Drug discovery and a new carcinogenic process in the clear cell adenocarcinoma of uterine body

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tokai University
• Principal Investigator: HIRASAWA Takeshi 東海大学, 医学部, 講師 (70307289)
• Project Period (FY): 2011 – 2013
• Keywords: 明細胞腺癌 / Type II 体癌 / mTOR / HIF-1 / HDAC7

Research Abstract

Purpose: We have reported that the mTOR-HIF pathway is specifically activated in ovarian clear cell adenocarcinoma (OCCA), and that its activation is a factor related to a poor prognosis of this cancer. In the present study, we focused on Type II endometrial cancer, which has a poor prognosis compared with Type I cancer, and studied the dynamics of mTOR-HIF-related factors. Methods: We performed immunohistochemical staining and clinicopathologic analysis of mTOR-HIF-related factors in 27 patients (Type II endometrial cancer). Results: Expression of phospho-mTOR (p-mTOR), HIF-1a, and HDAC7 was detected at different levels in all of the Type II endometrial cancers. The level of expression tended to be higher in clear cell adenocarcinoma, but the difference was not significant.Discussion: In the present study, activation of the mTOR-HIF pathway was observed in all patients with Type II endometrial cancer regardless of the histology.

Research Products

• [Journal Article] Predicting perioperative venous thromboembolism in Japanese gynecological patients (2014)
  • Author(s): Ikeda M, Kan-no H, Hayashi M, Tsukada H, Shida M, Hirasawa T, Muramatsu T, Ogushi Y, Mikami M
  • Journal Title: PLoS One Volume: (in press)
  • DOI: 10.1371/journal.pone.0089206
  • Peer Reviewed
• [Journal Article] Alterations of hypoxia-induced factor signaling pathway due to mammalian target of rapamycin (mTOR) suppression in ovarian clear cell adenocarcinoma : in vivo and in vitro explorations for clinical trial (2013)
  • Author(s): Hirasawa T, Miyazawa M, Yasuda M, Shida M, Ikeda M, Kajiwara H, Matsui N, Fujita M, Muramatsu T, Mikami M
  • Journal Title: Int J Gynecol Cancer Volume: 23(7) Pages: 1210-8
  • DOI: 10.1097/IGC.0b013e31829d2d51.
  • Peer Reviewed
• [Journal Article] Case of metastatic uterine cervical squamous cell carcinoma in the right atrium (2013)
  • Author(s): Togo A, Muramatsu T, Tsukada H, Ikeda M, Shida M, Hirasawa T, Maeda H, Mikami M
  • Journal Title: Tokai J Exp Clin Med Volume: 38(1) Pages: 42-5
  • Peer Reviewed
• [Journal Article] Enhanced expression of sulfatide, a sulfated glycolipid, in well-differentiated endometrial adenocarcinoma (2012)
  • Author(s): Sugiyama T, Miyazawa M, Mikami M, Goto Y, Nishijima Y, Ikeda M, Hirasawa T, Muramatsu T, Takekoshi S, Iwamori M
  • Journal Title: Int J Gynecol Cancer Volume: 22(7) Pages: 1192-7
  • DOI: 10.1097/IGC.0b013e31825f639f
  • Peer Reviewed
• [Journal Article] Long Term Prognostic Implications of Expression of Glucose Transporter-1 and Hexokinase II in Patients with Stage I Uterine Leiomyosarcoma (2012)
  • Author(s): Tsukada H, Muramatsu T, Miyazawa M, Iida T, Ikeda M, Shida M, Hirasawa T, Kajiwara H, Murakami M, Yasuda M, Mikami M
  • Journal Title: Acta Histochem Cytochem Volume: 45(2) Pages: 147-54
  • DOI: 10.1267/ahc.11063
  • Peer Reviewed
• [Journal Article] Analysis of mTOR inhibition-involved pathway in ovarian clear cell adenocarcinoma (2011)
  • Author(s): Harasawa M, Yasuda M, Hirasawa T, Miyazawa M, Shida M, Muramatsu T, Douguchi K, Matsui N, Takekoshi S, Kajiwara H, Yoshiyuki Osamura R, Mikami M
  • Journal Title: Acta Histochem Cytochem Volume: 44(2) Pages: 113-8
  • DOI: 10.1267/ahc.10029
  • Peer Reviewed
• [Journal Article] Surgical management of vulvar lymphangioma circumscriptum : two case reports (2011)
  • Author(s): Ikeda M, Muramatsu T, Shida M, Hirasawa T, Ishimoto H, Izumi S, Mikami M
  • Journal Title: Tokai J Exp Clin Med Volume: 36(1) Pages: 17-20
  • Peer Reviewed
• [Presentation] Type II子宮体癌の予後不良因子にmTOR-HIF-HDAC7 Pathwayが関与している (2013)
  • Author(s): 平澤猛,宮澤昌樹,宮澤麻里子,楢山知紗,矢坂美和,楢山知明,菅野秀俊,田島敏樹,井浦文香,塚田ひとみ,池田仁恵,信田政子,村松俊成,安田政実,三上幹男.
  • Organizer: 第54回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランパシフィックLE DAIBA
  • Year and Date: 20130719-21
• [Presentation] 卵巣明細胞腺癌の予後改善を目指して上皮性卵巣癌におけるHIF-1の転写活性とHDAC7発現の意義 (2013)
  • Author(s): 宮澤昌樹,平澤猛,宮澤麻里子,安田政実,加藤智美,梶原博,信田政子,池田仁惠,松井成明,村松俊成,三上幹男
  • Organizer: 第54回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランパシフィックLE DAIBA
  • Year and Date: 20130719-21
• [Presentation] (2013)
  • Author(s): 平澤猛,平野結希,菅野秀俊,田島敏樹,塚田ひとみ,池田仁恵,信田政子,村松俊成,石本人士,和泉俊一郎
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌、ホテルさっぽろ芸文館、札幌プリンスホテル、札幌市教育文化会館
  • Year and Date: 20130510-12
• [Presentation] New JGOG Trial Concept for Recurrent Clear cell Carcinoma of the Ovary (EVEROCC Phase II Trial). (2012)
  • Author(s): Hirasawa T
  • Organizer: 14^<th> Biennial Meeting of the International Gynecologic Cancer Society (IGCS)
  • Place of Presentation: Vancouver Convention Centre
  • Year and Date: 20121013-16
• [Presentation] 上皮性卵巣癌におけるHIF-1の転写とHDAC7との関連性 (2012)
  • Author(s): 宮澤昌樹,平澤猛,信田政子,池田仁惠,梶原博,松井成明,宮澤麻里子,村松俊成,安田政実,三上幹男
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランプリンスホテル新高輪
  • Year and Date: 20120719-21
• [Presentation] Type II体癌ではmTOR-HIF pathwayが亢進している (2012)
  • Author(s): 平澤猛,宮澤昌樹,西島義博,杉山太朗,池田仁惠,信田政子,村松俊成,三上幹男
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランプリンスホテル新高輪
  • Year and Date: 20120719-21