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Application of NO generating agents as radiosensitizer and their modes of action.

Research Project

Project/Area Number 13470181
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionFaculty of Medical Sciences, University of Fukui

Principal Investigator

MATSUMOTO Hideki  Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Associate Professor, 医学部, 助教授 (40142377)

Co-Investigator(Kenkyū-buntansha) JIN Zhao-hui  Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Assistant Professor, 医学部, 助手 (70324150)
HAYASHI Sachiko  Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Assistant Professor, 医学部, 助手 (00218570)
KANO Eiichi  Faculty of Medical Science, University of Fukui, Department of Experimental Radiology and Health Physics, Professor, 医学部, 教授 (70065910)
HATASHITA Masanori  The Wakasa Wan Energy Research Center, Research and Development, Researcher, 物性バイオグループ, 主査 (40359237)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsSCC / NSCLC / Radiotherapy / Hyperthermia / Drug for angina pectoris / p53 / Hsp70 / Apoptosis / apoptopsis / 放射線治療 / 温熱療法 / NOラジカル発生剤 / バイスタンダー効果 / Hsp72 / 放射線 / Nitric oxide / Nitric oxide発生剤 / 放射線感受性 / 細胞間シグナル伝達系 / アポトーシス
Research Abstract

We examined effects of a nitric oxide-generating agent, isosorbide dinitrate(ISDN), which is a quite popular drug for angina pectoris, on radiotherapy and hyperthermia to cancer cells in vifro and in vivo from an aspect of p53 functions.Transplantable p53-deficient human non-small cell lung cancer(NSCLC) H1299 cells were transfected with a vector carrying wild-type, mutant p53 gene or a neomycin-resistant gene(neo)alone as a control.
Radiosensitivity and thermosensitivity at 44℃ of these transfectants in vitro was increased with ISDN (0.3 mM) in a p53-independent manner, although ISDN revealed no cytotoxicity at 37℃ in vitro. Western blot analysis indicated that the increase of thermosensitivity was partially due to a stimulation of decay of heat-induced Hsp72.Growth delay of these transplanted tumors after irradiation at 10 Gy or heating at 43℃ in vivo was enhanced with ISDN (0.3 mM) regardless of their p53 gene status, although lSDN revealed no effect on tumor growth.Immunohistochemical analysis(TUNEL method) indicated that the enhancement of tumor growth delay was partially due to induction of p53-independent apoptosisin both cases.
These findings suggested that a p53-independent apoptosis induced an efficient cell killing and tumor growth delay by combined treatment with radiation or hyperthermia and ISDN.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (61 results)

All Other

All Publications (61 results)

  • [Publications] Matsumoto, H., 他8名: "Induction of radioresistance by nitric oxide-mediated bystander effect."Radiat.Res.. 155. 387-396 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsubo, T., 他7名: "Acidic environment modifies heat- or radiation-induced apoptosis in human maxillary cancer cells."Int.J.Radiat.Oncol.Biol.Phys.. 49. 1391-1398 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, A., 他8名: "Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation."Int.J.Radiat.Biol.. 77. 939-945 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, A., 他7名: "p53-dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET."Int.J.Radiat.Biol.. 77. 1043-1051 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, S., 他9名: "Modification of thermosensitivity and chemosensitivity induced by combined treatments with hyperthermia and adriamycin."Int.J.Mol.Med.. 8. 417-422 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsubo, T., 他7名: "Enhancement of cell killing by induction of apoptosis after treatment with mild hyperthermia at 42℃ and cisplatin."Radiat.Res.. 156. 103-109 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin, Z.H., 他6名: "Effects of combined treatment with 40℃ hyperthermia and bleomycin on the accumulation of heat shock protein in murine L cells."Int.J.Oncol.. 20. 137-142 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohnishi, K., 他5名: "Transfection of mutant p53 gene depresses X-ray- or CDDP-induced apoptosis in a human squamous cell carcinoma of the head and neck."Apoptosis. 7. 367-372 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto, H.: "Intercellular signaling mediated by nitric oxide in glioblastoma cells."Method.Enzymol.. 359. 280-286 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shao, C.L. 他4名: "Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells."Int.J.Radiat.Biol.. 78. 837-844 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto, H., 他1名: "Indirect influences of radiation on unirradiated cells through irradiated cells."Biol.Sci.Space. 17. 257-258 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Nagasawa, 他5名: "Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia inducible factor 1 signaling pathway."Anticancer Res.. 23. 4427-4434 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Takahashi, 他10名: "p53-dependent hyperthermic enhancement of tumour growth inhibition by X-ray or carbon-ion beam irradiation."Int.J.Hyperthermia. 19. 145-153 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Z.H.Jin, 他7名: "p53-independent thermosensitization by mitomycin C in human non-small cell lung cancer cells."Int.J.Radiat.Oncol.Biol.Phys.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 他4名: "放射線適応応答と放射線誘発バイスタンダー効果"放射線生物研究. 37. 420-430 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹: "p53"癌の臨床. 49. 1519-1523 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 加納永一: "NOラジカルをイニシエーターとする放射線誘発バイスタンダー効果"癌の臨床. 47. 8-11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 他4名: "ストレス応答研究の新展開 -放射線誘発バイスタンダー効果-"放射線生物研究. 36. 87-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 他4名: "NOラジカルによるバイスタンダー効果とアポトーシス"癌の臨床. 48. 366-369 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 他4名: "集学的癌治療の研究と臨床「集学的癌治療における活性窒素種の役割」"加納永一(篠原出版新社). 10-16(394) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 金 朝暉, 他5名: "集学的癌治療の研究と臨床「光力学的治療による制癌:沿革から現状まで」"加納永一(篠原出版新社). 17-23(394) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 畑下昌範, 他5名: "集学的癌治療の研究と臨床「癌関連遺伝子と細胞周期」"加納永一(篠原出版新社). 93-99(394) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 林 幸子, 他9名: "集学的癌治療の研究と臨床「細胞および分子レベルにおけるハイパーサーミアの基礎的局面"加納永一(篠原出版新社). 110-127(394) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 大坪俊雄, 他6名: "集学的癌治療の研究と臨床「癌化学療法剤殺細胞効果の温熱による増強」"加納永一(篠原出版新社). 128-135(394) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 松本英樹, 小松賢志: "低線量・低線量率放射線による生物影響発現「放射線誘発バイスタンダー効果」(大西武雄 監修)"(株)アイプリコム. 44-51(94) (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto, H at al.: "Induction of radioresistance by nitric oxidemediated bystander effect."Radiat.Res.. 155. 387-396 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsubo, T.et al.: "Acidic environment modifies heat-or radiation-induced apoptosis in human maxillary cancer cells."Int.J.Radiat.Oncol.Biol.Phys.. 49. 1391-1398 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, A.et al.: "Radiation response of apoptosis in C57BLJ6N mouse spleen after whole-body irradiation."Int.J.Radiat.Biol.. 77. 939-945 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, A.et al.: "p53-dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET."Int.J.Radiat.Blol.. 77. 1043-1051 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, S.et al.: "Modification of thermosensitivity and chemosensitivity induced by combined treatments with hyperthermia and adnamycin."Int.J.Mol.Med.. 8. 417-422 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsubo, T.et al.: "Enhancement of cell killing by induction of apoptosis after treatment with mild hyperthermia at 420C and cisplatin."Radiat.Res.. 156. 103-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin, Z.H.et al.: "Effects of combined treatment with 40℃ hyperthermia and bleomycin on the accumulation of heat shock protein in murine L cells."Int.J.Oncol.. 20. 137-142 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohnishi, K.et al.: "Transfection of mutant p53 gene depresses X-ray-or CDDP-induced apoptosis in a human squamous cell carcinoma of the head and neck."Apoptosis. 7. 367-372 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto, H.et al.: "Intercellular signaling mediated by nitric oxide in glioblastoma cells."Method.Enzymol.. 359. 280-286 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shao, C.L.et al.: "Nitric oxide-mediated bystander effect induced by heavy-Ions in human salivary gland tumour cells."Int.J.Radiat.Biol.. 78. 837-844 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumoto, H.et al.: "Indirect influences of radiation on unirradiated cells through irradiated cells."Biol.Sci.Space. 17. 257-258 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagasawa, H.et al.: "Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia-inducible factor 1 signaling pathway."Anticancer Res.. 23. 4427-4434 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, A.et al.: "p53-dependent hyperthermic enhancement of tumour growth inhibition by X-ray or carbon-ion beam irradiation."Int.J.Hyperthermia. 19. 145-153 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin, Z.H.et al.: "p53-independent thermosensitization by mitomycin C in human non-small cell lung cancer cells."Int.J.Radiat.Oncol.Biol.Phys.. (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] Z.H.Jin 他7名: "p53-independent thermosensitization by mitomycin C in human non-small cell lung cancer cells"Int.J.Radiat.Oncol.Biol.Phys.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Matsumoto, T.Ohnishi: "Indirect influences of radiation on unirradiated cells through irradiated cells"Biol.Sci.Space. 17・3. 257-258 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Nagasawa 他5名: "Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia-inducible factor 1 signaling pathway"Anticancer Res.. 23・6a. 4427-4434 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Takahashi 他10名: "p53-dependent hyperthermic enhancement of tumour growth inhibition by X-ray or carbon-ion beam irradiation"Int.J.Hyperthermia. 19・2. 145-153 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松本 英樹: "P53"癌の臨床. 49・12. 1519-1523 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松本英樹, 小松賢志: "低線量・低線量率放射線による生物影響発現「放射線誘発バイスタンダー効果」"大西武雄 監修((株)アイプリコム). 44-51(94) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jin, Z.H.他6名: "Effects of combined treatment with 40℃ hyperthermia and bleomycin on the accumulation of heat shock protein in murine L cells"Int.J.Oncol.. 20. 137-142 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohnishi, K.他5名: "Transfection of mutant p53 gene depresses X-ray-or CDDP-induced apoptosis in a human squamous cell carcinoma of the head and neck"Apoptosis. 7. 367-372 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsumoto, H.他6名: "Intercellular signaling mediated by nitric oxide in glioblastoma cells"Method.Enzymol.. 359. 280-286 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shao, C.L.他4名: "Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells"Int.J.Radial.Biol.. 78. 839-844 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松本英樹 他4名: "集学的癌治療の研究と臨床「集学的癌治療における活性窒素種の役割」"加納永一(篠原出版新社). 10-16 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 金 朝暉 他5名: "集学的癌治療の研究と臨床「光学的治療による制癌:沿革から現状まで」"加納永一(篠原出版新社). 17-23 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 畑下昌範 他5名: "集学的癌治療の研究と臨床「癌関連遺伝子と細胞周期」"加納永一(篠原出版新社). 93-99 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 林 幸子 他9名: "集学的癌治療の研究と臨床「細胞および分子レベルにおけるハイパーサーミアの基礎的局面」"加納永一(篠原出版新社). 110-127 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大坪俊雄 他6名: "集学的癌治療の研究と臨床「癌化学療法剤殺細胞効果の温熱による増強」"加納永一(篠原出版新社). 127-135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsumoto, H., 他8名: "Induction of radioresistance by nitric oxide-mediated bystander effect"Radiat. Res.. 155. 387-396 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsubo, T., 他7名: "Acidic environment modifies heat-or radiation-induced apoptosis in human maxillary cancer cells"Int J Radiation Oncol. Biol. Phys.. 49. 1391-1398 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, A., 他8名: "Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation"Int J Radiat. Biol.. 77. 939-945 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, A., 他7名: "p53-dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET"Int J Radiat. Biol.. 77. 1043-1051 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi, S, 他9名: "Modification of thermosensitivity and chemosensitivity induced by combined treatments with hyperthermia and adriamycin"Int. J. Mol. Med.. 8. 417-422 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsubo, T., 他7名: "Enhancement of cell killing by induction of apoptosis after treatment with mild hyperthermia at 42℃ and cisplatin"Radiat. Res.. 156. 103-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsumoto, H., 他5名: "Intercellular signaling mediated by nitric oxide in human glioblastoma cells. in"Methods in Enzymology""L.Packer, et al.(印刷中). (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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