148-159
• [Journal Article] Development and validation of handy rheumatoid activity score with 38 joints (HRAS38) in rheumatoid arthritis patients receiving infliximab. (2006)
  • Author(s): Kameda Hideto
  • Journal Title: Mod Rheumatol 16 Pages: 381-388
  • NAID: 10020584521
• [Journal Article] Recent advances in the treatment of interstitial lung disease in patients with polymyositis/dermatomvositis. (2006)
  • Author(s): Kameda Hideto.
  • Journal Title: Endocrine, Metabolic ＆ Immune Disorders - Drug Targets 6(4) Pages: 409-415
• [Journal Article] Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like cells and phosphorylation of Gab adapter proteins activated by platelet-derived growth factor.
  • Author(s): Kameda H, Ishigami H, Suzuki M, Abe T, Takeuchi T.
  • Journal Title: Clin Exp Immunol (In press)
• [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.
• [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
• [Presentation] 関節リウマチ患者末梢制御性T細胞の量的質的異常と治療薬のあたえる影響 (2008)
  • Author(s): 鈴木勝也, 瀬戸山由美子, 鈴木美由紀, 吉本桂子, 亀田秀人, 津坂憲政, 天野宏一, 竹内勤
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
• [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.
• [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
• [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.
• [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
• [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
• [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
• [Book] 治療薬ハンドブック (2008)
  • Author(s): 亀田秀人, 長澤逸人, 竹内勤
  • Total Pages: 7
  • Publisher: じほう
• [Book] 補体価、C3、C4 (2007)
  • Author(s): 亀田 秀人
  • Total Pages: 4
  • Publisher: 文光堂
• [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)
  • Publisher: メデイカルレビュー社 東京
• [Book] ファーマナビゲーター COX-2阻害薬編. (2006)
  • Author(s): 亀田秀人
  • Publisher: メデノカルレビュー社
• [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)
  • 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)
  • 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)
  • Publisher: 文光堂,東京
• [Book] 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
  • Publisher: 日本臨床社
• [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