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Development of oncolytic virotherapy against the refractory gynecologic cancers

Research Project

Project/Area Number 21390450
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University

Principal Investigator

INOUE Masaki  金沢大学, 医学系, 教授 (10127186)

Co-Investigator(Kenkyū-buntansha) KYO Satoru  金沢大学, 医学系, 講師 (50272969)
TAKAKURA Masahiro  金沢大学, 附属病院, 助教 (20313661)
NAKAMURA Mitsuhiro  金沢大学, 附属病院, 助教 (50377397)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsテロメラーゼ / 腫瘍融解ウイルス / 難治性がん / 腫瘍可視化 / 末梢血中腫瘍細胞 / 非侵襲性癌診断 / 遺伝子診断 / 先進医療 / Circulating tumor cell / Cancer screening / Telomerase / hTERT / Tumor-lysing virus / Gynecologic Cancer / 婦人科癌 / 卵巣癌 / 遺伝子治療 / 末梢血循環腫瘍細胞 / circulating tumor cells
Research Abstract

Despite tremendous development in chemotherapy for refractory gynecologic cancers over the past few decades, the prognosis of the advanced cases is still unsatisfactory, and novel treatment modalities are urgent needed. We developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses(OBP-301), in which the human telomerase reverse transcriptase(hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In vitro treatment of Ovarian cancer cell with OBP-301 induced significant cell death in dose-dependent manner, although normal cells showed no significant cell death. Xenograft mouse model of ovarian cancer cells showed the improved survival of mice treated with Telomelysin. These findings support the therapeutic potential of virotherapy using oncolytic virus.
OBP401 in which GFP gene is driven by the CMV-promotor, selectively replicates only in telomerase-positive cells, and therefore may be a tool for cancer screening. We collected a single cell with GFP from blood samples of cervical cancer patients and detected the same HPV-genotype in both CTC and original cancer tissues. This finding suggests that CTC detecting by OBP401 is the useful non-invasive diagnostic way for cancer screening and early detection of recurrent malignant tumors.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (28 results)

All 2011 2010 2009

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (16 results) Book (1 results)

  • [Journal Article] Stem cell endometrium and endometrial cancer2011

    • Author(s)
      Kyo S
    • Journal Title

      Cancer Letters

      Volume: 308巻 Pages: 123-133

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Forkhead transcription factor FOXO1 is a direct targer of progestin to inhibit endometrial epithelial cell growth2011

    • Author(s)
      Kyo S
    • Journal Title

      Clin Cancer Res

      Volume: 17巻 Pages: 525-537

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affect survival in a xenograft model with peritoneal dissemination2010

    • Author(s)
      Takakura M, Nakamura M, Kyo S, Hashimoto M, Mori N, Mizumoto Y, Fujiwara T, Inoue M
    • Journal Title

      Cancer Gene Therapy

      Volume: 17 Pages: 11-19

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of CD133 expression as a tumor initiating marker in endometrial cancer2010

    • Author(s)
      Nakamura M, Kyo S, Zhang B, MizumotoY, Takakura M, Maida Y, Mori N, Hashimoto M, Ohno S, Inoue M
    • Journal Title

      Human pathol

      Volume: 41 Pages: 1516-1529

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affect survival in a xen ograft model with peritoneal dissemination.2010

    • Author(s)
      Takakura M, Nakamura M, Kyo S, Hashimoto M, Mori N, Mizumoto Y, Fujiwara T, Inoue M
    • Journal Title

      Cancer Gene Therapy

      Volume: 17 Pages: 11-19

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of CD 133 expression as a tumor initiating marker in endometrial cancer2010

    • Author(s)
      Nakamura M, Takakura M, Kyo S, Zhang N, Hashimoto M, Mori N, Mizumoto Y, Fujiwara T, Inoue M, et al
    • Journal Title

      Human Pathol

      Volume: 41 Pages: 1516-1529

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo biological puriging for lymph node metastasis of human colorect al cancer by telomerase specific oncolytic virotherapy2010

    • Author(s)
      Kojima T, Watanabe Y, Kyo S, Fujiwara T, et al.
    • Journal Title

      Ann Surg

      Volume: 251 Pages: 1079-1086

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affect survival in a xenograft model with peritoneal dissemination.2010

    • Author(s)
      Takakura M, Nakamura M, Kyo S, Hashimoto M, Mori N, Mizumoto Y, Fujiwara T, Inoue M
    • Journal Title

      Cancer Gene Therapy 17

      Pages: 11-19

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients2009

    • Author(s)
      Ikoma T, Kyo S, Maida Y, Ozaki S, Takakura M, Nakao S, Inoue M
    • Journal Title

      Amer J Obstet Gynecol

      Volume: 201

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients.2009

    • Author(s)
      Ikoma T, Kyo S, Maida Y, Maida Y, Ozaki S, Takakura MMM, Nakao S, Inoue M
    • Journal Title

      Amer J Obstet Gynecol 201

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-specific stabilization of HIF-1 by human papillomaviruses2009

    • Author(s)
      Nakamura M, Bodily J, Beglin M, Kyo S, Inoue M, Laimins L
    • Journal Title

      Virology 387

      Pages: 442-448

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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
      第70回日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation]2011

    • Author(s)
      中村充宏,京哲,高倉正博,毎田佳子,水本泰成,保野由紀子,井上正樹
    • Organizer
      第63回日本産科婦人科学会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2011-08-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of telomerase-specific replication-selective adenovirus on ovarian cancer stem cells2010

    • Author(s)
      Takakura M, Kyo S, Inoue M, et al
    • Organizer
      第69回日本癌学会
    • Place of Presentation
      大阪府大阪国際会議場
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Detection of circulating tumor cells using telomerase-specific replication-selective adenovirus in gynecologic cancer2010

    • Author(s)
      Takakura M, Kyo S, Inoue M, et al
    • Organizer
      第69回日本癌学会
    • Place of Presentation
      大阪府大阪国際会議場
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] テロメラーゼ依存性腫瘍融解ウイルスは卵巣癌幹細胞に対して有効である2010

    • Author(s)
      高倉正博,京哲,中村充宏,毎田佳子,橋本学,森紀子,水本泰成,生駒友美,井上正樹
    • Organizer
      第62回日本産科婦人科学会
    • Place of Presentation
      東京フォーラム(東京都)
    • Year and Date
      2010-04-24
    • Related Report
      2011 Final Research Report
  • [Presentation] テロメラーゼ依存性腫瘍融解ウイルスは卵巣癌幹細胞に対して有効である2010

    • Author(s)
      高倉正博、京哲、中村充宏、毎田佳子、橋本学, 森紀子、水本泰成、生駒友美、井上正樹
    • Organizer
      第62回日本産科婦人科学会学術集会
    • Place of Presentation
      東京都東京国際フォーラム
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 子宮内膜癌幹細胞をターゲットにした分子標的治療の基礎的研究2010

    • Author(s)
      中村充宏、高倉正博、京哲、毎田佳子、橋本学, 森紀子、水本泰成、保野由紀子、井上正樹
    • Organizer
      第62回日本産科婦人科学会学術集会
    • Place of Presentation
      東京都東京国際フォーラム
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of subpopulation with more defined characteristics of cancer stem cells in endometrial cancer2010

    • Author(s)
      Nakamura M, Kyo S, Inoue M, et al
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      USA Walter E, Washington Convention Center
    • Related Report
      2010 Annual Research Report
  • [Presentation] Distinct roles of progesterone receptrors A and B in human endometrial epithelial cell2010

    • Author(s)
      Kyo S, Inoue M, Takakura M, Nakamura M, et al
    • Organizer
      第69回日本癌学会
    • Place of Presentation
      大阪府大阪国際会議場
    • Related Report
      2010 Annual Research Report
  • [Presentation] Virotherapy for platinum-resitant ovarian cancer to overcome CDDP resistance using tumor-specific replication-selective adenovirus.2009

    • Author(s)
      高倉正博,京哲,中村充宏,橋本学,森紀子,水本泰成,藤原俊義,浦田泰生,井上正樹
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Year and Date
      2009-10-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Virotherapy for platinum-resitant ovarian cancer to overcome CDDP resistance using tumor-specific replication-selective adenovirus.2009

    • Author(s)
      高倉正博、京哲、中村充宏、橋本学、森紀子、水本泰成、藤原俊義、浦田泰生、井上正樹
    • Organizer
      第68回日本癌学会学術集会
    • Place of Presentation
      (神奈川県横浜市)パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Involvement of hTERT in producing endogenous siRNA through ita RdRP activity.2009

    • Author(s)
      毎田佳子、安川麻美、岡本奈緒子、Vivi Kasim、Timo Lassmann、林崎良英、William C.Hahn、増富健吉
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      (神奈川県横浜市)パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 子宮内膜癌におけるがん幹細胞マーカーとしてのCD133発現とその意義2009

    • Author(s)
      中村充宏、京哲、高倉正博、橋本学、水本泰成、森紀子、生駒友美、井上正樹
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      (神奈川県横浜市)パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 子宮内膜癌における癌幹細胞マーカー候補分子の解析2009

    • Author(s)
      中村充宏、京哲、高倉正博、橋本学、水本泰成、森紀子、生駒友美、井上正樹
    • Organizer
      第8回日本婦人科がん分子標的研究会学術集会
    • Place of Presentation
      (福岡県福岡市)博多エクセルホテル東急
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 腫瘍特異的増殖性ウイルス療法の抗癌剤耐性卵巣癌への効果2009

    • Author(s)
      高倉正博、京哲、橋本学、森紀子、水本泰成、生駒友美、張波、中村充宏、井上正樹
    • Organizer
      第61回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      (京都府京都市)京都国際会館
    • Year and Date
      2009-04-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] The significance of CD133 expression as a potential marker of tumor in itiation and proliferation in endometrial cancer cells2009

    • Author(s)
      Mitsuhiro N, Satoru K, Masahiro T, Manabu H, Yasunari M, Noriko M, Tomomi I, Toshiyuki S, Masaki I
    • Organizer
      AACR 2009
    • Place of Presentation
      Denver, CO, (USA)
    • Related Report
      2009 Annual Research Report
  • [Book] 症例から学ぶ婦人科腫瘍学入門2011

    • Author(s)
      井上正樹
    • Publisher
      永井書店
    • Related Report
      2011 Annual Research Report 2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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