Enhancement of nanoparticle accumulation via regulation of tumor vasculature

• Project/Area Number: 19790282
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: KANO Mitsunobu The University of Tokyo, 大学院医学系研究科, 講師 (80447383)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 病理学 / 癌 / ナノバイオ

Research Abstract

我々はナノ粒子薬剤とTGF-β阻害剤の併用により難治固形癌の治療効率を高める可能性を示してきたが、本研究でその適応範囲を検討した。その結果、壁細胞被覆の多い新生血管はTGF-β阻害剤で漏出化し高分子物質の貯留が増加したが、被覆の少ない血管は、元来漏出性が高い上にVEGF 阻害剤で貯留が増加した。壁細胞被覆の多い新生血管は腫瘍モデルでは間質量の多い組織型のものに観察された。

Research Products

• [Journal Article] Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-b receptor inhibitor on extravasation of nanoparticles from neovasculature. (2009)
  • Author(s): Kano, M.R., Komuta, Y., Iwata, C., Oka, M., Shirai, Y., Morishita, Y., Ouchi, Y., Kataoka, K., Miyazono, K.
  • Journal Title: Cancer Sci. 100 Pages: 173-80
  • Peer Reviewed
• [Journal Article] EMT制御と分子標的薬 (2009)
  • Author(s): 狩野光伸, 宮園浩平
  • Journal Title: 実験医 27 Pages: 653-660
• [Journal Article] Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-b receptor inhibitor on extravasation of nanoparticles from neovasculature (2009)
  • Author(s): Kano, M.R., Komuta, Y., Iwata, C., Oka, M., Shirai, Y., Morishit a, Y., Ouchi, Y., Kataoka, K., and Miyazono, K.
  • Journal Title: Cancer Sci 100 Pages: 173-80
  • Peer Reviewed
• [Journal Article] EMT制御と分子標的薬 (2009)
  • Author(s): 狩野光伸・宮園浩平
  • Journal Title: 実験医学 27 Pages: 653-660
• [Journal Article] Inhibition of endogenous TGF-b signaling enhances lymphangiogenesis (2008)
  • Author(s): Oka, M., Iwata, C., Suzuki, H.I., Kiyono, K., Morishita, Y., Watabe, T., Komuro, A., Kano, M.R., Miyazono, K.
  • Journal Title: Blood 111 Pages: 4571-4579
  • Peer Reviewed
• [Journal Article] Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue. (2008)
  • Author(s): Miyata K, Oba M, Kano MR, Fukushima S, Vachutinsky Y, Han M, Koyama H, Miyazono K, Nishiyama N, Kataoka K.
  • Journal Title: Pharm Res. 25 Pages: 924-36
  • Peer Reviewed
• [Journal Article] 腫瘍発育、血管新生、治療反応性への動脈硬化と血管老化の影響 (2008)
  • Author(s): 狩野光伸
  • Journal Title: 分子細胞治療 7(1) Pages: 79-80
• [Journal Article] Inhibition of endogenous TGF-b signaling enhances lymphangiogenesis (2008)
  • Author(s): Oka, M., Iwata, C., Suzuki, H.I. , Kiyono, K., Morishita, Y., Watabe, T., Komuro, A., Kano, M.R., and Miyazono, K.
  • Journal Title: Blood 111 Pages: 4571-4579
  • Peer Reviewed
• [Journal Article] Polyplex Micelles from Triblock Copolymers Composed of Tandemly Alirned Segments with Biocompatible, Endosomal Escaping, and DNA-Contdeasing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue (2008)
  • Author(s): Miyata K, Oba M, Kano MR, F ukushima S, Vachutinsky Y, Han M, Koyama H, Miyazono K, Nishivama N. Kataoka K.
  • Journal Title: Pharm Res 25 Pages: 924-936
  • Peer Reviewed
• [Journal Article] 血管におけるTGF-βファミリーシグナル (2008)
  • Author(s): 狩野光伸・宮園浩平
  • Journal Title: 医学のあゆみ 223 Pages: 1037-1042
• [Journal Article] Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-β signaling. (2007)
  • Author(s): M. R. Kano, Y. Bae, C. Iwata, Y. Morishita, M. Yashiro, M. Oka, T. Fujii, A. Komuro, K. Kiyono, M. Kaminishi, K. Hirakawa, Y. Ouchi, N. Nishiyama, K. Kataoka, K. Miyazono
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 104(9) Pages: 3460-3465
  • Peer Reviewed
• [Journal Article] Inhibition of Cyclooxygenase-2 (COX-2) Suppresses Lymph Node Metastasis via Reduction of Lymphangiogenesis. (2007)
  • Author(s): C. Iwata, M. R. Kano, A. Komuro, M. Oka, K. Kiyono, E. Johansson, Y. Morishita, M. Kaminishi, M. Yashiro, K. Hirakawa, K. Miyazono
  • Journal Title: Cancer Res. 67 (21) Pages: 10181-10189
  • Peer Reviewed
• [Journal Article] ナノ粒子抗癌剤と低用量TGF-β阻害剤の併用による難治癌治療 (2007)
  • Author(s): 狩野光伸
  • Journal Title: 実験医学 25(9) Pages: 1344-1347
• [Journal Article] TGF-βシグナルの制御と癌治療 (2007)
  • Author(s): 狩野光伸
  • Journal Title: 細胞 39(8) Pages: 31-33
• [Journal Article] 血管におけるTGF-βファミリーシグナル (2007)
  • Author(s): 狩野光伸, 宮園浩平
  • Journal Title: 医学のあゆみ 223(12) Pages: 1037-1042
• [Journal Article] Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-β signaling (2007)
  • Author(s): M. R. Kano, Y. Bae, C. Iwata, Y. Morishita, M. Yashiro, M. Oka, T. Fujii, A. Komuro, K. Kiyono, M. Kaminishi, K. Hirakawa, Y. Ouchi, N. Nishiyama, K. Kataoka, and K. Miyazono
  • Journal Title: Proc, Natl. Acad. Sci. U.S.A. 104(9) Pages: 3460-3465
  • Peer Reviewed
• [Journal Article] Inhibition of Cyclooxygenase-2(COX-2)Suppresses Lymph Node Metastasis via Reduction of Lymphangiogenesis (2007)
  • Author(s): C. Iwata, M. R. Kano, A. Komuro, M. Oka, K. Kiyono, E. Johansson, Y. Morishita, M. Kaminishi, M. Yas hiro, K. Hirakawa, and K. Miyazono
  • Journal Title: Cancer Res. 67(21) Pages: 10181-10189
  • Peer Reviewed
• [Journal Article] 血管におけるTGF-βファミリーシグナル (2007)
  • Author(s): 狩野光伸・宮園浩平
  • Journal Title: 医学のあゆみ 223(12) Pages: 1037-1042
• [Presentation] 脈管制御を応用した難治がん治療法の開拓 (2009)
  • Author(s): 狩野光伸
  • Organizer: 第7回次世代バイオマテリアル研究会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2009-03-09
• [Presentation] 脈管制御を応用した難治がん治療法の開拓 (2009)
  • Author(s): 狩野光伸
  • Organizer: 第7回次世代バイオマテリアル研究会
  • Place of Presentation: 東京都文京区1東京医科歯科大学生体材料工学研究所
  • Year and Date: 2009-03-09
• [Presentation] Optimal manipulation of tumor vasculature for treatment of intractable solid tumors using nanoparticles. (2008)
  • Author(s): Kano, MR.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] Optimal manipulation of tumor vasculature for treatment of intractable solid tumors using nanoparticles (2008)
  • Author(s): 狩野光伸
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 愛知県名古屋市名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 難治性固形腫瘍に対するナノDDS治療の実現化 (2008)
  • Author(s): 狩野光伸
  • Organizer: 第24回日本DDS 学会学術総会
  • Place of Presentation: 六本木ヒルズ
  • Year and Date: 2008-06-30
• [Presentation] 難治性固形腫瘍に対するナノDDS治療の実現化 (2008)
  • Author(s): 狩野光伸
  • Organizer: 第24回日本DDS学会学術総会
  • Place of Presentation: 東京都港区六本木アカデミーヒルズ
  • Year and Date: 2008-06-30
• [Presentation] Manipulation of TGF-β signaling for cancer treatment. (2008)
  • Author(s): Kano, MR.
  • Organizer: 28th Sapporo Cancer Seminar International Symposium.
  • Place of Presentation: 北海道大学
  • Year and Date: 2008-06-27
• [Presentation] Manipulation of TGF-β signaling for cancer treatment (2008)
  • Author(s): 狩野光伸
  • Organizer: 28th Sapporo Cancer Seminar International Symposium ; Sapporo, Janan
  • Place of Presentation: 北海道札幌市北海道大学学術交流会館
  • Year and Date: 2008-06-27
• [Presentation] 腫瘍血管新生制御が薬剤送達に影響を与える際の組織学的要因の解明 (2008)
  • Author(s): 狩野光伸
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2008-05-16
• [Presentation] 腫瘍血管新生制御が薬剤送達に影響を与える際の組織学的要因の解明 (2008)
  • Author(s): 狩野光伸
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 石川県金沢市石川県立音楽堂
  • Year and Date: 2008-05-16
• [Presentation] Optimal Manipulation of Vasculature for Nanoparticles in Intractable tumors. (2007)
  • Author(s): Kano, MR.
  • Organizer: Swiss-Japan Symposium on Nanobio 2007.
  • Place of Presentation: 東京大学武田先端知ビル
  • Year and Date: 2007-10-11
• [Presentation] Optimal Manipulation of Vasculature for Nanoparticles in Intractable tumors. (2007)
  • Author(s): Kano, MR
  • Organizer: Swiss-Japan Symposium on Nanobio 2007
  • Place of Presentation: 東京
  • Year and Date: 2007-10-11
• [Presentation] TGF-beta signaling and regulation of cancer. (2007)
  • Author(s): Kano, MR, Miyazono, K.
  • Organizer: Queenstown Molecular Biology 2007 satellite symposium.
  • Place of Presentation: Queenstown, New Zealand
  • Year and Date: 2007-08-27
• [Presentation] TGF-beta signaling and regulation of cancer. (2007)
  • Author(s): Kano, MR, Miyazono, K
  • Organizer: Queenstown Molecular Biology 2007 satellite sympossum
  • Place of Presentation: Queenstown, New Zealand
  • Year and Date: 2007-08-27
• [Presentation] Low-dose TGF-beta inhibitor improves cancer-targeting therapy using nanocarriers for intractable solid tumors. (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Shirai, Y., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K.
  • Organizer: Gordon Research Conference, Angiogenesis and microcirculation.
  • Place of Presentation: Salva Regina University, Newport, RI, USA
  • Year and Date: 2007-08-22
• [Presentation] Low-dose TGF-beta inhibitor improves cancer-targeting therapy using nanocarriers for intractable solid tumors (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Shirai, Y., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K
  • Organizer: Gordon Research Conference, Angiogenesis and microcirculation
  • Place of Presentation: Newport, RI, USA
  • Year and Date: 2007-08-22
• [Presentation] Low-dose TGF-beta inhibitor improves cancer therapy using nanocarriers for intractable solid tumors. (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K
  • Organizer: The 34th Annual Meeting of the Controlled Release Society.
  • Place of Presentation: Long Beach, CA, USA
  • Year and Date: 2007-06-11
• [Presentation] Low-dose TGF-beta inhibitor improves cancer therapy using nanocarriers for intractable solid tumors (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K
  • Organizer: The 34th Annual Meeting of the Controlled Release Society
  • Place of Presentation: Long Beach, CA, USA
  • Year and Date: 2007-06-11
• [Presentation] Low-dose TGF-s inhibitor for effective nanotechnology-based chemotherapy in intractable solid tumors. (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K.
  • Organizer: The 2007 AACR Annual Meeting
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-14
• [Presentation] Low-dose TGF-β inhibitor for effective nanotechnology-based chemotherapy in intractable solid tumors (2007)
  • Author(s): Kano, MR, Bae, YS., Iwata, C., Oka, M., Fujii, T., Morishita, Y., Nishiyama, N., Kataoka, K., Miyazono, K
  • Organizer: The 2007 AACR Annual Meeting
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-14
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/index.html
• [Patent(Industrial Property Rights)] 腫瘍撮像用MRI造影剤 (2007)
  • Inventor(s): 片岡一則、熊谷康顕、狩野光伸、関野正樹、松浦哲也、西山伸宏、宮園浩平
  • Industrial Property Rights Holder: 東京大学TLO
  • Industrial Property Number: 2007-124908
  • Filing Date: 2007-06-25