Identification of new molecular target for ovarian cancer via functional genomic analysis

• Project/Area Number: 23791801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: TOYOSHIMA Masafumi 東北大学, 医学(系)研究科(研究院), 大学院非常勤講師 (70451581)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: c-Myc / 卵巣がん / siRNAスクリーニング / 合成致死 / CK1e / WEE1 / AuroraA / FURIN / CK-1e / 国際研究者交流 / アメリカ / マウスモデル / 合成致死作用 / カゼインキナーゼ1 epsilon / in vivo imaging system

Research Abstract

We searched new molecular target with a synthetic lethal effect with the high expression of oncogene c-Myc in ovarian cancer via large scale siRNA screening. Through bioinformatics analysis utilizing network analysis and database, and verification experiments both in vitro and in vivo, we identified CK1e, WEE1, Aurora A and FURIN as candidates molecule for the new therapeutic target.

Research Products

• [Journal Article] Molecular Pathogenesis of Uterine Serous Carcinoma (2014)
  • Author(s): Satoru Nagase, Fumihiko Suzuki, Hideki Tokunaga, Masafumi Toyoshima, Hiroki Utsunomiya, Hitoshi Niikura, Nobuo Yaegashi
  • Journal Title: Curr Obstet Gynecol Rep Volume: (3) Pages: 33-39
• [Journal Article] Paclitaxel–carboplatin for advanced or recurrent carcinosarcoma of the uterus : the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study (2014)
  • Author(s): Tadao Takano, Takeo Otsuki, Hideki Tokunaga, Masafumi Toyoshima, Hiroki Utsunomiya, Satoru Nagase, Hitoshi Niikura, Kiyoshi Ito, Nobuo Yaegashi, Hidekazu Yamada, Toru Tase, Masahiro Kagabu, Tadahiro Shoji, Toru Sugiyama, Naoki Sato, Toshio Fujimoto, Yukihiro Terada, Kenji Nakahara, Hirohisa Kurachi, Yoshihito Yokoyama, Hideki Mizunuma, Shu Soeda, Hiroshi Nishiyama, Takashi Matsumoto, Shinya Sato, Muneaki Shimada, Junzo Kigawa
  • Journal Title: Int J Clin Oncol Volume: (PMID : 24395448)
• [Journal Article] Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer. (2014)
  • Author(s): Tanaka S, Nagase S, Kaiho-Sakuma M, Nagai T, Kurosawa H, Toyoshima M, Tokunaga H, Otsuki T, Utsunomiya H, Takano T, Niikura H, Ito K, Yaegashi N.
  • Journal Title: Int J Clin Oncol Volume: 19 Issue: 1 Pages: 133-138
  • DOI: 10.1007/s10147-013-0534-9
  • Peer Reviewed
• [Journal Article] Molecular Pathogenesis of Uterine Serous Carcinoma (2014)
  • Author(s): Satoru Nagase ・ Fumihiko Suzuki ・ Hideki Tokunaga ・Masafumi Toyoshima ・ Hiroki Utsunomiya ・Hitoshi Niikura ・ Nobuo Yaegashi
  • Journal Title: Curr Obstet Gynecol Rep Volume: 3 Issue: 1 Pages: 33-39
  • DOI: 10.1007/s13669-013-0069-0
  • Peer Reviewed
• [Journal Article] Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study (2014)
  • Author(s): Tadao Takano,Takeo Otsuki,Hideki Tokunaga,Masafumi Toyoshima,Hiroki Utsunomiya,Satoru Nagase,Hitoshi Niikura,Kiyoshi Ito,Nobuo Yaegashi,Hidekazu Yamada,Toru Tase,Masahiro Kagabu,Tadahiro Shoji,Toru Sugiyama,Naoki Sato,Toshio Fujimoto,Yukihiro Terada, Junzo Kigawa,et al
  • Journal Title: Int J Clin Oncol. Volume: accepted Issue: 6 Pages: 1052-1058
  • DOI: 10.1007/s10147-013-0658-y
  • Peer Reviewed
• [Journal Article] Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer. (2013)
  • Author(s): Niikura H, Kaiho-Sakuma M, Tokunaga H, Toyoshima M, Utsunomiya H, Nagase S, Takano T, Watanabe M, Ito K, Yaegashi N
  • Journal Title: Gynecol Oncol. Volume: 131 Issue: 2 Pages: 299-303
  • DOI: 10.1016/j.ygyno.2013.08.018
  • Peer Reviewed
• [Journal Article] Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese Women (2013)
  • Author(s): Takayama S, Monma Y, Tsubota-Utsugi M, Nagase S, Tsubono Y, Numata T, Toyoshima M, Utsunomiya H, Sugawara J, Yaegashi N.
  • Journal Title: Nutr Cancer. Volume: 65 Issue: 7 Pages: 954
  • DOI: 10.1080/01635581.2013.818158
  • Peer Reviewed
• [Journal Article] Carcinosarcoma of the uterine cervix with a clear cell adenocarcinoma component (2013)
  • Author(s): Naomi Shiga, Masafumi Toyoshima, Jun-ichi Akahira, Satoru Nagase, Hitoshi Niikura, Nobuo Yaegashi
  • Journal Title: Int Canc Conf J Volume: Volume 2(3) Pages: 154-156
• [Journal Article] Small Cell Carcinoma of the Uteruine Cervix : Clinical Outcome of concurrent Chemoradiotherapy with a Multidrug Regimen (2013)
  • Author(s): Hideki Tokunaga, Satoru Nagase, Kosuke Yoshinaga, Sota Tanaka, Tomyuki Nagai, Hiroki Kurosawa, Michiko Kaiho-Sakuma, Masafumi Toyoshima, Takeo Otsuki, Hiroki Utsunomiya, Tadao Takano, Hitoshi Niikura, Kiyoshi ito and Nobuo Yaegashi
  • Journal Title: Tohoku J. Exp. Med. Volume: 229(1) Pages: 75-81
• [Journal Article] Carcinosarcoma of the uterine cervix with a clear cell (2013)
  • Author(s): Naomi Shiga, Masafumi Toyoshima, Jun-ichi Akahira, Satoru Nagase, Hitoshi Niikura, Nobuo Yaegashi
  • Journal Title: Int Canc Conf J Volume: 2(3) Issue: 3 Pages: 154-156
  • DOI: 10.1007/s13691-012-0080-8
  • Peer Reviewed
• [Journal Article] Small Cell Carcinoma of the Uterine Cervix: Clinical Outcome of Concurrent Chemoradiotherapy with a Multidrug Regimen (2013)
  • Author(s): Hideki Tokunaga, Satoru Nagase, Kosuke Yoshinaga, Sota Tanaka, Tomyuki Nagai, Hiroki Kurosawa, Michiko Kaiho-Sakuma, Masafumi Toyoshima, et al
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 229 Issue: 1 Pages: 75-81
  • DOI: 10.1620/tjem.229.75
  • NAID: 130004460037
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] MYC-driven tumorigenesis is inhibited by WRN syndrome gene deficiency (2012)
  • Author(s): Russell Moser, Masafumi Toyoshima, Kristin Robinson, Kay E. Gurley, Heather L. Howie, Jerry Davison, Martin Morgan, Christpher J. Kemp and Carla Grandori
  • Journal Title: Mol. Cancer Research Volume: 10 Issue: 4 Pages: 535-545
  • DOI: 10.1158/1541-7786.mcr-11-0508
• [Journal Article] Functional Genomics Identifies Therapeutic Targets for MYC-Driven Cancer (2012)
  • Author(s): Masafumi Toyoshima , Heather L Howie , Maki Imakura , Ryan M Walsh , James E Annis , Aaron N. Chang ,et al
  • Journal Title: PNAS Volume: 109 Issue: 24 Pages: 9545-9550
  • DOI: 10.1073/pnas.1121119109
  • Peer Reviewed
• [Journal Article] Hysterescopic inspection and total curettage are insufficient for discriminating endometrial cancer from atypical endometrial hyperplasia (2012)
  • Author(s): Hiroki Kurosawa, Kiyoshi ito, Hitoshi Nikura, Tadao Takano, Satoru Nagase, Hiroki Ustunomiya, Takeo Otsuki, Masafumi Toyoshima, Tomoyuki Nagai, Souta Tanaka, Mika Watanabe and Nobuo Yaegashi
  • Journal Title: Tohoku J. Exp. Med. Volume: 228(4) Pages: 365-370
• [Presentation] Epidemiology of the cervical cancer, and the Present State of Screening/Vaccination in Japan (2013)
  • Author(s): Masafumi Toyoshima
  • Organizer: Phnom Penh Hotel 12th SCGO annual meeting Invited Phnom Penh, Cambodia
  • Place of Presentation: Phnom Penh, Cambodia
  • Year and Date: 2013-08-09
• [Presentation] 大規模siRNAスクリーニングを通じた、卵巣がんに対する新規治療標的分子の同定 (2013)
  • Author(s): 豊島将文
  • Organizer: 勝山館TYCOONS Seminar 2013
  • Place of Presentation: 仙台
  • Year and Date: 2013-08-03
  • Invited
• [Presentation] c-Myc高発現をバイオマーカーとした卵巣がんにおける治療標的分子の同定 (2013)
  • Author(s): 豊島将文, 北谷和之, 増子さつき, 重田昌吾, 石橋ますみ, 八重樫伸生
  • Organizer: 第1回婦人科がんバイオマーカー研究会学術集会講演
  • Place of Presentation: 東京大学伊藤国際学術研究センター
  • Year and Date: 2013-02-16
• [Presentation] 大規模siRNAスクリーニングを用いた卵巣がんのシスプラチン抵抗性を克服する分子標的の検討 (2013)
  • Author(s): 石橋ますみ, 豊島将文, 北谷和之, 増子さつき, 重田昌吾, 八重樫伸生
  • Organizer: 第1回婦人科がんバイオマーカー研究会学術集会講演
  • Place of Presentation: 東京大学伊藤国際学術研究センター
  • Year and Date: 2013-02-16
• [Presentation] 卵巣がん転移を標的にした創薬 : スフィンゴ脂質の利用 (2013)
  • Author(s): 北谷和之, 豊島将文, 増子さつき, 重田昌吾, 石橋ますみ, 八重樫伸生
  • Organizer: 第12回日本婦人科がん分子標的研究会講演
  • Place of Presentation: 東大寺総合文化センター、奈良
• [Presentation] I dentification of Targeted Therapies for Ovarian Cancers by Functional Genomics (2013)
  • Author(s): Masafumi Toyoshima, Kazuyuki Kitatani, Satsuki Mashiko, Shogo Shigeta and Nobuo Yaegashi
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌(ポスター)
• [Presentation] 卵管上皮内腺癌におけるDNA二本鎖切断とp53発現の免疫組織学的検討 (2013)
  • Author(s): 重田昌吾, 豊島将文, 増子さつき, 北谷和之, 八重樫伸生
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌(ポスター)
• [Presentation] 卵巣明細胞腺癌におけるPAI-1の発現と血栓症発症の関連についての検討 (2013)
  • Author(s): 増子さつき, 豊島将文, 北谷和之, 重田昌吾, 八重樫伸生
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌(ポスター)
• [Presentation] 大規模siRNAスクリーニングを用いた卵巣がんのシスプラチン抵抗性を克服する分子標的の検討 (2013)
  • Author(s): 石橋ますみ・豊島将文・北谷和之・増子さつき・重田昌吾・八重樫伸生
  • Organizer: 第1回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター
• [Presentation] c-Myc高発現をバイオマーカーとした卵巣がんにおける治療標的分子の同定 (2013)
  • Author(s): 豊島将文・北谷和之・増子さつき・重田昌吾・石橋ますみ・八重樫伸生
  • Organizer: 第1回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター
• [Presentation] Identification of Targeted therapies for Ovarian Cancer by Functional Genomics (2012)
  • Author(s): Masafumi Toyoshima
  • Organizer: 9th Ovarian Cancer Research Symposium
  • Place of Presentation: Seattle, USA
• [Presentation] Identification of Targeted therapies for Ovarian Cancer by Functional Genomics (2012)
  • Author(s): Masafumi Toyoshima
  • Organizer: Marsha Rikin the 9th Ovarian Cancer Research Symposium
  • Place of Presentation: Seattle, USA
  • Invited
• [Presentation] 機能的ゲノミクスによる、卵巣がんにおけるc-Myc過剰発現と合成致死作用を持つ分子標的の探索 (2011)
  • Author(s): 豊島将文
  • Organizer: 第2回講習会講演
  • Place of Presentation: 東北大学薬学部化合物ライブラリー、仙台
  • Year and Date: 2011-12-20
• [Presentation] Therapeutic targets for MYC-driven cancer (2011)
  • Author(s): Masafumi Toyoshima
  • Organizer: Moscone Center West AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics
  • Place of Presentation: San Francisco, USA(ポスター)
  • Year and Date: 2011-11-15
• [Presentation] Identification of Targeted Therapies for c-Myc overexpressed Ovarian Cancers by Functional Genomics (2011)
  • Author(s): Masafumi Toyoshima
  • Organizer: 第70回日本癌学会講演
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] casein kinase 1 epsilonはc-Myc過剰発現を バイオマーカーとした、 卵巣がんの新規治療標的である (2011)
  • Author(s): 豊島 将文
  • Organizer: 第50回日本婦人科腫瘍学会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] 卵巣がんにおける新しい治療標的探索ツールとしての大規模siRNAスクリーニング、およびG2/Mチェックポイント関連分子の同定 (2011)
  • Author(s): 豊島 将文
  • Organizer: 第63回日本産科婦人科学会学術総会
  • Place of Presentation: リーガロイヤルホテル（大阪）
• [Presentation] Identification of Targeted Therapies for c-Myc overexpressed Ovarian Cancers by Functional Genomics (2011)
  • Author(s): 豊島 将文
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Therapeutic targets for MYC-driven cancer (2011)
  • Author(s): Masafumi Toyoshima, Heather L. Howie, Carla Grandori
  • Organizer: AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics(招待講演)
  • Place of Presentation: Moscone Center West (SanFranscisco, USA)
• [Presentation] 機能的ゲノミクスによる、卵巣がんにおけるc-Myc過剰発現と合成致死作用を持つ分子標的の探索 (2011)
  • Author(s): 豊島 将文
  • Organizer: 化合物ライブラリー第2回講習会
  • Place of Presentation: 東北大学薬学部
• [Presentation] Epidemiology of the cervical cancer, and the Present State of Screening/Vaccination in Japan
  • Author(s): Masafumi Toyoshima
  • Organizer: 12th SCGO annual meeting
  • Place of Presentation: Phnom Penh, Cambodia
  • Invited
• [Presentation] 大規模siRNAスクリーニングを通じた、卵巣がんに対する新規治療標的分子の同定
  • Author(s): 豊島将文
  • Organizer: TYCOONS Seminar 2013
  • Place of Presentation: 勝山館、仙台市
  • Invited
• [Presentation] 卵巣がん転移を標的にした創薬:スフィンゴ脂質の利用
  • Author(s): 北谷和之・豊島将文・増子さつき・重田昌吾・石橋ますみ・八重樫伸生
  • Organizer: 第12回日本婦人科がん分子標的研究会
  • Place of Presentation: 東大寺総合文化センター、奈良市
• [Presentation] 卵巣明細胞腺癌におけるPAI-1の発現と血栓症発症の関連についての検討
  • Author(s): 増子さつき・豊島将文・北谷和之・重田昌吾・八重樫伸生
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] 卵管上皮内腺癌におけるDNA二本鎖切断とp53発現の免疫組織学的検討
  • Author(s): 重田昌吾・豊島将文・増子さつき・北谷和之・八重樫伸生
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] Identification of Targeted Therapies for Ovarian Cancers by Functional Genomics
  • Author(s): Masafumi Toyoshima, Kazuyuki Kitatani, Satsuki Mashiko, Shogo Shigeta and Nobuo Yaegashi
  • Organizer: 第65回日本産科婦人科学会学術総会
  • Place of Presentation: 札幌市
• [Remarks] 研究室HP
  • URL: http://www.ob-gy.med.tohoku.ac.jp/laboratory/m-toyoshima-01.html
• [Remarks]
  • URL: http://www.ob-gy.med.tohoku.ac.jp/prize.html