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Effects of medroxyprogesterone acetate and synthetic analogue of fumagillin on endometrial cancer

Research Project

Project/Area Number 06454474
Research Category

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

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionTottori University, Faculty of Medicine

Principal Investigator

TERAKAWA Naoki  Tottori Univ., Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)

Co-Investigator(Kenkyū-buntansha) MINAGAWA Yukihisa  Tottori Univ., Dept.Obstet.Gynecol., Assistant Professor, 医学部・附属病院, 講師 (70190692)
KIGAWA Junzo  Tottori Univ., Dept.Obstet.Gynecol., Assistant Professor, 医学部, 講師 (00177784)
石原 浩  鳥取大学, 医学部附属病院, 助手 (80252865)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsEndometrial Cancer / Nood mouse model / Anti-tumor effect / Medroxyprogesterone acetate / Synthetic analogue of fumagillin / Growth inhibition / Inhibition of angiogenesis / 血管新生阻害剤 / プロゲスチン / 併用療法
Research Abstract

This study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) and synthetic analogue of fumagillin (TNP-470) on the growth of human endometrial adenocarcinoma. Endometrial adenocarcinoma cells, ECC-1 cells, were inoculated subcutaneously in male nude mice stimulated by sc implantation of E_2 pellet. When the tumor size reached to 8.0<plus-minus>0.2 mm at two weeks after inoculation, the animals with endometrial adenocarcinoma were randomly divided into four groups : mice treated with vehicle alone (control) , MPA (10mg/kg body weight) , TNP-470 (30mg/kg body weight) , or MPA and TNP-470 combination. Vehicle or the compounds were injected sc every two days for 8 weeks. Administration of MPA significantly inhibited the increase in tumor size, and the inhibition became evident 2 weeks after MPA treatment. On the other hand, the suppression of the increase in tumor size by TNP-470, an angiogenic inhibitor, was not significant. There was no difference in the degr … More ee of tumor reduction between the treatments of MPA alone and MPA and TNP-470 combination.
We next examined the mechanism of tumor reduction by MPA treatment. After MPA treatment necrosis was evident in the tumor grafts. Vessel counts and immunohistochemical stainings for angiogenic growth factors, bFGF and TGF-alpha, in tumors were carried out. Neither MPA nor TNP-470 significantly reduced the number of vessels and the intensity of immunostainings for bFGF and TGF-alpha in tumors. In order to know whether MPA treatment induced apoptosis of tumor cells and reduced the tumor size, TUNEL stainings were performed in tumor grafts. There was no significant difference in the intensity of staining between the control and MPA-treated groups. Finally, the proliferative ability of tumor cells was examined by the method of PCNA staining. It was found that the number of PCNA-positive cells was remarkably decreased in MPA-treated tumors.
In the present study with nude mouse model system, the mechanism of antitumor effect of MPA in endometrial adenocarcinoma was shown. However, antiproliferative effect of an angiogenic inhibitor on adenocarcinoma could not be found in this system. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Yukihisa Minagawa: "Synergistic Enhancement of cisplatin cytotoxicity by SN-38, an Active Metabolite of CPT-11, for Cisplatill-resistant Hera cells" Japanese Journal of Cancer Research. 85. 966-971 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tasuku Harada: "Murine Eibloblast Growth Factor Receptor 1 Grene Geneyates Multiple Mesce-ger RNAS Containing Two Open Reading Frames Via Arternative Splicing" Biochemical and Biophysical Research Communications. 205. 1057-1063 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoki Terakawa: "Hormonal Carcinogenesis II" Springer-Verlag New York, Inc., 167-175 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoki Terakawa: "Hormone-Dependent Cancer" marcel dekker, inc., 477-498 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yukihisa Minagawa: "Synergistic enhancement of cisplatin cytotoxicity by SN-38, an active metabolite of CPT-11, for cisplatin-resistant HeLa cells" Jpn J Cancer Res. 85 (9). 966-971 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tasuku Harada: "Murine fibroblast growth factor receptor 1 gene generates multiple messenger RNAs containing two open reading frames via alteernative splicing" Biochemical and Biophysical Research Communications. 205 (2). 1057-1063 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoki Terakawa: "Growth factors in Endometrial Cancer" Springer-Verlag New York, Inc., Hormonal Carcinogenesis II. 167-175 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoki Terakawa: "Endometrial Cancer" marcel dekker, inc., Hormone-Dependent Cancer. 477-498 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yukihisa Minagawa: "Synergistic Ennancement of Cisplatin Cytotoxicity by SN-38,an Active Metabolite of CPT-11,for Cisplatin-resistant HeLa Cells." Japanese Journal of Cancer Research. 85. 966-971 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tasuku Harada: "Murme Fibroblast Growth Factor Receptor I Gene Generates Multiple Messenger RNAs Containing Two Oper Reading Frimes via Artemative Splicing" Biochemical and Biophysical Research Communications. 205. 1057-1063 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoki Terakawa: "Hormonal Carcinogenesis II" Springer-Verlag New York,Inc., 167-175 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoki Terakawa: "Hormone-Dependent Cancer" marcel dekker,Inc., 477-498 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoki Terakawa: "Growth factors in endometrial cancer" In.J.J.Li(ed),Hormonal Carcinogenesis,Springer-Verlag,New York(in press), 300

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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