Development of novel detection system of circulating tumor cells with tumor-specific replication adenovirus and its clinical application for predicting the recurrence of ovarian cancer

• Project/Area Number: 23659775
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: KYO SATORU 金沢大学, 医学系, 准教授 (50272969)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: CTC / gynecological cancer / ovarian cancer / telomerase / adenovirus / GFP / 末梢血中循環癌細胞 / 卵巣癌 / 血中循環がん細胞 / 婦人科癌 / 増殖型アデノウイルス / 末梢血中循環がん細胞 / テロメレース

Research Abstract

We established the novel detection system for circulating tumor cells (CTC) with telomerase-specific replication adenovirus in which GFP cDNA was integrated for GFP fluorescence. Infection of these viruses with 5ml of blood samples from the patients with gynecological cancers successfully identified CTC, while no CTC was detectd in the samples from healthy volunteers. While the number or the presence of CTCs were not significantly correlated with clinicopathological characteristics, they were tightly related to the treatment outcome as well as the overall survival. Thus, the present study clearly found the clinical utility of this novel detection system for CTC.

Research Products

• [Journal Article] The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth (2013)
  • Author(s): Nakamura M, Takakura M, Fujii R, Maida Y, Bono Y, Mizumoto Y, Zhang X, Kiyono T and Kyo S
  • Journal Title: Cancer Lett Volume: 336 Pages: 68-75
  • Peer Reviewed
• [Journal Article] Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis (2013)
  • Author(s): Itoh F, Komohara Y, Takaishi K, Honda R, Tashiro H, Kyo S, Katabuchi H, Takeya M
  • Journal Title: Fertil Steril Volume: 99 Pages: 1705-1713
  • Peer Reviewed
• [Journal Article] Establishment and Characterization of Immortalized Human Amniotic Epithelial Cells (2013)
  • Author(s): Zhou K, Koike C, Yoshida T, Okabe M, Fathy M, Kyo S, Kiyono T, Saito S, Nikaido T
  • Journal Title: Cell Reprogram Volume: 15 Pages: 55-67
  • Peer Reviewed
• [Journal Article] Endometrial cancer stem cells : Are they a possible therapeutic target? (2013)
  • Author(s): Kyo S
  • Journal Title: Curr Obstet. Gynecol. Rep Volume: 2 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Plasma Membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer (2013)
  • Author(s): Yokoyama T, Enomoto T, Serada S, Morimoto A, Matsuzaki S, Ueda Y, Yoshino K, Fujita M, Kyo S, Iwahori K, Fujimoto M, Kimura T and Naka T
  • Journal Title: Int. J. Cancer Volume: 132 Pages: 472-484
  • Peer Reviewed
• [Journal Article] Establishment of Immortalized Human Amniotic Mesenchymal Stem Cells (2013)
  • Author(s): Teng Z, Yoshida T, Okabe M, Toda A, Higuchi O, Nogami M, Yoneda N, Zhou K, Kyo S, Kiyono T, Nikaido T
  • Journal Title: Cell Transplant Volume: 22 Pages: 267-278
  • Peer Reviewed
• [Journal Article] Circulating tumor cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynecologic cancers (2012)
  • Author(s): Takakura M, Kyo S, Nakamura M, Maida Y, Mizumoto Y, Bono Y, Zhang X, Hashimoto Y, Urata Y, Fujiwara T and Inoue M
  • Journal Title: Br. J. Cancer Volume: 107 Pages: 448-454
  • Peer Reviewed
• [Journal Article] Protease-activated receptor-stimulated interleukin-6 expression in endometriosis-like lesions in an experimental mouse model of endometriosis (2012)
  • Author(s): Shinohara A, Kutsutake M, Takahashi M, Kyo S, Tachikawa E and Tamura K
  • Journal Title: J. Pharmacol. Sci Volume: 19 Pages: 40-51
  • NAID: 10030760253
  • Peer Reviewed
• [Journal Article] Massive hemothorax due to diaphragmatic endometriosis after a laparoscopic cystectomy of an ovarian endometrioma in a patient without a history of thoracic endometriosis (2012)
  • Author(s): Kyo S, Takakura M, Nishida S, Ozaki S, Oda M and Inoue M
  • Journal Title: Arh. Gynecol. Obstet Volume: 286 Pages: 411-414
  • Peer Reviewed
• [Journal Article] Creation of immortalized epithelial cells from ovarian endometrioma (2012)
  • Author(s): Bono Y, Kyo S, Takakura M, Maida Y, Mizumoto Y, Nakamura M, Nomura K, Kiyono T and Inoue M
  • Journal Title: Br. J. Cancer Volume: 103 Pages: 1205-1213
  • Peer Reviewed
• [Journal Article] Circulating tumor cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynecologic cancers. (2012)
  • Author(s): Masahiro Takakura
  • Journal Title: Br.J.Cancer. Volume: 107 Pages: 448-454
  • Peer Reviewed
• [Journal Article] Dienogest inhibits Toll-like receptor 4 expression induced by co-stimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells Fertil (2011)
  • Author(s): Mita S, Shimizu Y, Notsu T, Imada K, Kyo S
  • Journal Title: Steril Volume: 96 Pages: 1485-1489
  • Peer Reviewed
• [Journal Article] Frequency of myeloid dendritic cells can predict the efficacy of wilms' tumor 1 Peptide vaccination (2011)
  • Author(s): Ohno S, Takano F, Ohta Y, Kyo S, Myojo S, Dohi S, Sugiyama H, Ohta T, Inoue M
  • Journal Title: Anticancer Res Volume: 31 Pages: 2447-2452
  • Peer Reviewed
• [Journal Article] WT1 Peptide Vaccine Stabilized Intractable Ovarian Cancer Patient for One Year : A Case Report (2011)
  • Author(s): Dohi S, Ohno S, Ohno Y, Takakura M, Kyo S, Soma G, Sugiyama H, Inoue M
  • Journal Title: Anticancer Res Volume: 31 Pages: 2441-2445
  • Peer Reviewed
• [Journal Article] Stem cells in endometrium and endometrial cancer : Accumulating evidence and unresolved questions (2011)
  • Author(s): Kyo S, Maida Y and Inoue M
  • Journal Title: Review article. Cancer Letters Volume: 308 Pages: 123-133
  • Peer Reviewed
• [Journal Article] Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission (2011)
  • Author(s): Ohno S, Sumiyoshi Y, Hashine K, Shirato A, Kyo S and Inoue M
  • Journal Title: Evid Based Complement Alternat Med Volume: vol. 2011, Article ID 192381 Issue: 1 Pages: 9-9
  • DOI: 10.1155/2011/192381
  • Peer Reviewed
• [Journal Article] Activation of NF-κB is a novel target of KRAS-induced endometrial carcinogenesis (2011)
  • Author(s): Mizumoto Y, Kyo S, Kiyono T, Takakura M, Nakamura M, Maida Y, Mori N, Bono Y, Sakurai H and Inoue M
  • Journal Title: Clin. Cancer Res Volume: 17 Pages: 1341-1350
  • Peer Reviewed
• [Journal Article] Dianogest, a synthetic progestine, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a sheroid culture system (2011)
  • Author(s): Shimizu Y, Mita S, Takeuchi T, Notsu T, Mizuguchi K, Kyo S
  • Journal Title: Steroids Volume: 76 Pages: 60-67
  • Peer Reviewed
• [Journal Article] Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth (2011)
  • Author(s): Kyo S, Sakaguchi J, Kiyono T, Shimizu Y, Maida Y, Mizumoto Y, Mori N, Nakamura M, Takakura M, Miyake M, Sakamoto M and Inoue M
  • Journal Title: Clin. Cancer Res Volume: 17 Pages: 525-537
  • Peer Reviewed
• [Journal Article] Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth. (2011)
  • Author(s): Kyo S, Sakaguchi J et al.
  • Journal Title: Clin.Cancer Res. Volume: 15 Pages: 525-537
  • Peer Reviewed
• [Journal Article] Expression of HER-2 affects patient survival and paclitaxel sensitivity in endometrial cancer (2010)
  • Author(s): Mori N, Kyo S, Nakamura M, Hashimoto M, Maida Y, Mizumoto Y, Takakura M, Ohno S, Kiyono T, Inoue M
  • Journal Title: Br. J. Cancer (Expression of HER2) Volume: 103 Pages: 889-898
  • Peer Reviewed
• [Presentation] サイトメトリーの進歩と細胞診断学への応用, テロメラーゼ特異的増殖型ウイルスを用いた末梢血中腫瘍細胞の検出・単離と遺伝子解析 (2012)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、水本泰成、保野由紀子、井上正樹、藤原俊義、浦田泰生
  • Organizer: 第51回日本臨床細胞学会・ワークショップ
  • Place of Presentation: 新潟市
  • Year and Date: 2012-11-10
• [Presentation] 子宮頸癌における腫瘍特異的増殖型アデノウイルス末梢血中腫瘍細胞の単離と遺伝子解析 (2012)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、水本泰成、保野由紀子、張英智、藤原俊義、井上正樹
  • Organizer: 第71回日本がん学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 2012-09-19
• [Presentation] 子宮頸癌症例における末梢血中腫瘍細胞の単離と遺伝子解析 (2012)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、水本泰成、保野由紀子、張秀智、藤原俊義、浦田泰生、井上正樹
  • Organizer: 第11回日本婦人科がん分子標的研究会
  • Place of Presentation: 日光市
  • Year and Date: 2012-06-22
• [Presentation] 子宮頸癌における末梢血中腫瘍細胞の単離と単一細胞からの遺伝子解析 (2012)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、水本泰成、保野由紀子、井上正樹
  • Organizer: 第64回日本産科婦人科学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-04-13
• [Presentation] 婦人科癌におけるGFP 発現テロメラーゼ特異的増殖型アデノウイルスを用いた末梢血中腫瘍細胞の検出 (2011)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、森紀子、水本泰成、保野由紀子、張秀智、井上正樹
  • Organizer: 金沢大学 産婦人科 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-03
• [Presentation] GFP 発現テロメラーゼ特異的増殖型アデノウイルスを用いた末梢血中腫瘍細胞の検出 (2011)
  • Author(s): 高倉正博、京 哲、中村充宏、毎田佳子、水本泰成、保野由紀子、井上正樹
  • Organizer: 金沢大学 産婦人科 第28回日本臨床細胞学会北陸支部連合学術集会
  • Place of Presentation: 金沢市
  • Year and Date: 2011-09-04
• [Presentation] A novel CTC detection technique and its clinical application
  • Author(s): 高倉正博、京 哲
  • Organizer: 第19回日本遺伝子治療学会年次学術集会
  • Place of Presentation: 岡山県岡山市 岡山コンベンションセンター
  • Invited