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Involvement of the abnormality of cyclins, cyclin-dependent kinases or tumor suppressor gene products in the acquisition of the malignant potential of the endometrial carcinomas.

Research Project

Project/Area Number 09470355
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

NIKAIDO Toshio  Shinshu University hospital, Assistant Professor, 医学部・附属病院, 講師 (50180568)

Co-Investigator(Kenkyū-buntansha) SHIOZAWA Tanri  Shinshu University School of Medicine, Instructor, 医学部, 助手 (20235493)
FUJII Shingo  Kyoto University School of Medicine, Professor, 医学研究科, 教授 (30135579)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1999: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1997: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordscell cycle / cyclins / cyclin-dependent kinases (cdks) / tumor suppressor gene / endometrial carcinomas / プロモーター / ER / PR / サイクリンA / p53 / サイクリン / 免疫組織染色 / RB
Research Abstract

Interactions of cyclins, cyclin-dependent kinases (cdks) and tumor suppressor gene products are essential in cell cycle progression, and deranged expression of these factors are reported to evoke malignant transformation of the cell. To elucidate the tumorigenetic process of the endometrial carcinomas, expression of the cell cycle related molecules in normal and malignant endometrial tissues was investigated by immunostaining. In the normal endometrium, expression of cyclin A, cyclin B1, cyclin E, cdc2, cdk2 and p16 was sporadically observed in the glandular epithelia of the proliferative phase. In 64 cases of endometrial carcinomas, the number of positive cases for cyclin A, cyclin B1, cyclin D1, cyclin E, cdc2, cdk2, cdk4, p53, P16 and RB was 11, 32, 22, 41, 43, 32, 8, 22, 39, and 32 cases, respectively. The topographical distribution of cyclin D1, cyclin A and p53 positive cells correlated each other. Above 64 cases were classified into two groups. The first group was consisted of the cases showing positive for only cyclin E, and the second group was consisted of those expressing cyclin D1, p53 and cyclin A. The first group tended to contain well differentiated cases, and poorly differentiated cases were more frequently found in the second group. These findings suggest that accumulations of abnormalities of the cell cycle related factors are involved in the acquisition of the malignant potential of the endometrial carcinomas.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Zai,Y. ,Nikaido,T. et al.: "Expression of steroid receptors, ki-67, and p53 in the uterine leiomyosarcoma"Int J Gyhecol Pathol. 18. 20-28 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu,M. ,Nikaido,T .et al.: "Clear cell Carcinoma has an Expression pattern of cell cycle regalatory molecules that is unipue among obarian adenocarcinomas"Cancer Genet. Cytogenet.. 85. 669-677 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kusama,H., Nikaido,T. et al.: "Tranilast may prebent restenosis afer pervrtaneous transluminal coronary angiopasty (PTCA) though the actibation of the p21 wafl and p53"Atherosclerosis. 143. 307-313 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Horiuchi,A., Nikaido,T. et al.: "Heparin inhibits proliferation and induces a-smooth musde Actin expression in human myometrium and leiomyomas, in vitro"Mol Hum Reprod. 5. 139-145 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toki,T., Nikaido,T, et al.: "Reverse relation between apoptosisi and bcl-2 expression in fibrin-type fibrinoid and synthytiotrophoblast of early gestation"Mol Hum Reprod. 5. 246-251 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lu,X., Nikaido,T. et al.: "Abnormal expression of sex steroid receptors, and cell cyclerelated molecles in adenocarcinoma in situ of the uterine cervix"Int J Gyhecol Pathol. 18. 109-114 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi Y, Zhai YL, 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."Mol Hum Reprod. 3. 91-99 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori A, Nakayama K, Suzuki J, Nikaido T, Isobe M, Fujii S: "Analysis of stem cell factor for mast cell proliferation in the human myometrium."Mol Hum Reprod. 3. 411-418 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori A, Zhai YL, Toki T, Nikaido T, Fujii S: "Distribution and heterogeneity of mast cells in the human uterus."Hum Reprod. 12. 368-372 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 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. 908-916 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiozawa T, Lu X, Nikaido T, Fujii S: "Immunohistochemical detection of cyclin A with reference to p53 expression in endometrial endometrioid carcinomas."Int J Gynecol Pathol. 16. 348-353 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiozawa T, Nikaido T, Shimizu M, Zhai YL, Fuji S: "Immunohistochemical analysis of the expression of cdk4 and p16ィイD1INK4ィエD1 in human endometrioid-type endometrial carcinoma."Cancer. 80. 2250-2256 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kanai, M., Shiozawa, T., Xin, L., Nikaido, T., and Shingo F.: "Immunohistochemical detection of sex steroid receptors, cyclins and cyclin-dependent kinases in the normal and neoplastic squamous epithelia of the human uterine cervix."Cancer. 82. 1709-1719 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lu, X., Toki, T., Konishi, I., Nikaido, T., and Fujii, S.: "Expression of p21waf1/cip1 in adenocarcinoma of the uterine cervix: A possible immunohistochemical marker for favorable prognosis."Cancer. 82. 2409-2417 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Horiuchi, A., Nikaido, T., Ito, K., Zhai, Y-1., Orii, A., Taniguchi, S., Toki, T., and Fujii, S.: "Reduced Expression of Calponin h1 in Leiomyosarcoma of the Uterus"Lab Invest. 78. 839-846 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinozawa, T., Li, S-f., Nikaido, T., Fujii, S.: "Involvement of the cyclin-dependent kinase inhibitor p27kip 1 in the growth inhibition of endometrium in the secretory phase and in hyperplastic endometrium in the secretory phase and in hyperplastic endometrium treated with progesterone."Mol Hum Reprod. 4. 899-905 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toki T, Mori A, Nikaido T, and Fujii S.: "Localization of apoptotic cells within the human endometrium and correlation between apoptotic cells and p21 expression."Mol Hum Reprod. 4. 1157-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, M., Nikaido, T., Nakayama, K., Shiozawa, T., Toki, T., Fujii, S: "Clear cell Carcinoma has an Expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas"Cancer. 85. 669-677 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Horiuchi, A., Nikaido, T., Zhai, Y-L., Ito, K., Orii, A., and Fujii, S.: "Heparin inhibits proliferation and induces a-smooth muscle Actin expression in human myometrium and leiomyomas, in vitro."MolHum Reprod. 5. 139-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toki T, Horiuchi, A., Ichikawa, N., Mori, A., Nikaido T, Fujii S.: "Reverse relation between apoptosis and bcl-2 expression in fibrin-type fibrinoid and synthytiotrophoblast of early gestation."Mol Hum Reprod. 5. 246-251 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Horiuchi, A., Nikaido, T., Taniguchi, S., and Fujii, S.: "Possible role of Calponin h1 as a tumor suppressor in human uterine leiomyosarcoma."J. Natl. Cancer I. 91. 790-796 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhai YL, Nikaido T, Shiozawa A, Orii A, Fujii S: "Expression of cyclins and cyclin-dependent kinases in smooth muscle tumors of the uterus."Int J Cancer. 84. 244-50 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhai YL, Nikaido T, Toki T, Shiozawa A, Orii A, Fujii S: "Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus."Brit. J Cancer. 80. 1658-1664 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno, M., Masutani, H., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J., and Nikaido, T: "Thioredoxin-dependent redox regulation of p53 mediated-p21 activation."J Biol Chem. 274. 35809-35815 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhai, Y-L., Nikaido, T., Orii, A., Horiuchi, A., Toki, T., and Shingo Fujii: "Microsatellite instability were high frequently detected in leiomyosarcomas compared to other smooth muscle tumors of the uterus."Gynecol Oncol. 75. 453-459 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhai,Y., Nikaido, T. et al.: "Expression of steroid receptors, Ki-67, and p53 in the uterine leiomyosarcoma."Int J Gynecol Pathol. 18. 20-28 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimizu, M., Nikaido, T. et al.: "Clear cell Carcinoma has an Expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas."Cancer. 85. 669-677 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kusama, H., Nikaido, T. et al.: "Tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) though the activation of the p21 wafl and p53."Atherosclerosis. 143. 307-313 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Horiuchi,A., Nikaido, T. et al.: "Heparin inhibits proliferation and induces a-smooth musde Actin expression in human myometrium and leiomyomas, in vitro."Mol Hum Reprod. 5. 139-145 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toki, T., Nikaido, T. et al.: "Reverse relation between apoptosis and bcl-2 expression in fibrin-type fibrinoid and synthytiotrophoblast of early gestation."Mol Hum Reprod.. 5. 246-251 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lu, X., Nikaido, T. et al.: "Abnormal expression of sex steroid receptors, and cell cycle-related molecules in adenocarcinoma in situ of the uterine cervix."Int J Gynecol Pathol. 18. 109-114 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuroiwa S.et al: "Aberrant expression of cell cycle-related genes in dying cells retinal ischemic injury." Invest Ophth Vis Sci.39. 610-617 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanai M.et al: "Immunohistochemical detection of sex steroid receptors, cyclins and cyclin-dependent kinases in the normal and neoplastic squamous epithelia of the human uterine cervix." Cancer. 82. 1709-1719 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ichikawa, N.et al: "Immunohistochemical analysis of cell cycle regulatory gene products in normal trophoblast and placental site trophoblastic tumor." Int J Gynecol Pathol. 17. 235-240 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Lu, X.et al: "Expression of p21waf1/cip in denocarcinoma of the uterine cervix : A possible immunohistochemical markerfor favorable prognosis." Cancer. 82. 2409-2417 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumoto, T.et al: "Cell Cycle-dependent modulation of promoter activities of RB and WAF1/Cip1 genes." Jpn J Cancer Res.89. 626-633 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Horiuchi, A.et al: "Reduced Expression of Calponin h1 in Leiomyosarcoma of the Uterus" Lab Invest. 78. 839-846 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori A.et al: "Distribution and heterogeneity of mast cells in the human uterus." Hum.Reprod. 12. 368-372 (1997)

    • 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." Mol.Hum.Reprod. 3. 91-99 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toki T.et al: "Minimal deviation adenocarcinoma of the uterine cervix has abnormal expression of sex steroid receptors,CA125,and gastric mucin." Int J Gynecol Pathol. 16. 111-116 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawa,S.et al: "Vitamin D analogues up-regulate p21 and p27 during growth inhibition of of pancreatic cancer cell lines." Brit.J.Cancer. 76. 884-889 (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." Mol.Hum.Reprod. 3. 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 human endometrioid-type carcinoma." Int J Gynecol Pathol. 16. 348-353 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiohara,S.et al: "Histochemical analysis of estrogen/progesterone receptors and gastric-type mucin in mucinous tumors of the ovary-with reference to a histogenetic consideration-" Cancer. 80. 908-916 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawa,S.et al: "The arotinoid mofarotene(Ro40-8757)up-regulate p21 and p27 during growth inhibition of of pancreatic cancer cells." Inter.J.Cancer.72. 906-911 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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