Development of selective and efficient drug delivery system for malignant brain tumors using polymeric nanomicelles.

• Project/Area Number: 21591864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: INO Yasushi 東京大学, 医科学研究所, 准教授 (50372371)
• Co-Investigator(Kenkyū-buntansha): KATAOKA Kazunori 東京大学, 大学院・工学系研究科, 教授 (00130245)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Nobuhiro 東京大学, 大学院・医学系研究科, 准教授 (10372385) ; TODO Tomoki 東京大学, 医学部附属病院, 教授 (80272566)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脳腫瘍学 / ドラッグデリバリーシステム / 悪性脳腫瘍 / ドラッグ・デリバリー / 癌 / 脳神経疾患 / ナノ材料 / 生体材料

Research Abstract

We performed a basic research on the method to enhance the efficacy of polymeric nanomicelles as a drug delivery system. The polymeric nanomicelles consist of block polymers which were meticulously designed to achieve highly selective accumulation to solid tumors. The effect of co-administration of chemicals which modify permeability of tumor vasculatures, or the effect of loading tumor cell specific ligands to outer layer of the micelles were studied. A new technology for detecting in vivo distribution of the micelle was also tested.

Research Products

• [Journal Article] Extended field stereotactic radiosurgery for recurrent glioblastoma (2011)
  • Author(s): Koga T, Maruyama K, Tanaka M, Ino Y, Saito N, Nakagawa K, Shibahara J, Todo T
  • Journal Title: Cancer Volume: 118 Issue: 17 Pages: 4193
  • DOI: 10.1002/cncr.27372
  • Peer Reviewed
• [Journal Article] Glioma-initiating cells retain their tumorigenicity through integration of the Sox axis and Oct4 protein (2011)
  • Author(s): Saito N, Miyazawa K, Miyazono K
  • Journal Title: J Biol Chem Volume: 286 Issue: 48 Pages: 41434
  • DOI: 10.1074/jbc.m111.300863
  • Peer Reviewed
• [Journal Article] 悪性脳腫瘍の遺伝子治療 (2011)
  • Author(s): 藤堂具紀、稲生靖
  • Journal Title: BIO Clinica Volume: 26巻、4号 Pages: 33-37
• [Journal Article] NKX2.2 suppresses self-renewal of glioma-initiating cells (2011)
  • Author(s): Muraguchi T, Tanaka S, Yamada D, Tamase A, Nakada M, Nakamura H, Hoshii H, Ooshio T, Tadokoro Y, Naka K, Ino Y, Todo T, Kuratsu J, Saya H, Hamada J
  • Journal Title: Cancer Res Volume: 71 Issue: 3 Pages: 1135
  • DOI: 10.1158/0008-5472.can-10-2304
  • Peer Reviewed
• [Journal Article] Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells (2011)
  • Author(s): Watanabe, A., et al
  • Journal Title: Proceedings of National Academy of Science U.S.A. Volume: 108 Issue: 30 Pages: 12384
  • DOI: 10.1073/pnas.0906930108
  • Peer Reviewed
• [Journal Article] 悪性神経膠腫に対するヘルペスウイルス療法 (2011)
  • Author(s): 稲生靖、藤堂具紀
  • Journal Title: Clinical Neuroscience Volume: 29巻、2号 Pages: 229-231
• [Journal Article] Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells (2011)
  • Author(s): Watanabe A, Ogiwara H, Ehata S, Mukasa A, Ishikawa S, Maeda D, Ueki K, Ino Y, Todo T, Yamada Y, Fukayama M, Saito N, Miyazono K, Aburatani H
  • Journal Title: Proc Natl Aced Sci USA Volume: 108 Pages: 12384-12389
  • Peer Reviewed
• [Journal Article] NKX2.2 suppresses self-renewal of glioma-initiating cells by induction of oligodendroglial differentiation (2011)
  • Author(s): Muraguchi T, Tanaka S, Tamase A, Nakada M, Nakamura H, Hoshii T, Ooshio T, Tadokoro Y, Naka K, Ino Y, Todo T, Kuratsu J, Saya H, Hamada J, Hirao A
  • Journal Title: Cancer Res Volume: 71 Pages: 1135-1145
  • Peer Reviewed
• [Journal Article] Gioma-initiating cells retain their tumorigenicity through integration of the Soxaxis and Oct4 protein (2011)
  • Author(s): Ikushima H, Todo T, Ino Y, Takahashi M, Saito N, Miyazawa K, Miyazono K
  • Journal Title: J Biol Chem Volume: 26 Pages: 41434-41441
  • Peer Reviewed
• [Journal Article] NKX2.2 suppresses self-renewal of glioma-initiating cells by induction of oligodendroglial differentiation. (2011)
  • Author(s): Muraguchi T, Tanaka S, Tamase A, Nakada M, Nakamura H, Hoshii T, Ooshio T, Tadokoro Y, Naka K, Ino Y, Todo T, Kuratsu J, Saya H, Hamada J, Hirao A
  • Journal Title: Cancer Res. Volume: 71(3) Pages: 1135-1145
• [Journal Article] 悪性脳腫瘍の遺伝子治療 (2011)
  • Author(s): 藤堂具紀、稲生靖
  • Journal Title: BIO Chnica Volume: 26(4) Pages: 33-37
• [Journal Article] 悪性脳腫瘍のウイルス療法 (2010)
  • Author(s): 稲生靖、藤堂具紀
  • Journal Title: Biotherapy Volume: 24巻、6号 Pages: 443-447
• [Journal Article] Clinical development of a third-generation oncolytic HSV-1(G47Δ) for malignant glioma (2010)
  • Author(s): Ino Y, Todo T.
  • Journal Title: Gene Therapy and Regulation Volume: Vol.5、No.1 Pages: 101-111
  • Peer Reviewed
• [Journal Article] 悪性脳腫瘍に対するウイルス療法 (2010)
  • Author(s): 稲生靖、藤堂具紀
  • Journal Title: 日本臨床(増刊号新時代の脳腫瘍学-診断・治療の最前線) Volume: 68巻 Pages: 473-477
• [Journal Article] 悪性脳腫瘍に対するウイルス療法 (2010)
  • Author(s): 稲生靖、藤堂具紀
  • Journal Title: 感染・炎症・免疫 Volume: 40巻、1号 Pages: 81-83
• [Journal Article] Clinical development of a third-generation oncolytic HSV-1 (G47Δ) for malignant glioma. (2010)
  • Author(s): Ino Y.Todo T.
  • Journal Title: Gene Therapy and Regulation Volume: 5(1) Pages: 101-111
• [Journal Article] Autocrine TGF-β Signaling Maintains Tumorigenicity of Glioma-Initiating Cells through Sry-Related HMG-Box Factors (2009)
  • Author(s): Ikushima H, Todo T, Ino Y, Takahashi M, Miyazawa K, Miyazono K.
  • Journal Title: Cell Stem Cell Volume: 5 Issue: 5 Pages: 504
  • DOI: 10.1016/j.stem.2009.08.018
  • Peer Reviewed
• [Journal Article] 悪性脳腫瘍に対するウイルス療法 (2009)
  • Author(s): 稲生靖、藤堂具紀
  • Journal Title: BRAIN and NERVE Volume: 61巻、7号 Pages: 442-446
  • Peer Reviewed
• [Journal Article] Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation (2009)
  • Author(s): Koga T, Morita A, Maruyama K, Tanaka M, Ino Y, Shibahara J, Louis DN, Reifenberger G, Itami J, Hara R, Saito N, Todo T
  • Journal Title: Neuro-Oncolog Volume: 11 Issue: 4 Pages: 446
  • DOI: 10.1215/15228517-2008-112
  • Peer Reviewed
• [Journal Article] Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation. (2009)
  • Author(s): Koga T, Morita A, Maruyama K, Tanaka M, 稲生靖, Shibahara J, Louis DN, Reifenberger G, Itami J, Hara R, Saito N, Todo T
  • Journal Title: Neuro-Oncology 11(4) Pages: 446-451
  • Peer Reviewed
• [Journal Article] 悪性脳腫瘍に対するウイルス療法 (2009)
  • Author(s): 稲生靖, 藤堂具紀
  • Journal Title: BRAIN and NERVE 61(7) Pages: 442-446
• [Journal Article] Autocrine TGF-β signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors (2009)
  • Author(s): Ikushima H, Todo T, 稲生靖, Takahashi M, Miyazawa K, Miyazono K
  • Journal Title: Cell Stem Cell 5(5) Pages: 504-514
  • Peer Reviewed
• [Presentation] 悪性グリオーマのウイルス療法 (2011)
  • Author(s): 藤堂具紀、稲生靖
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] A clinical study of a third-generation oncolytic HSV-1(G47Δ) in patients with recurrent glioblastoma (2011)
  • Author(s): 藤堂具紀、稲生靖
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
• [Presentation] A clinical study of a third-generation oncolytic HSV-1 (G47Δ) in patients with recurrent glioblastoma (2011)
  • Author(s): 藤堂具紀、稲生靖
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
• [Presentation] Oncolytic HSV-1(G47Δ) efficiently kills glioblastoma-derived cancer stem-like cells (2010)
  • Author(s): Todo T, Ino Y.
  • Organizer: The 18^<th> International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Travemuende, Germany
• [Presentation] Oncolytic HSV-1 (G47 Δ) efficiently kills glioblastoma-derived cancerstem cells (2010)
  • Author(s): Ino Y.Takahashi M, Saito N, Ikushima H, Miyazono K, Todo T
  • Organizer: The 18^<th> International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Travemuende, Germany
• [Presentation] 再発膠芽腫に対するウイルス療法:First-in-Man臨床研究の進捗状況 (2010)
  • Author(s): 藤堂具紀、田中実、高橋雅道、斎藤邦昭、辛正廣、甲賀智之、武笠晃丈、斉藤延人、稲生靖
  • Organizer: 日本脳神経外科学会第69回学術総会
  • Place of Presentation: 福岡
• [Presentation] 緩徐に増大する腫瘍にも高い治療効果を示す新世代がん治療用ヘルペスウイルスの開発 (2010)
  • Author(s): 稲生靖、福原浩、釣巻ゆずり、侯剣剛、竹島雄太、本間之夫、藤堂具紀
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 脳腫瘍に対するウイルス療法開発に見る我が国のトランスレーショナルリサーチ (2009)
  • Author(s): 藤堂具紀、稲生靖
  • Organizer: 第10回日本分子脳神経外科学会
  • Place of Presentation: 岡山
  • Year and Date: 2009-09-19