Study on the mechanism of LAM cell proliferation and disease progression in lymphangioleiomyomatosis

• Project/Area Number: 18390243
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: SEYAMA Kuniaki Juntendo University, 医学部, 准教授 (10226681)
• Co-Investigator(Kenkyū-buntansha): KUMASAKA Toshio 順天堂大学, 医学部, 准教授 (00286709) ; KODAMA Yuzo 順天堂大学, 医学部, 助教 (30384069)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,030,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥2,430,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
• Keywords: リンパ脈管筋腫症 / がん抑制遺伝子 / TSC遺伝子 / リンパ管新生 / 結節性硬化症 / 自然気胸 / 嚢胞性肺疾患 / リンパ行性転移 / 癌抑制遺伝子

Research Abstract

肺リンパ脈管筋腫症(LAM)の病因であるLAM細胞の増殖や転移機構の解明をめざし、LAM細胞クラスター(LCC)や組織よりLAM細胞を分離培養し、その細胞生物学的特性を検討した。また、LAM細胞を高度免疫不全マウスに移植し、治療や病態解明に役立つLAMモデルマウス作成を試みた。LAM細胞の多様性、培養中の性質変化、マウス内で生着の困難さなど、今後のLAM研究の発展への課題が明らかとなった。

Research Products

• [Journal Article] Matrix metalloproteinases in blood from patients with LAM (2009)
  • Author(s): Odajima N, Betsuyaku T, Nasuhara Y, Inoue H, Seyama K, Nishimura M
  • Journal Title: Respir Med 103 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinases in blood from patients with LAM. (2009)
  • Author(s): Odajima N, et al.
  • Journal Title: Respir Med. 103 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Sirolimus amelioration of clinical symptoms of recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation (2008)
  • Author(s): Sugimoto R, Nakao A, Yamane M, Toyooka S, Okazaki M, Aoe M, Seyama K, Date H, Oto T, Sano Y
  • Journal Title: J Heart Lung Transplant 27 Pages: 921-924
  • Peer Reviewed
• [Journal Article] Peritoneovenous shunting for intractable chylous ascites complicated with lymphangioleiomyoma-tosis (2008)
  • Author(s): Makino Y, Shimanuki Y, Fujiwara N, Morio Y, Sato K, Yoshimoto J, Gunji Y, Suzuki T, Sasaki S, Iwase A, Kawasaki S, Takahashi K, Seyama K
  • Journal Title: Intern Med 47 Pages: 281-285
  • NAID: 130000079736
  • Peer Reviewed
• [Journal Article] Sirolimus amelioration of clinical symptoms of recurrent lymphangiolei omyomatosis after living-donor lobar lung transplantation. (2008)
  • Author(s): Sugimoto R, et al.
  • Journal Title: J Heart Lung Transplant. 27 Pages: 921-924
  • Peer Reviewed
• [Journal Article] Peritoneovenous shunting for intractable chylous ascites complicated with lymphanioleiomvomatosis (2008)
  • Author(s): Makino Y, et. al.
  • Journal Title: Intern Med 47 Pages: 281-285
  • Peer Reviewed
• [Journal Article] Lymphangioleiomyomatosis diagnosed by immunocytochemical and genetic analysis of lymphangioleiomyoma-tosis cell clusters found in chylous pleural effusion (2007)
  • Author(s): Hirama M, Atsuta R, Mitani K, Kumasaka T, Gunji Y, Sasaki S, Iwase A, TakahashiK, Seyama K
  • Journal Title: Intern Med 46 Pages: 1593-1596
  • NAID: 130000076007
  • Peer Reviewed
• [Journal Article] Respiratory Failure Research Group of the Japanese Ministry of Health, Labor, and Welfare (2007)
  • Author(s): Hayashida M, Seyama K, Inoue Y, Fujimoto K, Kubo K
  • Journal Title: The epidemiology of lymphangioleiomyomatosisin Japan : a nationwide cross-sectionalstudy of presenting features andprognostic factors 12 Pages: 523-530
  • Peer Reviewed
• [Journal Article] The epidemiology of lymphangioleiomyomatosis in Japan:anationwide cross-sectioval study of presenting features and prognostic factors (2007)
  • Author(s): Hayashida M, et. al.
  • Journal Title: Respirology 12 Pages: 523-530
  • Peer Reviewed
• [Journal Article] Lymphangioleiomyomatosis diagnosed by immunocytochemical and genetic analysis of lymphangioleiomyomatosis cell clusters found in chvlous pleural effusion (2007)
  • Author(s): Hirama M, et. al.
  • Journal Title: Intern Med 46 Pages: 1593-1596
  • Peer Reviewed
• [Journal Article] LAMは腫瘍か? (2007)
  • Author(s): 瀬山邦明, 熊坂利夫ら
  • Journal Title: 呼吸 26 Pages: 23-30
• [Journal Article] Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis (2006)
  • Author(s): Seyama K, Kumasaka T, Souma S, Sato T, Kurihara M, Mitani K, Tominaga S, Fukuchi Y
  • Journal Title: Lymphat Res Biol 4 Pages: 143-52
  • Peer Reviewed
• [Journal Article] LAMと遺伝子多型 (2006)
  • Author(s): 佐藤輝彦, 三谷恵子
  • Journal Title: 呼吸と循環 54 Pages: 827-832
• [Journal Article] リンパ脈管筋腫症-TSC遺伝子解析からLAMの進展機序への展開- (2006)
  • Author(s): 瀬山邦明, 熊坂利夫
  • Journal Title: 二本内科学会雑誌 95 Pages: 1048-1057
  • NAID: 10018198718
• [Journal Article] 肺リンパ脈管筋腫症の病理と病態 (2006)
  • Author(s): 熊坂利夫, 瀬山邦明ら
  • Journal Title: 病理と臨床 24 Pages: 939-948
• [Journal Article] Cytological, immunocytochemical, and ultrastructural characterization of LAM cell clusters in chylous effusion of patients with lymphangioleiomyomatosis
  • Author(s): Mitani K, Kumasaka T, Takemura H, Hayashi T, Gunji Y, Kunogi M, Akiyoshi T, Takahashi K, Suda K, Seyama K
  • Journal Title: Acta Cytologica (in press)
  • Peer Reviewed
• [Presentation] Lymphangiogenesis in lymphangioleiomyomatosis -Lymphangiogenesis and GnRH therapy-9:25-9:50a. m. (2008)
  • Author(s): Seyama K
  • Organizer: LAM Foundation 2008 International Research Conference
  • Place of Presentation: Cincinnati, USA
  • Year and Date: 2008-04-05
• [Presentation] Lymphangiogenesis in lymphangioleiomyomatosis-Lymphangiogenesis and GnRH therapy- (2008)
  • Author(s): Seyama K
  • Organizer: LAM Foundation 2008 International Research Conference
  • Place of Presentation: in Cincinnati USA
• [Presentation] Genetic and Molecular Mechanism of Diffuse Lung Diseases 2. Lymphangioleiomyomatosis (2007)
  • Author(s): Seyama K
  • Organizer: The 4th international meeting of WASOG
  • Place of Presentation: Tokyo
  • Year and Date: 2007-10-20
• [Presentation] Effect of long term administration of gonadotropin-releasing hormone an alogues on chylous effusion in patients with lymphangioleiomyomatosis (2007)
  • Author(s): Seyama K
  • Organizer: The LAM foundation/NHLBI International Research Conference
  • Place of Presentation: Cincinnati,USA
  • Year and Date: 2007-04-21
• [Presentation] Effect of long term administration of gonadotropin-releasing hormone analogueson chylous effusion in patients with lymphangioleiomyomatosis (2007)
  • Author(s): Seyama K, Sato T, Gunji Y, Kumasaka T, Mitani K, Akiyoshi T, Tobino K, Hayashi T
  • Organizer: LAM Foundation2007 International Research Conference
  • Place of Presentation: in Cincinnati USA.
  • Year and Date: 2007-04-20
• [Presentation] Cytological, immunocytochemical, and ultrastructual characterization of LAM cell clusters in chylous effusion in patients with lymphangioleiomyomatosis (2007)
  • Author(s): Mitani K, Kumasaka T, Takemura H, Hayashi T, Hosokawa Y, Suda K, Gunji Y, Akiyoshi T, Seyama K
  • Organizer: LAM Foundation 2007 International Research Conference
  • Place of Presentation: in Cincinnati USA
  • Year and Date: 2007-04-20
• [Presentation] Loss of heterozygosity of the TSC genes and overexpression of mTOR-related proteins in multifocalmicronodular pneumocyte hyperplasia of the lung (2007)
  • Author(s): Hayashi H, Kumasaka T, Mitani K, Gunji Y, Suda K, Seyama K
  • Organizer: LAM Foundation 2007 International Research Conference
  • Place of Presentation: in Cincinnati USA
  • Year and Date: 2007-04-20
• [Presentation] LAM and Lymphangiogenesis (2007)
  • Author(s): Seyama K
  • Organizer: Global LAM summit
  • Place of Presentation: in Stockholm
  • Year and Date: 2007-02-25
• [Book] Stacker SD and Achen MG
  • Author(s): Seyama K, Kumasaka T, Sato T, and Mitani K
  • Publisher: Chapter 8. Lymphangioleiomyomatosis. In : Cancer and lymphatic metastasis
• [Remarks] 気胸・肺のう胞スタディグループ
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