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2000 Fiscal Year Final Research Report Summary

Development and evaluation of ultrasound therapeutic system for drug activation

Research Project

Project/Area Number 10558132
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biomedical engineering/Biological material science
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

KONDO Takashi  Toyama Med.Pharm.Univ., Sch.Med., Prof., 医学部, 教授 (40143937)

Co-Investigator(Kenkyū-buntansha) 梅村 晋一郎  (株)日立製作所, 中央研究所, 主任研究員
ADACH Isaso  Toyama Med.Pharm.Univ., Univ.Hospital, Prof., 附属病院, 教授 (30151070)
TANABE Kiyoshi  Toyama Med.Pharm.Univ., Sch.Med., Res.Asoc., 医学部, 助手 (30293301)
SHIN-ICHIRO Umemura  Hitachi Ltd.Central Res.Labo., Senior Invest.
Project Period (FY) 1998 – 2000
Keywordsultrasound / Frequency dependent / caritation / Transdermal absorption / Thrombolysis / Echo contrast agent
Research Abstract

Concerning development and evaluation of ultrasound therapeutic system for drug activation, multi-frequency ultrasonic generator was made. Frequency dependence of cell killing induced by ultrasound, enhancement of transdermal absorption of drugs, enhancement of biological and chemical effects by echo contrast agents and an echo contrast agent mimic, ultrasonic gene transfer and apoptosis induced by ultrasound were investigated.
1. The relative ratio of iodine release vs. cell killing of rat thymocytes was the order of frequencies, 0.5 MHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed on the cell killing after sonication with 0.5 MHz in Ar-saturated solution in the presence of a free radical scavenger, cysteamine.
2. An echo contrast agent mimic, PVC-AN (poly-vinylidene chloride-acrylonitryl copolymer), enhanced H_2O_2 production induced by ultrasound through the superoxide dependent pathway in air-saturated aqueous solution, although PVC-AN acted as a free radical scavenger to lower H_2O_2 formation by recombination of OH radicals. Enhancement of ultrasonically induced cell lysis and thrombolysis in the presence of PVC-AN was observed.
3. Enhancement of transdermal absorption of acetylcholine in rat due to ultrasonic exposure was observed.
4. Evidence of enhancement of gene transfer in HeLa cells and apoptosis in U937 cells induced by ultrasound in the presence of an echo contrast agent, Levovist, was also obtained.

  • Research Products

    (52 results)

All Other

All Publications (52 results)

  • [Publications] Kondo T. et al.: "Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound."Free Radical Biol.Med.. 25. 605-612 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura C. et al.: "Mechanism of UV-induced apoptosis in human leukemia cells. : Roles of Ca^<2+>/Mg^<2+>-dependent endonuclease, caspase 3, and stress-activated protein kinases."Exptl.Cell Res.. 239. 411-422 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sayama M. et al.: "Mutagenicities of 2,4-and 2,6-dinitrotoluenes, and their reduced products in Salmonella typhimurium nitroreductase and O-acetyltransferase overproducing Ames strains."Mutation Res.. 420. 27-32 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Viroonchatapan E. et al.: "Microdialysis assessment of 5-fluorouracil release from thermosensitive magnetoliposomes induced by an electromagnetic field in tumor-bearing mice."J.Drug Target. 5. 379-390 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yumita N. et al.: "Sonodynamically-induced cell damage with fluorinated anthracycline derivative, FAD104."Cancer Lett.. 125. 209-214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sasaki K. et al.: "Antitumor effect sonodynamically induced by focused ultrasound in combination with Ga-porphyrin complex."Jpn.J.Cancer Res.. 89. 452-456 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanabe K. et al.: "DX-9065a, an orally active factor Xa inhibitor, does not facilitate haemorrhage induced by tail transection orgastric ulcer at the effective doses in rat thrombosis model."Thrombosis Haemostasis. 81. 828-834 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanabe K. et al.: "A conspicuous adaptability to antibiotics in the Escherichia coli mutator, dnaQ49."FEMS Microbiol.Lett.. 176. 191-196 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanabe K. et al.: "DX-9065a, a specific inhibitor of factor Xa, exerts effective protection against experimental tumor-induced disseminated intravascular coagulation."Thrombosis Res.. 96. 135-143 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao Q.-L. et al.: "Mitochondrial and intracellular free-calcium regulation of radiation-induced apoptosis in human leukemic cells."Int.J.Radiat.Biol.. 75. 493-504 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato A. et al.: "Polyhydroxy pyrrolidine and pyrrolizidine alkaloids from Hyacinthoides non-scripta and Scilla campanulata."Carbohydrate Res.. 316. 95-103 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yumita N. et al.: "Sonodynamically induced cell damage with 4'-O-tetrahydropyranyl-adriamycin, THP."Anticancer Res.. 19. 281-284 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura S. et al.: "Sonodynamically induced effect of rose bengal on iosolated sarcoma 180 cells."Cancer Chemotherapy. Pharmacol.. 43. 382-393 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yumita N. et al.: "Sonodynamically induced effect of eosin Y on isolated sarcoma 180 cells."J.Med.Ultrasonics. 26. 11-16 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Li M. et al.: "Apoptosis induced by cadmium in human lymphoma U937 cells through Ca^<2+>-calpain and caspase-mitochondria dependent pathways."J.Biol.Chem.. 275. 39702-39709 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori M. et al.: "Secondary metabolism of dinitrobenzyl glucuronide related to production of genotoxic compounds of dinitrotoluene in male Wistar rat."J.Health Sci.. 46. 329-335 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Konishi,K. et al.: "Inhibitory Effect of Sanguiin H-11 on Chemotaxis of Neutrophil."Biol.Pharm.Bull.. 23-2. 213-218 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asano,N. et al.: "New polyhydroxylated pyrrolizidine alkaloids from Muscari armeniacum : structural determination and biological activity."Tetrahedron Asymm.. 11. 1-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yumita N. et al.: "Sonodynamically induced antitumor effect of 4-formyloximethylidene-3-hydroxy-2-vinyl-deuterio-porphyny (IX)-6,7-diasparic acid (ATX-S10)."Jpn.J.Cancer Res.. 91. 255-260 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jin Z.H. et al.: "Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice."J.Dermatol.. 27. 294-306 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji M. et al.: "A convenient method for discriminating between natural and depleted uranium by γ-ray spectrometry."Applied Radiat.Isotopes. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kameda K.et al.: "Role of intracellular Ca^<2+> in apoptosis induced by hyperthermia and its enhancement by verapamil in U937 cells."Int.J.Radiat.Oncol.Biol.Phys.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda S. et al.: "Frequency dependence of free radical formation by ultrasound in the presence of different rare gases."Jpn.J.Applied Phys.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Li F.-J. et al.: "Enhancement of hyperthermia-induced apoptosis by a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride, in human histiocytic lymphoma U 937 cells."Free Radical Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ngawhirunpat T. et al.: "Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats."Pharmazie. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ngawhirunpat T. et al.: "Age difference in simultaneous permeation and metabolism of ethyl nicotinate in rat skin."Biol.Pharm.Bull.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kondo T., Misik V., Riesz P.: "Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound."Free Radical Biol.Med.. 25. 605-612 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura C., Zhao Q.-L., Kondo T., Amatsu M., Fujiwara Y.: "Mechanism of UV-induced apoptosis in human leukemia cells. : Roles of Ca^<2+>/Mg^<2+>-dependent endonuclease, caspase-3, and stress-activated protein kinases."Exptl.Cell Res.. 239. 411-422 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sayama M., Mori M., Shoji M., Uda S., Kakikawa M., Kondo T., Kodaira K.: "Mutagenicities of 2,4-and 2,6-dinitrotoluenes, and their reduced products in Salmonella typhimurium nitroreductase and O-acetyltransferase overproducing Ames strains."Mutation Res.. 420. 27-32 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Viroonchatapan E., Sato H., Ueno M., Adachi I., Murata J., Saiki I., Tazawa K., Horikoshi I.: "Microdialysis assessment of 5-fluorouracil release from thermosensitive magneto-liposomes induced by an electromagnetic field in tumor-bearing mice."J.Drug Target.. 5. 379-390 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yumita N., Umemura S., Kaneuchi M., Okano Y., Magario N., Ishizaki M., Shimizu K., Sano Y., Umemura K., Nishigaki R.: "Sonodynamically-induced cell damage with fluorinated anthracycline derivative, FAD104."Cancer Lett.. 125. 209-214 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sasaki K., Yumita N., Nishigaki R., Umemura S.: "Antitumor effect sonodynamically induced by focused ultrasound in combination with Ga-porphyrin complex."Jpn.J.Cancer Res.. 89. 452-456 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanabe K., Morishima Y., Shibutani T., Terada Y., Hara T., Shinohara Y., Aoyagi K., Kunitada S., Kondo T.: "DX-9065a, an orally active factor Xa inhibitor, does not facilitate haemorrhage induced by tail transection orgastric ulcer at the effective doses in rat thrombosis model."Thrombosis Haemostasis.. 81. 828-834 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanabe K., Kondo T., Onodera Y., Furusawa M.: "A conspicuous adaptability to antibiotics in the Escherichia coli mutator, dnaQ49."FEMS Microbiol.Lett.. 176. 191-196 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanabe K., Terada Y., Shibutani T., Kunitada S., Kondo T.: "DX-9065a, a specific inhibitor of factor Xa, exerts effective protection against experimental tumor-induced disseminated intravascular coagulation."Thrombosis Res.. 96. 135-143 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhao Q.-L., Kondo T., Noda A., Fujiwara Y.: "Mitochondrial and intracellular free-calcium regulation of radiation-induced apoptosis in human leukemic cells."Int.J.Radiat.Biol.. 75. 493-504 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato A., Adachi I., Miyauchi M., Ikeda K., Komae T., Kizu H., Kameda Y., Watson A.A., Nash R.J., Wormald M.R., Fleet G.W.J., Asano N.: "Polyhydroxy pyrrolidine and pyrrolizidine alkaloids from Hyacinthoides non-scripta and Scilla campanulata."Carbohydrate Res.. 316. 95-103 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yumita N., Kaneuchi M., Okano Y., Nishigaki R., Umemura K., Umemura S.: "Sonodynamically induced cell damage with 4'-O-tetrahydropyranyladriamycin, THP."Anticancer Res.. 19. 281-284 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umemura S., Yumita N., Umemura K., Nishigaki R.: "Sonodynamically induced effect of rose bengal on iosolated sarcoma 180 cells."Cancer Chemotherapy. Pharmacol.. 43. 382-393 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yumita N., Umemura S.: "Sonodynamically induced effect of eosin Y on isolated sarcoma 180 cells."J.Med.Ultrasonics.. 26. 11-16 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Li M., Kondo T., Zhao Q.-L., Li F.-J., Li M., Tanabe K., Arai Y., Zou Z.-C., Kasuya M.: "Apoptosis induced by cadmium in human lymphoma U937 cells through Ca^<2+>-calpain and caspase-mitochondria dependent pathways."J.Biol.Chem.. 275. 39702-39709 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori M., Shoji M., Sayama M., Kondo T., Inoue M., Kodaira K.: "Secondaty metabolism of dinitrobenzyl glucuronide related to production of genotoxic compounds of dinitrotoluene in male Wistar rat."J.Health Sci.. 46. 329-335 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Konishi, K., Urada, M., Adachi, I., Tanaka, T.: "Inhibitory Effect of Sanguiin H-11 on Chemotaxis of Neutrophil."Biol.Pharm.Bull.. 23-2. 213-218 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asano, N., Kuroi, H., Ikeda, K., Kizu, H., Kameda, Y., Kato, A., Adachi, I., Watson A.A., Nash, R.J., Fleet, G.W.J.: "New polyhydroxylated pyrrolizidine alkaloids from Muscari armeniacum : structural determination and biological activity."Tetrahedron Asymm.. 11. 1-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yumita N., Nishigaki R., Sakata I., Nakajima S., Umemura S.: "Sonodynamically induced antitumor effect of 4-formyloximethylidene-3-hydroxy-2-vinyl-deuterio-porphyny (IX)-6,7-diasparic acid (ATX-S10)."Jpn.J.Cancer Res.. 91. 255-260 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jin Z.H., Miyoshi N., Ishiguro K., Umemura S., Kawabata K., Yumita N., Sakata I., Takaoka K., Udagawa T., Nakajima S., Tajiri H., Ueda K., Fukuda M., Kumakiri M.: "Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice."J.Dermatol.. 27. 294-306 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoji M., Hamajima Y., Takatsuka K., Honoki H., Nakajima T., Kondo T., Nakanishi T.: "A convenient method for discriminating between natural and depleted uranium by γ-ray spectrometry."Applied Radiat.Isotopes.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kameda K., Kondo T., Tanabe K., Zhao Q.-L., Seto H.: "Role of intracellular Ca^<2+> in apoptosis induced by hyperthermia and its enhancement by verapamil in U 937 cells."Int.J.Radiat.Oncol.Biol.Phys.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda S., Ogawa R., Kondo T.: "Frequency dependence of free radical formation by ultrasound in the presence of different rare gases."Jpn.J.Applied Phys.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Li F.-J., Kondo T., Zhao Q.-L., Tanabe K., Ogawa R., Li M., Arai Y.: "Enhancement of hyperthermia-induced apoptosis by a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride, in human histiocytic lymphoma U 937 cells."Free Radical Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ngawhirunpat T, Yoshikawa H, Hatanaka T, Koizumi T, Adachi I.: "Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats."Pharmazie.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ngawhirunpat T, Hatanaka T, Kawakami J, Adachi I.: "Age difference in simultaneous permeation and metabolism of ethyl nicotinate in rat skin."Biol.Pharm.Bull.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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