Precision medicine for ovarian cancer by DSRT and genomic analysis

• Project/Area Number: 18K09298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Keio University
• Principal Investigator: TOMINAGA Eiichiro 慶應義塾大学, 医学部(信濃町), 講師 (80276328)
• Co-Investigator(Kenkyū-buntansha): 角田 達彦 東京医科歯科大学, 難治疾患研究所, 教授 (10273468) ; 平沢 晃 岡山大学, 医歯薬学総合研究科, 教授 (90296658)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵巣癌 / 悪性腹膜中皮腫 / 薬剤感受性試験 / 薬剤感受性

Outline of Final Research Achievements

This study reported a new cell line of malignant peritoneal mesothelioma established from ascites for the purpose of performing DSRT for ovarian cancer.
The following research results were obtained. The characteristics of the tumor tissue and established cell line were verified to be the same using protein expression analysis of immunohistochemical staining. The established cell line mimicked the difference in environment between two- and three-dimensional culture, which clarified that the difference in culture environment causes the difference response of pemetrexed agents. The results obtained from this research project were reported in a treatise.

Academic Significance and Societal Importance of the Research Achievements

本邦における卵巣癌の治療成績向上には、本邦独自の対策や治療法の確立が必要と考えドラッグリポジショニング(既存薬再開発）に着目した。ドラッグリポジショニングの利点は、新規化合物を用いた新薬開発に比較して予期せぬ副作用が出現する確率が格段に低く、臨床試験（治験）にかかる時間とコストを削減できることが挙げられる。難治性卵巣癌に対する個別化治療戦略の確立には新薬の開発と並行し、ドラッグリポジショニングの概念を導入することが望ましいと考え本研究に至った。

Research Products

• [Journal Article] LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer (2020)
  • Author(s): Kunitomi Haruko, Kobayashi Yusuke, Wu Ren-Chin, Takeda Takashi, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke.
  • Journal Title: Journal of Gynecologic Oncology Volume: 31 Issue: 2
  • DOI: 10.3802/jgo.2020.31.e11
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cowden syndrome complicated by schizophrenia: A first clinical report (2020)
  • Author(s): Kobayashi Yusuke、Takeda Takashi、Kunitomi Haruko、Ueki Arisa、Misu Kumiko、Kowashi Ayari、Takahashi Takayuki、Anko Mayuka、Watanabe Keiko、Masuda Kenta、Uchida Takahito、Tominaga Eiichiro、Banno Kouji、Kosaki Kenjiro、Aoki Daisuke
  • Journal Title: European Journal of Medical Genetics Volume: 63 Issue: 8 Pages: 103959-103959
  • DOI: 10.1016/j.ejmg.2020.103959
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of safety and diagnostic performance for flexible hysteroscopy in 1591 outpatient cases (2020)
  • Author(s): Kobayashi Yusuke, Tsuji Kosuke, Nakamura Kanako, Nagai Shimpei, Takahashi Takayuki, Kobayashi Arata, Anko Mayuka, Hirano Takuro, Watanabe Keiko, Matoba Yusuke, Kunitomi Haruko, Adachi Masataka, Yamagami Wataru, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke.
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 50 Issue: 10 Pages: 1157-1161
  • DOI: 10.1093/jjco/hyaa098
  • Peer Reviewed / Open Access
• [Journal Article] Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies (2020)
  • Author(s): Sakai Kensuke, Nakamura Masaru, Yamagami Wataru, Chiyoda Tatsuyuki, Kobayashi Yusuke, Nishio Hiroshi, Hayashi Shigenori, Nomura Hiroyuki, Kataoka Fumio, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke.
  • Journal Title: International Journal of Gynecology & Obstetrics Volume: - Issue: 3 Pages: 438-442
  • DOI: 10.1002/ijgo.13507
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: a single-center experience (2020)
  • Author(s): Nogami Yuya, Kobayashi Yusuke, Tsuji Kosuke, Yokota Megumi, Nishio Hiroshi, Nakamura Masaru, Yamagami Wataru, Morisada Tohru, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke.
  • Journal Title: Journal of Ovarian Research Volume: 13 Issue: 1
  • DOI: 10.1186/s13048-020-00711-x
  • Peer Reviewed / Open Access
• [Journal Article] Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes (2020)
  • Author(s): Adachi Masataka, Masugi Yohei, Yamazaki Ken, Emoto Katsura, Kobayashi Yusuke, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke, Sakamoto Michiie.
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 50 Issue: 6 Pages: 643-652
  • DOI: 10.1093/jjco/hyaa026
  • Peer Reviewed / Open Access
• [Journal Article] Establishment and Characterization of a New Malignant Peritoneal Mesothelioma Cell Line, KOG-1, From the Ascitic Fluid of a Patient With Pemetrexed Chemotherapy Resistance (2020)
  • Author(s): Akahane Tomoko, Hirasawa Akira, Imoto Issei, Okubo Aki, Itoh Manabu, Nanki Yoshiko, Yoshihama Tomoko, Tominaga Eichiro, Aoki Daisuke.
  • Journal Title: Hum Cell Volume: 33 Issue: 1 Pages: 272-282
  • DOI: 10.1007/s13577-019-00286-w
  • Peer Reviewed / Open Access
• [Journal Article] Hysteroscopic Photodynamic Diagnosis Using 5-Aminolevulinic Acid: A High-Sensitivity Diagnostic Method for Uterine Endometrial Malignant Diseases (2019)
  • Author(s): Matoba Yusuke, Banno Kouji, Kisu Iori, Kobayashi Yusuke, Tsuji Kosuke, Nagai Shimpei, Yamagami Wataru, Nakamura Masaru, Tominaga Eiichiro, Kawaida Miho, Aoki Daisuke.
  • Journal Title: Journal of Minimally Invasive Gynecology Volume: Aug 12:S1553-4650(19) Issue: 5 Pages: 30372-30373
  • DOI: 10.1016/j.jmig.2019.08.012
  • Peer Reviewed / Open Access
• [Journal Article] Mutations of RAS genes in endometrial polyps (2019)
  • Author(s): Takeda Takashi, Banno Kouji, Kobayashi Yusuke, Adachi Masataka, Yanokura Megumi, Tominaga Eiichiro, Kosaki Kenjiro, Aoki Daisuke.
  • Journal Title: Oncology Reports Volume: 42 Pages: 2303-2308
  • DOI: 10.3892/or.2019.7353
  • Peer Reviewed / Open Access
• [Journal Article] Is antidyslipidemic statin use for cancer prevention a promising drug repositioning approach? (2019)
  • Author(s): Kobayashi Yusuke, Banno Kouji, Kunitomi Haruko, Nagai Shimpei, Takahashi Takayuki, Anko Mayuka, Iijima Moito, Takeda Takashi, Matoba Yusuke, Nakamura Kanako, Tsuji Kosuke, Tominaga Eiichiro, Aoki Daisuke.
  • Journal Title: European Journal of Cancer Prevention Volume: 28 Issue: 6 Pages: 562-567
  • DOI: 10.1097/cej.0000000000000497
  • Peer Reviewed / Open Access
• [Journal Article] Upregulation of IGF2R evades lysosomal dysfunction-induced apoptosis of cervical cancer cells via transport of cathepsins (2019)
  • Author(s): Takeda Takashi, Komatsu Masayuki, Chiwaki Fumiko, Komatsuzaki Rie, Nakamura Kanako, Tsuji Kosuke, Kobayashi Yusuke, Tominaga Eiichiro, Ono Masaya, Banno Kouji, Aoki Daisuke, Sasaki Hiroki.
  • Journal Title: Cell Death & Disease Volume: 10(876) Issue: 12 Pages: 1-17
  • DOI: 10.1038/s41419-019-2117-9
  • Peer Reviewed / Open Access
• [Journal Article] Profiling of the Causative Bacteria in Infected Lymphocysts after Lymphadenectomy for Gynecologic Cancer by Pyrosequencing the 16S Ribosomal RNA Gene Using Next-Generation Sequencing Technology (2019)
  • Author(s): Nogami Yuya, Banno Kouji, Adachi Masataka, Kunitomi Haruko, Kobayashi Yusuke, Tominaga Eiichiro, Aoki Daisuke.
  • Journal Title: Infectious Diseases in Obstetrics and Gynecology Volume: 2019 Pages: 1-5
  • DOI: 10.1155/2019/9326285
  • Peer Reviewed / Open Access
• [Journal Article] Laparoscopic Surgery for Ovarian Cyst Infection with Avoidance of Ureteral Injury and Uterine Perforation following Intrauterine Insemination after Abdominal Modified Radical Trachelectomy (2019)
  • Author(s): Iijima Moito, Hayashi Shigenori, Kobayashi Yusuke, Tsuji Kosuke, Tominaga Eiichiro, Banno Kouji, Aoki Daisuke.
  • Journal Title: Case Reports in Obstetrics and Gynecology Volume: 2019 Pages: 1-4
  • DOI: 10.1155/2019/8607417
  • Peer Reviewed / Open Access
• [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] Synchronous endometrial and ovarian cancer in Lynch syndrome with a MSH2 germline mutation: A case report. (2018)
  • Author(s): Takeda T, Banno K, Yanokura M, Anko M, Kobayashi A, Sera A, Takahashi T, Adachi M, Kobayashi Y, Hayashi S, Nomura H, Hirasawa A, Tominaga E, Aoki D.
  • Journal Title: Mol Clin Oncol Volume: Nov;9(5) Pages: 479-484
  • DOI: 10.3892/mco.2018.1723
  • 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
• [Presentation] 悪性腹膜中皮腫細胞株KOG-1の3次元立体培養と2次元平面培養によるPEM薬剤感受性の比較 (2020)
  • Author(s): 赤羽智子、平沢 晃、冨永英一郎、井本逸勢、大久保亜希、伊藤 学、南木佳子、吉浜智子、増田健太、千代田達幸、山上 亘、片岡史夫、青木大輔.
  • Organizer: 第61回 日本臨床細胞学会総会春期大会
• [Presentation] Insulin like growth factor 2 receptor is a novel prognostic biomarker and behaves as an oncogene in cervical cancer through escape from Golgi-centered catastrophe (2019)
  • Author(s): Takeda T,Komatsu M,Banno K,Tsuji K,Kobayashi Y,Tominaga E,Sasaki H,Tanaka M,Aoki D
  • Organizer: 第71回 日本産科婦人科学会学術講演会
• [Presentation] Evaluation of preoperative diagnosis of uterine sarcoma (2019)
  • Author(s): Tsuji K,Kobayashi Y,Banno K,Nagai S,Anko M,Takahashi T,Takeda T,Iida M,Yamagami W,Tominaga E,Tanaka M,Aoki D
  • Organizer: 第71回 日本産科婦人科学会学術講演会
• [Presentation] Postirradiation PD-L1 expression and low tumor-infiltrating CD8+ cytotoxic lymphocytes are predictors of an improved prognosis after carbon ion radiotherapy for uterine cervical adenocarcinoma (2019)
  • Author(s): Iijima M,Okonogi N,Banno K,Tsuji K,Kobayashi Y,Tominaga E,Hasegawa S,Tanaka M,Aoki D
  • Organizer: 第71回 日本産科婦人科学会学術講演会
• [Presentation] 子宮頸がんに対する治療戦略構築のための新規予後相関バイオマーカーの探索 (2019)
  • Author(s): 竹田 貴,中村加奈子,小松将之,千脇史子,辻 浩介,小林佑介,冨永英一郎,阪埜浩司,佐々木博己,青木大輔
  • Organizer: 第7回 婦人科がんバイオマーカー研究会学術集会