Development of the HIF-1-specific inhibitor in ovarian clear cell carcinoma

• Project/Area Number: 26861343
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Tokai University
• Principal Investigator: MIYAZAWA Masaki 東海大学, 医学部, 特定研究員 (30624572)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: HIF-1 / 卵巣明細胞腺癌 / HDAC7 / シリビニン / Vorinostat / HIF-1活性化阻害剤 / HDAC

Outline of Final Research Achievements

Histone Deacetylase (HDAC) is an enzyme deacetylating the histone which is a main constitution factor in chromatin structure and play an important role in genetic transcription control. HDAC is involved in intracellular signal transduction and the control of the cell cycle and in late years attracts attention as target molecule of the cancer therapy.In this study, focusing on HDAC7, we analyzed their immunohistochemical expression in ovarian cancer and assessed their mRNAs expression in cultured ovarian cancer cell lines. HDAC inhibitor (HDI)-induced changes in the expression of mRNAs for HDAC7, HIF-1α and VEGF were also attempted to assess the potential anti-cancer effect of HDI.
As a result, it was shown that the inhibitory effect of HDI on HDAC7 and HIF-1 varies among cell lines. We suppose that the response to HDI may vary greatly among patients with ovarian cancer and that the ovarian cancer with high expression of HDAC7 may be a suitable candidate for HDI treatment.

Research Products

• [Journal Article] Enhanced Expression of Hydroxylated Ceramide in Well-Differentiated Endometrial adenocarcinoma. (2016)
  • Author(s): Tajima T, Miyazawa M, Hayashi M, Asai S, Ikeda M, Shida S, Hirasawa T, Iwamori M, Mikami M.
  • Journal Title: Oncol Lett. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy. (2016)
  • Author(s): Shida M, Yasuda M, Fujita M, Miyazawa M, Kajiwara H, Hirasawa T, Ikeda M, Matsui N, Muramatsu T, Mikami M.
  • Journal Title: Oncol Lett. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Use of epithelial-specific antigen for cytological diagnosis of glandular lesions in the uterine cervix. (2016)
  • Author(s): Matsui N, Kajiwara H, Morishita A, Iida T, Nakazawa K, Miyazawa M, Mikami M, Ogawa T, Nakamura N, Sato S.
  • Journal Title: Pathol Int. Volume: 66(5) Pages: 305-8
  • DOI: 10.1111/pin.12379
  • Peer Reviewed / Open Access
• [Journal Article] Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2. (2015)
  • Author(s): Matsui N, Kajiwara H, Morishita A, Tsukada H, Nakazawa K, Miyazawa M, Mikami M, Nakamura N, Sato S.
  • Journal Title: Tokai J Exp Clin Med. Volume: 40(2) Pages: 29-35
  • Peer Reviewed / Open Access
• [Journal Article] Fully-sialylated alpha-chain of complement 4-binding protein:Diagnostic utility for ovarian clear cell carcinoma (2015)
  • Author(s): Mikio Mikami,Kazuhiro Tanabe,Koji Matsuo,Yuko Miyazaki,Masaki Miyazawa,Masaru Hayashi,Satoshi Asai,Masae Ikeda,Masako Shida,Takeshi Hirasawa,Nozomi Kojima,Ryuichiro Sho,Sadato Iijima
  • Journal Title: Gynecol Oncol. Volume: 138(3) Pages: 520-528
  • DOI: 10.1016/j.ygyno.2015.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Defect of tropomyosin-related kinase B isotype expression in ovarian clear cell adenocarcinoma (2014)
  • Author(s): Goto Y, Kametani Y*, Kikugawa A, Tsuda B, Miyazawa M, Kajiwara H, Terao Y, Takekoshi S, Nakamura N, Takeda S, Mikami M
  • Journal Title: BST Volume: 8 Issue: 2 Pages: 93-100
  • DOI: 10.5582/bst.8.93
  • NAID: 130005054667
  • ISSN: 1881-7815, 1881-7823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cytological analysis of uterine body endometrioid adenocarcinoma cells in peritoneal cavity: cytological findings and histological background. (2014)
  • Author(s): Matsui N, Kajiwara H, Tsukada H, Nakazawa K, Miyazawa M, Mikami M, Nakamura N, Sato S
  • Journal Title: Tokai J Exp Clin Med. Volume: 39 Pages: 95-102
  • Peer Reviewed
• [Presentation] 卵巣明細胞腺癌における Hypoxia Inducible Factor1α 遺伝子多型頻度および exon12 C1772T 遺伝子多型が臨床的予後に及ぼす影響 (2016)
  • Author(s): 鈴木裕之, 安田政実, 加藤智美, 鎌田孝一, 吉田正行, 宮澤昌樹, 岡垣竜吾, 藤原恵一, 石原理
  • 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] ヒト子宮頸癌由来細胞のGM2糖鎖を持つガングリオシドの合成酵素遺伝子 (2015)
  • Author(s): 田中京子, 宮澤昌樹, 三上幹男, 青木大輔, 木口一成, 岩森正男
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-10-08
• [Presentation] 高齢者子宮内膜癌の病理学的検討 (2015)
  • Author(s): 大金直樹, 鴨志田伸吾, 宮澤昌樹, 加藤久盛, 亀田陽一, 堀慎一, 加藤智美, 安田政実
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-04-30
• [Presentation] 卵巣明細胞腺癌におけるHDACsに着目したHIF-1活性化阻害薬の開発 (2014)
  • Author(s): 宮澤昌樹, 宮澤麻里子, 平澤猛, 花輪幸子, 松井成明, 梶原博, 加藤智美, 安田政実, 三上幹男
  • Organizer: 第12回がんとハイポキシア研究会
  • Place of Presentation: ホテルマリターレ創世
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] 卵巣明細胞腺癌におけるHDAC阻害剤を通じたHIF-1活性化機構の制御 (2014)
  • Author(s): 宮澤 昌樹, 宮澤 麻里子, 加藤 智美, 藤井 幸子, 松井 成明, 平澤 猛, 信田 政子, 池田 仁惠, 浅井 哲, 村松 俊成, 梶原 博, 安田 政実, 三上 幹男
  • Organizer: 第55回日本組織細胞化学会総会･学術集会
  • Place of Presentation: 松本市中央公民館
  • Year and Date: 2014-09-27 – 2014-09-28
• [Presentation] 子宮頸部腺癌においてSulfatideは高発現している(Enhanced Expression of Sulfatide, a Sulfated Glycolipid, In Uterine Cervical Adenocarcinomas) (2014)
  • Author(s): 宮澤 昌樹, 杉山 太朗, 宮澤 麻里子, 藤井 幸子, 池田 仁惠, 信田 政子, 平澤 猛, 村松 俊成, 松井 成明, 梶原 博, 岩森 正男, 三上 幹男
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 卵巣明細胞腺癌において多様なTrkBアイソフォームの発現が亢進している(Unique expression profile of tropomyosin-related kinase B variants in ovarian clear cell adenocarcinoma) (2014)
  • Author(s): 後藤 優美子, 亀谷 美恵, 宮澤 昌樹, 三上 幹男
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 子宮頸癌におけるSulfatideの発現とその機能について (2014)
  • Author(s): 宮澤 昌樹, 宮澤 麻里子, 松井 成明, 藤井 幸子, 杉山 太朗, 西島 義博, 池田 仁惠, 信田 政子, 平澤 猛, 梶原 博, 村松 俊成, 岩森 正男, 三上 幹男
  • Organizer: 第56回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] 明細胞腺癌におけるHDAC familyによるHIF-1活性化機序の解明 (2014)
  • Author(s): 平澤 猛, 宮澤 昌樹, 宮澤 麻里子, 天津 慎子, 楢山 知紗, 柏木 寛史, 浅井 哲, 池田 仁惠, 信田 政子, 安田 政実, 三上 幹男
  • Organizer: 第56回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] 子宮平滑筋肉腫I期におけるGlucose Transporter-1およびHexokinaseIIの免疫組織学的発現と予後検討 (2014)
  • Author(s): 塚田 ひとみ, 平野 有希, 菊池 公孝, 中沢 和美, 宮澤 昌樹, 松井 成明, 佐藤 慎吉, 村松 俊成, 三上 幹男
  • Organizer: 第56回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 栃木県総合文化センター
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] 卵巣明細胞腺癌188例の臨床病理学的検討 (2014)
  • Author(s): 鈴木 裕之, 安田 政実, 吉田 正行, 宮澤 昌樹, 岡垣 竜吾, 石原 理, 藤原 恵一
  • Organizer: 第66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
  • Year and Date: 2014-04-18 – 2014-04-20