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Study for the development of molecular therapy targeting the signal transduction pathway through epidermal growth factor receptor

Research Project

Project/Area Number 17390445
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KURACHI Hirohisa  Yamagata University, Faculty of Medicine, Professor and chairman (40153366)

Co-Investigator(Kenkyū-buntansha) NAKAHARA Kenji  Yamagata University, Faculty of Medicine, Associate Professor (80250934)
TAKAHASHI Kazuhiro  Yamagata University, Faculty of Medicine, Associate Professor (20292427)
HAYASAKA Tadashi  Yamagata University, Faculty of Medicine, Associate Professor (10375339)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,750,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordsovanan cancer / molecular tareeted therapy / EGF receptor / sienal transduction / anti cancer drug / EGF受容体(EGFR) / DNA損傷
Research Abstract

Treatment with gefitinib increased the efficacy of the cisplatin-induced inhibition in the intraabdominal dissemination and production of ascites in athymic nude mice inoculated intraperitoneally with cisplatin-resistant Caov-3cells. Immunofluorescent reactivity for phosphorylated EGFR in tumors treated with gefitinib alone and combination of cisplatin + gefitinib was clearly reduced compared with that in tumors treated with vehicle and cisplatin alone. Similar Results were found for the phosphorylation of ERK and Akt.
We next investigated the expression of DNA-PK by immunofluorescent staining with anti-DNA-PK antibody. Treatment with cisplatin significantly increased the expression of DNA-PK in nuclei compared with that in tumors treated with vehicle. Treatment with combination of cisplatin + gefitinib significantly reduced the expression of DNA-PK compared with treatment with cisplatin alone. These results suggested that inhibition of DNA repair by gefitinib enhanced the efficacy of cisplatin.
Moreover, we investigated the effects of platinum-based chemotherapy on the signaling cascades and apoptosis before and after chemotherapy in patients with ovarian cancers using specimens obtained during surgical procedures. The increase in ERK phosphorylation was more consistent than that of Akt. Increases in apoptotic marker expression were observed in all patients exposed to chemotherapy. Activation of ERK by chemotherapy may be associated with apoptosis of tumor cells in patients with ovarian cancers.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 Other

All Journal Article (16 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.2007

    • Author(s)
      Yin, L
    • Journal Title

      Mol Cancer Ther 6

      Pages: 1517-1525

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilation.2007

    • Author(s)
      Takahashi, K
    • Journal Title

      Menopause 14

      Pages: 656-661

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial versus aortic smooth muscle cells.2007

    • Author(s)
      Kawagoe, J
    • Journal Title

      Endocrinology 148

      Pages: 6092-6099

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo2007

    • Author(s)
      Yin L
    • Journal Title

      Mol Cancer Ther 6

      Pages: 1517-1525

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilation2007

    • Author(s)
      Takahashi K
    • Journal Title

      Menopause 14

      Pages: 656-661

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial versus aortic smooth muscle cells2007

    • Author(s)
      Kawagoe J
    • Journal Title

      Endocrinology 148

      Pages: 6092-6099

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.2007

    • Author(s)
      Yin L
    • Journal Title

      Mol Cancer Ther 6

      Pages: 1517-1525

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Raloxife improves the ovariectomy-induced impahment in endothelium-dependent vasodilation.2007

    • Author(s)
      Takahashi K
    • Journal Title

      Menopause 14

      Pages: 656-661

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial versus aortic smooth muscle cells.2007

    • Author(s)
      Kawagoe J
    • Journal Title

      Endocrinology 148

      Pages: 6092-6099

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilatation.2007

    • Author(s)
      Takahashi K, Mori-Abe A, Takata K, Ohta T, Kawagoe J, Tsutsumi S, Ohmichi M, Kurachi H.
    • Journal Title

      Menopause (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Usefulness of intraovarian artery pulsatility and resistance indices measurement on the day of follicle aspiration for the assessment of oocyte quality.2006

    • Author(s)
      Du B, Takahashi K, Ishida GM, Nakahara K, Saito H, Kurachi H.
    • Journal Title

      Fertil Steril 85(2)

      Pages: 366-370

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Change in pulse wave velocity throughout normal pregnancy and its value in predicting pregnancy-induced hypertension : a longitudinal study.2006

    • Author(s)
      Oyama-Kato M, Ohmichi M, Takahashi K, Suzuki S, Henmi N, Yokoyama Y, Kurachi H.
    • Journal Title

      Am J Obstet Gynecol 195(2)

      Pages: 464-469

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Raloxifene increases proliferation and upregulates telomerase activity in human umbilical vein endothelial cells.2006

    • Author(s)
      Doshida M, Ohmichi M, Tsutsumi S, Kawagoe J, Takahashi T, Du B, Mori-Abe A, Ohta T, Saitoh-Sekiguchi M, Takahashi K, Kurachi H.
    • Journal Title

      J Biol Chem 281(34)

      Pages: 24270-24278

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical outcome and risk factors for recurrence in borderline ovarian tumours.2006

    • Author(s)
      Yokoyama Y, Moriya T, Takano T, Shoji T, Takahasi O, Nakahara K, Yamada H, Yaegashi N, Okamura K, Izutsu T, Sugiyama T, Tanaka T, Kurachi H, Sato A, Tase T, Mizunuma H.
    • Journal Title

      Br J Cancer 94(11)

      Pages: 1586-1591

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models.2006

    • Author(s)
      Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, Takahashi K, Igarashi H, Du B, Doshida M, Ishida GM, Motoyama T, Tasaka K, Kurachi H.
    • Journal Title

      Endocrinology 147(4)

      Pages: 1761-1769

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitition of phosphatidy linostitol 3-kinase increase efficacy of cisplatinin in vivo ovarian cancer models.2006

    • Author(s)
      Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, Takahashi K, Igarashi H, Du B, Doshida M, Mirei IG, Motoyama T, Tasaka K, Kurachi H.
    • Journal Title

      Endocrinology (in press)

    • Related Report
      2005 Annual Research Report
  • [Presentation] 血管拡張剤fasudiはVEGFにより誘導される血管新生を抑制する.2007

    • Author(s)
      尹麗梅
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Vasodilator fasudil inhibits VEG-induced angiogenesis2007

    • Author(s)
      Yin L
    • Organizer
      59th Annual Congress of the Japan Society of Obstetrics and Gynecology
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 血管拡張剤fasudilはVEGFにより誘導される血管新生を抑制する.2007

    • Author(s)
      尹 麗梅
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.id.yamagata-u.ac.jp/ObGyn/gyoseki1.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.id.yamagata-u.ac.jp/ObGyn/gyoseki1.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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