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Analysis for the effect of C5a receptor on cancer cell and development for targeted therapeutic strategy to C5a receptor

Research Project

Project/Area Number 25462099
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

NITTA Hidetoshi  熊本大学, 医学部附属病院, 非常勤診療医師 (90555749)

Co-Investigator(Kenkyū-buntansha) BABA Hideo  熊本大学, 大学院生命科学研究部, 教授 (20240905)
NAKAHARA Osamu  熊本大学, 医学部附属病院, 非常勤診療医師 (40583042)
BEPPU Toru  熊本大学, 医学部附属病院, 特任教授 (70301372)
TAKAMAORI Hiroshi  熊本大学, 医学部附属病院, 非常勤診療医師 (90363514)
Research Collaborator KAIDA Takayoshi  熊本大学, 大学院生命科学研究部, 大学院生
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords補体C5a / C5a受容体 / 胃癌浸潤・転移 / 胃癌 / 補体 / 浸潤 / 肝転移 / C5aR / 浸潤、転移
Outline of Final Research Achievements

We examined the effect of C5a receptor (C5aR) on Gastric cancer (GC). Two human GC cell lines had high C5aR expression. An invasion assay revealed that C5a stimulation promoted the invasive ability of them. Moreover, overexpression of C5aR in GC cells enhanced the conversion of RhoA-GDP to RhoA-GTP after C5a stimulation and caused morphological changes, including increased expression of stress fibers and filopodia. Examination of tumor specimens from patients with GC revealed that high C5aR expression was associated with increased invasion depth, vascular invasion and advanced stage. The 5-year overall survival of patients with high C5aR expression was significantly worse than that of patients with low expression. This study is the first to demonstrate that C5aR promotes GC cell invasion by activating RhoA and is associated with a poor prognosis in GC patients. Therefore, this study provides a biomarker for GC patients who require an advanced therapeutic strategy.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2013

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Chemotherapy-induced Nausea and Vomiting in Patients with Hepatobiliary and Pancreatic Cancer Treated with Chemotherapy: A Prospective Observational Study by the CINV Study Group of Japan2016

    • Author(s)
      Hidetoshi Nitta, Hideo Baba, Kazuya Sugimori, Junji Furuse, Shinichi Ohkawa, Kazuhide Yamamoto, Hironobu Minami, Mototsugu Shimokawa, Go Wakabayashi and Keisuke Aiba
    • Journal Title

      Anticancer Research

      Volume: 36(4) Pages: 1929-1936

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a-receptor (CD88).2013

    • Author(s)
      Nitta, H. et al.
    • Journal Title

      Clinical Cancer Reseach

      Volume: 19 Issue: 8 Pages: 2004-2013

    • DOI

      10.1158/1078-0432.ccr-12-1204

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognosis assessment of patients with refractory ascites treated with a peritoneovenous shunt.2013

    • Author(s)
      Nitta H, Okamura S, Mizumoto T, Matsushita H, Nishimura T, Shimokawa Y, Kimura M, Baba H.
    • Journal Title

      Hepatogastroenterology

      Volume: 60 Pages: 1607-1610

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion.2013

    • Author(s)
      Nitta H, Beppu T, Imai K, Hayashi H, Chikamoto A, Baba H.
    • Journal Title

      Would Journal of Surgery

      Volume: 37 Issue: 5 Pages: 1034-1042

    • DOI

      10.1007/s00268-013-1957-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of the closing speed of stapler jaws on bovine pancreases.2013

    • Author(s)
      Chikamoto A, Hashimoto D, Ikuta Y, Tsuji A, Abe S, Hayashi H, Imai K, Nitta H, Ishiko T, Watanabe M, Beppu T, Baba H.
    • Journal Title

      Surgical endoscopyy

      Volume: 28(1) Issue: 1 Pages: 336-340

    • DOI

      10.1007/s00464-013-3157-3

    • URL

      http://link.springer.com/article/10.1007%2Fs00534-012-0587-6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancer of Zeste Homolog 2 (EZH2) Promotes Progression of Cholangiocarcinoma Cells by Regulating Cell Cycle and Apoptosis.2013

    • Author(s)
      Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H.
    • Journal Title

      Ann Surg Oncol

      Volume: 3 Issue: S3 Pages: 667-675

    • DOI

      10.1245/s10434-013-3135-y

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 補体C5aを介した胃癌浸潤能の亢進2015

    • Author(s)
      甲斐田剛圭、新田英利、北野雄希、山村謙介、有馬浩太、東孝暁、髙城克暢、林洋光、橋本大輔、近本亮、石河隆敏、別府透、馬場秀夫
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 胃癌におけるC5a受容体高発現の予後因子としての意義2015

    • Author(s)
      甲斐田剛圭、新田英利、東孝暁、髙城克暢、岡部弘尚、林洋光、橋本大輔、別府透、馬場秀夫、近本亮
    • Organizer
      第70回日本消化器外科学会総会
    • Place of Presentation
      アクトシティ浜松(鳥取県)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Relation between expression of C5a receptor and clinicopathological factors in patients with gastric cancer2015

    • Author(s)
      Takayoshi Kaida, Hidetoshi Nitta, Kota Arima, Hideaki Takeyama, Takaaki Higashi, Katunobu Taki, Hiromitsu Hayashi, Akira Chikamoto, Toru Beppu and Hideo Baba
    • Organizer
      AACR Annual Meeting 2015
    • Place of Presentation
      Pennsylvania Convention Center(米国・フィラデルフィア)
    • Year and Date
      2015-04-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancement of human cancer cell migration and invasion by anaphylatoxin C5a via aberrantly expressed C5a-receptor2013

    • Author(s)
      新田 英利
    • Organizer
      Federation of Asian Clinical Oncology
    • Place of Presentation
      厦門(中国)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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