アレルギーおよび癌の病態解析と分子標的治療薬の開発
メンバー： 松田浩珍
分野： 動物生命科学、基礎医学
所属： 農学研究院動物生命科学部門
キーワード： アレルギー、マスト細胞、創傷治癒、腫瘍、分子標的、シグナル伝達、再生、橋渡し研究
ウェブサイト：
研究概要
私たちの研究室では、動物やヒトを苦しめる様々な病気について、免疫学的・分子生物学的な手法を利用して、発症のメカニズムと有効な治療法の開発を目指して研究を進めています。主たる研究テーマは、アレルギーと腫瘍です。
１）アトピー性皮膚炎の病態解析
我々が世界で初めて報告したアトピー性皮膚炎自然発症モデルマウス（NC/Tndマウス）を用いて、病気の発症メカニズムの解析や新薬の評価試験を実施しており、アレルギー新薬・スキンケア商品・化粧品・サプリメント・食品などの開発に多くの実績を有しています。（東京農工大学で繁殖と維持を続けてきたNC/NgaTndマウスは、2010年12月より、正式にNC/Tndマウスとして認可を受けました。東京農工大学で維持されているNCサブラインは、NC/Tndマウスとなります。）
２）マスト細胞の腫瘍化メカニズムの解明
マスト細胞の基礎研究を実施してきた実績をもとに、イヌやネコに多発するマスト細胞腫の遺伝子や原因分子の探索を行っています。
３）アトピー性皮膚炎のかゆみ行動、あるいは関節リューマチなどで見られる歩行異常、腫瘍や神経疾患などの痛み行動など、病勢評価のための疾患特異的な行動の定量化を可能とする新システムを開発し、有効な新薬開発に貢献しています。
主要論文・参考事項
1. Amagai Y, Matsuda A, Jung K, Oida K, Jang H, Ishizaka S, Matsuda H, and Tanaka A: A point mutation in the extracellular domain of KIT promotes tumorigenesis of mast cells via ligand-independent auto-dimerization. Sci. Rep. in press.
2. Amagai Y, Oida K, Matsuda A, Jung K, Kakutani S, Tanaka T, Matsuda K, Jang H, Ahn G, Kawashima H, Shibata H, Matsuda H, Tanaka A: Dihomo-γ-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice. J. Dermatol. Sci. in press.
3. Jensen-Jarolim E, Fazekas J, Singer J, Hofstetter G, Oida K, Matsuda H, Tanaka A: Crosstalk of carcinoembryonic antigen and transforming growth factor-beta via their receptors: comparing human and canine cancer. in press.
4. Tanaka A, Matsuda A, Jung K, Jang H, Amagai Y, Oida K, Nishikawa S, Ishizaka S, Arkwrigh P, Matsuda H: Ultra-pure soft water ameliorates atopic skin disease by preventing metallic soap deposition in NC/Tnd mice. Act. Dermato-Venereol. in press.
5. Ultra-pure soft water improves skin barrier funcion in children with atopic dermatitis: A randomized, double-blind, placebo-controlled, crossover pilot study. J. Dermatol. Sci. 76: 269-271, 2014
6. Reiko Chiba, Yosuke Amagai, Akane Tanaka, Ken Katakura, Hirosi Matsuda: Nerve growth factor promotes killing of Leishmania donobani by macrophages through the induction of hydrogen peroxide. Microbes Infect. 16: 702-706, 2014
7. Nishikawa S, Tanaka A, Matsuda A, Oida K, Jang H, Jung K, Amagai Y, Ahn G, Okamoto N, Ishizaka S, Matsuda H: A molecular targeting against nuclear factor-kB, as a chemotherapeutic approach for human malignant mesothelioma. Cancer Med. 3: 416-425, 2014
8. Oida K, Matsuda A, Jung K, Xia Y, Jang H, Amagai Y, Ahn G, Nishikawa S, Ishizaka S, Jensen-Jarolim E, Matsuda H, Tanaka A: Nuclear factor-kB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells. Sci. Rep. doi: 10.1038/srep04057, 2014
9. Amagai Y, Tanaka A, Jung K, Matsuda A, Oida K, Nishikawa S, Jang H, Ishizaka S, Matsuda H: Production of stem cell factor in canine mast cell tumors. Res. Vet. Sci. 96: 124-126, 2014
10. Kobayashi T, Hayakawa K, Tanaka A, Matsuda H: Increased expression of gelatinase and caspase activities in the skin of NC/Tnd mice: a model for atopic dermatitis. Dermatology 24: 254-255, 2013
11. Amagai Y, Tanaka A, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Ishizaka S, Matsuda H: Topical application of ketoprofen improves gait disturbance in rat models of acute inflammation. Biomed. Res. Int. doi: 10.1155/2013/540231, 2013
12. Furusaka T, Matsuda A, Tanaka A, Matsuda H, Ikeda M: Superselective intra-arterial chemoradiation therapy for functional laryngeal preservation in advanced squamous cell carcinoma of the glottic larynx. Acta Otolaryngol. 133: 791-794, 2013
お問い合わせ先
東京農工大学・先端産学連携研究推進センター
urac[at]ml.tuat.ac.jp（[at]を@に変換してください）
Pathophysiologic analyses and development of novel molecularly-targeted therapy for allergy and tumors
Research members： Dr. Hiroshi Matsuda
Research fields： Animal life science, Basic medicine
Departments： Section of Animal Life Science, Institute of Agriculture
Keywords： allergy, mast cell, wound healing, tumor, molecular target, signal transduction, remodeling, translational research
Web site：
Summary
We study various diseases that affect both animals and humans to analyze pathogenic mechanisms and develop effective treatments, using immunologic and molecular biological techniques in our laboratories. Our research focuses on allergies and tumors. We have recently been working on establishing treatment to restore corneas in dogs.
1) Pathological Analysis of Atopic Dermatitis
We have conducted analysis of the pathogenic mechanism of diseases and evaluation tests for new drugs using a spontaneous atopic dermatitis model (NC/Tnd mouse), as first reported by Prof. Matsuda, et al. (The NC/NgaTnd mouse was bred and maintained by the Tokyo University of Agriculture and Technology (TUAT), and was officially certified as NC/Tnd mouse in December 2010. The NC subline maintained by TUAT is referred to as the “NC/Tnd mouse”.) Our efforts have led to many achievements in the development of new allergy drugs, skin care products, cosmetics, supplements, foods, and more.
2) The Tumorigenesis Mechanism of Mast Cells
We conduct studies on, genes and causal molecules that frequently appear in mast cell tumors in dogs and cats based on the actual results of basic mast cell research.
3) Behavior analysis and pathological evaluation of animal models for human diseases
We have contributed to the development of effective drugs by developing new systems for pathological evaluation in order to quantify specific behaviors associated with disease, such as scratching associated with atopic dermatitis, abnormal gait from rheumatoid arthritis, and pain due to tumors and neurological disorders.
Reference articles and patents
1. Amagai Y, Matsuda A, Jung K, Oida K, Jang H, Ishizaka S, Matsuda H, and Tanaka A: A point mutation in the extracellular domain of KIT promotes tumorigenesis of mast cells via ligand-independent auto-dimerization. Sci. Rep. in press.
2. Amagai Y, Oida K, Matsuda A, Jung K, Kakutani S, Tanaka T, Matsuda K, Jang H, Ahn G, Kawashima H, Shibata H, Matsuda H, Tanaka A: Dihomo-γ-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice. J. Dermatol. Sci. in press.
3. Jensen-Jarolim E, Fazekas J, Singer J, Hofstetter G, Oida K, Matsuda H, Tanaka A: Crosstalk of carcinoembryonic antigen and transforming growth factor-beta via their receptors: comparing human and canine cancer. in press.
4. Tanaka A, Matsuda A, Jung K, Jang H, Amagai Y, Oida K, Nishikawa S, Ishizaka S, Arkwrigh P, Matsuda H: Ultra-pure soft water ameliorates atopic skin disease by preventing metallic soap deposition in NC/Tnd mice. Act. Dermato-Venereol. in press.
5. Ultra-pure soft water improves skin barrier funcion in children with atopic dermatitis: A randomized, double-blind, placebo-controlled, crossover pilot study. J. Dermatol. Sci. 76: 269-271, 2014
6. Reiko Chiba, Yosuke Amagai, Akane Tanaka, Ken Katakura, Hirosi Matsuda: Nerve growth factor promotes killing of Leishmania donobani by macrophages through the induction of hydrogen peroxide. Microbes Infect. 16: 702-706, 2014
7. Nishikawa S, Tanaka A, Matsuda A, Oida K, Jang H, Jung K, Amagai Y, Ahn G, Okamoto N, Ishizaka S, Matsuda H: A molecular targeting against nuclear factor-kB, as a chemotherapeutic approach for human malignant mesothelioma. Cancer Med. 3: 416-425, 2014
8. Oida K, Matsuda A, Jung K, Xia Y, Jang H, Amagai Y, Ahn G, Nishikawa S, Ishizaka S, Jensen-Jarolim E, Matsuda H, Tanaka A: Nuclear factor-kB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells. Sci. Rep. doi: 10.1038/srep04057, 2014
9. Amagai Y, Tanaka A, Jung K, Matsuda A, Oida K, Nishikawa S, Jang H, Ishizaka S, Matsuda H: Production of stem cell factor in canine mast cell tumors. Res. Vet. Sci. 96: 124-126, 2014
10. Kobayashi T, Hayakawa K, Tanaka A, Matsuda H: Increased expression of gelatinase and caspase activities in the skin of NC/Tnd mice: a model for atopic dermatitis. Dermatology 24: 254-255, 2013
11. Amagai Y, Tanaka A, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Ishizaka S, Matsuda H: Topical application of ketoprofen improves gait disturbance in rat models of acute inflammation. Biomed. Res. Int. doi: 10.1155/2013/540231, 2013
12. Furusaka T, Matsuda A, Tanaka A, Matsuda H, Ikeda M: Superselective intra-arterial chemoradiation therapy for functional laryngeal preservation in advanced squamous cell carcinoma of the glottic larynx. Acta Otolaryngol. 133: 791-794, 2013
Contact
University Research Administration Center(URAC),
Tokyo University of Agriculture andTechnology
urac[at]ml.tuat.ac.jp
(Please replace [at] with @.)