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Cellular senescence induced by chemo/radio-therapy as new therapeutic opportunity of mammary tumors.

Research Project

Project/Area Number 16K10486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

Kawai Masaaki  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (80513530)

Co-Investigator(Kenkyū-buntansha) 島 礼  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (10196462)
角川 陽一郎  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (60221173)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords乳がん / 補助療法 / 細胞老化 / 代謝 / 化学療法 / 治療抵抗性 / 乳腺外科学
Outline of Final Research Achievements

Tumor cells often undergo cellular senescence when treated with DNA-damaging agent or radio-therapy (TIS: therapy-induced senescence) in addition to cell death. TIS cells are thought to survive longer time, and promotes relapse and/or emergence of therapy-resistant tumors by various mechanisms. In this study, we tried to understand metabolic reprograming during TIS, and to explore it as new therapeutic target in order to improve adjuvant therapy of mammary tumors.

Academic Significance and Societal Importance of the Research Achievements

近年、補助療法として各種分子標的治療の発展は目覚ましいが、それらの恩恵を受けられるのは一部患者に限られる。よって、従来型の化学療法・放射線療法は今後も引き続き重要で、より一層の治療効果向上や副作用改善が求められている。とくに前者に関し、治療抵抗性の解明が大きなブレークスルーになると期待されている。本研究にて、TISに伴う代謝変化や関連表現型、およびそれらの分子メカニズムの一部を明らかにすることが出来た。新たな乳がん補助療法の開発への応用が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(12 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (3 results)

  • [Journal Article] Reproductive history and breast cancer survival: a prospective patient cohort study in Japan2019

    • Author(s)
      Minami Yuko、Nishino Yoshikazu、Kawai Masaaki、Tada Hiroshi、Kanemura Seiki、Miyashita Minoru、Ishida Takanori、Kakugawa Yoichiro
    • Journal Title

      Breast Cancer

      Volume: - Pages: 687-702

    • DOI

      10.1007/s12282-019-00972-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Postmastectomy Radiotherapy After Neoadjuvant Chemotherapy in Breast Cancer Patients: A Study from the Japanese Breast Cancer Registry2019

    • Author(s)
      Miyashita Minoru、Niikura Naoki、Kumamaru Hiraku、Miyata Hiroaki、Iwamoto Takayuki、Kawai Masaaki、Anan Keisei、Hayashi Naoki、Aogi Kenjiro、Ishida Takanori、Masuoka Hideji、Iijima Kotaro、Masuda Shinobu、Tsugawa Koichiro、Kinoshita Takayuki、Tsuda Hitoshi、Nakamura Seigo、Tokuda Yutaka
    • Journal Title

      Annals of Surgical Oncology

      Volume: -

    • DOI

      10.1245/s10434-019-07453-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes enhances K-ras G12D -driven tumor promotion2018

    • Author(s)
      Kurosawa Koreyuki、Inoue Yui、Kakugawa Yoichiro、Yamashita Yoji、Kanazawa Kosuke、Kishimoto Kazuhiro、Nomura Miyuki、Momoi Yuki、Sato Ikuro、Chiba Natsuko、Suzuki Mai、Ogoh Honami、Yamada Hidekazu、Miura Koh、Watanabe Toshio、Tanuma Nobuhiro、Tachi Masahiro、Shima Hiroshi
    • Journal Title

      Cancer Science

      Volume: 109 Pages: 2178-2187

    • DOI

      10.1111/cas.13638

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018

    • Author(s)
      M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
    • Journal Title

      Cancer Cell

      Volume: 12 Pages: 355-367

    • DOI

      10.1016/j.ccell.2018.02.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alcohol Consumption and Breast Cancer Risk According to Hormone Receptor Status in Japanese Women: A Case-Control Study2018

    • Author(s)
      Takizawa Y, Kawai M, Kakugawa Y, Nishino Y, Ohuchi N, Minami Y.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 244(1) Issue: 1 Pages: 63-73

    • DOI

      10.1620/tjem.244.63

    • NAID

      130006316035

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.2017

    • Author(s)
      Sato T, Morita M, Tanaka R, Inoue Y, Nomura M, Sakamoto Y, Miura K, Ito S, Sato I, Tanaka N, Abe J, Takahashi S, Kawai M, Sato M, Hippo Y, Shima H, Okada Y, Tanuma N
    • Journal Title

      Oncol Lett

      Volume: 14(6) Pages: 6863-6868

    • DOI

      10.3892/ol.2017.7098

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug delivery of oral anti-cancer fluoropyrimidine agents.2017

    • Author(s)
      Miura K. et al.
    • Journal Title

      Expert Opin Drug Deliv

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Associations of obesity and physical activity with serum and intratumoral sex steroid hormone levels among postmenopausal women with breast cancer: analysis of paired serum and tumor tissue samples.2017

    • Author(s)
      Yoichiro Kakugawa, Hiroshi Tada, Masaaki Kawai, Takashi Suzuki, Yoshikazu Nishino, Seiki Kanemura, Takanori Ishida, Noriaki Ohuchi, Yuko Minami
    • Journal Title

      Breast Cancer Research and Treatment

      Volume: 162(1) Pages: 115-125

    • DOI

      10.1007/s10549-016-4094-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer2016

    • Author(s)
      Sekiguchi A. et al.
    • Journal Title

      Sci Rep

      Volume: 6 Pages: 34671-34671

    • DOI

      10.1038/srep34671

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 新規皮膚がん抑制遺伝子Ppp6c変異は、変異型K-RASによる腫瘍発生を強く促進する2016

    • Author(s)
      黒沢是之ほか
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Pyruvate kinase Mの両isoformを欠損するマウスの解析2016

    • Author(s)
      田中遼太ほか
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 形質膜シアリダーゼNEU3によるEGFRシグナリングの活性化機構2016

    • Author(s)
      山本晃司ほか
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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