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CONQUEST OF THE SCIRRHOUS GASTRIC CANCER: AUTOPHAGY OF CANCER STEM CELLS AND DEVELOPMENT OF MOLECULAR TARGET

Research Project

Project/Area Number 26293307
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionOsaka City University

Principal Investigator

Hirakawa Kosei  大阪市立大学, 大学院医学研究科, 医学部附属病院長 (40188652)

Co-Investigator(Kenkyū-buntansha) 八代 正和  大阪市立大学, 大学院医学研究科, 准教授 (60305638)
Research Collaborator 福岡 達成  , 大学院生
森崎 珠実  , 大学院生
木下 春人  , 大学院生
増田 剛  , 大学院生
笠島 裕明  , 大学院生
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywordsスキルス胃癌 / 難治癌 / オートファジー / 癌幹細胞 / クロロキン / 胃癌 / 癌幹細胞マーカー / p62 / LC-3 / beclin-1 / 癌微小環境
Outline of Final Research Achievements

Scirrhous gastric cancer is a refractory cancer. The aim of this study was to elucidate the intractable mechanisms of the scirrhous gastric cancer intractable from the viewpoint of autophagy of cancer stem cells. The expression of LC3A and LC3B was high in cancer stem cells of scirrhous gastric cancer. Autophagy was induced by oxidative stress. The proliferation of cancer stem cells was significantly inhibited by chloroquine. The expression of p62, LC-3, beclin-1 of the gastric cancer tissue was correlated with skills and metastasis. These findings suggested that autophagy was associated with the cancer stem cells of scirrhous gastric cancer, and suggested that autophagy inhibitor, chloroquine, might be useful for the inhibition of cancer stem cells.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (13 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] King's College London(英国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] CD9-positive exosomes from cancer-associated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells2018

    • Author(s)
      Miki Yuichiro、Yashiro Masakazu、Okuno Tomohisa、Kitayama Kishu、Masuda Go、Hirakawa Kosei、Ohira Masaichi
    • Journal Title

      British Journal of Cancer

      Volume: 118 Issue: 6 Pages: 867-877

    • DOI

      10.1038/bjc.2017.487

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells.2017

    • Author(s)
      Ishimoto T, Miyake K, Nandi T, Yashiro M, Onishi N, Huang KK, Joyce LN, Kalpana R, Tay ST, Suzuki Y, Cho BC, Kuroda D, Arima K, Izumi D, Iwatsuki M, Baba Y, Oki E, Watanabe M, Saya H, Hirakawa K, Baba H, Tan P.
    • Journal Title

      Gastroenterology

      Volume: in press Issue: 1 Pages: 191-204

    • DOI

      10.1053/j.gastro.2017.03.046

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer2017

    • Author(s)
      Kitayama Kishu、Yashiro Masakazu、Morisaki Tamami、Miki Yuichiro、Okuno Tomohisa、Kinoshita Haruhito、Fukuoka Tatsunari、Kasashima Hiroaki、Masuda Go、Hasegawa Tsuyoshi、Sakurai Katsunobu、Kubo Naoshi、Hirakawa Kosei、Ohira Masaichi
    • Journal Title

      Cancer Sci. 2017 Dec;108(12):2462-2469. doi: 10.1111/cas.13421. Epub 2017 Nov 27.

      Volume: 108 Issue: 12 Pages: 2462-2469

    • DOI

      10.1111/cas.13421

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells.2016

    • Author(s)
      Takahashi K, Tanaka M, Yashiro M, Matsumoto M, Ohtsuka A, Nakayama KI, Izumi Y, Nagayama K, Miura K, Iwao H, Shiota M.
    • Journal Title

      Cancer Lett.

      Volume: 378 Pages: 8-15

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL1-Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow-Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma.2016

    • Author(s)
      Kasashima H, Yashiro M, Nakamae H, Kitayama K, Masuda G, Kinoshita H, Fukuoka T, Hasegawa T, Nakane T, Hino M, Hirakawa K, Ohira M.
    • Journal Title

      Am J Pathol

      Volume: 186 Pages: 3028-3039

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer2016

    • Author(s)
      Masuda Go, Yashiro M, Kitayama K, Miki Y, Kasashima H, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, Toyokawa T, Kubo N, Tanaka H, Muguruma K, Masaichi O, Hirakawa K
    • Journal Title

      Anticancer Research

      Volume: 36 Pages: 129-136

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer.2014

    • Author(s)
      Kasashima H, Yashiro M, Kinoshita H, Fukuoka T, Morisaki T, Masuda G, Sakurai K, Kubo N, Ohira M, Hirakawa K
    • Journal Title

      Cancer Lett.

      Volume: 354 Issue: 2 Pages: 438-446

    • DOI

      10.1016/j.canlet.2014.08.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-beta signaling.2014

    • Author(s)
      Hasegawa T, Yashiro M, Nishii T, Matsuoka J, Fuyuhiro Y, Morisaki T, Fukuoka T, Shimizu K, Shimizu T, Miwa A, Hirakawa K.
    • Journal Title

      Int J Cancer

      Volume: 134 Issue: 8 Pages: 1785-95

    • DOI

      10.1002/ijc.28520

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation2014

    • Author(s)
      Kikuchi Y, Kunita A, Iwata C, Komura D, Nishiyama T, Shimazu K, Takeshita K, Shibahara J, Kii I, Morishita Y, Yashiro M, Hirakawa K, Miyazono K, Kudo A, Fukayama M, Kashima TG.
    • Journal Title

      Am J Pathol.

      Volume: 184 Issue: 3 Pages: 859

    • DOI

      10.1016/j.ajpath.2013.11.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 120.CXCL1-CXCR2 Signalling Might Recruit the Bone Marrow-derived Mesenchymal Cells to the Carcinoma-associated Fibroblasts of Gastric Cancer2017

    • Author(s)
      Masakazu Yashiro, Tomohisa Okuno, Hiroaki Kasashima, Yuichiro Miki, Hirohisa Nakamae, Kisyu Kitayama, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa
    • Organizer
      American Association for Cancer Research 107th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cancer Stem Cells Might Sustain Stemness by the Induction of Autophagy in Starvation Stress2016

    • Author(s)
      Go Masuda, Masakazu Yashiro, Kishu Kitayama, Yuichiro Miki, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Masaichi Ohira, Kosei Hirakawa
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      New Orleans (USA)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 1.Significance of an autophagy protein, microtubule-associated protein light chain 3 (LC3), in gastric cancer2015

    • Author(s)
      G Masuda, M Yashiro, Hiroaki Kasashima, Haruhito Kinoshita, Tatsunari Fukuoka, Tamami Morisaki, Tsuyoshi Hasegawa, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Hirakawa K.
    • Organizer
      American Association for Cancer Research 106th Annual Meeting
    • Place of Presentation
      Philadelphia, PA, (USA)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2022-02-28  

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