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Investigation of malignant cells in BCG failure cases using morphometrical and biological methods

Research Project

Project/Area Number 17K08744
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKyushu University

Principal Investigator

WATANABE Sumiko  九州大学, 医学研究院, 講師 (90404087)

Co-Investigator(Kenkyū-buntansha) 大喜 雅文  九州大学, 医学研究院, 教授 (10160441)
勝田 仁  九州大学, 医学研究院, 教授 (50333240)
加来 恒壽  九州大学, 医学研究院, 教授 (60185717)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsBCG failure症例 / 自然尿細胞診 / 膀胱癌 / 培養細胞 / 核形態指標 / 細胞周期関連タンパク / 診断基準作成 / BCG曝露 / pRB / p21 / 核内発現 / BCG曝露効果 / 核面積 / RD値 / BCG膀注療法 / p27 / Solidity値 / 核アスペクト比 / p21タンパク / BCG治療 / 予後不良 / siRNA
Outline of Final Research Achievements

Intravesical bacillus Calmette-Guerin (BCG) is the standard adjuvant therapy for high-grade non-muscle-invasive bladder tumor (BT). The number of patients for whom BCG treatment does not work (BCG-failure cases) is of concern. Here, we used two methods to examine the characteristics of malignant cells that are observed in the urine cytology of BCG-failure cases: morphologic measurement and intranuclear protein expression using 15 urine cytology with BT and culture cells: T24 and RT4. Using the staining of pRB and p21, the reactive cells for BCG of T24 was fewer than RT4. The malignant cells of 4 BCG-failure cases had the following nuclear features: small nuclear area, large morphological irregularity, and nuclear chromatin that has translocated to the center. It is suggested that the morphological change is correlated with biological activities for BCG exposure, and thus the evaluation of morphology of malignant cells might help determine the effectiveness of BCG treatment.

Academic Significance and Societal Importance of the Research Achievements

近年問題となっているBCG膀注療法が効かないBCG failure群に対しては、全く検討がなされておらず診断基準は確立されていない。BCG failure群に出現する異型細胞はBCGに対して反応しない細胞(BCG非感受性細胞)であると考えて形態学的および分子生物学的検討を行った。BCG failure群に出現するBCG非感受性異型細胞を正確にとらえる研究が進むことは、最適治療法の選択という視点から患者のQOLにとり重要なことであると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results) Presentation (15 results) (of which Invited: 1 results)

  • [Journal Article] Automated approach for estimation of grade groups for prostate cancer based on histological image feature analysis2019

    • Author(s)
      Hossain Alamgir、Arimura Hidetaka、Kinoshita Fumio、Ninomiya Kenta、Watanabe Sumiko、Imada Kenjiro、Koyanagi Ryoma、Oda Yoshinao
    • Journal Title

      The Prostate

      Volume: 80 Issue: 3 Pages: 291-302

    • DOI

      10.1002/pros.23943

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear Co-expression of p21 and p27 Induced Effective Cell-cycle Arrest in T24 Cells Treated with BCG2019

    • Author(s)
      Sumiko Watanabe, Shota Yamaguchi, Naoto Fujii, Natsuki Eguchi, Hitoshi Katsuta, Setsuo Sugishima, Tsuyoshi Iwasaka, Tsunehisa Kaku
    • Journal Title

      Cytotechnology

      Volume: 71 Issue: 1 Pages: 219-229

    • DOI

      10.1007/s10616-018-0278-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serum starvation induces abnormal spindle location, RhoA delocalization, and extension of intercellular bridge with the middy.2018

    • Author(s)
      Nishimura K, Watanabe S, Kaku T, Sugishima S
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 2 Issue: 5 Pages: 1-6

    • DOI

      10.1080/09168451.2018.1443791

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytological findings associated with human papillomavirus infection in uterine cervical squamous lesions2018

    • Author(s)
      下代清香, 渡邊壽美子, 加来恒壽, 桑岡勲, 杉島節夫, 大屋正文
    • Journal Title

      The Journal of the Japanese Society of Clinical Cytology

      Volume: 57 Issue: 5 Pages: 251-258

    • DOI

      10.5795/jjscc.57.251

    • NAID

      130007506203

    • ISSN
      0387-1193, 1882-7233
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 腺癌細胞の核内所見と細胞周期の関連性:培養細胞を使用して2019

    • Author(s)
      渡辺寿美子、中司成、上原俊貴、遠峰由希恵、加藤聖子、小田義直、加来恒壽、岩坂剛
    • Organizer
      第60回日本臨床細胞学会総会 春期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BCG曝露T24細胞におけるpRbとp21発現の関連性 II2019

    • Author(s)
      中司成、渡辺寿美子、上原俊貴、加来恒壽、岩坂剛
    • Organizer
      第60回日本臨床細胞学会総会 春期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 蛍光染色を用いたタンパク質発現判定法の検討 -シングルセル解析-2019

    • Author(s)
      上原俊貴、渡辺寿美子、前田 裕亮,加来恒壽、岩坂剛
    • Organizer
      第60回日本臨床細胞学会総会 春期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 内膜細胞診におけるDeep Learningの有用性の検討2019

    • Author(s)
      上原俊貴、大喜雅文、渡邊壽美子、大久保文彦、山元英崇、加藤聖子、小田義直、加来恒壽、岩坂剛
    • Organizer
      第35回日本臨床細胞学会九州連合会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BCG曝露T24細胞におけるpRBとp27の関連性2019

    • Author(s)
      細山田理葉、中司成、上原俊貴、加来恒壽、岩坂剛、渡邊壽美子
    • Organizer
      第58回日本臨床細胞学会秋期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 二核細胞の分裂に関する検討2019

    • Author(s)
      岩崎遥菜、近藤守、上原俊貴、加来恒壽、岩坂剛、渡邊壽美子
    • Organizer
      第58回日本臨床細胞学会秋期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞周期関連タンパク発現からみたBCG膀胱内注入療法の効果判定:実験的考察2018

    • Author(s)
      渡邊壽美子、平井絵梨花、藤井直人、江口奈津希、山口将太、加来恒壽、岩坂剛
    • Organizer
      第59回日本臨床細胞学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] BCG曝露によるT24細胞のp21・p27発現における客観的検討2018

    • Author(s)
      前田裕亮, 渡邊壽美子, 藤井直人, 加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第59回日本臨床細胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] BCG failure症例の自然尿細胞診に出現する異型細胞の形態学的検討2018

    • Author(s)
      森山拓人、渡邊壽美子、軍馬麻紀、鷺山和幸、加来恒壽、杉島節夫
    • Organizer
      第59回日本臨床細胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 栄養状態と二核細胞の細胞周期に関する検討2018

    • Author(s)
      近藤守,渡邊壽美子,鶴留えりか,西村和徳,加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第59回日本臨床細胞学会
    • Related Report
      2018 Research-status Report
  • [Presentation] BCG曝露T24細胞におけるpRbとp21発現の関連性2018

    • Author(s)
      中司成、渡辺寿美子、平井絵梨花、加来恒壽、岩坂剛
    • Organizer
      第57回日本臨床細胞学会秋期大会
    • Related Report
      2018 Research-status Report
  • [Presentation] BCG曝露とpRBの関連性2017

    • Author(s)
      平井絵梨花, 渡邊 壽美子, 加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第56回日本臨床細胞学会秋期大会
    • Related Report
      2017 Research-status Report
  • [Presentation] BCG曝露におけるT24細胞のp21発現へのp27の影響2017

    • Author(s)
      前田裕亮, 渡邊壽美子, 藤井直人, 加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第56回日本臨床細胞学会秋期大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血清飢餓状態における培養日数と二核細胞の生存能力に関する検討2017

    • Author(s)
      鶴留えりか, 渡邊 壽美子, 加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第56回日本臨床細胞学会秋期大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 培養日数と二核細胞の変化に関する検討2017

    • Author(s)
      近藤守,渡邊壽美子,西村和徳,加来恒寿, 岩坂剛, 杉島節夫
    • Organizer
      第56回日本臨床細胞学会秋期大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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