Towards precision medicine for ovarian cancer using drug sensitivity and resistance testing and genomic analysis

• Project/Area Number: 15K10730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Eichirou Tominaga 慶應義塾大学, 医学部(信濃町), 講師 (80276328)
• Co-Investigator(Kenkyū-buntansha): 赤羽 智子 慶應義塾大学, 医学部(信濃町), 特任助教 (40398699) ; 平沢 晃 慶應義塾大学, 医学部(信濃町), 講師 (90296658)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 薬剤感受性 / 卵巣癌 / 初代培養 / 薬剤感受性試験 / ドラッグリポジショニング / precision medicine

Outline of Final Research Achievements

The following results were raised within this research project.
①We successfully established a new cell line from malignant mesothelioma ascites. This cell line is a valuable biological resource to study the　mechanisms underlying carcinogenesis in peritoneal mesothelioma and for drug sensitivity tests (DSRT).②DSRT were conducted in two dimensional and three dimensional cultures using established cell lines. The pemetrexed (PEM) is used for standard therapy of malignant mesothelioma. PEM was drug susceptibility in two dimensional culture by DSRT, but there was no drug effect in three dimensional culture. Those results were consistent with the clinical course and it was possible to conduct a DSRT that mimics the in vivo environment.③Cell cultured from ovarian carcinoma tumor tissue fragments formed spheroids and succeeded in creating a ductal structure similar to the in vivo structure. We succeeded in forming spheroids derived from ovarian cancer tumor tissue.

Research Products

• [Journal Article] Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer (2018)
  • Author(s): Takeda Takashi、Tsuji Kosuke、Banno Kouji、Yanokura Megumi、Kobayashi Yusuke、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Journal of Gynecologic Oncology Volume: 29 Issue: 3
  • DOI: 10.3802/jgo.2018.29.e29
  • Peer Reviewed / Open Access
• [Journal Article] The 5th Biennial Meeting of the Asian Society of Gynecologic Oncology, November 30th to December 2nd, 2017 (2018)
  • Author(s): Tominaga Eiichiro、Kobayashi Yusuke、Aoki Daisuke
  • Journal Title: Journal of Gynecologic Oncology Volume: 29 Issue: 2
  • DOI: 10.3802/jgo.2018.29.e33
• [Journal Article] Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian and endometrial cancer (2017)
  • Author(s): Iijima Moito、Banno Kouji、Okawa Ryuichiro、Yanokura Megumi、Iida Miho、Takeda Takashi、Kunitomi-Irie Haruko、Adachi Masataka、Nakamura Kanako、Umene Kiyoko、Nogami Yuya、Masuda Kenta、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Oncology Letters Volume: 13 Issue: 3 Pages: 1063-1070
  • DOI: 10.3892/ol.2017.5582
  • Peer Reviewed / Open Access
• [Journal Article] Recent advances in the molecular mechanisms of Mayer-Rokitansky-Kuster-Hauser syndrome (2017)
  • Author(s): Watanabe Keiko、Kobayashi Yusuke、Banno Kouji、Matoba Yusuke、Kunitomi Haruko、Nakamura Kanako、Adachi Masataka、Umene Kiyoko、Kisu Iori、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Biomedical Reports Volume: 7 Issue: 2 Pages: 123-127
  • DOI: 10.3892/br.2017.929
  • Peer Reviewed / Open Access
• [Journal Article] New use of microsatellite instability analysis in endometrial cancer (2017)
  • Author(s): Kunitomi Haruko、Banno Kouji、Yanokura Megumi、Takeda Takashi、Iijima Moito、Nakamura Kanako、Iida Miho、Adachi Masataka、Watanabe Keiko、Matoba Yusuke、Kobayashi Yusuke、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Oncology Letters Volume: 14 Issue: 3 Pages: 3297-3301
  • DOI: 10.3892/ol.2017.6640
  • Peer Reviewed / Open Access
• [Journal Article] Drug repositioning of mevalonate pathway inhibitors as antitumor agents for ovarian cancer (2017)
  • Author(s): Kobayashi Yusuke、Kashima Hiroyasu、Rahmanto Yohan Suryo、Banno Kouji、Yu Yu、Matoba Yusuke、Watanabe Keiko、Iijima Moito、Takeda Takashi、Kunitomi Haruko、Iida Miho、Adachi Masataka、Nakamura Kanako、Tsuji Kosuke、Masuda Kenta、Nomura Hiroyuki、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Oncotarget Volume: 8 Issue: 42 Pages: 72147-72156
  • DOI: 10.18632/oncotarget.20046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aberrant chromatin remodeling in gynecological cancer (Review) (2017)
  • Author(s): Okawa Ryuichiro、Banno Kouji、Iida Miho、Yanokura Megumi、Takeda Takashi、Iijima Moito、Kunitomi-Irie Haruko、Nakamura Kanako、Adachi Masataka、Umene Kiyoko、Nogami Yuya、Masuda Kenta、Kobayashi Yusuke、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Oncology Letters Volume: 14 Pages: 5107-5113
  • DOI: 10.3892/ol.2017.6891
  • Peer Reviewed / Open Access
• [Journal Article] Recent findings on epigenetic gene abnormalities involved in uterine cancer (2017)
  • Author(s): Yanokura Megumi、Banno Kouji、Kobayashi Yusuke、Nomura Hiroyuki、Hayashi Shigenori、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Molecular and Clinical Oncology Volume: 7 Issue: 5 Pages: 733-737
  • DOI: 10.3892/mco.2017.1428
  • Peer Reviewed / Open Access
• [Journal Article] [Corrigendum] Recent advances in the molecular mechanisms of Mayer-Rokitansky-Kuster-Hauser syndrome (Review) (2017)
  • Author(s): Watanabe Keiko、Kobayashi Yusuke、Banno Kouji、Matoba Yusuke、Kunitomi Haruko、Nakamura Kanako、Adachi Masataka、Umene Kiyoko、Kisu Iori、Tominaga Eiichiro、Aoki Daisuke
  • Journal Title: Biomedical Reports Volume: 8 Pages: 106-106
  • DOI: 10.3892/br.2017.1018
  • Peer Reviewed / Open Access
• [Journal Article] Radiation-induced angiosarcoma of the omentum diagnosed by laparoscopy: A case report (2017)
  • Author(s): Kunitomi Haruko、Banno Kouji、Iseki Hayato、Sera Asako、Miyauchi Azumi、Kobayashi Yusuke、Hayashi Shigenori、Tominaga Eiichiro、Sasaki Aya、Kawaida Miho、Kameyama Kaori、Aoki Daisuke
  • Journal Title: Molecular and Clinical Oncology Volume: 8 Pages: 264-268
  • DOI: 10.3892/mco.2017.1513
  • Peer Reviewed / Open Access
• [Journal Article] UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan. (2017)
  • Author(s): Yoshihama T, Hirasawa A, Nomura N, Akahane T, Nanki Y, Yamagami W, Kataoka F, Tominaga T, Susumu N, Mushiroda T, Aoki D.
  • Journal Title: Jpn J Clin Oncol Volume: 47(2) Issue: 2 Pages: 170-174
  • DOI: 10.1093/jjco/hyw163
  • Peer Reviewed / Open Access
• [Journal Article] Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report. (2017)
  • Author(s): Adachi M, Banno K, Masuda K, Yanokura M, Iijima M, Takeda T, Kunitomi H, Kobayashi Y, Yamagami W, Hirasawa A, Kameyama K, Sugano K, Aoki D.
  • Journal Title: J Obstet Gynaecol Res Volume: 43(2) Issue: 2 Pages: 416-420
  • DOI: 10.1111/jog.13202
  • Peer Reviewed / Open Access
• [Journal Article] Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis. (2016)
  • Author(s): Takeda T, Banno K, Yanokura M, Adachi M, Iijima M, Kunitomi H, Nakamura K, Iida M, Nogami Y, Umene K, Masuda K, Kobayashi Y, Yamagami W, Hirasawa A, Tominaga E, Susumu N, Aoki D
  • Journal Title: Genes (Basel) Volume: 7 Issue: 10 Pages: 86-97
  • DOI: 10.3390/genes7100086
  • Peer Reviewed / Open Access
• [Journal Article] Drug repositioning for gynecologic tumors: a new therapeutic strategy for cancer (2015)
  • Author(s): Banno K, Iida M, Yanokura M, Irie H, Masuda K, Kobayashi Y, Tominaga E, Aoki D.
  • Journal Title: ScientificWorldJournal Volume: 2015 Issue: 1 Pages: 341362-341362
  • DOI: 10.1155/2015/341362
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 手術前禁忌薬剤（経口避妊薬）に関する医療安全対策. (2017)
  • Author(s): 高柳裕子, 冨永英一郎, 小林佑介, 仲村 勝, 片岡史夫, 平沢 晃, 阪埜浩司, 田中 守, 青木大輔.
  • Organizer: 第381回東京産科婦人科学会例会
  • Place of Presentation: JA共済ビルカンファレンスホール(東京都千代田区）
  • Year and Date: 2017-02-25
• [Presentation] 血縁腫瘍歴聴取票を用いた婦人科関連遺伝性腫瘍のスクリーニングに関する検討. (2016)
  • Author(s): 平野卓朗，平沢 晃，真壁 健, 坂井健良, 赤羽智子，増田健太，小林佑介, 山上 亘，野村弘行，片岡史夫，冨永英一郎, 阪埜浩司，進 伸幸，青木大輔.
  • Organizer: 第2回日本産科婦人科遺伝診療学会学術講演会
  • Place of Presentation: メルパルク京都(京都府京都市）
  • Year and Date: 2016-12-16
• [Presentation] 子宮体癌206例の末梢血を用いたDNAミスマッチ修復遺伝子のメチル化解析. (2016)
  • Author(s): 竹田 貴, 阪埜浩司，矢野倉恵, 安達将隆, 小林佑介, 山上 亘, 平沢 晃，冨永英一郎，進 伸幸，青木大輔.
  • Organizer: 第2回日本産科婦人科遺伝診療学会学術講演会
  • Place of Presentation: メルパルク京都(京都府京都市）
  • Year and Date: 2016-12-16
• [Presentation] 腹水細胞中から樹立したヒト悪性腹膜中皮腫由来細胞株の特性に関する検討. (2016)
  • Author(s): 赤羽智子, 冨永英一郎, 平沢 晃, 青木大輔.
  • Organizer: 第55回日本臨床細胞学会秋期大会
  • Place of Presentation: 別府国際コンベンションセンター（大分県別府市）
  • Year and Date: 2016-11-18
• [Presentation] 自己記入式がん家族歴聴取票を使用した遺伝高リスク家系の抽出. (2016)
  • Author(s): 國富晴子, 増田健太, 平沢 晃, 赤羽智子, 小林佑介, 山上 亘, 野村弘行, 片岡史夫, 冨永英一郎, 阪埜浩司, 進 伸幸, 青木大輔.
  • Organizer: 第22回日本家族性腫瘍学会学術集会
  • Place of Presentation: ひめぎんホール（愛媛県松山市）
  • Year and Date: 2016-06-03
• [Presentation] MSH6の生殖細胞系列変異によりLynch症候群と診断された体下部発生子宮体癌の1例. (2016)
  • Author(s): 安達将隆, 阪埜浩司, 植木有紗, 増田健太, 矢野倉恵, 飯島茂異人, 竹田 貴, 小林佑介, 山上 亘, 冨永英一郎, 平沢 晃, 菅野康吉, 青木大輔.
  • Organizer: 第22回日本家族性腫瘍学会学術集会
  • Place of Presentation: ひめぎんホール（愛媛県松山市）
  • Year and Date: 2016-06-03
• [Presentation] TAS-117, a novel allosteric AKT inhibitor, shows potent antitumor activity on ovarian clear cell adenocarcinoma cells from fresh surgical samples in 3-dimentional culture. (2016)
  • Author(s): Tsuta K, Tominaga E, Tozawa A, Akahane T, Uekawa A, Ohara T, Nomura H, Kataoka F, Hirasawa A, Bonno K, Suzuki N, Aoki D.
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京都千代田区）
  • Year and Date: 2016-04-21
• [Presentation] Mutation of any DNA mismatch gene can cause lower uterine segment cancer with Lynch syndrome. (2016)
  • Author(s): Iijima M, Banno K, Masuda K, Yanokura M, Adachi M, Nogami Y, Yamagami W, Tominaga E, Hirasawa A, Susumu N, Tanaka M, Aoki D.
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京都千代田区）
  • Year and Date: 2016-04-21