Development of a new therapeutic strategy against hematopoietic cellmalignancy by modulating cell cycle regulatory proteins as molecular targets

• Project/Area Number: 18380187
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: TANAKA Akane Tokyo University of Agriculture and Technology, 大学院・共生科学技術研究院, 准教授 (80418673)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Hiroshi 東京農工大学, 大学院・共生科学技術研究院, 教授 (80145820) ; ARAI Katsuhiko 東京農工大学, 大学院・共生科学技術研究院, 准教授 (60175940)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Hiroshi 東京農工大学, 大学院・共生科学技術研究院, 教授 (80145820) ; ARAI Katsuhiko 東京農工大学, 大学院・共生科学技術研究院, 教授 (60175940)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,880,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: 癌 / シグナル伝達 / 獣医学 / 動物 / 臨床

Research Abstract

本研究計画における細胞周期研究では、有糸分裂制御メカニズムを分子レベルで解析することによって、造血系細胞腫瘍の増殖および拡大を制御する新たな標的分子を探索し、腫瘍性増殖を誘導する新たなカスケードを提唱することができた。特に、伴侶動物の肥満細胞腫やリンパ腫・白血病細胞の有糸分裂におけるG1/Sチェックポイント調節タンパクの発現動態やその相互作用を分子レベルで解析、細胞増殖の抑制に重要な標的分子を見出すとともに、新規薬物による治療効果を検討した。

Research Products

• [Journal Article] Prevention of atopicdermatitis in NC/NgaTnd mice by oral supplementation with Lactobacillusrhamnosus CGMCC 1 (2009)
  • Author(s): Tanaka A, Jung K, Benyacoub J, PrioultG, Ohmori K, Blum S, Mercenier A, Matsuda H
  • Journal Title: Exp. Dermatol (In press) Pages: 3724-3724
  • Peer Reviewed
• [Journal Article] Oral supplementation with Lactobacillus rhamnosus CGMCC 1.3724prevents development of atopic dermatitis in NC/NgaTnd mice possibly by modulating local production of IFN-γ (2009)
  • Author(s): Tanaka A., Kyungsook J., Benyacoub J., Prioult G., Okamoto N., Ohmori K., Blum s., Mercenier A., Matsuda H.
  • Journal Title: Exp. Dermatol. (In press)
  • Peer Reviewed
• [Journal Article] Prophylactic effect oforal administration of Lactobacillus johnsonii NCC533(La1)during the weaning period on atopic dermatitis in NC/NgaTnd mice (2008)
  • Author(s): Tanaka A, Fukushima Y, Benyacoub J,Blum S, Matsuda H
  • Journal Title: Eur.J.Dermatol 18 Pages: 136-40
  • Peer Reviewed
• [Journal Article] Identification of c-kit mutations-independent neoplastic cell proliferation of canine mast cells (2008)
  • Author(s): Ohmori K, Kawarai S, Yasuda N, Tanaka A, Matsuda H, Nishimura R, Sasaki N, Tsujimoto H, Masuda K
  • Journal Title: Vet.Immunol. Immunopathol 126 Pages: 43-53
  • Peer Reviewed
• [Journal Article] Establishment of a novel high-affinity IgE receptor-positive canine mast cell line with wild-type c-kit receptors (2008)
  • Author(s): Amagai Y, Tanaka A, Ohmori K, Matsuda H
  • Journal Title: Biochem. Biophys. Res. Commun 366 Pages: 857-61
  • Peer Reviewed
• [Journal Article] Oral administration of bepotastine besilate suppressed scratching behavior of atopicdermatitis model NC/Nga mice (2008)
  • Author(s): Tanizaki H, Kambe N, Nakamura Y,Tanaka A, Matsuda H, Miyachi Y
  • Journal Title: Int. Arch.Allergy Immunol 145 Pages: 277-82
  • Peer Reviewed
• [Journal Article] Oral administration ofdihomo-gamma-linolenic acid prevents development of atopic dermatitis in NC/Nga mice (2008)
  • Author(s): Kawashima H, Tateishi N, Shiraishi A,Teraoka N, Tanaka T, Tanaka A, MatsudaH, Kiso Y
  • Journal Title: Lipids 43 Pages: 37-43
  • Peer Reviewed
• [Journal Article] Superficial keratectomy and topical mitomycin C as therapy for a corneal squamous cell carcinoma in a dog (2008)
  • Author(s): Karasawa K, Matsuda H, Tanaka A
  • Journal Title: J. Small.Anim. Pract 4 Pages: 208-10
  • Peer Reviewed
• [Journal Article] Establishment of a novel high-affinity IgE receptor-positive canine mast cell line with wild type c-kit receptors (2008)
  • Author(s): Amagai Y., Tanaka A., Matsuda H.
  • Journal Title: Biochem. Biophys. Res. Commun. 366 Pages: 857-61
  • Peer Reviewed
• [Journal Article] Prophylacic effect of oral administration of Lactobacillus johnsonii NCC533(La1)during weaning period on atopic dermatitis in NC/NgaTnd mice (2008)
  • Author(s): Tanaka A., Fukushima Y., Benyacoub J., Blum S., Matsuda H.
  • Journal Title: Eur. J. Dermatol 18 Pages: 136-140
  • Peer Reviewed
• [Journal Article] Prophylacic effect of oral administration of Lactobacillus johnsonii NCC533 (La1) during weaning period on atopic dermatitis in NC/NgaTnd mice (2008)
  • Author(s): Akane Tanaka
  • Journal Title: Europian J. Dermatol 18 Pages: 136-140
  • Peer Reviewed
• [Journal Article] Establishment of a novel high-affinity IgE receptor-positive canine mastcell line with wild type c-kit receptors (2008)
  • Author(s): Yosuke Amagai
  • Journal Title: Biochem Biophys Res Commun. 366 Pages: 857-61
  • Peer Reviewed
• [Journal Article] Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice (2007)
  • Author(s): Tanaka A, Muto S, Jung K, Itai A,Matsuda H
  • Journal Title: J.Invest.Dermatol 127 Pages: 855-863
  • Peer Reviewed
• [Journal Article] Ingestion of heat-TREATED lactobacillus rhamnosusGG Prevents Development of atopic dermatitis in NC/Nga mice (2007)
  • Author(s): Sawada J, Morita H, Tanaka A,Salminen S, He F, Matsuda H
  • Journal Title: Clin. Exp.Allergy 37 Pages: 296-303
  • Peer Reviewed
• [Journal Article] The tyrosine kinase inhibitor imatinib(STI571)induces regression of xenografted canine mast cell tumors in SCID mice (2007)
  • Author(s): Kobie K, Kawabata M, Hioki K, TanakaA, Matsuda H, Mori T, Maruo K
  • Journal Title: Res.Vet.Sci 2 Pages: 239-241
  • Peer Reviewed
• [Journal Article] 伴侶動物の腫瘍治療:分子病的治療 (2007)
  • Author(s): 田中あかね
  • Journal Title: アニテックス 19 Pages: 25-31
  • Peer Reviewed
• [Journal Article] The tyrosine kinase inhibitor imatinib [STI571] induces regression of xenografted canine mast cell tumors in SCID mice. (2007)
  • Author(s): Kobie K, Kawabata M, Hioki K, Tanaka A, Matsuda H, Mori T, Maruo K.
  • Journal Title: Research in Veterinary Science 82・2 Pages: 239-241
• [Journal Article] Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice. (2007)
  • Author(s): Tanaka A, Muto S, Jung K, Itai A, Matsuda H.
  • Journal Title: Journal of Investigative Dermatology 127・4 Pages: 855-862
• [Journal Article] A new IkappaB kinase betainhibitor prevents human breast cancerprogression through negative regulation ofcell cycle transition (2006)
  • Author(s): Tanaka A, Muto S, Konno M, Itai A,Matsuda H
  • Journal Title: Cancer Res. 66 Pages: 419-26
  • Peer Reviewed
• [Journal Article] マスト細胞の組織浸潤機構 (2006)
  • Author(s): 田中あかね, 松田浩珍
  • Journal Title: アレルギー・免疫 13・6 Pages: 65-71
• [Presentation] 肥満細胞腫におけるアポトーシス耐性獲得機構の解析 (2009)
  • Author(s): 松田彬
  • Organizer: 第147回日本獣医学会学術集会臨床分科会シンポジウム
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-04-04
• [Presentation] 肥満細胞腫におけるアポトーシス耐性獲得機構の解析 (2009)
  • Author(s): 松田彬, 田中あかね, 大森啓太郎, 松田浩珍
  • Organizer: 第147回日本獣医学会
  • Place of Presentation: 栃木県宇都宮市
  • Year and Date: 2009-04-04
• [Presentation] S-1少量維持療法-その奏効と完遂について (2008)
  • Author(s): 古阪徹
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] Does a strategy thatinterferes with the NF-kappa B pathwaybrings a new insight into thehematopoietic tumor therapy? (2008)
  • Author(s): Tanaka A.
  • Organizer: 13th World Congress on Advances in Oncology and 11th International Symposium on Molecular Medicine
  • Place of Presentation: Creta
  • Year and Date: 2008-10-10
• [Presentation] NF-kappaB阻害剤によるイヌ白血病細胞の増殖抑制効果 (2008)
  • Author(s): 松田彬, 田中あかね, 大森啓太郎, 松田浩珍
  • Organizer: 第1466回日本獣医学会
  • Place of Presentation: 宮崎県宮崎市
  • Year and Date: 2008-09-25
• [Presentation] Bel-2ファミリータンパクの肥満細胞腫細胞増殖への関与 (2008)
  • Author(s): 田中あかね, 大森啓太郎, 松田浩珍
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎県宮崎市
  • Year and Date: 2008-09-25
• [Presentation] Bcl-2ファミリータンパクの肥満細胞腫細胞増殖への関与 (2008)
  • Author(s): 田中あかね
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
  • Year and Date: 2008-09-24
• [Presentation] NF-kappaB阻害剤によるイヌ白血病細胞の増殖抑制効果 (2008)
  • Author(s): 松田彬
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
  • Year and Date: 2008-09-24
• [Presentation] ヒト乳がん細胞株における腫瘍化抑制標的分子の検討 (2008)
  • Author(s): 種田久美子
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
  • Year and Date: 2008-09-24
• [Presentation] 人とペットが快適に暮らすために-犬の気持ちを知ろう-、田無タワー (2008)
  • Author(s): 田中あかね
  • Organizer: 第一回講演会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-21
• [Presentation] アトピー性皮膚炎治療標的としてのIKK-NFkappaB経路の可能性 (2008)
  • Author(s): 田中あかね
  • Organizer: The 7th Cell Biology Summer Meeting(CBSM2008)
  • Place of Presentation: 千葉
  • Year and Date: 2008-07-05
• [Presentation] Bathing in ultra-pure softwater improves skin barrier functions bothin patients with atopic dermatitis and inatopic NC/Nga mice (2008)
  • Author(s): Tanaka A
  • Organizer: XXVII Congress of the European Academy of Allergology and Clinical Immunology
  • Place of Presentation: Barcelona
  • Year and Date: 2008-06-08
• [Presentation] アトピー性皮膚炎治療標的としてのIKKbata-NFkappaB経路の可能性 (2007)
  • Author(s): 田中あかね
  • Organizer: 生体機能と創薬シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2007-09-13
• [Presentation] 犬肥満細胞腫における腫瘍抑制標的分子の検討 (2007)
  • Author(s): 雨貝陽介
  • Organizer: 第144回日本獣医学会学術集会
  • Place of Presentation: 北海道
  • Year and Date: 2007-09-03
• [Presentation] イヌ肥満細胞腫における腫瘍抑制標的分子の検討 (2007)
  • Author(s): 雨貝陽介
  • Organizer: 144回日本獣医学会学術集会
  • Place of Presentation: 北海道・江別
  • Year and Date: 2007-09-03
• [Presentation] ヒト白血病細胞に対するNF-kappaB阻害剤IMD-0354の細胞増殖抑制効果 (2006)
  • Author(s): 田中あかね
  • Organizer: 第44回日本癌治療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-10-20
• [Presentation] イヌ肥満細胞腫の先端的治療法確立に向けて (2006)
  • Author(s): 田中あかね
  • Organizer: 第142回日本獣医学会臨床分科会シンポジウム
  • Place of Presentation: 山口
  • Year and Date: 2006-09-23
• [Presentation] 白血病細胞の増殖機構における転写因子NF-kappaBの役割 (2006)
  • Author(s): 蛇島武久
  • Organizer: 第142回日本獣医学会学術集会
  • Place of Presentation: 山口
  • Year and Date: 2006-09-22
• [Presentation] イヌ肥満細胞腫の腫瘍性増殖におけるPI3Kシグナル伝達系の役割 (2006)
  • Author(s): 雨貝陽介
  • Organizer: 第142回日本獣医学会学術集会
  • Place of Presentation: 山口
  • Year and Date: 2006-09-22
• [Remarks]
  • URL: http://www.tuat.ac.jp/?mol_path/
• [Remarks]
  • URL: http://kenkyu-web.tuat.ac.jp/Profiles/11/0001076/profile.html
• [Remarks] 獣医分子病態治療学研究室ホームページ
  • URL: http://www.tuat.ac.jp/~mol_path/
• [Remarks]
  • URL: http://www.tuat.ac.jp/~mol_path/topicofresearch.html