An exploratory analyses for for the development of novel therapeutic strategies against lung cancer brain metastases

• Project/Area Number: 24591166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: HANIBUCHI Masaki 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (80335794)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺がん / 脳転移 / 血管新生 / 宿主因子

Outline of Final Research Achievements

In the present study, we performed exploratory analyses for the development of novel therapeutic strategies against lung cancer brain metastases.
The expression of various angiogenesis factors was observed in brain metastatic lesions of lung cancer, indicating the significance of angiogenesis in the metastasis formation to the brain. In an experimental brain metastasis model of human lung cancer, an anti-angiogenic agent significantly inhibited the growth of brain metastasis and revealed a striking survival prolongation of tumor-bearing mice.
These results suggest that the inhibition of angiogenesis could be a promising therapeutic strategy for the brain metastases of human lung cancer.

Research Products

• [Journal Article] IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators. (2015)
  • Author(s): Tezuka T, Ogawa H, Azuma M, Goto H, Uehara H, Aono Y, Hanibuchi M, Yamaguchi Y, Fujikawa T, Itai A, Nishioka Y
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of IgG4-related interstitial lung disease showing usual interstitial pneumonia pattern: Unusual case for histological features with pathological proof. (2015)
  • Author(s): Sato S, Hanibuchi M, Tobiume M, Kishi J, Toyoda Y, Kawano H, Takahashi M, Fukuda Y, Nishioka Y
  • Journal Title: Case Rep Clin Pathol Volume: 2 Pages: 6-11
  • Peer Reviewed / Open Access
• [Journal Article] A case of atypical Takayasu arteritis initially presenting with peripheral artery disease. (2015)
  • Author(s): Kawano H, Hanibuchi M, Yoshijima T, Toyoda Y, Kishi J, Tezuka T, Nishioka Y
  • Journal Title: Case Rep Clin Pathol Volume: 2 Pages: 34-40
  • Peer Reviewed / Open Access
• [Journal Article] The molecular biology of lung cancer brain metastasis: an overview of current comprehensions and future perspectives. (2014)
  • Author(s): Hanibuchi M, Kim SJ, Fidler IJ, Nishioka Y
  • Journal Title: J Med Invest Volume: 61 Pages: 241-253
  • NAID: 130004822728
  • Peer Reviewed / Open Access
• [Journal Article] Serum biomarkers for personalization of nanotherapeutics-based therapy in different tumor and organ microenvironments. (2014)
  • Author(s): Yokoi K, Tanei T, Godin B, van de Ven AL, Hanibuchi M, Matsunoki A, Alexander J, Ferrari M
  • Journal Title: Cancer Lett Volume: 345 Pages: 48-55
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thymidine phosphorylase regulates the expression of CXCL10 in rheumatoid arthritis fibroblast-like synoviocytes. (2014)
  • Author(s): Toyoda Y, Tabata S, Kishi J, Kuramoto T, Mitsuhashi A, Saijo A, Kawano H, Goto H, Aono Y, Hanibuchi M, Horikawa H, Nakajima T, Furukawa T, Sone S, Akiyama S, Nishioka Y
  • Journal Title: Arthritis Rheumatol Volume: 66 Pages: 560-568
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Idiopathic pleuroparenchymal fibroelastosis is characterized by an elevated serum level of Surfactant Protein-D, but not Krebs von den Lungen-6. (2014)
  • Author(s): Sato S, Hanibuchi M, Fukuya A, Yabuki Y, Bando H, Yoshijima T, Goto H, Ogawa H, Nishioka Y
  • Journal Title: Lung Volume: 192 Pages: 711-717
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment (2013)
  • Author(s): Sato S, Hanibuchi M, Kuramoto T, Yamamori N, Goto H, Ogawa H, Mitsuhashi A, Van TT, Kakiuchi S, Akiyama S, Nishioka Y, Sone S
  • Journal Title: Clin Exp Metastasis Volume: 30 Pages: 333-344
  • Peer Reviewed
• [Journal Article] Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages (2013)
  • Author(s): Mitsuhashi A, Goto H, Kuramoto T, Tabata S, Yukishige S, Abe S, Hanibuchi M, Kakiuchi S, Saijo A, Aono Y, Uehara H, Yano S, Ledford JG, Sone S, Nishioka Y
  • Journal Title: Am J Pathol Volume: 182 Pages: 1843-1853
  • Peer Reviewed
• [Journal Article] A novel targeting therapy of malignant mesothelioma using anti-podoplanin antibody (2013)
  • Author(s): Abe S, Morita Y, Kaneko MK, Hanibuchi M, Tsujimoto Y, Goto H, Kakiuchi S, Aono Y, Huang J, Sato S, Kishuku M, Taniguchi Y, Azuma M, Kawazoe K, Sekido Y, Yano S, Akiyama S, Sone S, Minakuchi K, Kato Y, Nishioka Y
  • Journal Title: J Immunol Volume: 190 Pages: 6239-6249
  • Peer Reviewed
• [Journal Article] Identification of pregnancy-associated plasma protein A as a migration-promoting gene in malignant pleural mesothelioma cells: a potential therapeutic target (2013)
  • Author(s): Huang J, Tabata S, Kakiuchi S, Van TT, Goto H, Hanibuchi M, Nishioka Y
  • Journal Title: Oncotarget Volume: 4 Pages: 1172-1184
  • Peer Reviewed
• [Journal Article] Dll4-Fc, an inhibitor of Dll4-Notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-kappaB activity (2012)
  • Author(s): Kuramoto T, et al
  • Journal Title: Mol Cancer Ther Volume: 11 Pages: 2578-2587
  • Peer Reviewed
• [Presentation] 当院における間質性肺炎合併肺癌の治療の現状 (2014)
  • Author(s): 柿内聡司, 大塚憲司, 佐藤正大, 西條敦郎, 坂口暁, 後東久嗣, 埴淵昌毅, 西岡安彦
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館 (京都府, 京都市)
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] ベバシズマブに対する獲得耐性メカニズムとしての線維細胞 (fibrocytes) の役割 (2014)
  • Author(s): 後東久嗣, 三橋惇志, 西條敦郎, 柿内聡司, 埴淵昌毅, 上原久典, 矢野聖二, 西岡安彦
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 (神奈川県, 横浜市)
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Role of human fibrocytes in regulating pulmonary fibrosis: comprehensive analysis of their gene expression profile and growth factor production. (2014)
  • Author(s): Yasuhiko Nishioka, Shuichi Abe, Seidai Sato, Yoshinori Aono, Hisatsugu Goto, Masami Kishi, Terumi Yoshijima, Hiroyasu Okazaki, Masaki Hanibuchi
  • Organizer: The 18th International Colloquium on Lung and Airway Fibrosis
  • Place of Presentation: St Joseph's Hospital, Mont-Tremblant, Quebec (Canada)
  • Year and Date: 2014-09-20 – 2014-09-24
• [Presentation] 高齢者進行非小細胞肺癌患者を対象としてPRO評価を取り入れたTS-1療法の臨床第II相試験 (2014)
  • Author(s): 大塚憲司, 後東久嗣, 葉久貴司, 兼松貴則, 浦田知之, 柿内聡司, 埴淵昌毅, 大串文隆, 曽根三郎, 西岡安彦
  • Organizer: 第12回日本臨床腫瘍学会学術集会
  • Place of Presentation: 福岡国際会議場 (福岡県, 福岡市)
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] 肺癌多臓器転移モデルにおけるsphere形成癌幹細胞様分画の役割 (2014)
  • Author(s): 後東久嗣, 三橋惇志, 倉本卓哉, 田畑祥, 西條敦郎, 柿内聡司, 埴淵昌毅, 上原久典, 西岡安彦
  • Organizer: 第23回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール (石川県, 金沢市)
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] ヒト小細胞肺癌骨転移に対するRANKL標的治療におけるIGF-1の関与 (2014)
  • Author(s): .山子泰斗, 後東久嗣, 三橋惇志, 倉本卓哉, 田畑祥, 西條敦郎, 柿内聡司, 埴淵昌毅, 小川博久, 上原久典, 西岡安彦
  • Organizer: 第23回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール (石川県, 金沢市)
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 胸膜中皮腫同所移植モデルにおける抗ポドプラニン抗体の抗腫瘍効果 (2014)
  • Author(s): 大塚憲司, 阿部真治, 埴淵昌毅, 木宿昌俊, 川添和義, 加藤幸成, 西岡安彦
  • Organizer: 第18回日本がん分子標的治療学会学術集会
  • Place of Presentation: 仙台市情報・産業プラザ (宮城県, 仙台市)
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] Effect of Nintedanib (BIBF1120) on fibrocyte-induced fibroblast activation. (2014)
  • Author(s): Seidai Sato, Hisatsugu Goto, Shuichi Abe, Masami Kishi, Katsuhiro Kinoshita, Momoyo Azuma, Akio Takezaki, Jun Kishi, Yoshinori Aono, Masaki Hanibuchi, Yasuhiko Nishioka
  • Organizer: ATS 2014 International Conference
  • Place of Presentation: San Diego Conventin Center, San Diego, CA (USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] The role of fibrocytes in the resistance to anti-angiogenic therapy in malignant pleural mesothelioma and lung cancer. (2014)
  • Author(s): Hisatsugu Goto, Atsushi Mitsuhashi, Atsuro Saijo, Trung The Van, Yoshinori Aono, Hirohisa Ogawa, Soji Kakiuchi, Masaki Hanibuchi, Seiji Yano, Keisuke Izumi, Yasuhiko Nishioka
  • Organizer: ATS 2014 International Conference
  • Place of Presentation: San Diego Conventin Center, San Diego, CA (USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 悪性胸膜中皮腫同所移植モデルにおける抗ポドプラニン抗体の抗腫瘍効果 (2014)
  • Author(s): 埴淵昌毅, 阿部真治, 加藤幸成, 金子美華, 東満美, 後東久嗣, 西岡安彦
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場 (大阪府, 大阪市)
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] 当院における間質性肺炎合併肺癌の治療の現状 (2014)
  • Author(s): 柿内聡司, 大塚憲司, 佐藤正大, 西條敦郎, 坂口暁, 後東久嗣, 埴淵昌毅, 西岡安彦
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場 (大阪府, 大阪市)
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Acquired resistance to anti-VEGF therapy via angiogenic switch in orthotopically implanted human malignant pleural mesothelioma in SCID mice (2013)
  • Author(s): Atsushi Mitsuhashi, Hisatsugu Goto, Trung The Van, Takuya Kuramoto, Sho Tabata, Masaki Hanibuchi, Soji Kakiuchi, Atsuro Saijo, Yoshinori Aono, Hisanori Uehara, Seiji Yano, Saburo Sone, Yasuhiko Nishioka
  • Organizer: Ninth AACR-Japanese Cancer Association Joint Conference: Breakthroughs in Basic and Translational Cancer Research
  • Place of Presentation: Hyatt Regency Maui, Maui, HI(USA)
• [Presentation] Therapeutic efficacy of RNA interference targeting focal adhesion kinase against orthotropic xenograft of human malignant pleural mesothelioma in SCID mice (2013)
  • Author(s): Jun Huang, Dai-Shun Liu, Soji Kakiuchi, Hisatsugu Goto, Masaki Hanibuchi, Yasuhiko Nishioka
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington Convention Center, Washington DC(USA)
• [Presentation] Surfactant protein A suppresses lung cancer progression by regulating tumor-associated macrophage polarization (2013)
  • Author(s): Hisatsugu Goto, Atsushi Mitsuhashi, Takuya Kuramoto, Sho Tabata, Sawaka Yukishige, Masaki Hanibuchi, Soji Kakiuchi, Atsuro Saijo, Yoshinori Aono, Hisanori Uehara, Seiji Yano, Julie G. Ledford, Saburo Sone, Yasuhiko Nishioka
  • Organizer: ATS 2013 Conference
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA(USA)
• [Presentation] Phase II study of S-1 with patient-reported outcome evaluation in elderly patients with advanced non-small cell lung cancer (2013)
  • Author(s): Hisatsugu Goto, Fumitaka Ogushi, Takashi Haku, Tomoyuki Urata, Takanori Kanematsu, Soji Kakiuchi, Masaki Hanibuchi, Saburo Sone, Yasuhiko Nishioka
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Pacifico Yokohama, Yokohama(Kanagawa), Japan
• [Presentation] Therapeutic efficacy of endothelin receptor blockade on experimental brain metastases of human non-small cell lung cancer (2013)
  • Author(s): Masaki Hanibuchi, Sun-Jin Kim, Kenji Otsuka, Atsushi Mitsuhashi, Hisatsugu Goto, Yasuhiko Nishioka, Isaiah J. Fidler
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Pacifico Yokohama, Yokohama(Kanagawa), Japan
• [Presentation] ヒトNK細胞を介した抗ポドプラニン抗体NZ-8の悪性胸膜中皮腫に対する抗腫瘍効果 (2013)
  • Author(s): 阿部真治, 加藤幸成, 金子美華, 木宿昌俊, 川添和義, 東満美, 埴淵昌毅, 水口和生, 西岡安彦
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京都)
• [Presentation] Endothelin受容体拮抗剤による肺癌脳転移抑制効果の検討 (2013)
  • Author(s): 埴淵昌毅, 大塚憲司, 後東久嗣, 倉本卓哉, 三橋惇志, 西岡安彦, 曽根三郎, Fidler IJ
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] がん細胞の遊走におけるthymidine phosphorylaseとCXCL11の役割 (2013)
  • Author(s): 西條敦郎, 後東久嗣, 田畑祥, 三橋惇志, 豊田優子, 埴淵昌毅, 柿内聡司, 秋山伸一, 西岡安彦
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: ホテルブエナビスタ松本(長野県)
• [Presentation] 呼吸器疾患のControversy 高齢者肺癌にベバシズマブは必要か? (2013)
  • Author(s): 埴淵昌毅, 柿内聡司, 後東久嗣, 西岡安彦
  • Organizer: 第49回日本呼吸器学会中国・四国地方会 第20回呼吸器セミナー
  • Place of Presentation: アルファあなぶきホール(香川県)
• [Presentation] 高齢者進行非小細胞肺癌患者を対象としてPRO評価を取り入れたTS-1療法の臨床第II相試験 (2013)
  • Author(s): 岡野義夫, 後東久嗣, 葉久貴司, 兼松貴則, 浦田知之, 柿内聡司, 埴淵昌毅, 大串文隆, 曽根三郎, 西岡安彦
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: ホテルニューオータニ(東京都)
• [Presentation] 肺癌脳転移に対する新規治療法の探索的検討 (2013)
  • Author(s): 埴淵昌毅, 他
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Place of Presentation: 国立京都国際会館 (京都府)
• [Presentation] ヒト肺がん多臓器転移モデルにおけるMacrophage-stimulating proteinの役割に関する検討 (2012)
  • Author(s): 倉本卓哉, 他
  • Organizer: 第16回日本がん分子標的治療学会学術集会
  • Place of Presentation: 西日本総合展示場AIM3F (福岡県)
• [Presentation] Endothelin受容体拮抗剤による肺癌脳転移抑制効果の検討 (2012)
  • Author(s): 大塚憲司, 他
  • Organizer: 第21回日本がん転移学会学術集会・総会
  • Place of Presentation: オリエンタルホテル広島 (広島県)
• [Presentation] Eradication of experimental brain metastases of human non-small cell lung cancer by macitentan, a dual antagonist of the endothelin A and B receptor, combined with paclitaxel (2012)
  • Author(s): Masaki Hanibuchi, et al
  • Organizer: A Joint Meeting by ASCO, EORTC, and NCI. Markers in Cancer
  • Place of Presentation: Westin Diplomat (USA)