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The mechanisms of resistance to anti-angiogenic agents in ovarian cancer.

Research Project

Project/Area Number 21791554
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

MABUCHI Seiji  Osaka University, 医学系研究科, 助教 (00452441)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords上皮性卵巣癌 / 明細胞腺癌 / VEGF / 抗血管新生治療 / Bevacizumab / 耐性化 / 卵巣明細胞腺癌 / 卵巣漿液性腺癌 / 血管新生促進因 / 耐性化機構 / 血管新生促進因子
Research Abstract

We first examined the role of VEGF as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histological subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early stage and advanced stage CCC of the ovary. In early stage CCCs, patients who had tumors with high levels of VEGF had significantly shorter survival than those with low levels of VEGF. In vivo treatment with bevacizumab markedly inhibited the growth of both CCC cells-derived tumors as a result of inhibition of tumor angiogenesis. These results indicate that VEGF is frequently expressed and can be a promising therapeutic target in the management of CCC. We next examined the mechanism of resistance to bevacizumab in epithelial ovarian cancer. By using a mouse model, we have identified several pro-angiogenic factors during the ciurse of bevacizumab treatment.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (20 results)

All 2011 2010 2009

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (1 results)

  • [Journal Article] The activity of trabectedin as a single agent or in combination with everolimus for clear cell carcinoma of the ovary.2011

    • Author(s)
      Mabuchi S, Hisamatsu T, Kawase C, Hayashi M, Sawada K, Mimura K, Takahashi K,Takahashi T, Kurachi H, Kimura T.
    • Journal Title

      Clin Cancer Res. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting mTOR signaling pathway in ovarian cancer.2011

    • Author(s)
      Mabuchi S, Hisamatsu T, Kimura T.
    • Journal Title

      Current Medicinal Chemistry. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Calcaneal metastasis in uterine cervical cancer : a case report and review of the literature.2011

    • Author(s)
      Kanayama T, Mabuchi S, Kimura T.
    • Journal Title

      Eur J Gynecol Oncol. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pretreatment Leukocytosis Is an Indicator of Poor Prognosis in Patients with Cervical Cancer.2011

    • Author(s)
      Mabuchi S, Matsumoto Y, Isohashi F, Yoshioka Y, Ohashi H, Morii E, Hamasaki T, Aozasa K, Mutch DG, Kimura T.
    • Journal Title

      Gynecol Oncol. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Activity of Pegylated Liposomal Doxorubicin for Extragenital Mullerian Adenosarcoma with Sarcomatous Overgrowth : A Case Report and a Review of the Literature.2011

    • Author(s)
      Maeda M, Mabuchi S, Matsumoto Y, Hisamatsu T, Ohashi H, Kimura T.
    • Journal Title

      Eur J Gynaecol Oncol. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nedaplatin, a radiosensitizing agent for patients with cervical cancer.2011

    • Author(s)
      Mabuchi S, Kimura T.
    • Journal Title

      Chemotherapy Research and Practice. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases.2011

    • Author(s)
      Mabuchi S, Okazawa M, Isohashi F, Ota Y, Maruoka S, Yoshioka Y, Enomoto T, Morishige K, Kamiura S, Kimura T.
    • Journal Title

      Gynecol Oncol. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The first two cases of granulocyte colony stimulating factor producing adenocarcinoma of the uterine cervix.2010

    • Author(s)
      Mabuchi S, Matsumoto Y, Morii E, Morishige K, Kimura T.
    • Journal Title

      Int J Gynecol Pathol. 29

      Pages: 483-487

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Squamous cell carcinoma of the uterine cervix producing granulocyte colony-stimulating factor : a report of 4 cases and a review of the literature.2010

    • Author(s)
      Matsumoto Y, Mabuchi S, Muraji M, Morii E, Kimura T.
    • Journal Title

      Int J Gynecol Cancer. 20

      Pages: 417-21

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer : A Comparison with a Cohort Treated by Radiotherapy Alone.2010

    • Author(s)
      Mabuchi S, Ugaki H, Isohashi F, Yoshioka Y, Temma K, Yada-Hashimoto N, Takeda T, Yamamoto T, Yoshino K, Nakajima R, et. al.
    • Journal Title

      Gynecol Obstet Invest 69

      Pages: 224-232

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Use of monoclonal antibodies in the treatment of ovarian cancer.2010

    • Author(s)
      Mabuchi S, Morishige K, Kimura T.
    • Journal Title

      Curr Opin Obstet Gynecol. 22

      Pages: 3-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carboplatin and paclitaxel as an initial treatment in patients with stage IVb cervical cancer : a report of 7 cases and a review of the literature.2010

    • Author(s)
      Mabuchi S, Morishige K, Enomoto T, Kimura T.
    • Journal Title

      J Gynecol Oncol. 21

      Pages: 93-96

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of ovarian cancer by monoclonal antibodies.2010

    • Author(s)
      Mabuchi S, Kimura T.
    • Journal Title

      Discov Med 9

      Pages: 197-203

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.2010

    • Author(s)
      Mabuchi S, Kawase C, Altomare DA, Morishige K, Hayashi M, Sawada K, Ito K, Terai Y, Nishio Y, Klein-Szanto AJ, et. al.
    • Journal Title

      Mol Cancer Ther 9

      Pages: 2411-2422

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic factors for survival in patients with recurrent cervical cancer previously treated with radiotherapy.2010

    • Author(s)
      Mabuchi S, Isohashi F, Yoshioka Y, Temma K, Takeda T, Yamamoto T, Enomoto T, Morishige K, Inoue T, Kimura T.
    • Journal Title

      Int J Gynecol Cancer 20

      Pages: 834-840

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.2010

    • Author(s)
      Mabuchi S, Kawase C, Altomare DA, et al.
    • Journal Title

      Mol Cancer Ther

      Volume: 9 Pages: 2411-2422

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of monoclonal antibodies in the treatment of ovarian cancer.2010

    • Author(s)
      Mabuchi S, Morishige K, Kimura T.
    • Journal Title

      Curr Opin Obstet Gynecol

      Volume: 22 Pages: 3-8

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of ovarian cancer by monoclonal antibodies.2010

    • Author(s)
      Mabuchi S, Kimura T.
    • Journal Title

      Discov Med

      Volume: 9 Pages: 197-203

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary2009

    • Author(s)
      Mabuchi S, et al.
    • Journal Title

      Clin Cancer Res 15

      Pages: 5404-5413

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] mTORをターゲットとした卵巣明細胞腺癌の治療戦略2010

    • Author(s)
      河瀬千晶, 馬淵誠士, 澤田健二郎, 森重健一郎, 木村正, 他
    • Organizer
      第62回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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