Control of angiogenesis by attenuation of oxygen tension in the metastatic tumor of the lung

• Project/Area Number: 16591410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Keio University
• Principal Investigator: HORINOUCHI Hirohisa Keio University, Department of Medicine, Assistant Professor (60173647)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Koichi Keio University, Department of Medicine, Professor (80051704) ; WATANABE Masazumi Keio University, Department of Medicine, Instructor (90201227) ; IZUMI Youtaro Keio University, Department of Medicine, Instructor (90245506) ; 藤本 博行 慶應義塾大学, 医学部, 助手 (20338073)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000); Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: cancer / tumor microcirculation / angiogenesis / hypoxia / oxymetry / 放射線治療 / 組織酸素分圧 / 人工酸素運搬体 / 腹水肝癌 / 腫瘍内酸素分圧

Research Abstract

Oxygen and nutrition for the metastatic tumor was supplied through tumor microcirculation. If angiogenesis of this tumor microcirculation could be controlled, we may achieve new therapy.
Oxygen supply is determined by flow of tumor microcirculation, oxygen content of microcirculatory blood volume, and geographical distribution of microcirculation. To control tissue oxygen tension in tumor tissue, distribution of tumor microcirculation or tumor angiogensis is the main target because flow and oxygen content is more difficult to intervene.
First, to understand the microcirculatory characteristics of tumor, we analyzed cast model infused with silicon rubber. Although dense increase of venule network was found out, capillary network less than 10micrometer in diameter couldn't be well identified in this method. We used intravital microscopy using FITC albumin to visualize tumor microcirculation under Dorsal Skin fold Window Chamber method. We used Donryu rat and LY80 syngenic tumor to the species. We checked the microvessel density, oxygen mapping, and histological microvessel distribution before and after irradiation.
Oxygen tension was higher in central area of the tumor and lower in peripheral zone. After irradiation, microvessel density decreased while increase of tumor diameter is not evident. This phenomenon may decrease the oxygen tension in tumor tissue followed by growth retardation.

Research Products

• [Journal Article] Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation (2009)
  • Author(s): Yamamoto M, Izumi Y, Horinouchi H, Teramura Y, Sakai H, Kohno M, Watanabe M, Kawamura M, Adachi T, Ikeda E, Takeoka S, Tsuchida E, Kobayashi K
  • Journal Title: J Surg Res 151 Pages: 48-54
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation. (2009)
  • Author(s): Yamamoto M, Izumi Y, Horinouchi H, Teramura Y, Sakai H, Kohno M, Watanabe M, Kawamura M, Adachi T, Ikeda E, Takeoka S, Tsuchida E, Kobayashi K.
  • Journal Title: J Surg Res. (Epub 2008 Jan 17) 151(1) Pages: 48-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme'. (2008)
  • Author(s): Horinouchi H, Yamamoto H, Komatsu T, Huang Y, Tsuchida E, Kobayashi K.
  • Journal Title: Cancer Science 99 Pages: 1274-8
  • NAID: 10024007807
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme'. (2008)
  • Author(s): Horinouchi H, Yamamoto H, Komatsu T, Huang Y, Tsuchida E, Kobayashi K.
  • Journal Title: Cancer Sci. 99(6) (Epub 2008 Apr 21) Pages: 1274-8
  • NAID: 10024007807
  • Description: 「研究成果報告書概要(欧文)」より