A new therapeutic target of platinum resistance ovarian cancer

• Project/Area Number: 15K20142
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: Matsuzaki Shinya 大阪大学, 医学部附属病院, 助教 (00467565)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 婦人科腫瘍 / プラチナ耐性卵巣癌 / IMP-2

Outline of Final Research Achievements

In this study, we investigated the role of IMP-2 in platinum resistance ovarian cancer cells which had high level expression of IMP-2. In platinum resistance ovarian cancer lines, knockdown the expression of IMP-2 improved the sensitivity of cisplatin in vitro. Compared with control platinum resistance ovarian cancer cells (A2780/CisR cells), knockdown of IMP-2 induced roughly 3-fold greater chemosensitization to cisplatin (IC50: 167μM to 54 μM; p<0.01) To elucidate the mechanism underlying platinum resistance induced by IMP-2, intracellular platinum accumulation of A2780/CisR control cells, A2780/CisR silencing IMP-2 cells after cisplatin exposure were analyzed. No significantly chage of platinum had accumulated in A2780/CisR silencing IMP-2 cells compared with control cells (p= 0.24). Thus, intracellular platinum accumulation was not changed in A2780/CisR silencing IMP-2 cells. To perform further investigation, we generate stable IMP-2 over expression in A2780 cell lines.

Research Products

• [Journal Article] Potential Targets for Ovarian Clear Cell Carcinoma: A Review of Updates and Future Perspectives (2015)
  • Author(s): Matsuzaki, S. Yoshino, K. Ueda, Y. Matsuzaki, S. Kakuda, M. Okazawa, A. Egawa-Takata, T. Kobayashi, E. Kimura, T.
  • Journal Title: Cancer Cell Int Volume: 15 Issue: 1 Pages: 117-117
  • DOI: 10.1186/s12935-015-0267-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ATP7A is a promising therapeutic target for uterine leiomyosarcoma (2016)
  • Author(s): Kakuda, M. Matsuzaki, S. Tanaka, Y. Takata, T. Kobayashi, E. Ueda, Y. Yoshino, K. Kimura, T.
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Lipolysis-stimulated lipoprotein receptor（LSR）can be a new therapeutic target for ovarian cancer. (2016)
  • Author(s): Satoko, M. Hiramatsu, K. Serata, S. Nakagawa, S. Shinya, M. Fujimoto, Y. Ueda, Y. Yoshino, K. Enomoto, T. Kimura, T. Naka, T.
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] ATP7A は子宮平滑筋肉腫の治療標的で;ある (2016)
  • Author(s): 角田守 松崎慎哉 田中佑典 森本晶子 高田友美 小林栄仁 上田豊 吉野潔 木村正
  • Organizer: 第15回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-19
• [Presentation] ATP7Bは子宮平滑筋肉腫の治療標的である (2016)
  • Author(s): 角田守 松崎慎哉 田中佑典 高田友美 小林栄仁 上田豊 吉野潔 木村正
  • Organizer: 第58回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 鳥取
  • Year and Date: 2016-07-08
• [Presentation] ATP7A is a promising therapeutic target for uterine leiomyosarcoma (2016)
  • Author(s): Kakuda, M. Matsuzaki, S. Tanaka, Y. Takata, T. Kobayashi, E. Ueda, Y. Yoshino, K. Kimura, T.
  • Organizer: 第68回日本産科婦人科学学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] ATP7B is a promising therapeutic target for uterine leiomyosarcoma (2016)
  • Author(s): Kakuda, M. Matsuzaki, S. Tanaka, Y. Takata, T. Kobayashi, E. Ueda, Y. Kimura, T.
  • Organizer: The 107th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: New Orleans, U.S.A.
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] PHASE Ⅰ/Ⅱ TRIAL OF GLIF FOR TAXANE/PLATINUM-RESISTANT ENDOMETRIAL CANCER (2015)
  • Author(s): Nakagawa, S. Ueda, Y. Matsuzaki, S. Takata, T. Kobayashi, E. Yoshino, K. Kimura, T.
  • Organizer: 19th International Meeting of the European Society of Gynaecological Oncology (ESGO 2015)
  • Place of Presentation: Nice, France
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] Metabolic change in FDG-PET by measuring the single largest lesion one cycle after initiation of chemotherapy for gynecologic malignancies predicts chemotherapeutic effects and patients’survival (2015)
  • Author(s): Tanaka, Y. Ueda, Y. Takata, T. Matsuzaki, S. Kobayashi, E. Mabuchi,S. Sawada, K. Yoshino, K. Kimura, T.
  • Organizer: XXI FIGO World Congress of Gynecology and Obstetrics
  • Place of Presentation: Canada
  • Year and Date: 2015-10-04
  • Int'l Joint Research
• [Presentation] 人工核酸を用いたアネキシンA4 発現抑制は卵巣癌におけるプラチナ耐性を改善する (2015)
  • Author(s): 中川慧 小比賀聡 世良田聡 笠原勇矢 松崎聖子 森本晶子 松崎慎哉 高田友美 小林栄仁 上田豊 吉野潔 仲哲治 木村正
  • Organizer: 第57回日本婦人科腫瘍学会
  • Place of Presentation: 岩手
  • Year and Date: 2015-08-07
• [Presentation] 人工核酸を用いたアネキシンA4アンチセンスは卵巣明細胞腺癌の薬剤耐性を改善する (2015)
  • Author(s): 中川慧 吉野潔 松崎聖子 松崎慎哉 髙田友美 小林栄仁 上田豊 世良田聡 笠原勇矢 小比賀聡 仲哲治 木村正
  • Organizer: 第14回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 長野
  • Year and Date: 2015-07-17
• [Presentation] 長期生存を認めた遠隔転移を伴う子宮体部原発小細胞癌の1例 (2015)
  • Author(s): 澤田真明 松崎慎哉 吉田 晋 小宮慎之介 甲村奈緒子 串本卓哉 後藤摩耶子 張良実 佐藤敦 福井温 鹿戸佳代子 横井猛 荻田和秀
  • Organizer: 第132回近畿産科婦人科学会総会ならびに学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2015-06-27
• [Presentation] SOCS-1はJAK/STATシグナル伝達経路の抑制およびp53の発現安定を介した複数のシグナルで卵巣癌の増殖を抑制する (2015)
  • Author(s): 中川慧 平松宏祐 森本晶子 高田友美 松崎慎哉 小林栄仁 上田豊 吉野潔 仲哲治 木村正
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-09
• [Presentation] ATP7Bは平滑筋肉腫の治療標的である(高得点演題 (2015)
  • Author(s): 角田守 松崎慎哉 高田友美 小林栄仁 上田豊 吉野潔 木村正
  • Organizer: 第67回日本産科婦人科学術講演会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-09
• [Book] Frontiers in Drug Design & Discovery Volume 7 (2016)
  • Author(s): Otake, A. Matsuzaki, S. Ueda, Y. Yoshino, K.
  • Total Pages: 13
  • Publisher: Betham Science