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

2010 Fiscal Year Final Research Report

• Project/Area Number: 21791554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: MABUCHI Seiji Osaka University, 医学系研究科, 助教 (00452441)
• Project Period (FY): 2009 – 2010
• Keywords: 上皮性卵巣癌 / 明細胞腺癌 / VEGF / 抗血管新生治療 / Bevacizumab / 耐性化

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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed