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Characterization of tumorigenic features of uterine leiomyoma

Research Project

Project/Area Number 08457438
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSHINSHU UNIVERSITY

Principal Investigator

FUJII Shingo  Shinshu University, School of Medicine, Professor, 医学部, 教授 (30135579)

Co-Investigator(Kenkyū-buntansha) NIKAIDO Toshio  Shinshu University Hospital, Assistant Professor, 附属病院, 講師 (50180568)
森 篤  信州大学, 医学部・産科婦人科, 助手 (80210110)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsLeiomyoma / ball-like aggregations / MR image / Mast cells / GnRH analogue / p53 / ovarian steroid receptors / 子宮平滑筋 / ステロイドホルモン / サイクリン / サイクリン依存性リン酸化酵素 / 腫瘍抑制因子
Research Abstract

The mechanisms regarding to the shrinkage of leiomyoma during the treatment with GnRH analogue (GnRH) analogue have been investigated using this in vitro system of uterine leiomyoma. Previously, we demonstrated that the cells from leiomyoma formed ball-like aggregations which we named "ball-like aggregations (BLAs)". Since the ball-like aggregations of cells from leiomyoma seem to be close to the features of uterine leiomyoma in vivo, this allows us to evaluate the efficiency of GnRH analogue currently used for chemotherapy of uterine leiomyomas. The results showed that the addition of GnRH analogue caused disappearance of the figure of the ball-like aggregations of cells from leiomyoma. The results also showed that GnRH directly binds to the cultured cells from leiomyoma and that the existence of GnRH receptor as well as GnRH expression in the cells from leiomyomas. Furthermore, the addition of small and short doses of GnRH analogue stimulates the proliferation of smooth muscle cells … More of leiomyoma, but the late G1 phase cell cycle related genes' expression were suppressed by the addition of high doses GnRH analogue for long treatment. These results suggested that GnRH analogue may directly regulate the growth of uterine leiomyomas, and that the in vivo system of uterine leiomyoma is useful to evaluate the efficiency of drugs currently used for chemotherapy of uterine leiomyomas. Mast cells (MCs) are widely distributed in most human tissues and neoplasms, including a leiomyoma. GnRHa has been recently applied for the treatment of a leiomyoma. To elucidate the role of MCs in a leiomyoma, the relationship between the number of MCs in leiomyomas and the histological features was analyzed, furthermore, the number of MCs in untreated leiomyomas was compared with that of MCs in the leiomyomas treated with GnRHa. The results showed that the number of MCs in untreated leiomyomas was widely distributed, but there were more Mcs in leiomyomas with fewer collagen matrix, with higher cellularity, and with high intensity of T2 weighted MR image. In addition, the leiomyomas which had highly shrinked with GnRHa contained a larger number of MCs, and these MCs were not increased by GnRHa, but before therapy they had existed in the leiomyomas The findings suggest that MCs may associated with prolierative activity of leiomyoma and play a role in shirnkage of the size in GnRHa therapy.Both ER and PR are immunohistochemically expressed in all ULs. PR was definitely experssed in UL irrespective of the phase of the menstrual cycle. This staining pattern of PR was also observed in CL,UMP and BL,although BL showed variable staining for ER.Compared to these tumors, the expression of both ER and PR was markedly reduced in LMS.The results of ER and PR transcripts by RT-PCR amplification were compatible with those of immunohistochemistry. The number of Ki-67 positive cells in LMS was extraordinary and significantly higher than in UMP,BL,CL and UL.P53 immunoreactivity was seen Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Li, SF.et al: "Stepwise Abnormality of Sex Steroid Hormone Receptors,Tumor Suppressor Gene Products(p53 and Rb),and Cyclin E in Uterine Endometriloid Carcinoma." Cancer. 77・2. 321-329 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nikaido, T.et al: "Co-abnormal expression of cyclin D1 and p53 protein in human uterine endometrial carcinomas." Cancer. 78・6. 1248-1253 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi, Y.et al: "In Vitro Model of Uterine Leimyomas:Formation of Ball-Like Aggregates" Human Reproduction. 11・8. 1724-1730 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T.et al: "Relationship between the expression of ciclins/cyclin-dependent kinases and sex-steroid receptors-Ki67 in normal human endometrial glands and stroma during the menstrual cycle-" Molecular Human Reproduction. 2・10. 745-752 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi, Y.et al: "Effects of a GnRH analogue on human smooth muscle cells cultured from normal myometrial and from uterine leiomyomal tissues" Molecular Human Reproduction. 3・2. 91-99 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori, A.et al: "Distribution and heterogeneity of mast cells in the human uterus" Human Reproduction. 12・2. 368-372 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori, A.et al: "Analysis of stem cell factor for mast cell proliferation in the human myometrium" Molecular Human Reproduction. 3・5. 411-418 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T.et al: "Immunohistochemical Detection of Cyclin A with Reference to p53 Expression in Endometrial Endometrioid Carcinomas" International Journal of Gynecological Pathology. 16・4. 348-353 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiohara, S.et al: "Histochemical Analysis of Estrogen and Progesterone Receptors and Gastric-Type.Mucin in Mucinous Ovarian Tumors with Reference to Their Pathogenesis" Cancer. 80・5. 908-916 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T.et al: "Immunohistochemical analysis of the expression of cdk4 and p16INK4 in human endometrioid-type carsinomas." Cancer. 80・12. 2250-2256 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 藤井 信吾: "子宮筋腫、子宮腺筋症" TODAY'S THERAPY 1996(今日の治療指針). 688-689 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 塩沢 丹里 他: "子宮筋腫とステロイドホルモン" Hormone Frontier in Gynecology. 3・1. 39-45 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 藤井 信吾: "子宮肉腫" TODAY'S THERAPY1997(今日の治療指針). 709 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 藤井 信吾: "子宮筋腫の診断" 実験治療. 645号. 5-10 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 二階堂 敏雄 他: "子宮筋腫増殖機構の分子生物学的解析" 図説産婦人科VIEW27. 46-57 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 折井 文香 他: "組織発生" 臨床婦人科産科. 51・12. 1248-1252 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 藤井 信吾: "子宮筋腫" 別冊NHKきょうの健康(これだけは知っておきたい子宮筋腫、子宮内膜症、月経異常). 76-96 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Li, SF., Shiozawa, T., Nakayama, K., Nikaido, T., Fujii, S.: "Stepwise Abnormality of Sex Steroid Hormone Receptors, Tumor Suppressor Gene Products (p53 and Rb), and Cyclin E in Uterine Endometriloid Carcinoma." Cancer. 77 (2). 321-329 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nikaido, T., Li, SF., Shiozawa, T., Fujii, S.: "Co-abnormal expression of cyclin D1 and p53 protein in human uterine endometrial carcinomas." Cancer. 78 (6). 1248-1253 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi, Y., Nikaido, T., Zhai, Y.L., Iinuma, M., Shiozawa, T., Shirota, M., Fujii, S.: "In-Vitro Model of Uterine Leimyomas : Formation of Ball-Like Aggregates" Human Reproduction. 11 (8) :. 1724-1730 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T., Li, SF., Nakayama, K., Nikaido, T., Fujii: "Relationship between the expression of ciclins/cyclin-dependent kinases and sex-steroid receptors-Ki67 in normal human endomentrial glands and stroma during the menstrual cycle-" Molecular Human Reproduction. 2(10). 745-752 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi, Y., Zhai, Y.L., Iinuma, M., Horiuchi, A., Nikaido, T., Fujii, S.: "Effects of a GnRH analogue on human smooth muscle cells cultured from normal myometrial and from uterine leiomyomal tissues" Molecular Human Reproduction. 3 (2). 91-99 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori, A., Zhai, Y.L., Toki, T., Nikaido, T., Fujii, S.: "Distribution and heterogeneity of mast cells in the human uterus" Human Reproduction. 12 (2). 368-372 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mori, A., Nakayama, Y., Suzuki, J., Nikaido, T., Isobe, M., Fujii, S.: "Analysis of stem cell factor for mast cell proliferation in the human myometrium" Molecular Human Reproduction. 3 (5). 411-418 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T., Lu, Xin, Nikaido, T., Fujii, S.: "Immunohistochemical Detection of Cyclin A with Reference to p53 Expression in Endometrial Endometrioid Carcinomas" International Journal of Gynecological Pathology. 16 (4). 348-353 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiohara, S., Shiozawa, T., Shimizu, M., Toki, T., Ishii, K., Nikaido, T., Fujii, S.: "Histochemical Analysis of Estrogen and Progesterone Receptors and Gastric-Type Mucin in Mucinous Ovarian Tumors with Reference to Their Pathogenesis" Cancer. 80 (5). 908-916 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shiozawa, T., Li, S-f., Nikaido, T., Fujii, S.: "Immunohistochemical analysis of the experssion of cdk4 and p16INK4 in human endometrioid-type carsinomas." Cancer. 80 (12). 2250-2256 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Li,SF.et al: "Stepwise Abnormality of Sex Steroid Hormone Receptors,Tumor Suppressor Gene Products(p53 and Rb),and Cyclin E in Uterine Endometriloid Carcinoma." Cancer. 77・2. 321-329 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nikaido,T.et al: "Co-abnormal expression of cyclin D1 and p53 protein in human uterine endometrial carcinomas." Cancer. 78・6. 1248-1253 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kobayashi,Y.et al: "In-Vitro Model of Uterine Leimyomas:Formation of Ball-Like Aggregates" Human Reproduction. 11・8. 1724-1730 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiozawa,T.et al: "Relationship between the expression of ciclins/cyclin-dependent kinases and sex-steroid receptors-Ki67 in normal human endometrial glands and stroma during the menstrual cycle" Molecular Human Reproduction. 2・10. 745-752 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kobayashi,Y.et al: "Effects of a GnRH analogue on human smooth muscle cells cultured from normal myometrial and from uterine leiomyomal tissues" Molecular Human Reproduction. 3・2. 91-99 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mori,A.et al: "Distribution and heterogeneity of mast cells in the human uterus" Human Reproduction. 12・2. 368-372 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mori,A.et al: "Analysis of stem cell factor for mast cell proliferation in the human myometrium" Molecular Human Reproduction. 3・5. 411-418 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiozawa,T.et al: "Immunohistochemical Detection of Cyclin A with Reference to p53 Expression in Endometrial Endometrioid Carcinomas" International Journal of Gynecological Pathology. 16・4. 348-353 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiohara,S.et al: "Histochemical Analysis of Estrogen and Progesterone Receptors and Gastric-Type. Mucin in Mucinous Ovarian Tumors with Reference to Their Pathogenesis" Cancer. 80・5. 908-916 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiozawa,T.et al: "Immunohistochemical analysis of the expression of cdk4 and p16INK4 in human endometrioid-type carsinomas." Cancer. 80・12. 2250-2256 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤井信吾: "子宮筋腫、子宮腺筋症" TODAY'S THERAPY 1996(今日の治療指針). 688-689 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 塩沢丹里 他: "子宮筋腫とステロイドホルモン" Hormone Frontier in Gynecology. 3・1. 39-45 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤井信吾: "子宮肉腫" TODAY'S THERAPY 1997(今日の治療指針). 709 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤井信吾: "子宮筋腫の診断" 実験治療. 645号. 5-10 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 二階堂敏雄 他: "子宮筋腫増殖機構の分子生物学的解析" 図説産婦人科VIEW27. 46-57 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 折井文香 他: "組織発生" 臨床婦人科産科. 51・12. 1248-1252 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤井信吾: "子宮筋腫" 別冊NHKきょうの健康(これだけは知っておきたい子宮筋腫、子宮内膜症、月経異常). 76-96 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Kobayashi: "In-yitro model of uterine leiomyomas : formation of ball-like aggregates" Human Reproduction. 11・8. 1724-1730 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Kobayashi: "Effects of a GNRH analogue on human smooth muscle ceils cultured from normal myometrial and from uterine leimyomal Tissues" Molecular Human Reproduction. 3・2(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Mori: "Distribution and heterogeneity of mast cells in the human Uterus" Human Reproduction. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤井信吾: "子宮筋腫、子宮腺筋症" Today's Therapy 1996(今日の治療指針). 688-689 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 塩沢丹里: "子宮筋腫とステロイドホルモン" Hormone Frontier in Gynecology. 3・1. 39-45 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 今井直美: "子宮筋腫の画像診断" 産婦人科治療. 72・5. 762-771 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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