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Efficacy and toxicity of systemic transduction of p16 antitumor peptide in inhibition of metastases of urological tumors

Research Project

Project/Area Number 24592375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHIMAZUI Toru  筑波大学, 医学医療系, 教授 (80235613)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Jun  筑波大学, 医学医療系, 准教授 (10550246)
NISHIYAMA Hiroyuki  筑波大学, 医学医療系, 教授 (20324642)
YOSHIKAWA Kazuhiro  愛知医科大学, 医学部, 教授 (60109759)
UCHIDA Kazuhiko  筑波大学, 医学医療系, 准教授 (90211078)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膀胱癌 / p16 / レチノブラストーマ / ペプチド / 細胞周期 / 分子標的 / 肺転移 / 毒性 / Rb / マウスモデル / 浸潤性 / リン酸化Rb / 薬剤デリバリー / 腎癌
Outline of Final Research Achievements

P16 is a key molecule of bladder tumor (BT) development. Here, we evaluate the efficacy and toxicity of p16 peptide administration on mouse lung metastasis model for BT. Mouse lung metastases were developed by tail vein injection of MBT-2 cell line and single or triple times of p16 peptide were also injected (10 to 12 mice in each group). The toxicity was also evaluated after p16 peptide administration by blood test and histological examination.
The lung metastases were observed in 100% (12/12), 41.7% (5/12), and 30% (3/10) in above three groups, respectively. Size and number of lung metastatic tumor were significantly different between control and treatment groups. In high dose peptide group, leukocytosis was observed but not statistically significant. No remarkable change was also observed histologically in bone marrow of treatment groups. In conclusion, Systemic p16 delivery could prevent lung tumor development on mouse BT metastatic model without severe adverse events.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2013 2012

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (3 results)

  • [Journal Article] Concurrent urothelial carcinoma in the renal pelvis of an allograft kidney and native recipient bladder: evidence of donor origin2014

    • Author(s)
      Takaoka E, Miyazaki J, Nishiyama H, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 44 Issue: 4 Pages: 366-369

    • DOI

      10.1093/jjco/hyu015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nanoparticulation of BCG-CWS for application to bladder cancer therapy2014

    • Author(s)
      Nakamura T, Miyazaki J, Nishiyama H, et al.
    • Journal Title

      J Contorl Release

      Volume: 176 Pages: 44-53

    • DOI

      10.1016/j.jconrel.2013.12.027

    • NAID

      120005476196

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular targeting of neuroblastoma with a novel p16INK4a transporter system2014

    • Author(s)
      Kawaguchi T, Yoshikawa K, et al.
    • Journal Title

      Int J Oncol

      Volume: 44 Issue: 6 Pages: 1879-1885

    • DOI

      10.3892/ijo.2014.2372

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Assessment and Management of Renal Impairment in Chemotherapy for Urogenital Cancer2013

    • Author(s)
      Kawai K, Ichioka D, Inai H, Miyazaki J, Nishiyama H
    • Journal Title

      Jpn J Clin Oncol

      Volume: 12 Issue: 11 Pages: 1055-1063

    • DOI

      10.1093/jjco/hyt132

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts2013

    • Author(s)
      Shimazui T, Yoshikawa K, Miyazaki J, Kojima T, Inai H, Ando S, Uemura H, Uchida K, Nishiyama H
    • Journal Title

      Int. J. Oncol

      Volume: Vo l .42 Issue: 2 Pages: 543-54

    • DOI

      10.3892/ijo.2012.1752

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors for intravesical recurrence in patients with high-grade T1 bladder cancer in the second TUR era2013

    • Author(s)
      Takaoka E, Miyazaki J, Kawai K, Nishiyama H.
    • Journal Title

      Int. J Urol

      Volume: 20(7) Issue: 4 Pages: 22-716

    • DOI

      10.1093/jjco/hyt016

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of Intravesical Recurrence After Bladder-preserving Therapy for Muscle-invasive Bladder Cancer2012

    • Author(s)
      Onozawa M, Miyazaki J, Kawai K, Nishiyama H
    • Journal Title

      JJCO

      Volume: 42(9) Issue: 9 Pages: 30-825

    • DOI

      10.1093/jjco/hys105

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Systemic transduction of p16INK4a antitumor peptide inhibits lung metastasis of MBT-2 bladder tumor cell line in mice2015

    • Author(s)
      Shimazui T, Yoshikawa K, Miyazaki J, Uchida K, Yamauchi A, Ohtani M, Nishiyama H
    • Organizer
      American Urological Association 2015 Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2015-05-15 – 2015-05-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] MBT-2マウス膀胱癌細胞株の肺転移モデルに対するp16INK4a機能性ペプチドの全身投与による転移抑制と毒性の検討2015

    • Author(s)
      島居 徹、吉川和宏、宮崎 淳、内田和彦、山内 敦、大谷幹伸、西山博之
    • Organizer
      第103回日本泌尿器科学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2015-04-18 – 2015-04-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Systemic transduction of p16INK4a antitumor peptide inhibits lung metastasis of MBT-2 bladder tumor cell line in mice2014

    • Author(s)
      Shimazui T, Yoshikawa K, Miyazaki J, Uchida K, Yamauchi A, Ohtani M, Nishiyama H
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2023-03-16  

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