Searching for effective drugs against ovarian clear cell carcinoma based on microarray analysis

• Project/Area Number: 19890114
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: MATSUMURA Noriomi Kyoto University, 医学研究科, 助教 (20452336)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,085,000 (Direct Cost: ¥2,680,000、Indirect Cost: ¥405,000); Fiscal Year 2008: ¥1,755,000 (Direct Cost: ¥1,350,000、Indirect Cost: ¥405,000); Fiscal Year 2007: ¥1,330,000 (Direct Cost: ¥1,330,000)
• Keywords: 卵巣明細胞腺癌 / マイクロアレイ / バイオインフォマティックス / 分子標的薬 / 卵巣癌 / キナーゼ阻害剤 / チョコレートのう胞 / 薬剤抵抗性 / メチル化 / 組織型 / 明細胞腺癌 / Src / Oncogene

Research Abstract

卵巣癌細胞株のマイクロアレイ解析によって、明細胞腺癌を特徴づける遺伝子群を同定した。その結果、1) 卵巣明細胞腺癌を特徴づける遺伝子群には、チョコレートのう胞内の酸化ストレス環境によって上昇する遺伝子が多く含まれること、2) 明細胞腺癌は腎細胞癌と類似し、キナーゼ活性との関連が深いRas活性が高く、増殖能との関連が深いE2F活性が低いことを明らかにした。したがって、明細胞腺癌に対して、増殖をターゲットとする抗がん剤ではなく、キナーゼ活性を阻害する分子標的薬が有用と考えられた。

Research Products

• [Journal Article] Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer : high expression of ULBP2 is an indicator of poor prognosis (2009)
  • Author(s): Li K, Mandai M, Hamanishi J, Matsumura N, Suzuki A, Yagi H, Yamaguchi K, Baba T, Fujii S, Konishi I.
  • Journal Title: Cancer Immunol Immunother 58 Pages: 641-52
  • Peer Reviewed
• [Journal Article] Classification using hierarchical clustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression (2009)
  • Author(s): Liu M, Matsumura N, Mandai M, Li K, Yagi H, Baba T, Suzuki A, Hamanishi J, Fukuhara K.
  • Journal Title: Konishi I. Mod Pathol 22 Pages: 373-84
  • Peer Reviewed
• [Journal Article] Yin yang 1 modulates taxane response in epithelial ovarian cancer (2009)
  • Author(s): Matsumura N, Huang Z, Baba T, Lee PS, Barnett JC, Mori S, Chang JT, Kuo WL, Gusberg AH, Whitaker RS, Gray JW, Fujii S, Berchuck A
  • Journal Title: Murphy SK. Mol Cancer Res 7 Pages: 210-20
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells (2009)
  • Author(s): Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A
  • Journal Title: Murphy SK. Oncogene 28 Pages: 209-18
  • Peer Reviewed
• [Journal Article] Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells : utilization for ovarian cancer treatment (2009)
  • Author(s): Matsumura N, Mandai M, Hamanishi J, Yamaguchi K, Fukuhara K, Yagi H, Higuchi T, Takakura K
  • Journal Title: Fujii S. Oncol Rep 19 Pages: 505-15
  • Peer Reviewed
• [Journal Article] Yin yang 1 modulates taxaane response in epithelial ovarian cancer. (2009)
  • Author(s): Matsumura N, Huang Z, Baba T, Lee PS, Barnett JC, Mori S, Chang JT, Kuo WL, Gusberg AH, Whitaker RS, Gray JW, Fujii S, Berchuck A, Murphy SK.
  • Journal Title: Molecular Cancer Research 7 Pages: 210-220
  • Peer Reviewed
• [Journal Article] Classification using hierarchicl cclustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression. (2009)
  • Author(s): Fujii S, Takakura K, Matsumura N, Higcohi T, Yura S, Mandai M, Baba T, Yoshioka S.
  • Journal Title: Modern Pathology 22 Pages: 373-384
  • Peer Reviewed
• [Journal Article] Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer : high expression of ULBP2 is an indicator of poor prognosis. (2009)
  • Author(s): Li K, Mandai H, Hamanishi J, Matsumura N, Suzuki A, Yagi H, Yamaguchi K, Baba T, Fujii S, Konishi I.
  • Journal Title: Cancer Immunology, Immunotherapy 58 Pages: 641-652
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of CD133 and tumorigenicity of CD133+ovvarian cancer cells. (2009)
  • Author(s): Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fuji S, Marks JR, Berchuck A, Murphy SK.
  • Journal Title: Oncogene. 15 Pages: 209-118
  • Peer Reviewed
• [Journal Article] Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and antural killer cells: utilization for ovarian cancer treatment. (2008)
  • Author(s): Matsumura N, Mandai M, Hamanishi J, Yamaguchi K, Fukuhara K, Yagi H, Higuchi T, Takakura K, Fujii S.
  • Journal Title: Oncology reports 19 Pages: 505-515
  • Peer Reviewed
• [Journal Article] Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy (2007)
  • Author(s): Fujii S, Takakura K, Matsumura N, Higuchi T, Yura S, Mandai M, Baba T
  • Journal Title: Yoshioka S. Gynecol Oncol 107 Pages: 4-13
  • Peer Reviewed
• [Journal Article] Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity (2007)
  • Author(s): Baba T, Mori S, Matsumura N, Kariya M, Murphy SK, Kondoh E, Kusakari T, Kuroda H, Mandai M, Higuchi T, Takakura K, Fukuda MN
  • Journal Title: Fujii S. Biochem Biophys Res Commun 360 Pages: 363-9
  • Peer Reviewed
• [Journal Article] Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition (2007)
  • Author(s): Baba T, Kariya M, Higuchi T, Mandai M, Matsumura N, Kondoh E, Miyanishi M, Fukuhara K, Takakura K
  • Journal Title: Fujii S. Gynecol Oncol 105 Pages: 703-11
  • Peer Reviewed
• [Journal Article] Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. (2007)
  • Author(s): Fujii S, Takakura K, Matsumura N, Higuchi T, Yura S, Mandai M, Baba T, Yoshioka S.
  • Journal Title: Gynecologic oncology 107 Pages: 4-13
  • Peer Reviewed
• [Journal Article] Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity. (2007)
  • Author(s): Baba T, Mori S, Matsumura N, Kariya M, Murphy SK, Kondoh E, Kusakari T, Kuroda H, Mandai M, Higuchi T, Takakura K, Fukuda MN, Fujii S.
  • Journal Title: Biochemical and biophysical research communications 360 Pages: 363-369
  • Peer Reviewed
• [Presentation] 卵巣癌腹膜播種の新生血管を標的として、ケモカインCCL19遺伝子導入胚性血管内皮細胞を用いて局所免疫賦活を目指した新規免疫療法開発の基礎的検討 (2009)
  • Author(s): 濱西潤三、万代昌紀、松村謙臣、馬場長、八木治彦、山口建、樋口壽宏、高倉賢二、小西郁生、藤井信吾
  • Organizer: 第61回日本産科婦人科学会学術集会高得点演題口演
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-05
• [Presentation] 免疫細胞の浸潤パターンに基づく階層的クラスター解析により、COX高発現/予後不良の卵巣癌を同定できる (2009)
  • Author(s): 吉岡弓子、松村謙臣、八木治彦、馬場長、鈴木彩子、濱西潤三、福原健、万代昌紀、小西郁生
  • Organizer: 第61回日本産科婦人科学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-05
• [Presentation] 卵巣癌における化学療法感受性バイオマーカーの開発と組織型による分子標的の同定-治療個別化に向けたBioinformaticsの応用 (2009)
  • Author(s): 松村謙臣
  • Organizer: 第61回日本産科婦人科学会学術集会シンポジウム口演
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-04
• [Presentation] 卵巣癌大網転移におけるメチル化遺伝子群の発現とTGF-β活性の亢進 (2009)
  • Author(s): 山村省吾、松村謙臣、山口建、濱西潤三、馬場長、万代昌紀、小西郁生
  • Organizer: 第61回日本産科婦人科学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-04
• [Presentation] 卵巣癌における化学療法感受性バイオマーカーの開発と組織型による分子標的の同定-治療個別化に向けたBioinformaticsの応用 (2009)
  • Author(s): 松村謙臣
  • Organizer: 第61回日本産婦人科学会シンポジウム
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-04
• [Presentation] 卵巣明細胞腺癌において、マイクロアレイ解析により特徴付けられる生物学的特性は特有の発癌環境を反映している (2009)
  • Author(s): 山口建、万代昌紀、松村謙臣、山村省吾、濱西潤三、馬場長、藤井信吾、小西郁生
  • Organizer: 第61回日本産科婦人科学会学術集会婦人科腫瘍学部門優秀演題賞口演
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-04-03
• [Presentation] Activated local immunity by chemokine CCL19-transduced embryonic encothelial progenitor cells suppresses lung metastasis of murine ovarian cancer (2009)
  • Author(s): J.Hamanishi, M.Mandai, N.Matsumura, T.Higuchi, K.Takakura, K.Yamaguchi, S.Fujii, I.Konishi
  • Organizer: 40th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: San Antonio, TX
• [Presentation] Gene signature specific for ovarian clear cell carcinoma is induced by the contents of endometriotic cysts (2009)
  • Author(s): K.Yamaguchi, M.Mandai, N.Matsumura, T.Baba, T.Oura, S.Matsui, S.K.Murphy, A.Berchuck, S.Fujii, I.Konishi
  • Organizer: 40th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: San Antonio, TX
• [Presentation] 7-hydroxystaurosporine(UCN-01)is effective in targeting ovarian cancer spheroids (2009)
  • Author(s): E.Kondoh, T.Baba, N.Matsumura, I.Konishi, S.Fujii, A.Berchuck, S.K.Murphy
  • Organizer: 40th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: San Antonio, TX
• [Presentation] BIGH3, target of methylation in ovarian cancer, is up-regulated in omental metastasis (2008)
  • Author(s): 山村省吾、松村謙臣、万代昌紀、 馬場長、濱西潤三、山口建、小西郁生、Susan Murphy, Zhiqing Huang, Andrew Berchuck
  • Organizer: 第67回日本癌学会学術総会ワークショップ口演
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] Activated local immunity by CCL19-transfected embryonic endothelial progenitor cells suppresses lung metastasis (2008)
  • Author(s): 濱西潤三、万代昌紀、松村謙臣、山口建、藤井信吾、小西郁生
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] The Characteristic Biology of Ovarian Clear Cell Ca. defined by Microarray Reflects the Specific Carcinogenetic Process (2008)
  • Author(s): 山口建、万代昌紀、山村省吾、濱西潤三、馬場長、松村謙臣、豊國伸哉、藤井信吾、小西郁生
  • Organizer: 第67回日本癌学会学術総会ワークショップ口演
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] 卵巣癌におけるNKG2Dリガンド発現の臨床的意義 (2008)
  • Author(s): 濱西潤三、李奎、万代昌紀、樋口壽宏、松村謙臣、八木治彦、福原健、劉敏、山口建、高倉賢二、藤井信吾
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-04-15
• [Presentation] 卵巣癌におけるメチル化は予後不良と相関し、TGFb 経路の抑制をもたらす (2008)
  • Author(s): 松村謙臣、Susan Murphy、万代昌紀、福原健、鈴木彩子、樋口壽宏、高倉賢二、藤井信吾
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-04-13
• [Presentation] 卵巣癌の組織型によって特徴づけられる癌遺伝子シグナル伝達経路のマイクロアレイを用いた解析 (2008)
  • Author(s): 山口建、万代昌紀、松村謙臣、濱西潤三、鈴木彩子、八木治彦、福原健、高尾由美、巽啓司、樋口壽宏、高倉賢二、藤井信吾
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-04-13
• [Presentation] Targeting dormant ovarian cancer cells (2008)
  • Author(s): E.Kondoh, T.Baba, N.Matsumura, S.Fujii, A.Berchuck, S.K.Murphy
  • Organizer: 39th Annual Meeting of the Society of Gynecologic Oncologists. Focused Plenary Session
  • Place of Presentation: Tampa, FL
  • Year and Date: 2008-03-10
• [Presentation] Transcriptome analysis of DNA methylation status in ovarian cancer-Correlation of aggressiveness and TGFb pathway (2008)
  • Author(s): N.Matsumura, Z.Huang, T.Perry, D.Kroyer, T.Baba, S.Mori, M.Mandai, I.Konishi, S.Fujii, A.Berchuck, S.K. Murphy
  • Organizer: 39th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: Tampa, FL
• [Presentation] Gene signature-based oncogene pathway analysis in ovarian cancer ; difference by hisotologic subtypes (2008)
  • Author(s): K.Yamaguchi, M.Mandai, N.Matsumura, J.Hamanishi, T.Higuchi, K.Takakura, I.Konishi
  • Organizer: 39th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: Tampa, FL
• [Presentation] Microarray analysis identifies NSC668814 as a potentially active chemotherapeutic agent for platinum-resistant ovarian cancer cells with TP53 mutations (2008)
  • Author(s): T.Baba, S.Mori, N.Matsumura, M.Bernardini, S.Fujii, A.Berchuck, S.K.Murphy
  • Organizer: 39th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: Tampa, FL
• [Presentation] Stem cell marker CD133 (PROMININ-1) is epigenetically regulated in ovarian cancer (2008)
  • Author(s): T.Baba, P.A.Convery, N.Matsumura, R.S.Whitaker, T.Perry, Z.Huang, S.Mori, E.Kondoh, R.C.Bentley, S.Fujii, J.R.Marks, A.Berchuck, S.K.Murphy
  • Organizer: 39th Annual Meeting of the Society of Gynecologic Oncologists
  • Place of Presentation: Tampa, FL
• [Presentation] Transcriptome analysis of DNA methylation status in ovarian cancer-Correlation of aggressiveness and TGFb pathway (2008)
  • Author(s): Noriomi Matsumura, Zhiqing Huang, Tiffany Perry, Darby Kroyer, Tsukasa Baba, Seiichi Mori, Masaki Mandai, Ikuo Konishi, Shing Fujii
  • Organizer: SGO 39th Annual Meeting on Women's Cancer
  • Place of Presentation: Tampa, FL, USA