DEVELOPMENT OF CANCER CHEMO-IMMUNOTHERAPEUTIC SYSTEM USING REDOX CONTROLLABLE DDS

• Project/Area Number: 20390010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: NISHIKAWA Makiya Kyoto University, 薬学研究科, 准教授 (40273437)
• Co-Investigator(Kenkyū-buntansha): TABATA Yasuhiko 京都大学, 再生医科学研究所, 教授 (50211371) ; YURIMOTO Hiroya 京都大学, 農学研究科, 准教授 (00283648) ; TAKAKURA Yoshinobu 京都大学, 薬学研究科, 教授 (30171432)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: ドラッグデリバリー / 活性酸素 / カタラーゼ / 癌転移 / 高血糖 / 活性酵素 / ハイドロゲル / デイバリー / デリバリー

Research Abstract

We tried to develop therapeutic systems by efficiently inhibiting reactive oxygen species, which have attracted much attention on the involvement in a variety of diseases, including cancer, inflammation and life-related diseases. We synthesized catalase derivatives with diverse tissue distribution characteristics and, with or without gelatin hydrogels, developed long-lasting systems. The application of these systems to mouse disease models have proved that they are effective in inhibiting the peritoneal dissemination of colon carcinoma cells and in ameliorating the insulin resistance.

Research Products

• [Journal Article] Improvement of insulin resistance by removal of systemic hydrogen peroxide by PEGylated catalase in obese mice. (2010)
  • Author(s): Ikemura M, Nishikawa M, Hyoudou K, Kobayashi Y, Yamashita F, Hashida M.
  • Journal Title: Mol Pharm 7(6) Pages: 2069-2076
  • Peer Reviewed
• [Journal Article] Improvement of insulin resistance by removal of systemic hydrogen peroxide by PEGylated catalase in obese mice (2010)
  • Author(s): Ikemura M, Nishikawa M, et al.
  • Journal Title: Molecular Pharmacy Volume: 7(6) Pages: 2069-2076
  • Peer Reviewed
• [Journal Article] Control of hypoxia-induced tumor cell adhesion by cytophilic human catalase. (2009)
  • Author(s): Yata T, Nishikawa M, Nishizaki C, Oku M, Yurimoto H, Sakai Y, Takakura Y.
  • Journal Title: Free Radic Biol Med 47(12) Pages: 1772-1778
  • NAID: 120001815090
  • Peer Reviewed
• [Journal Article] Prevention of ischemia/reperfusion injury by hepatic targeting of nitric oxide in mice. (2009)
  • Author(s): Katsumi H, Nishikawa M, Yasui H, Yamashita F, Hashida M.
  • Journal Title: J Control Release 140(1) Pages: 12-17
  • Peer Reviewed
• [Journal Article] Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase. (2009)
  • Author(s): Hyoudou K, Nishikawa M, Ikemura M, Kobayashi Y, Mendelsohn A, Miyazaki N, Tabata Y, Yamashita F, Hashida M.
  • Journal Title: J Control Release 137(2) Pages: 110-115
  • Peer Reviewed
• [Journal Article] Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. (2009)
  • Author(s): Nishikawa M, Hashida M, Takakura Y.
  • Journal Title: Adv Drug Delivery Rev 61(4) Pages: 319-326
  • Peer Reviewed
• [Journal Article] Control of hypoxia-induced tumor cell adhesion by cytophilic human catalase (2009)
  • Author(s): Yata T, et al.
  • Journal Title: Free Radical Biology & Medicine 47 Pages: 1772-1778
  • Peer Reviewed
• [Journal Article] Prevention of ischemia/reperfusion injury by hepatic targeting of nitric oxide in mice (2009)
  • Author(s): Katsumi H, et al.
  • Journal Title: Journal of Controlled Release 140 Pages: 12-17
  • Peer Reviewed
• [Journal Article] Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase (2009)
  • Author(s): Hyoudou K, et al.
  • Journal Title: Journal of Controlled Release 137 Pages: 110-115
  • Peer Reviewed
• [Journal Article] Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis (2009)
  • Author(s): Nishikawa M, et al.
  • Journal Title: Advanced Drug Delivery Reviews 61 Pages: 319-326
  • Peer Reviewed
• [Journal Article] Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase (2009)
  • Author(s): Hyoudou K, et al.
  • Journal Title: Journal of Controlled Release
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide-mediated nuclear factor κB activation in both liver and tumor cells during initial stages of hepatic metastasis. (2008)
  • Author(s): Kobayashi Y, Nishikawa M, Hyoudou K, Yamashita F, Hashida M.
  • Journal Title: Cancer Sci 99(8) Pages: 1546-1552
  • NAID: 10024009582
  • Peer Reviewed
• [Journal Article] Reactive oxygen species in tumor metastasis. (2008)
  • Author(s): Nishikawa M.
  • Journal Title: Cancer Lett 266(1) Pages: 53-59
  • Peer Reviewed
• [Journal Article] SOD derivatives prevent metastatic tumor growth aggravated by tumor removal. (2008)
  • Author(s): Hyoudou K, Nishikawa M, Kobayashi Y, Ikemura M, Yamashita F, Hashida M.
  • Journal Title: Clin Exp Metastasis 25(5) Pages: 531-536
  • Peer Reviewed
• [Journal Article] Hydrogen peroxide-mediated nuclear factor κB activation in both liver and tumor cells during initial stages of hepatic metastasis (2008)
  • Author(s): Kobayashi Y, et al.
  • Journal Title: Cancer Science 99 Pages: 1546-1552
  • Peer Reviewed
• [Journal Article] SOD derivatives prevent metastatic tumor growth aggravated by tumor removal (2008)
  • Author(s): Hyoudou K, et al.
  • Journal Title: Clinical & Experimental Metastasis 25 Pages: 531-536
  • Peer Reviewed
• [Journal Article] Reactive oxygen species in tumor metastasis (2008)
  • Author(s): Nishikawa M
  • Journal Title: Cancer Letters 266 Pages: 53-59
  • Peer Reviewed
• [Journal Article] Inhibition of surgical trauma-enhanced peritoneal dissemination of tumor cells by human catalase derivatives in mice.
  • Author(s): Nishizaki C, Nishikawa M, Yata T, Yamada T, Takahashi Y, Oku M, Yurimoto H, Sakai Y, Nakanishi K, Takakura Y.
  • Journal Title: Free Radic Biol Med (印刷中) Pages: 2011-2011
  • NAID: 120003255726
  • Peer Reviewed
• [Presentation] Acceleration of tumor metastasis in obese or diabetic mice and its inhibition by PEGylated catalase. (2010)
  • Author(s): 池村舞, 西川元也, et al.
  • Organizer: 4th Pharmaceutical Sciences World Congress
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] 持続的活性酸素消去による糖尿病状態における癌細胞接着亢進の抑制 (2010)
  • Author(s): 池村舞、西川元也, 他
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 細胞親和性ペプチド融合による動態制御型ヒトカタラーゼの開発とその癌転移抑制効果 (2010)
  • Author(s): 西崎智香、西川元也, 他
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 肥満・糖尿病における癌転移の亢進と活性酸素消去による転移抑制 (2010)
  • Author(s): 池村舞、西川元也, 他
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 細胞親和性ペプチド融合による動態制御型ヒトカタラーゼの開発とその癌転移抑制効果 (2010)
  • Author(s): 西崎智香、西川元也, 他
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪国際交流センター (大阪)
• [Presentation] 持続的活性酸素消去による糖尿病状態における癌細胞接着亢進の抑制 (2010)
  • Author(s): 池村舞、西川元也, 他
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪国際交流センター (大阪)
• [Presentation] Acceleration of tumor metastasis in obese or diabetic mice and its inhibition by PEGylated catalase (2010)
  • Author(s): Ikemura M, Nishikawa M, et al.
  • Organizer: 4^<th> Pharmaceutical Sciences World Congress
  • Place of Presentation: Morial Convention Center (New Orleans, LA, USA)
• [Presentation] Improveddelivery of catalase to bone by conjugation of bisphosphonate and polyethylene glycol. (2009)
  • Author(s): Yunlong Z, Nishikawa M, et al.
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
• [Presentation] Effective inhibition of hypoxia-induced tumor cell adhesion by cytophilic human catalase. (2009)
  • Author(s): 西崎智香, 西川元也, et al.
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
• [Presentation] Inhibition of insulin resistance by continuous removal of hydrogen peroxide using catalase derivatives. (2009)
  • Author(s): 池村舞, 西川元也, et al.
  • Organizer: The Fifth iCeMS International Symposium
  • Place of Presentation: 京都
• [Presentation] Effective inhibition of hypoxia-induced tumor cell adhesion by cytophilic human catalase (低酸素で誘導される癌細胞接着の細胞親和性ヒトカタラーゼによる効果的抑制) (2009)
  • Author(s): Nishizaki C, et al.
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
• [Presentation] Improved delivery of catalase to bone by conjugation of bisphosphonate and polyethylene glycol (2009)
  • Author(s): Yunlong Z, et al.
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
• [Presentation] Inhibition of insulin resistance by continuous removal of hydrogen peroxide using catalase derivatives (2009)
  • Author(s): 池村舞, et al.
  • Organizer: The Fifth iCeMS International Symposium
  • Place of Presentation: 京都
• [Presentation] Continuous removal of hydrogen peroxide by polyethylene glycol-conjugated catalase for the inhibition of insulin resistance. (2008)
  • Author(s): 池村舞, 西川元也, et al.
  • Organizer: AAPS Annual Meeting and Exposition 2008
  • Place of Presentation: Altanta, GA, USA
• [Presentation] Differentiation of immature myeloid cells by PEGylated catalase for cancer immunotherapy. (2008)
  • Author(s): 古林裕貴、西川元也, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Targeted delivery of catalase to liver cells for inhibition of NF-κB activation in tumor and liver cells during hepatic tumor metastasis. (2008)
  • Author(s): Kobayashi Y, Nishikawa M, et al.
  • Organizer: GPEN2008
  • Place of Presentation: Leuven, Belgium
• [Presentation] Receptor-mediated delivery of drugs, proteins and genes. (2008)
  • Author(s): 西川元也
  • Organizer: 2nd Asian Pacific Regional Meeting of International Society of Xenobiotics
  • Place of Presentation: Shanghai, China
• [Presentation] Continuous Removal of Hydrogen Peroxide by polythylene Glycol-Conjugated Catalase for the Inhibition of Insulin Resiitance (2008)
  • Author(s): Ikemura M, et al.
  • Organizer: AAPS Annual Meeting and Exposition 2008
  • Place of Presentation: Altanta, GA, USA
• [Presentation] Differentiation of Immature Myeloid Cells by PEGylated Catalase for Cancer Immunotherapy (2008)
  • Author(s): 古林裕貴, ほか
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Targeted Delivery of Catalase to Liver Cells for Inhibition of NF-κB Activation in Tumor and Liver Cells during Hepatic Tumor Metastasis (2008)
  • Author(s): Kobayashi Y, et al.
  • Organizer: GPEN2008
  • Place of Presentation: Leuven, Belgium
• [Presentation] Receptor-Mediated Delivery of Drugs, Proteins and Genes (2008)
  • Author(s): Nishikawa M
  • Organizer: 2nd Asian Pacific Regional Meeting of International Society of Xenobiotics
  • Place of Presentation: Shanghai, China