悪性黒色腫の骨の転移のメカニズムの解明

• Project/Area Number: 20013014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 野田 政樹 Tokyo Medical and Dental University, 難治疾患研究所, 教授 (50231725)
• Co-Investigator(Kenkyū-buntansha): 江面 陽一 東京医科歯科大学, 難治疾患研究所, 准教授 (50333456) ; 早田 匡芳 東京医科歯科大学, 難治疾患研究所, 助教 (40420252)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥8,600,000 (Direct Cost: ¥8,600,000); Fiscal Year 2009: ¥4,300,000 (Direct Cost: ¥4,300,000); Fiscal Year 2008: ¥4,300,000 (Direct Cost: ¥4,300,000)
• Keywords: B16 / 細胞接着 / 癌細胞 / 転移 / 破骨細胞 / 悪性黒色腫 / JunD / AP-1 / 癌細胞増殖 / 骨芽細胞

Research Abstract

癌の進展においては細胞の接着、及びインテグリンからのシグナルによる細胞の生存、増殖さらには活性化した細胞からのサイトカインの発現により骨の場合には局所のマクロファージや前駆細胞の活性化からはじまる破骨細胞の分化とその活動性の亢進がおこる。このような一連の骨に転移させる活性の高い細胞における転移のメカニズムの解明を目的とし、悪性黒色腫のマウスB16細胞についての検討を行なった。マウスB16細胞の細胞接着とその形態を観察する目的で、まず、細胞における接着反分子の解析について検討した。その結果、細胞接着反のAdhesion Complexの分子群を構成するCIZの発現がB16細胞において確認された。この発現は細胞質にあるとともにまた細胞接着反においても認められた。この分子の接着とのかかわりが推察された。悪性黒色腫の中でも特に転移活性の高いB16F10の細胞とその親株であるB16における細胞の転移活性と接着との相関を検討するとCIZのレベルがB16F10細胞において親株のB16との大きな相違が認められ、この相関が細胞転移活性に関与することが示唆された。更に、癌細胞の骨への転移によって生じる、骨の破壊に関わる破骨細胞の制御について検討を行った。この結果、破骨細胞においてはDicerの特異的なカテプシンKcreに基づくノックアウトより骨量が増加すること、海綿骨の厚さの増加がみられることが明らかになった。この転移のおける破骨破壊をもたらず破骨細胞の分化のレベルの低下は細胞において内因性であり、コンディショナルノックアウトマウスの骨髄細胞の破骨細胞への分化も抑制が観察された。以上の研究成果は悪性黒色腫の骨への転移とその骨における腫瘍に基づく骨破壊の主たる細胞である破骨細胞のメカニズムを明らかにしたものであり、今後これらの分子を抑止する薬剤の探索など癌の転移に対する対策の基盤となる起点が確立された。

Research Products

• [Journal Article] Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption (2010)
  • Author(s): Mizoguchi F, Izu Y, Hayata T, Hemmi H, Nakashima K, Nakamura T, Kato S, Miyasaka N, Ezura Y, Noda M
  • Journal Title: Journal of Cellular Biochemistry 109 Pages: 866-75
  • Peer Reviewed
• [Journal Article] Cbl-b Enhances Runx2 Protein Stability and Augments Osteocalcin Promoter Activity in Osteoblastic Cell Lines (2010)
  • Author(s): Ampornaramveth Salingcarnboriboon, R., Pavasant, P., Noda, M.
  • Journal Title: Journal of Cellular Physiology (in press)
  • Peer Reviewed
• [Journal Article] Nemo-like kinase(NLK)expression in osteoblastic cells and suppression of osteoblastic differentiation (2010)
  • Author(s): Nifuji A, Ideno H, Ohyama Y, Takanabe R, Araki R, Abe M, Noda M, Shibuya H.
  • Journal Title: Experimental Cell Research 316 Pages: 1127-1136
  • Peer Reviewed
• [Journal Article] ANA deficiency enhances BMP-induced ectopic bone formation via transcriptional events (2009)
  • Author(s): Miyai K, Yoneda M, Hasegawa U, Toida S, Izu Y, Hemmi H, Hayata T, Ezura Y, Mizutani S, Miyazono K, Akiyoshi K, Yamamoto T, Noda M
  • Journal Title: Journal of Biological Chemistry 284 Pages: 10593-600
  • Peer Reviewed
• [Journal Article] Combinatory effects of androgen receptor deficiency and hindlimb unloading on bone (2009)
  • Author(s): Saita Y, Takashi Nakamura, Fumitaka Mizoguchi, Kazuhisa Nakashima, Tadayoshi Hayata, Yoichi Ezura, Hisashi Kurosawa, Shigeaki Kato, Masaki Noda
  • Journal Title: Thime ejournals 41 Pages: 822-8
  • Peer Reviewed
• [Journal Article] Osteoblastic Bone Formation Is Induced by Using Nanogel-Crosslinking Hydrogel as Novel Scaffold for Bone Growth Factor (2009)
  • Author(s): Hayashi C, Hasegawa U, Saita Y, Hemmi H, Hayata T, Nakashima K, Ezura Y, Amagasa T, Akiyoshi K, Noda M
  • Journal Title: Journal of Cellular Physiology 220 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Methylation status of CpG-islands in the promoter regions of signature genes during chondrogenesis of human synovium-derived mesenchymal stem cells (2009)
  • Author(s): Ezura Y, Koga H, Muneta T, Sekiya I, Noda M
  • Journal Title: Arthritis & Rheumatism 60 Pages: 1416-1426
  • Peer Reviewed
• [Journal Article] Angiotensin II type 2 receptor blockade increases bone mass (2009)
  • Author(s): Izu Y, Mizoguchi F, Kawamata A, Hayata T, Nakamoto T, Nakashima K, Inagami T, Ezura Y, Noda M
  • Journal Title: Journal of Biological Chemistry 284 Pages: 4857-64
  • Peer Reviewed
• [Journal Article] ANA deficiency enhances BMP-induced ectopic bone formation viatranscriptional events (2009)
  • Author(s): Miyai K, Yoneda M, Hasegawa U, Toida S, Izu Y, Hiroaki H, Hayata T, Ezura Y, Mizutani S, Miyazono K, Akiyoshi K, Yamamoto T, Noda M.
  • Journal Title: Journal of Biological Chemistry
  • Peer Reviewed
• [Journal Article] Methylation status of CpG-islands in the promoter regions of signature genes during chondrogenesis of human synovium-derived mesenchymal stem cells (2009)
  • Author(s): Ezura Y, Koga H, Muneta T, Sekiya I, Noda M
  • Journal Title: Arthritis & Rheumatism (In press)
  • Peer Reviewed
• [Journal Article] Osteoblastic Bone Formation Is Induced by Using Nanogel-Crosslinking Hydrogel as Novel Scaffold for Bone Growth Factor (2009)
  • Author(s): Hayashi C, Hasegawa U, Saita Y, Hemmi H, Hayata T, Nakashima K, Ezura Y, Amagasa T, Akiyoshi K, Noda M.
  • Journal Title: Journal of Cellular Physiology (In press)
  • Peer Reviewed
• [Journal Article] OPN deficiency suppresses appearance of odontoclastic cells and resorption of the tooth root induced by experimental force application (2008)
  • Author(s): Chung CJ, Soma K, Rittling SR, Denhardt DT, Hayata T, Nakashima K, Ezura Y, Noda M
  • Journal Title: Journal of Cellular Physiology 214 Pages: 614-20
  • Peer Reviewed
• [Journal Article] Jun D suppresses bone formation and contributes to low bone mass induced by estrogen depletion (2008)
  • Author(s): Kawamata A., Izu Y., Yokoyama H., Hayata T., Amagasa T., Wagner E.F., Nakashima K., Ezura Y., Noda M.
  • Journal Title: Journal of Cellular Biochemistry 103 Pages: 1037-45
  • Peer Reviewed
• [Journal Article] Transient Receptor Potential Vanilloid 4 Deficiency Suppresses Unloading-Induced Bone Loss (2008)
  • Author(s): Mizoguchi F., Mizuno A., Hayata T., Nakashima K., Heller S., Ushida T., Sokabe M., Miyasaka N., Suzuki M., Ezura Y., Noda M.
  • Journal Title: Journal of Cellular Physiology 216 Pages: 47-53
  • Peer Reviewed
• [Journal Article] Involvement of the klotho protein in dentin formation and mineralization (2008)
  • Author(s): Suzuki H, Amizuka N, Oda K, Noda M. Ohshima H. Maeda T
  • Journal Title: Anatomical Record 291 Pages: 183-190
  • Peer Reviewed
• [Journal Article] Histological and elemental analyses of impaired bone mineralization in klotho-deficient mice (2008)
  • Author(s): Suzuki H, Amizuka N, Oda K, Noda M. Ohshima H. Maeda T
  • Journal Title: J Anat 212 Pages: 275-285
  • Peer Reviewed
• [Journal Article] Osteopontin Negatively Regulates parathyroid hormone receptor signaling in osteoblasts (2008)
  • Author(s): Ono N., Nakashima K., Rittling S.R., Schipani E., Hayata T., Ezura Y., Soma K., Denhardt D.T., Kronenberg H.M., Noda M.
  • Journal Title: Journal of Biological Chemistry 283 Pages: 19400-19409
  • Peer Reviewed
• [Journal Article] Ciz, a transcription factor with a nucleocytoplasmic shuttling activity, interacts with C-propeptides of type I collagen (2008)
  • Author(s): Hayata T, Nakamoto T., Ezura Y., Noda M.
  • Journal Title: Biochemical and Biophysical Research Communications 368 Pages: 19400-409
  • Peer Reviewed
• [Journal Article] Expression and tyrosine phosphorylation of Crk associated substrate lymphocyte type (Cas-L) protein in human neutrophils (2008)
  • Author(s): Nakamoto T, Seo S, Sakai R, Kato T, Kutsuna H, Kurokawa M, Noda M, Miyasaka N, Kitagawa S
  • Journal Title: Journal of Cellular Biochemistry 105 Pages: 121-128
  • Peer Reviewed
• [Journal Article] Osteoporotic bone formation in mice lacking tob2 ; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation (2008)
  • Author(s): Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T
  • Journal Title: FEBS Lett 582 Pages: 1313-8
  • Peer Reviewed
• [Journal Article] Functional analysis of Src homology 3-encoding exon (exon 2) of p130Cas in primary fibroblasts derived from exon 2-specific knockout mice (2008)
  • Author(s): Tazaki T, Miyazaki K, Hiyama E, Nakamoto T, Sakai R, Yamasaki N, Honda Z, Noda M, Miyasaka N, Sueda T, Honda H
  • Journal Title: Genes Cells 13 Pages: 145-57
  • Peer Reviewed
• [Journal Article] A new Trem family member, Trem14, binds to dead cells and is a DAP12 linked marker for subsets of mouse macrophages and dendritic cells (2008)
  • Author(s): Hemmi H, Idoyaga J, Suda K Suda N, Kennedy K, Noda M, Aderem A, Steinman RM
  • Journal Title: Journal of Immunology 182 Pages: 1278-86
  • Peer Reviewed
• [Presentation] Bone biology in PTH signaling (2009)
  • Author(s): 野田政樹
  • Organizer: OGEKM Autumn Symposium 2009
  • Place of Presentation: Wien, Austria
  • Year and Date: 2009-11-21
• [Presentation] 骨形成の制御機構 (2009)
  • Author(s): 野田政樹
  • Organizer: 第20回栃木県骨・カルシウム代謝研究会
  • Place of Presentation: 栃木、日本
  • Year and Date: 2009-06-19
• [Presentation] 骨の形成とその調節機構 (2009)
  • Author(s): 野田政樹
  • Organizer: 第29回日本骨形態計測学会
  • Place of Presentation: 大阪、日本
  • Year and Date: 2009-05-29
• [Presentation] 骨と骨の分子破壊と再構築のフロンティア (2009)
  • Author(s): 野田政樹
  • Organizer: 第63回日本口腔科学会
  • Place of Presentation: 静岡、日本
  • Year and Date: 2009-04-17
• [Presentation] The hypermethylated high-density CpG-region(-1112/-888)of the stromal cell-derived factor 1(SDF1)is demethylated in the synovium derived mesenchymal stem cells during chondrogenesis (2009)
  • Author(s): Ezura Y, Sekiya I, Muneta T, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Dullard, a novel phosphatase, that dephosphorylates and degrades BMP receptors, suppresses signaling in osteoblasts (2009)
  • Author(s): Hayata T, Ezura Y, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] The identification and characterization of a new Trem-like molecule (2009)
  • Author(s): Hemmi H, Idoyaga J, Suda K, Noda M, Steinman R.M.
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Anabolic Action of PTH/PTHrP Receptor Signaling in Bone i Suppressed by a Nucleocytoplasmic Shuttling Protein CIZ (2009)
  • Author(s): Nakamoto T, Ono N, Hanyu R, Sakuma T, Hayata T, Ezura Y, Schipani E, Kronenberg HM, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Pacemaker channel HCN1 affects osteoclast function in vitro and bone remodeling in vivo (2009)
  • Author(s): Notomi T, Tanaka S, Amano H, Nakamura T, Noda M, Skerry TM, Kuno M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Sympathetic nervous tone modulates constitutively active parathyroid hormone receptor signaling in vivo (2009)
  • Author(s): Hanyu R, Takeda S, Notomi T, Hemmi H, Hayata T, Ezura Y, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Schnurri-2(SHN-2)deficiency counteracts against bone loss induced by ovariectomy (2009)
  • Author(s): Nagao M, Saita Y, Hanyu R, Hemmi H, Notomi T, Nakamoto T, Hayata T, Ezura Y, Kurosawa H, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Nanogel scaffold delivery of Prostaglandin E2 Receptor(EP4)specific agonist in combination with BMP repairs microstructure of bone produced in the defect via potentiation of transcription activity of smad response element (2009)
  • Author(s): Kamolratanakul P, Kawamata A, Yamamoto Y, Hayata T, Ezura Y, Akiyoshi K, Amagasa T, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Deficiency of Ciz, Cas Interactive Zinc Finger Protein, suppresses tumor invasion into bone (2009)
  • Author(s): Sakuma T, Nakamoto T, Hayata T, Miyai K, Amagasa T, Ezura Y, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] PTH signaling and Osteopontin deficiency coordinately enhance progenitor niche for the cells to support tooth development (2009)
  • Author(s): Morishita M, Ono N, Hanyu R, Kamolratanakul P, Nagao M, Hemmi H, Hayata T, Noda M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] Cbl-b enhanced Runx2 function on osteocalcin promoter activity in osteoblastic cell line (2009)
  • Author(s): Ampornaramveth, R, Pavasant, Noda, M
  • Organizer: The 31^<st> Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Denver, Colorado, USA
• [Presentation] A role of ANA in osteoblast and in bone formation (2008)
  • Author(s): Miyai K., Yoneda M., Hayata T Ezura Y., Nakashima K., Yamamoto T., Mizutani S., Noda M.
  • Organizer: Harvard School of Dental Medicine Student Research Day 2008
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 2008-04-22
• [Presentation] Ovariectomy induced bone loss was prevented by the deficiency of JunD which reduces basal levels of bone mass (2008)
  • Author(s): Kawamata A., Izu Y., Yokoyama H., Hayata T., Amagasa T., Wagner E. F., Nakashima K., Ezuria Y., Noda M.
  • Organizer: Harvard School of Dental Medicine Student Research Day 2008
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 2008-04-22
• [Presentation] Osteoclast Specific Dicer Deficiency Suppress Osteoclast Differentiation and Increase Bone Mass (2008)
  • Author(s): Mizoguchi F., Izu Y., Hayata T., Hemmi H., Nakashima K., Nakamura T.,Kohsaka H., Miyasaka N., Harfe B., Kato S., Ezura Y., Noda M.
  • Organizer: 2nd International Conference of Osteoimmunology (Aegean Conferences)
  • Place of Presentation: Rhodes, Greece
• [Presentation] Osteoblast-specific constitutive activation of PTH/PTHrP receptor enhances marrow-ablation-induced osteoprogenitor activities (2008)
  • Author(s): Ono N., Nakashima K., Schipani E., Hayata T., Ezura Y., Soma K, Kronenberg H. M., Noda M.
  • Organizer: International Association for Dental Research General Session
  • Place of Presentation: Toronto, Ganda
• [Presentation] Increased Expression of Osteopontin in Peripheral Blood Mononuclear Cells is Associated with Alteration in the Fractions of Lymphocytes in Hindlimb-unloaded Mice (2008)
  • Author(s): Ezura Y., Nagata J., Hemmi H., Hayata T, Nakamoto T., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Interaction of Ciz, a Nucleo-cytoplasmic Shuttling transcription factor with C-propeptides of type I collagen (2008)
  • Author(s): Hayata T., Nakamoto T., Ezura Y., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Deficiency of the Nucleocytoplasmic Shuttling Protein CIZ Suppresses K/BxN Serum-Induced Model of Rheumatoid Arthritis (2008)
  • Author(s): Nakamoto T., Mizogucni Izu Y., Hayata T., Ezura Y., Mathis D., C. Benoist, Miyasaka N., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Angiotensin II type 2 receptor blockade increases bone mass (2008)
  • Author(s): Izu Y., Hayata T., Mizoguchi F. Kawamata A., Nakamoto T., Ezura Y., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Aging dependent and independent effects of b2 adrenergic receptor signaling on bone formation induced by intermittent PTH treatment in female mice (2008)
  • Author(s): Hanyu R., Saita Y., Nagata J., Izu Y., Hayata T, Henmi H., Takeda S.,Ezura Y., Kurosawa H., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Nanotechnological Scaffold with Combination, of Prostaglandin E2 Receptor EP4 Agonist and rhBMP2, Enhances Bone Repair in the Defect of Mouse Calvarium Bone (2008)
  • Author(s): Kamolratanakul P., Kawamata A., Yamamoto Y., Ezura Y., Akiyoshi K., Amagasa T., Noda M.
  • Organizer: The 30th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada
• [Presentation] Identification and characterization of a Trenn-like molecule expressed on mouse splenic DCs and macrophages (2008)
  • Author(s): Hemmi H., Idoyaga J., Suda K Suda N., Noda M., Steinman R.M.
  • Organizer: The 10th International Symposium on Dendritic Cells
  • Place of Presentation: Kobe, Japan
• [Presentation] 尾部懸垂マウス大腿骨における網羅的遺伝子発現の部位別解析 (2008)
  • Author(s): 江面陽一、永田純史、野田政樹
  • Organizer: 第28回日本骨形態計測学会
  • Place of Presentation: 東京、日本
• [Presentation] 核-細胞質シャトリングタンパク質Cizは、I型コラーゲンのC-プロペプチドと相互作用する (2008)
  • Author(s): 早田匡芳、中元哲也、江面陽一、野田政樹
  • Organizer: 第28回日本骨形態計測学会
  • Place of Presentation: 東京、日本
• [Presentation] アンギオテンシンIItype2受容体阻害剤は骨量を増加させる (2008)
  • Author(s): 伊豆弥生、早田匡芳、中元哲也、江面陽一、野田政樹
  • Organizer: 第28回日本骨形態計測学会
  • Place of Presentation: 東京、日本
• [Presentation] ANAは骨芽細胞におけるBMP2シグナルのネガティウフィードバックに関与し骨形成を抑制する (2008)
  • Author(s): 宮井健太郎、野田政樹
  • Organizer: 第28回日本骨形態計測学会
  • Place of Presentation: 東京、日本
• [Presentation] AP-1構成因子であるJunDは骨量増加を抑制し、エストロゲン欠乏による骨量減少に関与する (2008)
  • Author(s): 川俣綾、野田政樹、天笠光雄
  • Organizer: 第53回日本口腔外科学会学術大会
  • Place of Presentation: 徳島、日本
• [Presentation] 交感神経β刺激による骨吸収と骨形成にオステオポチンは必要である (2008)
  • Author(s): 長尾雅史、斎田良知、永田純史、伊豆弥生、早田匡芳、辺見弘明、江面陽一、黒澤尚、野田敏樹
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都、日本
• [Presentation] アドレナリンβ2受容体遺伝子欠損の高週令(1年)マウスにおけるPTHによる骨形態計測学的検討 (2008)
  • Author(s): 羽生亮、斎田良知、伊豆弥生、竹田秀、江面陽一、黒澤尚、野田政樹
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都、日本
• [Presentation] ヒト滑膜由来間葉系幹細胞の軟骨細胞分化過程における主な遺伝子上流CpGアイランドのメチル化状態は定常的に維持される (2008)
  • Author(s): 江面陽一、関矢一郎、宗田大、野田政樹
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪、日本
• [Presentation] I型コラーゲンC-プロペプチドは、骨形成抑制因子Cizと結合する (2008)
  • Author(s): 早田匡芳、中元哲也、江面陽一、野田政樹
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪、日本
• [Presentation] 破骨細胞特異的Dicer欠損は破骨細胞分化を抑制し骨量を増加させる (2008)
  • Author(s): 溝口史高、伊豆弥生、早田匡芳、辺見弘明、中島和久、中村貴、Brian Harfe、加藤茂明、宮坂信之、江面陽一、野田政樹
  • Organizer: 第36回日本臨床免疫学会総会
  • Place of Presentation: 東京、日本