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Analysis of oxygen transport to malignant tumor and mechanism of enhancing effect of treatment by oxygenation of tumor tissue

Research Project

Project/Area Number 21591824
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKeio University

Principal Investigator

HORINOUCHI Hirohisa  慶應義塾大学, 医学部・外科, 准教授 (60173647)

Co-Investigator(Kenkyū-buntansha) TSUKADA Kosuke  慶應義塾大学, 理工学部, 講師 (00351883)
KOHNO Mitsutomo  慶應義塾大学, 医学部, 講師 (10276272)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腫瘍循環 / 酸素拡散係数 / 組織酸素分圧 / 低酸素状態 / 癌 / 低酸素 / 血管新生 / 酸素拡散係 / 細動脈 / 酸素消費率 / 酸素ガス / 人工酸素運搬体
Research Abstract

Usually, tissue oxygen tension is low in malignant tumor. This hypoxic state is due to the imbalance of tumor cell growth and development of tumor circulation. Tumor tissue is supplied oxygen from systemic circulation. Main oxygen supply is suspected to be derived from capillary by diffusion. However, some part of oxygen might be derived from the oxygen molecule diffused from arteriolar lesion.
We have developed the microscope system that enabled us to determine the oxygen diffusion constant of arteriolar wall. We have applied this system to tumor burden animals and examine the oxygen diffusion constant of the subcutaneous arteriolar wall.
We used Balb/c mouse and mouse mammalian tumor(MMT060562). To measure the oxygen diffusion constant of the arteriolar wall, we placed Dorsal Skin Window Chamber on Balb/c mouse. In small tumor group, tumor was implanted in the DSC and let it grow to 2mm. In large tumor group, tumor was implanted at the left arm pit.
Oxygen diffusion constant of arteriolar wall in control group was 5. 3±1. 1×10^<-11> [(cm2/s)(ml O_2. cm^<-3> tissue. mmHg^<-1>)], while in the small tumor group, K was 3. 9±0. 4×10^<-11> [(cm2/s)(ml O_2. cm^<-3> tissue. mmHg^<-1>)] and in the large tumor group K was 3. 1±0. 6×10^<-11> [(cm2/s)(ml O_2. cm^<-3> tissue. mmHg^<-1>)]. There are significant difference between control group and tumor burden groups.
This phenomenon indicated that in tumor burden animals, the amount of oxygen molecules that pass through the arteriolar lesion increases according to the size of tumor. The increase of oxygen diffusion constant around arteriole level seems beneficial for the tumor cells in regards to the survival and growth of malignant tumor.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (18 results)

All 2012 2011 2010 2009 Other

All Journal Article (11 results) (of which Peer Reviewed: 1 results) Presentation (7 results)

  • [Journal Article] A new method for measuring the oxygen diffusion constant and oxygen consumption rate of arteriolar walls2012

    • Author(s)
      Sasaki N, Horinouchi H, Ushiyama A, Minamitani H
    • Journal Title

      Keio J Med

      Volume: (in press)

    • NAID

      10030771368

    • Related Report
      2011 Final Research Report
  • [Journal Article] Removal of cellular-type hemoglobin-based oxygen carrier(hemoglobin-vesicles) from blood using centrifugation and ultrafiltration2012

    • Author(s)
      Sakai H, Sou K, Horinouchi H, Tsuchida E, Kobayashi K
    • Journal Title

      Artif Organs

      Volume: 36(2) Pages: 202-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Hemoglobin vesicle improves recovery of cardiac function after ischemia-reperfusion by attenuating oxidative stress in isolated rat hearts2011

    • Author(s)
      Nakajima J, Bessho M, Adachi T, Yamagishi T, Tokuno S, Horinouchi H, Ohsuzu F
    • Journal Title

      J. Cardiovasc Pharmacol

      Volume: 58(5) Pages: 528-34

    • Related Report
      2011 Final Research Report
  • [Journal Article] Spatiotemporal measurement of tumor oxygeneation reveals repeat hypoxic phenomenon in mice2011

    • Author(s)
      Yamada R, Horinouchi H, Tsukada K
    • Journal Title

      Conf Proc IEEE Eng Med Biol Soc

      Volume: 2011 Pages: 5965-5968

    • Related Report
      2011 Annual Research Report
  • [Journal Article] A transient inflammatory reaction in the lung after experimental hemorrhagic shock and resuscitation with a hemoglobin-vesicles solution compared with rat RBC transfusion2009

    • Author(s)
      Yamanashi Y, Mori M, Terajima K, Tsueshita T, Horinouchi H, Sakai H, Sakamoto A
    • Journal Title

      ASAIO J.

      Volume: 55(5) Pages: 478-83

    • Related Report
      2011 Final Research Report
  • [Journal Article] Pharmacokinetics of single and repeated injection of hemoglobin-vesicles in hemorrhagic shock rat model2009

    • Author(s)
      Taguchi K, Maruyama T, Iwao Y, Sakai H, Kobayashi K, Horinouchi H, Tsuchida E, Kai T, Otagiri M
    • Journal Title

      J Control Release

      Volume: 136 Pages: 232-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Review of hemoglobin-vesicles as artificial oxygen carriers2009

    • Author(s)
      Sakai H, Sou K, Horinouchi H, Kobayashi K, Tsuchida E
    • Journal Title

      Artif Organs

      Volume: 33(2) Pages: 139-45

    • Related Report
      2011 Final Research Report
  • [Journal Article] Hemoglobin vesicles and red blood cells as carriers of carbon monoxide prior to oxygen for resuscitation after hemorrhagic shock in a rat model2009

    • Author(s)
      Sakai H, Horinouchi H, Tsuchida E, Kobayashi K
    • Journal Title

      Shock

      Volume: 31 Pages: 507-14

    • Related Report
      2011 Final Research Report
  • [Journal Article] Histopathological changes of rat brain after direct injection of Hb-vesicles(artificial oxygen carriers) and neurological impact in an intracerebral hemorrhage model2009

    • Author(s)
      Sakai H, Okamoto M, Ikeda E, Horinouchi H, Kobayashi K, Tsuchida E
    • Journal Title

      J Biomed Mater Res A

      Volume: 90 Pages: 1107-19

    • Related Report
      2011 Final Research Report
  • [Journal Article] Effect of the cellular-type artificial oxygen carrier Hb-vesicle as a resuscitative fluid for pre-hospital treatment

    • Author(s)
      Seishi Y, Horinouchi H, Sakai H, Kobayashi K
    • Journal Title

      Experiments in a rat uncontrolled hemorrhagic shock model Shock

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] A new method for measuring the oxygen diffusion constant and oxygen consumption rate of arteriolar walls

    • Author(s)
      Sasaki N, Horinouchi H、Ushiyama A, Minamitani H
    • Journal Title

      Keio Journal of Medicine

      Volume: (In press)

    • NAID

      10030771368

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Spatiotemporal measurement of tumor oxygeneation reveals repeat hypoxic phenomenon in mice2011

    • Author(s)
      山田遼、塚田孝祐、堀之内宏久
    • Organizer
      33th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Boston, MA (U.S.A)
    • Year and Date
      2011-09-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Influence of Hemoglobin vesicle on oxygen diffusion constant of arteriolar wall in microcirculation of mouse dorsal skin window chamber2011

    • Author(s)
      Horinouchi H, Sasaki N, Seishi Y, Kobayashi K, Sakai H
    • Organizer
      XIII ISBS
    • Place of Presentation
      Boston MA USA
    • Year and Date
      2011-07-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Fluid resuscitation using large volume of hemoglobin vesicle in rat continuous hemorrhage model(2^<nd> report)2011

    • Author(s)
      Seishi Y, Horinouchi H, Sakai H, Kobayashi K
    • Organizer
      XIII ISBS
    • Place of Presentation
      Boston MA USA
    • Year and Date
      2011-07-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Influence of hemoglobin vesicle on oxygen diffusion constant of arteriolar wall in microcirculation of mouse dorsal skin window chamber2011

    • Author(s)
      堀之内宏久
    • Organizer
      第13回血液代替物国際会議
    • Place of Presentation
      Boston, MA (U.S.A)
    • Year and Date
      2011-07-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Hb小胞体の動物投与の成績2010

    • Author(s)
      堀之内宏久
    • Organizer
      第17回血液代替物学会年次大会
    • Place of Presentation
      熊本(熊本市国際交流会館)
    • Year and Date
      2010-10-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Resuscitation with Hemoglobin-Vesicle can improve survival and oxygen metabolism in uncontrolled hemorrhage model in rats2009

    • Author(s)
      Horinouchi H, Seishi Y, Kobayashi K, Izumi Y, Kohno M, Sakai H, Tsuchida E
    • Organizer
      Hemorrhage from large vessel model XII ISBS
    • Place of Presentation
      Parma, Italy
    • Year and Date
      2009-08-26
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of large volume resuscitation with the cellular type artificial oxygen carrier(Hb-vesicle) in rat model of uncontrolled hemorrhagic shock via caudal artery2009

    • Author(s)
      Seishi Y, Horinouchi H, Sakai H, Tsuchida E, Kobayashi K
    • Organizer
      XII ISBS
    • Place of Presentation
      Parma, Italy
    • Year and Date
      2009-08-26
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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