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Study on vascular shutdown effects of carcinoma blood vessels and cytotoxic effects of carcinoma cells induced by photochemical reaction.

Research Project

Project/Area Number 14380410
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionKeio University

Principal Investigator

MINAMITANI Haruyuki  Keio University, Faculty of Science and Technology, Professor, 理工学部, 教授 (70051779)

Co-Investigator(Kenkyū-buntansha) SUEMATSU Makoto  Keio University, School of Medicine, Professor, 医学部, 教授 (00206385)
NAGATA Hiroji  Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (00146599)
TANISHITA Kazuo  Keio University, Faculty of Science and Technology, Professor, 理工学部, 教授 (10101776)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥17,100,000 (Direct Cost: ¥17,100,000)
Fiscal Year 2003: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
KeywordsPhotodynamic therapy / Active oxygen / Apoptosis / Platelet thrombosis / Endothelial cell / Cancer cell / Porphyrin / Confocal laser microscopy
Research Abstract

Photodynamic therapy (PDT) is a clinically effective cancer treatment which is based on cytotoxicity of reactive oxygen species (ROS) generated by an interaction between photosensitizer and light. PDT induces vascular shutdown (VSD) effects based on thrombus formation realized by administration of photosensitizing agent. This treatment results in a sequence of photochemical processes to produce cytotoxic ROSS which bring irreversible photo damage to tissue cells. ^1O_2 and O_2^-strongly activated adhesive function of platelet and leukocyte, and also induced endothelial cell retraction resulted in increase in sub endothelial area. Activation of both platelet and endothelial cells also released adhesion molecules that followed strong cell interaction indispensable for the platelet aggregation and thrombus formation. The platelet adhesion and thrombus formation in the microvessels accelerated under photodynamic reaction. For visualization of flow behavior of erythrocytes, leukocytes and p … More latelets, fluorescent dye probes were used and the flow images were observed under fluorescent microscope. Blood oxygen pressure was also measured by using phosphorescence quenching of Pd porphyrin with oxygen molecules. In order to measure erythrocyte velocity and to evaluate the degree of platelet adhesion and leukocyte sticking, high-speed CCD camera and image processing system were used and made possible to evaluate the contribution of ROSS to the VSD and pharmacological effect on the VSD. ROSs induced protein transformation of cytoplasm in the endothelial cells, especially actin filament polymerisation was observed that affected on increase in subendothelial area. These phenomena accelerated activation of platelets and leukocytes which progressively adhered on the endothelial cells and subendothelial area. On the other hand, cytotoxic effect of PDT on tumor cells, mainly apoptosis, was induced by ROSs attributed to photochemical reaction. Ca^<2+> is one of the most famous second messenger in cell function, especially, the cytoplasmic concentration of free calcium ions[Ca^<2+>]i has important role in apoptosis. In this study, we examined the role of Ca^<2+> in PDT-induced apoptosis of human lung small carcinoma (Ms-1) and human leukemia cell line (HL-60 cells). We performed the imaging of Ca^<2+> and monitoring Ca^<2+> concentration in apoptosis induced by PDT. With intracellular calcium indicator Fluo3-AM, increase of [Ca^<2+>]i was observed for 6 hours after PDT and was inhibited by extracellular Ca^<2+> chelator BAPTA. Agarose gel electrophresis revealed that PDT-induced apoptosis was inhibited by BAPTA. PDT induced loss of mitochondrial membrane potential and increase of Ca^<2+> in mitochondria. As a result, we have revealed that increase of [Ca^<2+>]i is induced by transcellular calcium influx from extracellular fluid to intracellular fluid, and induce apoptosis in Ms-1 and HL-60 cells. These results indicate that Ca^<2+> plays an important role in apoptosis induced by PDT. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Tsukada K, Minamitani H, Sekizuka E, Oshio C: "Red blood cell velocity and oxygen tension measurement in cerebral microvessels by double-wavelength photoexcitation"Journal of Appied.Physiology. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Minamitani H, Tsukada K, Sekizuka E, Oshio C: "Optical imaging : From living tissue to a single molecule : Imaging and functional analysis of blood flow in organic microcirculation"Japanese Journal of Pharmacology. 93. 227-233 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Minamitani H: "Functional analysis of microcirculation disorder by using nano-molecular probes and bioimaging technique."Microcirculation Anuual. 19. 27-28 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagao M, Takahshi M, Matsuzaki K, Minamitani H: "Application of bioimaging techniques to mechanistic studies on photodynamic therapy"Bioimages. 11,2. 53-60 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukada K, Sakai S, Hase K, Tsujioka K, Minamitani H: "Development of catheter-type optical oxygen sensor and applications to bioinstrumentation"Biosensors and Bioelectronics. 18,12. 1439-1445 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 塚田孝祐, 緒方嘉貴, 辻岡克彦, 南谷晴之: "人工酸素運搬体Neo Red Cell交換輸血時の脳微小循環動態および酸素分圧計測"脳循環代謝. 15,4. 196-197 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukada K, Minamitani H, Sekizuka E, Oshio C: "Red blood cell velocity and oxygen tension measurement in cerebral microvessels by double-wavelength photoexcitation."Journal of Appied.Physlology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Minamitani H, Tsukada K, Sekizuka E, Oshio C: "Optical imaging From living tissue to a single molecule : Imaging and functional analysis of blood flow in organic microcirculation."Journal of Pharmacological Science. 93(3). 227-233 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Minamitani H: "Functional analysis of microcirculation disorder by using nano-molecular probes and bioimaging technique."Microcirculation Anuual. 19. 27-28 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagao M, Takahashi M, Matsuzaki K, Minamitani H: "Application of bioimaging techniques to mechanistic studies on photodynamic therapy."Bloimages. 11(2). 53-60 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukada K, Sakai S, Hase K, Tsujioka K, Minamitani H: "Development of catheter-type optical oxygen sensor and applications to bioinstrumentation."Biosensors and Bioelectronics. 18(12). 1439-1445 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukada K, Ogata Y, Tsujioka K, Minamitani H: "Measurement of blood flow dynamics and blood oxygen tension in cerebrall microcirculation during exchange blood transfusion with hemoglobin encapsulated liposomes NRC."Journal of Brain Circulation and Metabolism (Nou Junkan Taisha), in Japanese. 15(4). 196-197 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahshi M., Nagao T., Imazeki Y, Matsuzaki K., Minamitani M.: "Roles of reactive oxygen species in monocyte activation induced by photochemical reaction during photodynamic therapy"Frontiers of Med.Biol.Engng.. 11(4). 279-294 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishikawa M., Sekizuka E., Oshio C., Sato S., Yamaguchi N., Terao S., Tsukada K., Minamitani M., Kawase T.: "Platelet adhesion and arterior dilation during photothrombosis -Observation with rat closed cranial and spinal windows."J Neurological Scl.. 194(1). 59-69 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagao T., Matsuzaki K., Takahashi M., Imazeki Y., Minamitani H.: "Apoptotic signaling cascade of 5-aminolaevulinic acid-based photodynamic therapy in human promyelocytic leukemia HL-60 cells."J Photoscience. 9(2). 509-511 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi M., Nagao T., Matsuzaki K., Nishimura T., Minamitani H.: "Photodynamically induced endothelial cell injury and neutrophil-like HL-60 adhesion."J.Photoscience. 9(2). 518-520 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagao T., Matsuzaki K., Takahashi M., Imazeki Y., Minamitani H.: "Quantitative analysis for intracellular distribution of a photosensitizer using confocal laser scanning microscope."IEICE Transactions on Information and Systems. E85-D(1). 152-159 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi M., Nagao T., Imazeki Y., Matsuzaki K., Minamitani H.: "Fluorescence image analysis for quantification of reactive oxygen species derived from monocytes activated by photochemical reaction."IEICE Transactions on Information and Systems. E85-D(1). 160-166 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukada K, Minamitani H, Sekizuka E, Oshio C: "Red blood cell velocity and oxygen tension measurement in cerebral microvessels by double-wavelength photoexcitation"Journal of Appied.Physiology. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Minamitani H, Tsukada K, Sekizuka E, Oshio C: "Optical imaging : From living tissue to a single molecule : Imaging and functional analysis of blood flow in organic microcirculation"Journal of Pharmacological Science. 93, 3. 227-233 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Minamitani H: "Functional analysis of microcriculation disorder by using nano-molecular probes and bioimaging technique"Microcirculation Anuual. 19. 27-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagao M, Takahshi M, Matsuzaki K, Minamitani H: "Application of bioimaging techniques to mechanistic studies on photodynamic therapy"Bioimages. 11, 2. 53-60 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsukada K, Sakai S, Hase K, Tsujioka K, Minamitani H: "Development of catheter-type optical oxygen sensor and applications to bioinstrumentation"Biosensors and Bioelectronics. 18, 12. 1439-1445 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 塚田孝祐, 緒形嘉貴, 辻岡克彦, 南谷晴之: "人工酸素運搬体Neo Red Cell交換輸血時の脳微小循環動態および酸素分圧計測"脳循環代謝. 15, 4. 196-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Takahshi, T.Nagao, Y.Imazeki, K.Matsuzaki, H.Minamitani: "Roles of reactive oxygen species in monocyte activation indued by photochemical reaction during photodynamic therapy"Frontiers of Biomedical Engineering. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Ishikawa, E.Sekizuka, C.Oshio, K.Tsukada, H.Minamitani: "Platelet adhesion and arterior dilation during photothrombosis -Observation with rat closed cranial and spinal windows"J. Neurological Science. 194・1. 59-69 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Nagao, K.Matsuzaki, Y.Imazeki, M.Takahashi, H.Minamitani: "Apoptotic signaling cascade of 5-aminolaevulinic acid-based photodynamic therapy in human promyelocytic leukemia HL-60 cells"J. Photoscience. 9・2. 509-511 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Takahashi, T.Nagao, K.Matsuzaki, H.Minamitani: "Photodynamically induced endothelial cell injury and neutrophil-like HL-6O adhesion"J. Photoscience. 9・2. 518-520 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagao, K.Matsuzaki, Y.Imazeki, M.Takahashi, H.Minamitani: "Quantitative analysis for intracellular distribution of a photosensitizer using confocal laser scanning microscope"IEICE Trans. Information and Systems. 85D・5. 152-159 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Takahashi, T.Nagao, Y.Imazeki, K.Matsuzaki, H.Minamitani: "Fluorescence image analysis for quantification of reactive oxygen species derived from monocytes activated by photochemical reaction"IEICE Trans. Information and Systems. 85D・5. 160-166 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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