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Deveropment of novel treatment and analysis in molecular mechanism of cell-cell interaction for Hepatobliriary pancreato carcimona

Research Project

Project/Area Number 15K19875
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Aihara Arihiro  東京医科歯科大学, 医学部附属病院, 非常勤講師 (90451939)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞間相互作用 / ASPH / 膵癌 / 肝細胞癌 / Notch signaling / 胆管癌 / Notch / 肝内胆管癌
Outline of Final Research Achievements

Hepatobiliary pancreatic cancer is well known as poor prognostic cancers. Our purpose is development of novel treatment and investigation of cell-cell interaction in hepatobiliary pancreatic cancer. Overexpresion of aspartate beta-hydroxylase (ASPH) is frequently obeserved not only in hepatocellular carcinoma but also in pancreatic and biliary cancer, which positively regulates Notch signaling pathway. The biological effects of ASPH inhibitors on the Notch signaling cascade were evaluated. The ASPH inhibitor reduced suppressed cell migration, invasion in pancreatic and biliary cancer. Furthermore, substantial inhibition of tumor growth and progression was observed in animal models. ASPH is promising for treatment of hepatobiliary pancreatic cancer. Additionally experiments to investigate cell-cell interaction in Neuroendocrine tumor were established and novel animal model was developed to analyze molecular mechanisms acquiring resistance for anti-cancer treatment.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (5 results)

  • [Journal Article] Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma.2017

    • Author(s)
      Ohata Y, Akiyama Y, Shimada S, Mogushi K, Nakao K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: in press Issue: 6 Pages: 1155-1165

    • DOI

      10.1158/1535-7163.mct-16-0728

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ARID2 modulates DNA damage response in human hepatocellular carcinoma cells.2017

    • Author(s)
      Oba A, Shimada S, Akiyama Y, Nishikawaji T, Mogushi K, Ito H, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Asahara H, Kaida A, Miura M, Tanabe M, Tanaka S.
    • Journal Title

      Journal of Hepatology

      Volume: in press Issue: 5 Pages: 942-951

    • DOI

      10.1016/j.jhep.2016.12.026

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Preoperative direct bilirubin to prothrombin time ratio index to prevent liver failure after minor hepatectomy.2016

    • Author(s)
      Furuyama T, Kudo A, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Tanaka S, Tanabe M.
    • Journal Title

      Journal of Hepatobiliary Pancreatic Sciences

      Volume: 23 Issue: 12 Pages: 763-770

    • DOI

      10.1002/jhbp.400

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression of transforming growth factor β1 promotes cholangiocarcinoma development and progression.2016

    • Author(s)
      Huang CK, Aihara A, Iwagami Y, Yu T, Carlson R, Koga H, Kim M, Zou J, Casulli S, Wands JR.
    • Journal Title

      Cancer Lett.

      Volume: 1 Issue: 1 Pages: 153-162

    • DOI

      10.1016/j.canlet.2016.05.038

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Proteasome activity is required for the initiation of precancerous pancreatic lesions.2016

    • Author(s)
      Furuyama T, Tanaka S, Shimada S, Akiyama Y, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Fukamachi H, Arii S, Kawaguchi Y, Tanabe M.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 27044-27044

    • DOI

      10.1038/srep27044

    • NAID

      120006775931

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Molecular pathology of advanced hepatocellular carcinoma2016

    • Author(s)
      Aihara A, Wands JR, Tanaka S.
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 113 Issue: 5 Pages: 790-797

    • DOI

      10.11405/nisshoshi.113.790

    • NAID

      130005150376

    • ISSN
      0446-6586, 1349-7693
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Journal Article] Anti-Tumor Effects of Second Generation β-Hydroxylase Inhibitors on Cholangiocarcinoma Development and Progression.2016

    • Author(s)
      Huang CK, Iwagami Y, Aihara A, Chung W, de la Monte S, Thomas JM, Olsen M, Carlson R, Yu T, Dong X, Wands J.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 3 Pages: e0150336-e0150336

    • DOI

      10.1371/journal.pone.0150336

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm.2016

    • Author(s)
      Katsuta E, Kudo A, Akashi T, Mitsunori Y, Matsumura S, Aihara A, Ban D, Ochiai T, Tanaka S, Eishi Y, Tanabe M.
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: -

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.2016

    • Author(s)
      Ito H, Tanaka S, Akiyama Y, Shimada S, Adikrisna R, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Yamaoka S, Tanabe M.
    • Journal Title

      Plos One

      Volume: - Issue: 1 Pages: e0146564-e0146564

    • DOI

      10.1371/journal.pone.0146564

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic risk factors.2016

    • Author(s)
      Akahoshi K, Tanaka S, Mogushi K, Shimada S, Matsumura S, Akiyama Y, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Tanabe M.
    • Journal Title

      Journal of Gastroenterology

      Volume: -

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells.2016

    • Author(s)
      Katsuta, E., Tanaka, S., Mogushi, K., Shimada, S., Akiyama, Y., Aihara, A., Matsumura, S., Mitsunori, Y., Ban, D., Ochiai, T., Kudo, A., Fukamachi, H., Tanaka, H., Nakayama, K., Arii, S., Tanabe, M.
    • Journal Title

      Int. J. Oncol.

      Volume: 48 Issue: 2 Pages: 657-669

    • DOI

      10.3892/ijo.2015.3299

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aspartate β-Hydroxylase expression promotes a malignant pancreatic cellular phenotype.2015

    • Author(s)
      Dong X, Lin Q, Aihara A, Li Y, Huang CK, Chung W, Tang Q, Chen X, Carlson R, Nadolny C, Gabriel G, Olsen M, Wands JR.
    • Journal Title

      Oncotarget

      Volume: 6(2) Pages: 1231-48

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肝胆膵領域癌に対する治療標的としてのASPHの解析2015

    • Author(s)
      藍原有弘, Chiung-kuei Huang, Mark Olsen, Waihong Chung, Qi Tang, Xiaoqun Dong, 田中真二、田邉稔、Jack Wands
    • Organizer
      第53回癌治療学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
  • [Presentation] A cell surface beta-hydroxylase is a novel therapeutic target for pancreatic cancer2015

    • Author(s)
      藍原 有弘、田中真二、松村聡、光法雄介、伴大輔、落合高徳、工藤篤、田邉稔、Jack Wands
    • 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(静岡県浜松市)
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 肝胆膵領域癌に対する新規治療標的の探索2015

    • Author(s)
      藍原 有弘, 田中 真二, 田邉 稔, Wands Jack
    • Organizer
      第27回日本肝胆膵外科学会学術集会
    • Place of Presentation
      ホテルグランパシフィック台場(東京都港区)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 藍原有弘、松永浩子、田中真二2015

    • Author(s)
      肝細胞癌に対するAurora kinase Bを標的とした治療開発
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 肝細胞癌に対する新規治療標的としてのAspartyl-(Asparaginyl)-beta-hydroxylase (ASPH)2015

    • Author(s)
      藍原 有弘、Chiung-Kuei Huang、Waihong Chung、松村 聡、伴 大輔、落合 高徳、工藤 篤、田中 真二、田邉 稔、Jack Wands
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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