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Identification of the regulatory genes of telomerase activity and apoptosis in the treatment of gynecological cancers.

Research Project

Project/Area Number 14571565
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionHiroshima University

Principal Investigator

NAGAI Nobutaka  Hiroshima University, Graduate School of Biomedical Sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (90198292)

Co-Investigator(Kenkyū-buntansha) SHIGEMASA Kazushi  Hiroshima University, Graduate School of Biomedical Sciences, Assistant professor, 大学院・医歯薬学総合研究科, 助手 (30294557)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsapoptosis / telomerase / uterine cancer / ovarian cancer / chemotherapy / neoadjubant chemotherapy
Research Abstract

1.In advanced cervical cancer, patients were treated with intraarterial infusion of 120 mg/body as neoadjuvant chemotherapy(NAC)and the expression of apoptosis related genes, BAX,BCL-2 were examined. The expression of BAX and apoptotic index(AI)was significantly increased by NAC(P=0.02). These results showed that NAC for advanced cervical cancer induced apoptosis of tumor cells, and its anti-tumor elect related with the expression of apoptosis genes, BAX.
2.IPatients with advanced cervical cancer, were treated with oral fluoropyrimidine(UFT), and the relationship between thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD) and apoptosis were examined. The AI increased after UFT, and the DPD activity before UFT showed an inverse relationship with the AI after UFT(γ= 0.6938). Theses results indicated that the DPD activity of advanced cervical cancer is a determinant to UFT, suggesting an association between UFT therapy and the induction of apoptosis.
3.The expression of apoptosis … More related genes, BAX, BCL-2 and BCL-X and the clinicopathological features were examined in ovarian tumors (benign, borderline malignant and malignant tumore). In malignant ovarian tumor, the expression rate of BAX, BCL-2 and BCL-x were 35.1%, 33.8% and 36.5%, respectively. The prognosis was poor in patients with ice expression of BAX and BCL-2. These results showed that there was the relationship between the expression of BAX, BCL-2 and the prognosis in malignant ovarian tumoes.
4.The overexpressin of COX-2 protein and its relationship to apoptosis in cervical cancer patients treated with neoadjuvant chemotherapy(NAC)was examined A higher incidence of COX-2 protein overexpression was observed in patients with 11.82 respectively. In COX-2 pmtei-negative patients with sqoamous cell carcinoma, the AI ratio significantly increased before and after NAC(P=0.0098). Our findings suggest that COX-2 protein expressin could be used as a predictor of chemoresistance.
5.By cDNA microarray assay and real-time PT-PCR analysis, we detected some CDDP and or TXL resistant related genes in ovarian cancer and study these functions, now. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (30 results)

All 2004 2003 2002 Other

All Journal Article (22 results) Publications (8 results)

  • [Journal Article] Human papillomavirus DNA status after loop excision for cervical intraepithelial neoplasia grade III-A prospective study2004

    • Author(s)
      Nagai N et al.
    • Journal Title

      Int. J. Mol. Med. 13

      Pages: 589-593

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Telomerase activation on endometrial epithelial cells by paracrine effector from stromal cells in primary cultured human endometrium2004

    • Author(s)
      Oshita T, Nagai N et al.
    • Journal Title

      Int. J. Mol. Med. 13

      Pages: 425-430

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinicopathological study og 56 patients with endometrial cancer during or after adjuvant tamoxifen use for their breast cancers2004

    • Author(s)
      Hachisuga T, Nagai N et al.
    • Journal Title

      Gynecol. Oncol. 95

      Pages: 139-144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expressin of human kallikrein 7 and its inhibitor antileukoprotease in uterin cervical lands and cervical adenocarcinoma2004

    • Author(s)
      Tian X, Nagai N et al.
    • Journal Title

      Oncol. Rep. 12

      Pages: 1001-1006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Telomerase activation in endometrial cells by paracrine effectors from stromal cells in primary cultured human endometrium.2004

    • Author(s)
      Oshita T, Nagai N, Mukai K, Shigemasa K, Hiura M, Ohama K
    • Journal Title

      Int.J.Mol.Med 13

      Pages: 425-430

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human papillamavirus DNA status after loop excision for cervical intraepithelial neoplasia grade III-A prospective study.2004

    • Author(s)
      Nagai N, Mukai K, Oshita T, Shiroyama Y, Ohama K
    • Journal Title

      INT.J.Mol.Med. 13

      Pages: 589-593

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of human kallikrein 7(hK7/SCCE)and its inhibitor anti-leukoprotease(ALP/SLPI)in uterine endocervical glands and in cervical adenocarcinomas.2004

    • Author(s)
      Tian X, Shigemasa K, Hirata E, Gu L, Uebaba Y, Nagai N, O'brien TJ, Ohama K
    • Journal Title

      Oncol.Rep. 12

      Pages: 1001-10067

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinicopathological study of 56 patients with endometrial cancer during or after adjuvant tamoxifen use for their breast cancers2004

    • Author(s)
      Hachisuga T, Magai N, Saitou T, Kigawa J, Ohwada M, Yamazawa K, Yasue A, Iwasaka T, Sugiyama T, Kita T
    • Journal Title

      Gynecol.Oncol. 95

      Pages: 139-144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human papillomavirus DNA status after loop excision for cervical intraepitherial neoplasia grade III-A prospective study.2004

    • Author(s)
      Nagai N et al.
    • Journal Title

      Int.J.Mol.Med. 13

      Pages: 589-593

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Telomerase activation in endometrial epithelial cells by paracrine effectors from stromal cells in primary cultured human endometrium2004

    • Author(s)
      Oshita T, Nagai N. et al.
    • Journal Title

      Int.J.Mol.Med. 13

      Pages: 425-430

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinicopathological study of 56 patients with endometrial cancer during or after adiuvant tamoxifen use for their breast cancers2004

    • Author(s)
      Hachisuga T, Nagai N. et al.
    • Journal Title

      Gynecol.Oncol. 95

      Pages: 139-144

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of human kallikrein 7 and its inhibitor antileukoprotease in uterin endocervical glands and cervical adenocarcinoma2004

    • Author(s)
      Tian X, Nagai N. et al.
    • Journal Title

      Oncol.Rep. 12

      Pages: 1001-1006

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Overexpression of cyclooxygenase-2 protein and its relationship to apoptosis in cervical carcinoma treated with neoadjuvant chemotherapy.2003

    • Author(s)
      Nagai N, Tian X, Mukai K, Hirata E, Kusuda T, Shiroyama Y, Shigemasa K, Ohama K
    • Journal Title

      Int.J.Mol.Med. 12

      Pages: 709-714

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Validation of a simple gas chromatographic-mass spectrometric method for the determination of GBL in human plasma.2003

    • Author(s)
      Fukai Y, Matsushima E, Nagai N, Muramoto K, Ohama K, Yamashita K
    • Journal Title

      J.Chromatography 785

      Pages: 73-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] GnRH agonist inhibits human telomerase reverse transcriptase mRNA expression in endometrial cells.2002

    • Author(s)
      Nagai N, Oshita T, Mukai K, Shiroyama Y, Shigemasa K, Ohama K
    • Journal Title

      Int.J.Mol.Med. 10

      Pages: 593-597

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma.2002

    • Author(s)
      Nagai N, Shiroyama Y, Oshita T, Mukai K, Shigemasa K, Fujii T, Katube Y, Matsubayashi S, Murakami T, Ohama K
    • Journal Title

      Oncol.Rep. 9

      Pages: 1033-1040

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p27 cyclin E and CDK2 expression in normal and cancerous endometrium.2002

    • Author(s)
      Oshita T, Nagai N, Shigemasa K, Ohama K
    • Journal Title

      Int.J.Oncol. 21

      Pages: 737-743

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endometrial cytodiagnosis using a new softcyte versus a conventional endocyte.2002

    • Author(s)
      Nagai N, Uebaba Y, Oshita T, Sakata K, Murakami J, Shigemasa K, Ohama K
    • Journal Title

      Oncol.Rep. 9

      Pages: 483-487

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased MCL-1 expression is associated poor prognosis in ovarian carcinomas.2002

    • Author(s)
      Shigemasa K, Shiroyama Y, Mukai K, Nagai N, Ohama K
    • Journal Title

      Jpn.J.Cancer Res. 93

      Pages: 542-550

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of matrix matelloproteinases-2 and 9 by cells isolated from the peritoneal fluid of woman with ovarian carcinomas2002

    • Author(s)
      Sakata K, Shigemasa K, Uebaba Y, Nagai N, Ohama K
    • Journal Title

      Acta Cytol. 46

      Pages: 697-703

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of cyclooxygenase-2 and its relationship of p53 accumulation in ovarian adenocarcinomas.2002

    • Author(s)
      Shigemasa K, Tian X, Gu L, Shiroyama Y, Nagai N, Ohama K
    • Journal Title

      Int.J.Oncol. 22

      Pages: 99-105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor dihydropyrimidine dehydrogenase activity in advanced cervica 1 carcinoma.2002

    • Author(s)
      Mukai K, Nagai N, Shiroyama Y, Oshita T, Shigemasa K, Ohama K
    • Journal Title

      Int.Gyn.Cancer 12

      Pages: 595-596

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nagai N.: "Overexpression of COX-2 protein and its relationship to apoptosis in cervical carcinoma treated with neoadjuvant chemotherapy"Int J Mol Med. 12. 709-714 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukai Y.: "Validation of a simple gas chromatographic-mass spectrometric method for the determination of GBL in human plasma"J.chromatography. 785. 73-80 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oshita T.: "Telomerase activation in endometrial epithelial cells by paracrine effectors from stromal cells in primary cultured human endometrium"Int J Mol Med. 13. 425-430 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagai N. et al.: "GnRH agonist inhibits human telomerare reverse transcriptase mRNA expression in endometrial cancer cells"Int. J. Mol. Med. 10. 593-597 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagai N. et al.: "Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma"Oncol. Rep.. 9. 1033-1040 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oshita T. et al.: "P27. cyclin E and CDK2 expression in normal and canerous endometrium"Int. J. Oncol. 21. 737-743 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagai N. et al.: "Endometrial cytodiagnosis using a new softcyte versus a conventional endocyte"Oncol. Rep.. 9. 483-487 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shigemasa K. et al.: "Increased MCL-1 expression is associated poor prognosis in ovarian carcinomas"Jpn. J. Cancer Res.. 93. 542-550 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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