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TUMOR REGRESSION CAUSED BY ACTIVATED VITAMIN D_3 IN MURINE RENAL CARCINOMA.

Research Project

Project/Area Number 05671331
Research Category

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

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionIWATE MEDICAL UNIVERSITY SCHOOL of MEDICINE

Principal Investigator

FUJIOKA Tomoaki  IWATE MEDICAL UNIVERSITY SCHOOL OF MEDICINE,DEPARTMENT OF UROLOGY,ASSOCIATE PROFESSOR, 医学部・泌尿器科, 助教授 (80173409)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsActivated vitamin D_3 / Antitumoral effercts / Tumor angiogenesis / Microangiography / Colorimetric assay / 腫瘍血管新生阻害剤 / 腎癌 / 1,25(OH)_2D_3 / 1a(OH)D_3 / 22-oxa-1a,25(OH)_2D_3 / Renca
Research Abstract

The effect of anti-tumoral therapy using 1alpha-hydroxvitamin D_3 [1alpha (OH) D_3] which is converted by liver cells to active from of vitamin D_3 [1alpha, 25 (OH) _2D_3], 22-Oxa-1alpha, 25 (OH) _2 D_3 and 1alpha, 25 (OH) _2D_3 WAS inveatigated in BALB/c mice inoculated with murine renal cell carcinoma (Renca). Tumor-inoculated mice were given i.p. 2.5 nmol/kg and 5.0 nmol/kg of these vitamin D_3 analogues every 2 days from Day 1 after tumor inoculation. Treatment with these analogues significantly suppressed the growth of Renca in a dose-dependent manner compared with control mice on Days 14 and 21. Toxic effect of 22-oxa-1,25 (OH) _2D_3 was only minimally by dosed of 5.0 nmol/kg. However 1alpha (OH) D_3 and 1alpha, 25 (OH) _2D_3 caused a decrease in body weight of the mice. Treatment with 1a (OH) D_3 and 22-Oxa-1alpha, 25 (OH) _2D_3 caused no appreciated hypercalcemia and did not counteract the decrese of serum inorganic phosphorus level in mice bearing Renca. Histological examination showed that i.p. treatment of these analogues caused coagulative necrosis of the tumors on Day 21, while hemorrhargic necrosis and lymphocyte infiltration were not observed. The antitumoral effect of these analogues was also demonstrated in athymic nude mice and it did not altered by treatment with anti-asialo GM1. Tumor angiogenic activity was measured quantitatively using a colorimetric assay and it was inhibited to 72-85% of the control level in a dose-dependent manner by these analogues. Microangiography showed a lower density of angiogenesis and thinner novessels than control tumors.
From these results, it was concluded that 1,25 (OH) _2D_3,1alpha (OH) D_3 and 22-oxa-1,25 (OH) _2 D_3 were potensially effective for renal cell carcinoma. The potent antiangiogenic action of these analogues was also demonstrated. Host immune response mediated T cells and NK cells did not any role in antitumoral effect of these vitamin D_3 analogues.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 藤岡 知昭 他: "マウス腎癌に対するビタミンD_3の抗腫瘍効果" 医学のあゆみ. 164. 221-222 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 藤岡 知昭 他: "マウス腎癌に対する活性ビタミンD_3およびコルチゾンの血管新生阻害作用" 医学のあゆみ. 166. 619-620 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 藤岡 知昭 他: "マウス腎癌におけるビタミンD_3誘導体による血管新生阻害作用と抗腫瘍効果" BIOTHERAPY. 8. 196-200 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 鈴木 泰: "ヒト腎癌における血管新生活性の検討" BCG・BRM学会誌. 17. 63-66 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 藤岡 知昭 他: "血管新生阻害作用TNP-470のマウス腎癌に対する抗腫瘍効果" 医学のあゆみ. 172. 671-675 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujioka, T.et al.: "Antitumor effect of activated vitamin D_3 in mice with murine renal cell carcinoma." IGAKU NO AYUMI. 164. 221-223 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujioka, T.et al.: "Tumor angiogenesis inhibited by vitamin D_3 analogue or cortisone in BALB/c mice." IGAKU NO AYUMI. 164. 619-620 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujioka, T.et al.: "Vitamin D_3 analogues suppressed tumor angiogenesis and inhibited growth of renal adenocarcinoma in mice." BIOTHERAPY. 8. 196-200 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzuki, Y.et al.: "Tumor angiogenesis in human renal cell carcinoma." Ann Soci BCG ・ BRM. 17. 63-66 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujioka, T.et al.: "Antitumoraleffect of angiogenesis inhibitor TNP-470 against murine renal cell carcinoma." IGAKU NO AYUMI. 172. 675-676 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 藤岡知昭 他: "マウス腎癌におけるビタミンD_3誘導体による血管新生阻害作用と抗腫瘍効果" BIOTHERAPY. 8. 196-200 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 藤岡知昭 他: "血管新生阻害剤TNP-470のマウス腎癌に対する抗腫瘍効果" 医学のあゆみ. 172. 675-679 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 藤岡知昭、他: "マウス腎癌に対する活性型ビタミンD_3の抗腫瘍効果" 医学のあゆみ. 164(4). 221-222 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 藤岡知昭、他: "マウス腎癌に対する活性ビタミンD_3およびコルチゾンの血管新生阻害作用" 医学のあゆみ. 166(9). 619-620 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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