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1997 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1996 – 1997
KeywordsLeiomyoma / ball-like aggregations / MR image / Mast cells / GnRH analogue / p53 / ovarian steroid receptors
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

  • Research Products

    (27 results)

All Other

All Publications (27 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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