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Development of therapeutic and prophylactic method for the uterine smooth muscle tumors bu understanding novel aspect of its etiology

Research Project

Project/Area Number 15209053
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University, Graduate School of Medicine

Principal Investigator

FUJII Shingo  Kyoto Univ.Med, Gynecol & Obstet., Professor, 医学研究科, 教授 (30135579)

Co-Investigator(Kenkyū-buntansha) FUJITA Jun  Kyoto Univ.Med, Professor, 医学研究科, 教授 (50173430)
TOGASHI Kaori  Kyoto Univ.Med, Professor, 医学研究科, 教授 (90135484)
TAKAKURA Ken  Kyoto Univ.Med, Associate Professor, 医学研究科, 助教授 (10221350)
KARIYA Masatoshi  Kyoto Univ.Med, Associate Professor, 医学研究科, 講師 (90243013)
NIKAIDO Toshio  Toyama Univ.Med, Professor, 教授 (50180568)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2005: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2004: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2003: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
Keywordsuterine smooth muscle tumor / oxidative stress / re-perfusion / gray zone / p53 / microarray / 月経 / 子宮収縮 / ストレス / 肥満細胞 / アクログラニン / MRI / 子宮筋腫 / 子宮肉腫 / 細胞株 / Acrogranin / 性ステロイド受容体 / TGF-β / 不死化 / p53 / アポトーシス / タイプIIIコラーゲン
Research Abstract

We have investigated various biological and clinical aspects of uterine smooth muscle tumors in the past. In the current study, in view of past and ongoing insights, we tried to develop new and rational approach to handle smooth muscle tumors of the uterus. First, we set unique criteria of "gray zone" from the MR image that contains potentially malignant tumors and calls for handling with special attention. This criterion allows clinically appropriate follow up of a group of uterine smooth muscle tumors that may turn out to be malignant. Second, we further investigated our hypothesis that uterine smooth muscle tumors originate under the influence of hypoxia caused by uterine contraction in the time of menstruation. Immunostaining of p53 and p21 in normal myometrium in menstrual cycle revealed that the expression of these proteins are observed in outer layer of uterine myometrium exclusively in follicular phase of menstrual cycle, suggesting that this part of the uterus are under the hypoxic stress and prone to damage in cycle, and may leads to the development of uterine smooth muscle tumors.
Third, we have performed comparative microarray analysis among the normal uterine smooth muscle, benign leiomyomas, and sarcomas. According the result, we investigated the role of PEP-19 protein and Acrogranin in the development of uterine smooth muscle tumors, that revealed that both genes play important roles in various stages of the occurrence of them.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004 2003 Other

All Journal Article (20 results) Book (1 results) Publications (6 results)

  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis.2006

    • Author(s)
      Matsumura N
    • Journal Title

      Clin Cancer Res. 12(5)

      Pages: 1402-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Oncogenic property fo ACROGRANIN in humanuterin leiomyosarcoma.2006

    • Author(s)
      Matsumura-N, Mandai-M, Fujii-s, 他
    • Journal Title

      Clinical Cancer Research 12

      Pages: 1402-1402

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 子宮筋腫をめぐる最近の話題2006

    • Author(s)
      鈴木彩子, 刈谷方俊, 藤井信吾
    • Journal Title

      産婦人科治療 92.No.3

      Pages: 217-217

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Spectrum of MR features in adenomyosis.2006

    • Author(s)
      Tamai K, Koyama T, Umeoka S, Saga T, Fujii S, Togashi K.
    • Journal Title

      Best Pract Res Clin Obstet Gynaecol. 22(Epub ahead of)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Oral contraceptives and uterine peristalsis : evaluation with MRI.2005

    • Author(s)
      Kido A
    • Journal Title

      J Magn Reson Imaging. 22(2)

      Pages: 265-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A semiautomated technique for evaluation of uterine peristalsis.2005

    • Author(s)
      Kido A
    • Journal Title

      J Magn Reson Imaging. 21(3)

      Pages: 249-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel.2005

    • Author(s)
      Konishi M
    • Journal Title

      J Control Release. 103(1)

      Pages: 7-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 非定型子宮筋腫(グレーゾーン)2005

    • Author(s)
      鈴木 彩子
    • Journal Title

      日本産科婦人科学会雑誌 57

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Positron emission tomography application for gynecologic tumors.2005

    • Author(s)
      Nakamoto Y, Saga T, Fujii S.
    • Journal Title

      Int J Gynecol Cancer. 15(5)

      Pages: 701-709

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas.2005

    • Author(s)
      Nishino M, Togashi K, Nakai A, Hayakawa K, Kanao S, Iwasaku K, Fujii S.
    • Journal Title

      Eur J Radiol. 53(1)

      Pages: 142-146

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel.2005

    • Author(s)
      Konishi M et al.
    • Journal Title

      Journal of Control Release 103(1)

      Pages: 7-19

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells.2005

    • Author(s)
      Kishi Y et al.
    • Journal Title

      J. Neurosci. Res. 79(3)

      Pages: 279-286

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Crucial role of FOXP3 in the development and function of human CD25+CD4+regulatory T cells.2004

    • Author(s)
      Yagi H
    • Journal Title

      Int Immunol. 16(11)

      Pages: 1643-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In creased expression of calcium-binding protein S100 in human uterine smooth muscle tumous.2004

    • Author(s)
      kanamori T et al.
    • Journal Title

      Mol Hum Reprod 10(10)

      Pages: 735-742

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Crucial role of FOXP3 in the development and function of human CD25 +CD4+ regulatory T cells.2004

    • Author(s)
      Yagi H et al.
    • Journal Title

      Int. Immunol. 16(11)

      Pages: 1643-1456

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 17beta-estradiol up-regulates prostacyclin production in cultured human uterine myometrial cells via augmentation of both cyclooxygenase-1 and prostacycl in synthase expression.2004

    • Author(s)
      Korita D et al.
    • Journal Title

      J Soc Gynecol Investig 11(7)

      Pages: 457-464

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Uterine peristalsis : comparison of transvaginal ultrasound and two different sequences of cine MR imaging.2004

    • Author(s)
      Nakai A et al.
    • Journal Title

      J Magn Reson imaging 20(3)

      Pages: 463-469

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PEP-19 overexpression in human uterine leiomyoma.2003

    • Author(s)
      Kanamori T
    • Journal Title

      Mol Hum Reprod. 9(11)

      Pages: 709-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Uterine peristalsis shown on cine MR imaging using ultrafast sequence.2003

    • Author(s)
      T, Ueda H, Koyama T, Kobayashi H, Kagimura T, Fujii S, Konishi J.
    • Journal Title

      J Magn Reson Imaging. 18(6)

      Pages: 726-733

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diffusely enlarged uterus : evaluation with MR imaging.2003

    • Author(s)
      Kido A, Togashi K, Koyama T, Yamaoka T, Fujiwara T, Fujii S.
    • Journal Title

      Radiographics. 23(6)

      Pages: 1423-1439

    • Related Report
      2005 Annual Research Report
  • [Book] 「子宮の腫瘍・類腫瘍 子宮筋腫」産婦人科研修の必修知識2004

    • Author(s)
      福原 健
    • Publisher
      日本産科婦人科学会、杏林舎
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Kanamori T, et al.: "PEP-19 overexpression in human uterine leiomyoma"Mol Hum Reprod. 9. 709-717 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kato K, et al.: "Expression of the mitogen-inducible gene-2(mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas"Hum Pathol. 35. 55-60 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujiwara T, et al.: "Kinematics of the Uterus : Cine Mode MR Imaging"Radiographics. (Epub ahead of print). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kido A, et al.: "Diffusely Enlarged Uterus : Evaluation with MR Imaging"Radiographics. 23. 1423-1439 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakai A, et al.: "Uterine peristalsis shown on cine MR imaging using ultrafast sequence"J Magn Reson Imaging. 18. 726-733 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kusakari T, et al.: "C-erbB-2 or mutant Ha-ras induced malignant transformation of immortalized human ovarian surface epithelial cells in vitro"Br J Cancer. 89. 2293-2298 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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