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Analysis of gene alterations associated with endometrial cancers and the target of the gene therapy

Research Project

Project/Area Number 06454473
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University (1995-1996)
Osaka University (1994)

Principal Investigator

INOUE Masaki  Kanazawa University, School of Medicine, Professor, 医学部, 教授 (10127186)

Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1994: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsGynecologic cancer / Oncogene / Anti-oncogenes / DNA repair genes / Telomerase / Gene therapy / Endometrial cancer / Multistep carcinogenesis / 細胞の不死化 / 遺伝子治療 / テロメラーゼ / 子宮癌 / prot on cogene / anti-oncogene / multistep carcinoglvesis / p53 / Rb / DCC / HDV / MTS
Research Abstract

Recent advances in molecular biology have allowed us to study cancer at the level of individual genes. Such works have led to the theory of multistep carcinogenesis.
The present study showed that activation of oncogenes, inactivation of tumor-suppresor genes, inactivation of mismatched-DNA repair genes and infection of human papillomavirus were closely involved in the carcinogenesis of uterine endometrium. Alterations of Ras, p53, DCC,P16, C-kit/SCF,RB were totally found in 17/26 (65%) G1 adenocarcinmas, 5/7 (71%) G2 adenocarcinomas and 12/13 (92%) G3 adenocarcinomas. However, the each abnormality of a single gene is quite low in its incidence.
A frequent genetic change which takes place in carcinogenesis should be choosed as the target molecule of gene therapy. Our modified non-Rl TRAP (telomeric repeat amplification protocol) assay found that the telomerase activation was common (more than 90%) in endometrial cancer and was a critical step in their pathogenesis. Then, in the present time, the best target of gene therapy might be a telomerase molecule.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kyo S, et al.: "Teromerase activity in human endometrium" Cancer Res. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kyo S, et al.: "Teromerase activity in gynecologic tumors." Clin Cancer Res. 2,. 2023-2028 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Enomoto T, et al.: "Alteration of the p53 tumor supressor gene and activation of the c-K-ras-2 protooncogene in endometrioid adenocarcinoma of the uterus" Am J Clin Pathol. 103. 224-230 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M, et al.: "Association of humann papillomavirus with malignant premalignant lesions of the uterine endometrium." Hum Pathol. 26. 650-658, (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M, et al.: "A case control study on risk factors for uterine endometrial cancer" Jpn J Cancer Res,. 85. 346-350 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M, et al.: "Clinicopathological characteristics of p53 overexpression in endometrial cancer." Int J Cancer. 58. 14-19 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitagawa K,et al.: "Epithelial-mesencymal transformation of a newly established cell line from ovarian adenocarcinoma by transforming growth factor-beta 1" Int J Cancer. 66. 91-97 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Application of clonal analysis" Am J Clin Pathol. 105. 350-359 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Enomoto T,et al.: "Alteration of the p53 tumor supressor gene and activation of the c-K-ras-2 protooncogene in endometrioid adenocarcinoma of the uterus : comparison between samples from Colorado, USA and Osaka, Japan" Am J Clin Pathol. 103. 224-230 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Enomoto T,et al.: "Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human reproductive tract." Br J Cancer. 71. 426-467 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Enomoto T,et al.: "Alteration of the p53 tumor suppressor gene and activation of c-k-ras-2 protooncogene in endometrial adenocarcinoma from colorado." Am J Clin Pathol. 103. 224-230 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Microsatellite instability and alterations in the HMSH2 gene in human ovarian cancer." Int J cancer. 64. 361-366 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Association of humann papillomavirus with malignant premalignant lesions of the uterine endometrium." Hum Pathol. 26. 650-658 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M,et al.: "A case control study on risk factors for uterine endometrial cancer in Japan." Jpn J Cancer Res. 85. 346-350 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M,et al.: "Coexpression of the c-kit receptor and the stem cell factor in gynecologic tumors." Cancer Res. 54. 3049-3053 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M,et al.: "Immunohistochemical analysis of p53 in gynecologic tumors." Am J Clin Pathol. 102. 665-670 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M,et al.: "Clinicopathological characteristics of p53 overexpression in endometrial cancer." Int J Cancer. 58. 14-19 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kyo S,et al.: "Teromerase activity in gynecologic tumors." Clin Cancer Res. 2. 2023-2028 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kyo S,et al.: "Teromerase activity in human endometrium" Cancer Res. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kyo S,et al.: "Teromerase activity in human endometrium" Cancer Res. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kyo S,et al.: "Teromerase activity in gynecologic tumors." Clin Cancer Res. 2,. 2023-2028 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita M,Inoue M,: "Association of human papillomavirus with malignant premalignant lesions of the uterine endometrium." Human Pathol,. 26. 650-658 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inoue M,Fukuda H,: "Adenosarcomas originating from sites other than uterine endometrium" Int J Gynecol Obstet. 48,. 299-306, (1995.)

    • Related Report
      1995 Annual Research Report
  • [Publications] Enomoto T Inoue M: "Loss of expression and loss of heterozygosity in the DCC gene in neoplasma of the human female reproductive tract." British J Cancer. 71,. 462-467 (1995.)

    • Related Report
      1995 Annual Research Report
  • [Publications] Enomoto,T,Fujita M,Inoue M.: "Alteration of the p53 tumor suppressor gene and activation of c-k-ras-2 protooncogene in endometrial adenocarcinoma from colorado" Am J Clin Pathol. 103. 224-230 (1995.)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kitagawa K,Inoue M,: "Epithelial-mesencymal transformation of a newly established cell line from ovarian adenocarcinoma by transforming growth factor-beta 1." Int J Cancer. (in press 1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujita M,Enomoto,T,Inoue M.: "Microsatellite instability and alterations in the HMSH2 gene in human ovarian cancer" Int J cancer. 64. 361-366, (1996.)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujita M et al.: "Associdtion of HPD with malignast and precemalignast lesione of the vtevine endbmetriclw" Human Pathol. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Enomoto T et al: "Alterations of the RB gene cmd its agsosiation with Ki-ras aetivation and p53 inact:vation in evdm metrial adluscoruvoma" Molecular cer in nogeres:s. 8. 132-137 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inoue M et al.: "Clinicopathological charactarist:cs of p53 ouerexpression in endometr:al camurs" Int J Camor. 58. 14-19 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inoue M et al.: "Immuro to devnical analgsis of the p53 in Gyveatagic tumors" Am J clin pathol. 102. 665-670 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Enomoto T et al: "Alterations of the p53 turron suppresson glne and its associdtion with aretivation of the ck-ras protoovicogenl in prenalignat and moignet lesiong of the bemiam uterire eudomatrium." Camcer Ras. 55. 1883-1888 (1993)

    • Related Report
      1994 Annual Research Report

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

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