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Fundamental study of combination treatment of fibrinolytic agents, radiohypersensitizer and repair-inhibitor of DNA to enhance radiation effects on experimental tumor in mice and rabbits.

Research Project

Project/Area Number 02454562
Research Category

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

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionChiba University

Principal Investigator

MIYOSHI Takeyoshi  Dept.Radiol.Sch.Med. Chiba Univ., 医学部, 講師 (10114331)

Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsRadiation / Fibrinolytic agent / Low molecular weight dextran / Urokinase / Radiohypersensitizer / TNF( Tumor necrosis factor ) / Ara-A / Vx-2 tumor / 低分子デキストラン / TNF(腫瘍壞死物質) / Vx-2腫瘍 / ウロキナ-ゼ / アンジオテンシンーII / TNF(腫瘍壊孔物質) / Vxー2腫瘍 / 血流改善 / マイソニダゾ-ル
Research Abstract

To strengthen radiation effects on tumors, each one of fibrinolytic agents and radiohypersensitizers have been used jointly with radiation,however this approach has not always produced good results in cancer patients. Fibrinolytic agents can not improve blood flow in capillary vessels in which micro-thrombus become old and fibrotic. While, radiohypersensitizers are unable to permeate deeply and sufficiently in hypoxic and anoxic areas of large tumor, because this agents have neuro-toxic effects when administered in large amounts.
We carried out a combination treatment with fibrinolytic agents (a mixture of Low Molecular Weight Dextran and Urokinase) and a radiohypersensitizer(misonidazol) to supply deficiencys of these agents. In our studies on mouse Ehrlich solid tumor, we found the same result could be obtained with 300 mg/kg of misonidazol as with 500 mg/kg of misonidazol in case of misonidazol, alone a reduction of 40%. However, the effect of this combination treatment had been redu … More ced in experiments when large sized Vx-2 tumors on rabbits were used, and it was thought that permeation of misonidazol was not sufficient in wide hypoxic and anoxic areas of large tumors. In other studies, we foundthat low doses of TNF(Tumor Necrosis Factor) remarkably increased drug accumulation in tumor tissures. From these results, a new combination treatment of fibrinolytic agents, TNF and misonidazol was studied on large Vx-2 tumor. By this new treatment, radiation effects were greatly enhanced, and the effective dosage of misonidazol reduced to 200 mg/kg.
By this combination treatment system, RK-28( an improved type substance of misonidazol ) was studied instead of misonidazol, and the same result were obtained. To further augment radiation effects, at the same time, Ara-A( as a repair-inhibitor of damaged DNA ) was studied with this systemic combination treatment of fibrinolytic agents, TNF and RK-28, but it failed to show enhancement of radiation effects.
These results indicated that our combination treatment of fibrinolytic agents, TNF and radiohypersensitizers is worthy of clinical trial for cancer therapy. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 三好 武美,他: "線溶機能亢進剤によるEhrlilh固型腫瘍に対する放射線効果の増強作用" 日本医学放射線学会雑誌. 4.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 竹田 明彦,三好 武美,他: "線溶機能亢進剤によるモノクローナル抗体の腫瘍集積増強効果" 日本消化器外科学会雑誌. 24. 2004-2011 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 竹田 明彦,三好 武美他: "Angiotensin IIとTumornecrosis Factor(TNF)併用によるモノクローナル抗体の腫瘍集積増強効果" Biotherapy. 6. 1451-1455 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 三好 武美,竹田 明彦: "線溶機能亢進剤、TNF(Tumor Necrosis Factor)併用によるモノクロール抗体の腫瘍集積増強効果"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 三好 武美他: "線溶機能亢進剤と放射線増感剤併用による放射線効果の増強効果"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 三好 武美他: "線溶機能亢進剤,TNF(Tumor Necrosis Factor),放射線増感剤併用による放射線効果の増強作用"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Edwards, E.A.: "Migrating thrombophlebitis associated with carcinoma." New Eng. J.Mes.240. 1031--1035 (1949)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiramoto, R,,Bernecky, J., Jurandowski,J. and Pressman, D.: "Fibrin in human tumors." Cancer Res.20. 592--593 (1960)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Clarke, N.: "Intracellular location of tissue thromboplastin and possible relation of fibrin deposits in human neoplasms." Nature, London. 205. 608--610 (1965)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Astedt, B., Bergentz, S.E. and Svanberg, C.: "Effects of irradiation on the plasminogen activator content in rat vessels." Experientia. 30. 1466--1467 (1974)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Svanberg, L., Astedt, B. and Kullander,S.: "ON radiation-decreased fibrinolytic activity of vessel wall." Acta. Obst. Gyn. Scand. 55. 49--51 (1976)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Thmlison, R.H.and Craddock,E.A.: "The gross response of an experimental tumor to single doses of X-rays." Br. J. Cancer. 21. 108 (1966)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Murray, J.C.,Randhawa, V. and Denekamp, J.: "The effects of melphalan and misonidazole on the vasculature of a mutine sarcoma." Br. J. Cancer. 55. 233--238 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Chin,J.B. and Rauth,A.M.: "The metabolism and pharmacokinetics of the hypoxic cell radiosensitizer and cytotoxic agent misonidazole in C3H mice." Radiat. Res.86. 341 (1981)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hilmas,D.E. and Gillette,E.L.: "Morphometric analyses of the microvasculature of tumors during and after X-irradiation" Cancer. 33. 103 (1973)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Sato,N., Sawasaki,Y. and Haranaka, K., et al.: "Growth inhibitory and cytotoxic action of rabbit tumor necrosis factor agenst bovine cappllary endothelial cells in vitro." Proc. Jpn. Acad.61(B). 471--474 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Iliakis,G., Pantelias,G. Okuyasu,R. and Seaner,R.: "Comparative studies on repair inhibition by Ara , AraC and aphidicolin of radiation induced DNA and chromosome damage in rodent cells:Comparison with fixation of PLD." Int. J. Radiation Oncology Bio. Phys.16. 1261--1265 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 竹田 明彦、三好 武美 他: "線溶機能亢進剤によるモノクローナル抗体の腫瘍集積増強効果" 日本消化器外科学会雑誌. 24. 2004-2011 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 竹田 明彦、三好 武美 他: "AngiotensinIIとTumor Necrosis Factor(TNF)併用によるモノクローナル抗体の腫瘍集積増強効果" Biotherapy. 6. 1451-1455 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 竹田 明彦,三好 武美, 他: "線溶機能亢進剤による標識モノクロ-ナル抗体の腫瘍集積増強効果" 日本消化器外科学会雑誌. 24. 2004-2011 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 竹田 明彦,三好 武美 他: "AngrotensinIIとTumor necrosis factor(TNF)併用によるモノクロ-ナル抗体の腫瘍集積増強効果" 日本外科学会雑誌. 92. 475 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 三好 武美 他: "線容機能亢進剤によるEhrlich固型腫瘍に対する放射線効果の増強作用" 日本医学放射線学会雑誌. 42. 895-898 (1982)

    • Related Report
      1991 Annual Research Report
  • [Publications] 竹田 明彦,三好 武美,磯野 可一,他: "Angiotensin IIとTumor necrosis factor(TNF)併用によるモノクロ-ナル抗体の腫瘍集積増強効果" 日本外科学会雑誌. 92. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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