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2011 Fiscal Year Final Research Report

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

Research Project

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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
Keywords腫瘍循環 / 酸素拡散係数 / 組織酸素分圧 / 低酸素状態
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.

  • Research Products

    (13 results)

All 2012 2011 2009 Other

All Journal Article (9 results) Presentation (4 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)

  • [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

  • [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

  • [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

  • [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

  • [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

  • [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

  • [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

  • [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)

  • [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
  • [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
  • [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
  • [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

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Published: 2013-07-31  

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