Pathological examination of tubal fimbria and blood circulating DNA measurement toward the ultra-early detection of fallopian tubal cancer

• Project/Area Number: 26670710
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: YAEGASHI Nobuo 東北大学, 大学病院, 教授 (00241597)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Masafumi 東北大学, 大学病院, 助教 (70451581)
• Co-Investigator(Renkei-kenkyūsha): KITATANI Kazuyuki 東北大学, 東北メディカル・メガバンク機構, 助教 (40539235)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵巣がん / 漿液性腺癌 / p53変異 / 卵管采 / DNA損傷 / トランスフェリン / 卵胞液 / 循環腫瘍DNA

Outline of Final Research Achievements

Serous adenocarcinoma is the most common tissue type of ovarian cancer, and is thought to be originated from tubal fimbria in recent years. We are focusing on DNA damage response, which is considered the cause of p53 mutations, because serous ovarian cancer has p53 mutations even at the precursor lesions. Using γ-H2AX as a marker of DNA2 double strand breaks, we found that transferrin cause DNA damage response in cells. We confirmed that this is specifically dependent on transferrin receptor 1 by siRNA knockdown. The above results were published in the oncogene, and are considered to be a significant achievement in understanding the pathogenesis of ovarian cancer.

Research Products

• [Journal Article] Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report (2016)
  • Author(s): Toyoshima M* (*corresponding author), Momono Y, Makino H, Kudo T, Oka N, Sakurada J, Suzuki H, Kodama H, Yoshinaga K
  • Journal Title: World Journal of Surgical Oncology Volume: - Issue: 1
  • DOI: 10.1186/s12957-016-0774-z
  • Peer Reviewed / Open Access
• [Journal Article] Ceramide limits phosphatidylinositol-3-kinase C2β-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid (2015)
  • Author(s): Kitatani K, Usui T, Sriraman S, Toyoshima M, Ishibashi M, Shigeta S, Nagase S, Sakamoto M, Hannun Y, Torchilin V, Okazaki T, Ogiso H, Yaegashi N
  • Journal Title: Oncogene Volume: - Issue: 21 Pages: 2801-2812
  • DOI: 10.1038/onc.2015.330
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1:the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer. (2015)
  • Author(s): Shigeta S, Toyoshima M* (*corresponding author), Ishibashi M, Usui T, Kitatani K*, Yaegashi N
  • Journal Title: Oncogene Volume: - Issue: 27 Pages: 3577-3586
  • DOI: 10.1038/onc.2015.425
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer. (2015)
  • Author(s): Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N
  • Journal Title: Cancer Biology & Therapy Volume: 16 Issue: 2 Pages: 253-260
  • DOI: 10.1080/15384047.2014.1001271
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report. (2015)
  • Author(s): Toyoshima M, Iwahashi H, Shima T, Hayasaka A, Kudo T, Makino H, Igeta S, Matsuura R, Ishigaki N, Akagi K, Sakurada J, Suzuki H, Yoshinaga K
  • Journal Title: Journal of Medical Case Reports Volume: 9 Issue: 1 Pages: 47-47
  • DOI: 10.1186/s13256-014-0511-6
  • Peer Reviewed / Open Access
• [Journal Article] Spontaneous retroperitoneal hemorrhage caused by rupture of an ovarian artery aneurysm: a case report and review of the literature. (2015)
  • Author(s): Toyoshima M, Kudo T, Igeta S, Makino H, Momono Y, Shima T, Matsuura R, Ishigaki N, Akagi K,Takeyama Y, Iwahashi H, Rikimaru H, Sato A, Yoshinaga K.
  • Journal Title: Journal of Medical Case Reports Volume: 9 Issue: 1 Pages: 84-84
  • DOI: 10.1186/s13256-015-0553-4
  • Peer Reviewed / Open Access
• [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] Outcomes of Abdominal Radical Trachelectomy: Results of a Multicenter Prospective Cohort Study in a Tohoku Gynecologic Cancer Unit. (2014)
  • Author(s): Tokunaga H, Watanabe Y, Niikura H, Nagase S, Toyoshima M, Shiro R, Yoshihito Yokoyama Y, Mizunuma H, Ohta T, Nishiyama H, Watanabe T, Sato N, Sugiyama T, Takano T, Takahashi F, Yaegashi N
  • Journal Title: International Journal of Clinical Oncology Volume: in press Issue: 4 Pages: 776-780
  • DOI: 10.1007/s10147-014-0763-6
  • Peer Reviewed
• [Journal Article] Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan (2013)
  • Author(s): Takano T, Niikura H, Ito K, Nagase S, Utsunomiya H, Otsuki T, Toyoshima M, Tokunaga H, Kaiho-Sakuma M, Shiga N, Nagai T, Tanaka S, Otsuki A, Kurosawa H, Shigeta S, Yamaguchi T, Yaegashi N.
  • Journal Title: International Journal of Clinical Oncology. Volume: - Issue: 5 Pages: 897-905
  • DOI: 10.1007/s10147-013-0627-5
  • Peer Reviewed
• [Presentation] Transferrin in follicular fluid can facilitate DNA double-strand breaks to fallopian tube epithelium: possible involvement of transferrin in the carcinogenesis of high-grade serous ovarian cancer. (2016)
  • Author(s): Shogo Shigeta, Masafumi Toyoshima, Kazuyuki Kitatani, Masumi Ishibashi, Toshinori Usui, Junko Minato, Nobuo Yaegashi
  • Organizer: Society for Reproductive Investigation 63th scientific annual meeting
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [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 (2016)
  • Author(s): 石橋 ますみ、豊島 将文、Mahy Egiz、張 雪薇、湊 純子、重田 昌吾、北谷 和之、八重樫 伸生
  • Organizer: 第4回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 岐阜大学サテライトキャンパス（岐阜市）
  • Year and Date: 2016-02-27
• [Presentation] 卵巣がん転移に関わるセラミド生成代謝酵素 (2016)
  • Author(s): 北谷和之，張雪薇，臼井利典，豊島将文，重田昌吾，石橋ますみ，湊純子， 小木曽英夫， 岡崎俊朗，八重樫伸生
  • Organizer: 第4回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 岐阜大学サテライトキャンパス（岐阜市）
  • Year and Date: 2016-02-27
• [Presentation] Transferrin facilitates the formation of DNA-double strand breaks via Transferrin receptor 1 in fallopian tube epithelial cells. (2015)
  • Author(s): Shogo Shigeta, Masafumi Toyoshima, Kazuyuki Kitatani, Junko Minato, Masumi Ishibashi, Toshinori Usui, Nobuo Yaegashi
  • Organizer: AACR special conference Advance in Ovarian Cancer Research
  • Place of Presentation: Orland, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 卵巣癌におけるc-mycと合成致死作用を持つ治療標的分子の探索 (2015)
  • Author(s): 湊純子、豊島将文、北谷和之、重田昌吾、石橋ますみ、臼井利典、八重樫伸生
  • Organizer: 第14回日本婦人科がん分子標的研究会
  • Place of Presentation: 美ヶ原温泉ホテル翔峰（長野県松本市）
  • Year and Date: 2015-07-18
• [Presentation] 月経血や卵胞液に含まれるトランスフェリンはⅠ型トランスフェリン受容体を介して卵管上皮細胞におけるDNA二重鎖切断を誘導・増幅する (2015)
  • Author(s): 重田昌吾・豊島将文・北谷和之・石橋ますみ・八重樫伸生
  • Organizer: 第67回日本産科婦人科学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-10
• [Presentation] Transferrin facilitates DNA-double strand breaks via transferrin receptor 1 in human fallopian tube epithelial cells: possible involvement of transferrin in carcinogenesis. (2015)
  • Author(s): Shigeta S, Toyoshima M, Kitatani K, Ishibashi M, Usui T, Yaegashi N.
  • Organizer: Society for Reproductive Investigation 62th scientific annual meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2015-03-27
• [Presentation] セラミドによる卵巣がん播種転移制御 (2015)
  • Author(s): 北谷和之、豊島将文、臼井利典、重田昌吾、石橋ますみ、永瀬智、八重樫伸生
  • Organizer: 第3回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 九州大学医学部百年講堂（福岡市）
  • Year and Date: 2015-02-21
  • Invited