Inhibition of trigger in angiogenesis and prevention of angiogenic diseases by marine algae-specific matter

• Project/Area Number: 17590481
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: ASHNI Hiromi Tokyo Metropolitan Organization for Medical Research, Tokyo Metropol.Org.Med.Res.Tokyo Metropol.Inst.Med.Sci., Senior Research Scientist (40222608)
• Co-Investigator(Kenkyū-buntansha): TOMIO Ono Tokyo Metropol. Org. Med. Res., Research Scientist (60231239)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥2,510,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
• Keywords: Angiogenesis / Sulfated polysaccharide / Microvascular endothelial cells / Marine algae / Chicken embryo chorioallantoic membrane / Tube formation / 酸性多糖 / 血管内皮細胞 / 抗酸化成分 / 血管新生因子bFGF / 漿尿膜 / フコイダン

Research Abstract

We have reported a possibility that sulfated polysaccharide inhibits an action of the angiogenic factor used as the trigger of angiogenesis. It is guessed that sulfated polysaccharide becomes the rare medicine which was high in validity since there is also almost no toxicity to normal cells. We examined the possibility as inhibitor paying attention to there being seaweed as a natural material which contains characteristic and various sulfated polysaccharides abundantly. Then, what kind of seaweed origin acidic polysaccharide has a powerful inhibition of neovascularization, or what happened to the action with change in a structure and influenced to utilization as a medicine, or what kind of mechanism has acted in microvascular endothelial cells, we examined these points, and acquired the following knowledge. 1. Fucoidan derived from brown-algae inhibited angiogenesis strongly. On the other hand, low alginic acid of the anti-tumor effect in solid cancer was weak in angiogenic inhibition with the acidic polysaccharide which exists in the same brown-algae. 2. Even if it formed the low molecule fucoidan was maintaining anti-angiogenic activity. 3. The rough extractive fraction of sulfated polysaccharide extracted from green-algae by which structure and a special feature are hardly investigated.However, the tendency which this fraction controls angiogenesis weakly was shown. 4. The tendency which seaweed origin sulfated polysaccharides inhibit the function of trigger was shown. From the above result, a possibility that control of angiogenesis by seaweed origin sulfated polysaccharide will contribute to the anti-tumor effect, and a possibility of becoming the new angiogenic inhibitory substance which was excellent also from the absorption side since activity was held even if it forms a low molecule were suggested.

Research Products

• [Journal Article] Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo. (2007)
  • Author(s): Oikawa, T., Onozawa, C., Kuranuki, S., Igarashi, Y., Sato, M., Ashino, H., Shimamura, M., Toi, M.and Kurakata, S.
  • Journal Title: Cancer Sci. 98・2 Pages: 219-25
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hippocalcin protects hippocampal neurons against excitotoxindamage by enhancing calcium extrusion. (2007)
  • Author(s): Masuo, Y., Ogura, A.Kobayashi, M., Masaki, T., Furuta, Y., Ono, T.and Takamatsu, K.
  • Journal Title: Neurosciene 145 Pages: 495-504
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo. (2007)
  • Author(s): Oikawa,T., Onozawa, C.,Kuranuki, S., lgarashi, Y., Sato, M., Ashino, H., Shimamura. M.,Toi, M. and Kurakata, S.
  • Journal Title: Cnacer Sci 98-2 Pages: 219-25
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion. (2007)
  • Author(s): Masuo, Y., Ogura, A ., Kobayashi, M., Masaki, T., Furuta, Y., Ono, T. and Takamatsu, K.
  • Journal Title: Neurosciene 145 Pages: 495-504
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dipalmitoylation of radicicol results in improved efficacy against tumorgrowth and angiogenesis in vivo. (2007)
  • Author(s): Oikawa, T., Onozawa, C., Kuranuki, S., Igarashi, Y., Sato, M., Ashino, H., Shimamura, M., Toi, M.and Kurakata, S.
  • Journal Title: Cancer Sci. 98・2 Pages: 219-25
  • Peer Reviewed
• [Journal Article] Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion. (2007)
  • Author(s): Masuo, Y., Ogura, A. Kobayashi, M., Masaki, T., Furuta, Y., Ono, T.and Takamatsu, K.
  • Journal Title: Neurosciene 145 Pages: 495-504
  • Peer Reviewed
• [Journal Article] Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo (2007)
  • Author(s): Oikawa, T., Onozawa, C., Kuranuki, S., Igarashi, Y., Sato, M., Ashino, H., Shimamura, M., Toi, M., Kurakata, S.
  • Journal Title: Cancer Sci. 98・2 Pages: 219-225
• [Presentation] NF-kBを介したカルパインインヒビターの血管新生抑制 (2007)
  • Author(s): 芦野洋美、鈴木直子、島村眞里子
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ジペプチドL-carnosineによる血管新生の阻害と抗腫瘍作用 (2007)
  • Author(s): 島村眞里子、芦野洋美、飯郷正明、山本行男
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Anti-angiogenic effect of calpain inhibitors on vascular network of chick chorioallantoic membrane and migration of vascular endothelial cells. (2007)
  • Author(s): Ashino, H., Sekino-Suzuki, N.and Shimamura, M.
  • Organizer: 5^<th> General Meeting of the Intemational Proteolysis Society.
  • Place of Presentation: ギリシャ,パトラ
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Angiogenic suppression of calpain inhibitor through regulation of NF-kB. (2007)
  • Author(s): Ashino, H., Suzuki, N.and Shimamura, M.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] L-carnosine, an endogenous bioactive dipeptide inhibits angiogenesis and tumor metastasis. (2007)
  • Author(s): Shimamura, M., Ashino, H., Shimizu, M., Yamamoto, Y., Minamikawa-Tachino, R. and Takahashi, S.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Anti-angiogenic effect of calpain inhibitors on vascular nerwork of chick chorioallantoic membrane and migration of vascular endothelial cells. (2007)
  • Author(s): Ashino, H, Sekino-Suzuki,N, and Shimamura,M.
  • Organizer: 5th General Meeting of the International Proteolysis Society.
  • Place of Presentation: Patras(Greece).
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Angiogenic suppression of calpain inhibitor through regulation of NF-KB. (2007)
  • Author(s): Ashino, H, Suzuki, N. and Shimamura, M.
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama(Japan).
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] L-carnosine, an endogenous bioactive dipeptide inhibits angiogenesis and tumor metastasis. (2007)
  • Author(s): Shimamura, M, Ashino, H, Shimizu, M, Yamamoto, Y, Minamikawa-Tachino, R. and Takahashi, S.
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama(Japan).
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Anti-angiogenic effect of calpain inhibitors on vascular network of chick chorioallantoic membrane and migration of vascular endothelial cells. (2007)
  • Author(s): Ashino, H., Sekino-Suzuki, N. and Shimamura, M.
  • Organizer: 5^<th> General Meeting of the International Proteolysis Society.
  • Place of Presentation: ギリシャ,パラト
• [Presentation] Angiogenic suppression of calpain inhibitor through regulation of NF-kB. (2007)
  • Author(s): Ashino, H., Suzuki, N. and Shimamura, M.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] L-carnosine,an endogenous bioactive dipeptide inhibits angiogenesis and tumor metastasis. (2007)
  • Author(s): Shimamura, M., Ashino, H., Shimizu, M., Yamamoto, Y., Minamikawa-Tachino, R.and Takahashi, S.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
• [Presentation] 低分子化フコイダンによる微小血管新生の阻止. (2006)
  • Author(s): 芦野洋美, 島村眞里子, 中島宏, 浜田博喜
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] carnosineの血管新生阻害作用と抗腫瘍作用. (2006)
  • Author(s): 島村眞里子, 芦野洋美, 清水本武, 山本行男, 高橋周七
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 血管新生におけるプロテアーゼの関与(VII);カルパスタチンペプチドによる血管新生の制御. (2006)
  • Author(s): 芦野洋美, 島村眞里子, 鈴木直子
  • Organizer: 第11回病態と治療におけるプロテアーゼとインヒビター研究会
  • Place of Presentation: 仙台
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Anti-angiogenic function of ascorbic acid and 6-O-palmitoyl ascorbate. (2006)
  • Author(s): Ashino, H., Shimamura, M. and Suzuki, N
  • Organizer: XIVth International Vascular Biology Meeting
  • Place of Presentation: レーヴェンホルスト、オランダ
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Angiogenesis inhibition of arginine-rich dendrimers,TX-1943 and TX-1944,which mimic the surface structure of endostatin. (2006)
  • Author(s): Shimamura, M., Kasai, S., Nagasawa, H., Ashino, H., Yamamoto Y., Uto, and Hori, H.
  • Organizer: XIVth International Vascular Biology Meeting
  • Place of Presentation: レーヴェンホルスト、オランダ
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Anti-angiogenic function of ascorbic acid and 6-0-palmitoyl ascorbate. (2006)
  • Author(s): Ashino, H, Shimamura, M. and Suzuki, N.
  • Organizer: XIVth International Vascular Biology Meeting
  • Place of Presentation: Leewenhorst(The Nederlands)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Angiogenesis inhibition of arginine-rich dendrimers,TX-1943 and TX-1944, which mimic the surface structure of endostatin. (2006)
  • Author(s): Shimamura, M, Kasai,S, Nagasawa, H, Ashino, H, YamamotoY, Uto,and Hori, H.
  • Organizer: XIVth International Vascular Biology Meeting
  • Place of Presentation: Leewenhorst(The Nederlands)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 新規のrhoGEF遺伝子は初代培養小脳顆粒神経細胞のアポトーシスのコミットメント時間に同期して一過性に発現する. (2005)
  • Author(s): 小野富男、米川博通
  • Organizer: 第28回分子生物学会年会
  • Place of Presentation: 福岡
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 脂溶性アスコルビン酸誘導体、アスコルビン酸-6-パルミテートによる血管新生の阻止. (2005)
  • Author(s): 芦野洋美, 島村眞里子, 中島宏
  • Organizer: 第13回日本血管生物医学会
  • Place of Presentation: 仙台
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Endostatinの表面構造と類似性を示すarginine-rich dendrimerの血管新生阻害作用. (2005)
  • Author(s): 島村眞里子, 葛西宋江, 芦野洋美, 山本行男, 永澤秀子, 宇都義浩, 堀 均
  • Organizer: 第13回日本血管生物医学会
  • Place of Presentation: 仙台
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] フコイダンによる微小血管新生の阻止. (2005)
  • Author(s): 芦野洋美, 島村眞里子, 中島宏
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 内因性生理活性ペプチドcarnosineによる血管新生の制御, (2005)
  • Author(s): 島村眞里子, 芦野洋美, 山本行男, 高橋周七
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 血管新生におけるプロテアーゼの関与(VI):NF-kB活性の制御と血管新生調節におけるカルパインの役割. (2005)
  • Author(s): 芦野洋美, 島村眞里子, 鈴木直子
  • Organizer: 第10回病態と治療におけるプロテアーゼとインヒビター研究会
  • Place of Presentation: 福岡
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Inhibition of angiogenesis by fucoidan. (2005)
  • Author(s): Ashino, H, Shimamura,M. and Nakajima,H.
  • Organizer: The 64th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Sapporo(Japan)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] L-carnosine, an endogenous bioactive dipeptide inhibits angiogenesis. (2005)
  • Author(s): Shimamura, M, Ashino, H, Yamamoto, Y. and Takahashi, S.
  • Organizer: The 64th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Sapporo(Japan)
  • Description: 「研究成果報告書概要(欧文)」より