Targeted therapy for ovarian clear cell carcinoma, focusing on MET amplifcation and oxidative stress.

• Project/Area Number: 26460423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nagoya City University
• Principal Investigator: YAMASHITA Yoriko 名古屋市立大学, 大学院医学研究科, 准教授 (90303643)
• Co-Investigator(Renkei-kenkyūsha): TOYOKUNI Shinya 名古屋大学, 大学院医学系研究科, 教授 (90252460)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Met遺伝子 / 卵巣明細胞癌 / 子宮体癌 / 乳癌 / MET遺伝子 / 遺伝子増幅 / 卵巣癌 / MET / FISH / copy number assay / 酸化ストレス / 分子標的治療

Outline of Final Research Achievements

At this moment, we do not have definite data about positive effects of Met inhibitors against transplanted ovarian clear cell carcinoma model. There are multiple reasons, but an important factor is that cell lines of ovarian clear cell carcinoma are slow-growing and difficult to obtain stable grafts in nude mice. We have analyzed tumors other than ovarian clear cell carcinomas, and Met amplification was confirmed in a subpopulation of endometrial cancers. On the other hand, breast cancers mostly had no amplification of the Met gene.

Research Products

• [Journal Article] Connexin 32 dysfunction promotes ethanol-related hepatocarcinogenesis via activation of Dusp1-Erk axis. (2016)
  • Author(s): Kato H, Naiki-Ito A, Naiki T, Suzuki S, Yamashita Y, Sato S, Sagawa H, Kato A, Kuno T, Takahashi S.
  • Journal Title: Oncotarget. Volume: 7 Issue: 2 Pages: 2009-2021
  • DOI: 10.18632/oncotarget.6511
  • Peer Reviewed / Open Access
• [Journal Article] Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis. (2016)
  • Author(s): Wang Y, Okazaki Y, Shi L, Kohda H, Tanaka M, Taki K, Nishioka T, Hirayama T, Nagasawa H, Yamashita Y, Toyokuni S.
  • Journal Title: Cancer Sci Volume: 107(3) Issue: 3 Pages: 250-257
  • DOI: 10.1111/cas.12865
  • Peer Reviewed / Open Access
• [Journal Article] Pain-reducing anesthesia prevents oxidative stress in human term placenta (2016)
  • Author(s): Tsuzuki Y, Yamashita Y, Hattori Y, Hua Li G, Akatsuka S, Kotani T, Kikkawa F, Naiki-Ito A, Takahashi S, Nishiwaki K, Toyokuni S.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 58 Issue: 2 Pages: 156-160
  • DOI: 10.3164/jcbn.15-138
  • NAID: 130005132524
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Ovarian cancer: new developments in clear cell carcinoma and hopes for targeted therapy. (2015)
  • Author(s): Ｙａｍａｓｈｉｔａ Ｙ．
  • Journal Title: Jpn J Clin Oncol Volume: 45 Issue: 5 Pages: 405-407
  • DOI: 10.1093/jjco/hyu221
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats. (2015)
  • Author(s): Sagawa H, Naiki-Ito A, Kato H, Naiki T, Yamashita Y, Suzuki S, Sato S, Shiomi K, Kato A, Kuno T, Matsuo Y, Kimura M, Takeyama H, Takahashi S.
  • Journal Title: Carcinogenesis Volume: 36 Pages: 1539-49
  • DOI: 10.1093/carcin/bgv143
  • Peer Reviewed / Open Access
• [Journal Article] Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation (2014)
  • Author(s): Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S
  • Journal Title: Int J Cancer Volume: 135 Issue: 2 Pages: 308-318
  • DOI: 10.1002/ijc.28692
  • Peer Reviewed
• [Journal Article] Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin. (2014)
  • Author(s): Fujii K, Yamashita Y, Yamamoto T, Takahashi K, Hashimoto K, Miyata T, Kawai K, Kikkawa F, Toyokuni S, Nagasaka T
  • Journal Title: Hum Pathol Volume: 45 Issue: 4 Pages: 717-724
  • DOI: 10.1016/j.humpath.2013.10.031
  • Peer Reviewed
• [Journal Article] Napsin A is a specific marker for ovarian clear cell adenocarcinoma. (2014)
  • Author(s): Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M, Takahashi S.
  • Journal Title: Mod Pathol Volume: Apr 11 Issue: 1 Pages: 111-7
  • DOI: 10.1038/modpathol.2014.61
  • Peer Reviewed
• [Journal Article] Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in ovarian serous borderline tumors. (2014)
  • Author(s): Hayashi Y, Sasaki H, Takeshita S, Nishikawa R, Nishikawa H, Arakawa A, Yamashita Y, Takahashi S, Sugiura-Ogasawara M.
  • Journal Title: Oncol Rep Volume: 32 Issue: 5 Pages: 1815-9
  • DOI: 10.3892/or.2014.3442
  • Peer Reviewed
• [Journal Article] Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma (2014)
  • Author(s): Jiang L, Yamashita Y, Chew SH, Akatsuka S, Ukai S, Wang S, Nagai H, Okazaki Y, Takahashi T, Toyokuni S
  • Journal Title: J Pathol Volume: 233 Issue: 4 Pages: 402-414
  • DOI: 10.1002/path.4377
  • Peer Reviewed / Open Access
• [Presentation] MET gene amplification in ｅｎｄｏｍｅｔｒｉａｌ ｃｌｅａｒ ｃｅｌｌ ｃａｒｃｉｎｏｍａ (2015)
  • Author(s): Yoriko Yamashita, Aya Naiki-Ito, Hiroyuki Kato, Shinya Sato, Shugo Suzuki, Toshiya Kuno, and Satoru Takahashi
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 （名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] トリプルネガテイブ乳癌ではMet遺伝子の増幅はない (2014)
  • Author(s): 山下 依子、浅野 倫子、遠山 竜也、内木 綾、佐藤 慎哉、鈴木 周五、高橋 智
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 卵巣粘液性腫瘍は成熟奇形腫より発生する-分子遺伝学的アプローチによる組織起源の解明- (2014)
  • Author(s): 山下 依子、 藤井 佳穂、 高橋 智、豊國 伸哉、長坂 徹郎
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島県・広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] 酸化ストレスの医学 2-17 婦人科疾患と酸化ストレス (2014)
  • Author(s): 山下 依子
  • Total Pages: 5
  • Publisher: 診断と治療社
• [Book] 腫瘍病理鑑別診断アトラス 子宮体癌 3-9 子宮体部腫瘍における免疫染色の有用性 (2014)
  • Author(s): 山下 依子、長坂 徹朗
  • Total Pages: 6
  • Publisher: 文光堂