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Effective anti-cancer immunotherapy by controling autophagy

Research Project

Project/Area Number 24501331
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor immunology
Research InstitutionShimane University

Principal Investigator

HARADA Mamoru  島根大学, 医学部, 教授 (50260716)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords癌免疫療法 / アポトーシス / TRAIL / オートファジー / 癌
Outline of Final Research Achievements

Autophagy is a cell survival system under starvation or stress. Cancer cells utilize this system to acquire therapy-resistance and adjust hypoxic tumor microenvironment. I found that autophagy is induced when human pancreatic cancer cells are treated with apoptosis-inducing TRAIL. Additionally, their susceptibility to TRAIL is significantly augmented by the treatment with RNA interference or molecular-targeted drugs to inhibit autophagy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (47 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (29 results) (of which Invited: 2 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Intermittent chemotherapy can retain the therapeutic potential of anti-CD137 antibody during the late tumor-bearing state.2015

    • Author(s)
      Tongu M, Harashima N, Tamada K, Chen L, Harada M
    • Journal Title

      Cancer Science

      Volume: 106 Issue: 1 Pages: 9-17

    • DOI

      10.1111/cas.12568

    • NAID

      120005982740

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New polycomb group protein enhancer of zeste homolog (EZH) 2-derived peptide with the potential to induce cancer-reactive cytotoxic T lymphocytes in prostate cancer patients with HLA-A3 supertype alleles2015

    • Author(s)
      Minami T, Minami T, Shimizu N, Yamamoto Y, De Velasco M A, Nozawa M, Yoshimura K, Harashima N, Harada M, Uemura H.
    • Journal Title

      International Immunopharmacology

      Volume: 26 Issue: 1 Pages: 133-138

    • DOI

      10.1016/j.intimp.2015.03.023

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transfection of poly(I:C) can induce ROS-triggered apoptosis and IFN--mediated growth arrest in human renal cell carcinoma cells via innate adjuvant receptors and the 2-5A system2014

    • Author(s)
      Harashima N, Minami T, Uemura H, Harada M
    • Journal Title

      Molecular Cancer

      Volume: 13 Issue: 1 Pages: 217-217

    • DOI

      10.1186/1476-4598-13-217

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bcl-2 family inhibition sensitizes human prostate cancer cells to docetaxel and promotes unexpected apoptosis under caspase-9 inhibition2014

    • Author(s)
      amaki H, Harashima N, Hiraki M, Arichi N, Nishimura N, Shiina H, Naora K, Harada M
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 11399-11412

    • NAID

      120005982736

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of erythropoietin receptor-derived peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from HLA-A24+ patients with renal cell carcinoma.2014

    • Author(s)
      Minami T, Minami T, Shimizu N, Yamamoto Y, De Velasco M, Nozawa M, Yoshimura K, Harashima N, Harada M, Uemura H.
    • Journal Title

      International Immunopharmacology

      Volume: 20 Issue: 1 Pages: 59-65

    • DOI

      10.1016/j.intimp.2014.02.018

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.2014

    • Author(s)
      Umemoto Y, Okano S, Matsumoto Y, Nakagawara H, Matono R, Yoshiya S, Yamashita YI, Yoshizumi T, Ikegami T, Soejima Y, Harada M, Aishima S, Oda Y, Shirabe K, Maehara Y.
    • Journal Title

      J Gastroenterol.

      Volume: not determined Issue: 1 Pages: 65-75

    • DOI

      10.1007/s00535-014-0933-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The HSP70 and autophagy inhibitor pifithrin-mu enhances the antitumor effects of TRAIL on human pancreatic cancer2013

    • Author(s)
      Monma H, Harashima N, et al.
    • Journal Title

      Mol Cancer Ther

      Volume: 12 Issue: 4 Pages: 341-351

    • DOI

      10.1158/1535-7163.mct-12-0954

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pifithrin-mu, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells2013

    • Author(s)
      Sekihara M, Harashima N, Tongu M, Tamaki Y, Uchida N, Inomata T, Harada M.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e78772-e78772

    • DOI

      10.1371/journal.pone.0078772

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo2012

    • Author(s)
      Miki Tongu, Nanae Harashima, Hiroyuki Monma, Touko Inao, Takaya Yamada, Hideyuki Kawauchi, Mamoru Harada
    • Journal Title

      Cancer Immunol Immunother

      Volume: 62 Issue: 2 Pages: 383-391

    • DOI

      10.1007/s00262-012-1343-0

    • NAID

      120005982738

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum2012

    • Author(s)
      Harada M, et al.(5人中5番目)
    • Journal Title

      Oncology Reports

      Volume: 27 Pages: 325-332

    • DOI

      10.3892/or.2011.1549

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of humna prostate cancer cells.2012

    • Author(s)
      Harashima N, Inao T, Imamura R, Okano S, Suda T, Harada M.
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 61 Pages: 667-676

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I : C), on human breast cancer2012

    • Author(s)
      Harada M., et al.(8人中8番目)
    • Journal Title

      Breast Cancer Research and Treatment

      Volume: (in press) Issue: 1 Pages: 89-100

    • DOI

      10.1007/s10549-011-1930-3

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combining a peptide vaccine with oral ingestion of Lentinula edodes mycelia extract enhances anti-tumor activity in B16 melanoma-bearing mice2012

    • Author(s)
      Tanaka K, Harashima N, et al.
    • Journal Title

      Cancer Immunol Immunother

      Volume: 61 Issue: 11 Pages: 2143-2152

    • DOI

      10.1007/s00262-012-1275-8

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A is involved in enhancement of tumor progression in murine intestine2011

    • Author(s)
      K.Oshiro
    • Journal Title

      Immunobiology

      Volume: 217 Issue: 1 Pages: 54-60

    • DOI

      10.1016/j.imbio.2011.08.002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Combination of low-dose and intermittent chemotherapy with cyclophosphamide and gemcitabine restores efficacy of anti-CD137 antibody therapy at the late tumor-bearing state2014

    • Author(s)
      Harada M, Tamada K, Harashima N
    • Organizer
      第43回日本免疫学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] HIF-2の阻害はヒト膵がん細胞のTRAIL感受性を増強する2014

    • Author(s)
      原嶋奈々江、波里瑶子、門馬浩行、秋元美穂、竹永啓三、田島義証、原田守
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ABT-263はヒト前立腺癌PC3細胞のドセタキセル感受性を増強する2014

    • Author(s)
      玉木宏樹、原嶋奈々江、原田守
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 可溶性ST2は炎症性のがん微小環境を修飾し膵臓がんの腫瘍血管新生と増殖を抑制する2014

    • Author(s)
      秋元美穂、原田守、竹永啓三
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ABT-263はヒト膵がん細胞のTRAILによるアポトーシスを増強する2014

    • Author(s)
      波里瑶子、原嶋奈々江、門馬浩行、田島義証、原田守
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] シイタケ菌糸体抽出物とgemcitabineの併用はTregとMDSCを抑制することで相乗的な抗腫瘍効果を発揮す2014

    • Author(s)
      石川悟、和知俊、松井保公、山口博史、原田
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pifithrin-, an inhibitor of HSP70, can increase the antitumor effects of hyperthermia against human prostate cancer cells2014

    • Author(s)
      Mamoru Harada
    • Organizer
      、The 6th ACHO & the 31st JCTM
    • Place of Presentation
      福井県民ホールAOSSA(福井市)
    • Year and Date
      2014-09-04 – 2014-09-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 抗がん剤やBRMによる免疫抑制の軽減と抗がんT細胞応答の誘導2014

    • Author(s)
      原田守
    • Organizer
      第52回日本癌治療学会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] :低酸素誘導因子 HIF 阻害によるヒト膵癌細胞のTRAIL感受性の増強2014

    • Author(s)
      原嶋奈々江、門馬浩行、波里瑶子、秋元美穂、竹永啓三、原田守
    • Organizer
      第18回日本がん免疫学会
    • Place of Presentation
      ひめぎんホール(松山市)
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Bcl-2 family 阻害剤によるヒト膵癌細胞のTRAIL抵抗性の克服2014

    • Author(s)
      波里瑶子、原嶋奈々江、門馬浩行、田島義証、原田守
    • Organizer
      第18回日本がん免疫学会
    • Place of Presentation
      ひめぎんホール(松山市)
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト膵癌細胞に対するTRAILとchloroquine の併用効果の検討2014

    • Author(s)
      門馬浩行、原嶋奈々江、波里瑶子、田島 義証、原田守
    • Organizer
      第18回日本がん免疫学会
    • Place of Presentation
      ひめぎんホール(松山市)
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Poly(I:C)トランスフェクションによるROS産生を伴った癌細胞死誘導とインターフェロン制御分子の関与2013

    • Author(s)
      原嶋奈々江、岡野慎士、原田守
    • Organizer
      第17回日本がん免疫学会
    • Place of Presentation
      全日空ホテル(宇部)
    • Related Report
      2013 Research-status Report
  • [Presentation] HSP70阻害剤pifithrin-muがPanc-1膵癌細胞に対するTRAIL誘導性アポトーシスを増強する機序2013

    • Author(s)
      門馬浩行、原嶋奈々江、波里瑶子、田島 義証、原田守
    • Organizer
      第17回日本がん免疫学会
    • Place of Presentation
      全日空ホテル(宇部)
    • Related Report
      2013 Research-status Report
  • [Presentation] 低用量 chemotherapyと抗CD137抗体の併用により誘導される持続的な抗腫瘍免疫応答2013

    • Author(s)
      頓宮美樹、原嶋奈々江、山田高也、岡野慎士、玉田耕治、原田守
    • Organizer
      第17回日本がん免疫学会
    • Place of Presentation
      全日空ホテル(宇部)
    • Related Report
      2013 Research-status Report
  • [Presentation] Persistent antitumor immune response after the combination therapy with low-dose chemotherapy and anti-CD137 (4-1BB) antibody2013

    • Author(s)
      Tongu M, Harashima N, Yamada T, Okano S, Tamada K
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Restoration of the TRAIL susceptibility of human pancreatic cancer cells by inhibition2013

    • Author(s)
      Harashima N, Hari Y, Monma H, Tajima Y, Harada M
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Mechanisms of an HSP70 inhibitor pifithrin-mu to enhance TRAIL-induced apoptosis of pancreatic cancer cells2013

    • Author(s)
      Monma H, Harashima N, Hari Y, Tajima Y, Harada M
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens2013

    • Author(s)
      Okano S, Yamashita Y, Harashima N, Ikegami T, Yoshizumi T, Shirabe K, Harada M, Yoshikai Y, and Maehara Y
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel HSP70 inhibitor pifithrin-mu enhances the antitumor effect of radiation on human prostate cancer.2013

    • Author(s)
      Sekihara K, Harashima N, Tamaki Y, Hieda Y, Uchida N, Inomata T, Harada M
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Long-lasting suppression of CT26 growth after low-dose chemotherapy with cyclophosphamide plus gemcitabine followed by anti-CD137 antibody.2013

    • Author(s)
      Harada M, Okano S, Tanada K, Harashima N
    • Organizer
      第42回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Research-status Report
  • [Presentation] 膵臓癌細胞に対するTRAILとHSP70阻害剤pifithrin-mu併用による抗腫瘍効果。2012

    • Author(s)
      門馬浩行 他7名
    • Organizer
      日本膵臓癌学会
    • Place of Presentation
      ホテルメトロポリタン山形(山形市)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト乳癌細胞お抗癌剤抵抗性におけるオートファジーの役割。2012

    • Author(s)
      稲尾瞳子 他7名
    • Organizer
      日本乳癌学会
    • Place of Presentation
      熊本市民会館(熊本市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Ploy(I:C)トランスフェクションによるヒト腎癌さいぼうでのROS賛成とアポトーシスの誘導2012

    • Author(s)
      原嶋奈々江 他2名
    • Organizer
      日本がん免疫学会
    • Place of Presentation
      北海道大学学術交流会館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] シイタケ菌糸体抽出物の経口摂取は担癌に伴うTregの増加を抑制することでペプチドワクチンによるCTL活性を維持できる2012

    • Author(s)
      石川悟 他5名
    • Organizer
      日本がん免疫学会
    • Place of Presentation
      北海道大学学術交流会館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] オートファジーの阻害はアジュヴァント受容体リガンドでpoly(I:C)による細胞死を増強する2012

    • Author(s)
      原嶋奈々江 他3名
    • Organizer
      日本癌学会
    • Place of Presentation
      ロイトン札幌、さっぽろ芸文館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] HSP70およびオートファジー阻害剤pifithrin-muの膵癌細胞に対するTRAIL誘導性アポトーシス増強効果。2012

    • Author(s)
      門馬浩行 他6名
    • Organizer
      日本癌学会
    • Place of Presentation
      ロイトン札幌、さっぽろ芸文館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 新規HSP70阻害剤であるpifithrin-muは、ヒト前立腺癌において温熱療法の抗腫瘍効果を増強する可能性がある。2012

    • Author(s)
      関原和正 他5名
    • Organizer
      日本癌学会
    • Place of Presentation
      ロイトン札幌、さっぽろ芸文館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 低用量cyclophosphamideとgemcitabine の間歇的投与による抗腫瘍T細胞のin vivo誘導。2012

    • Author(s)
      頓宮美樹 他5名
    • Organizer
      日本癌学会
    • Place of Presentation
      ロイトン札幌、さっぽろ芸文館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 免疫療法後のドーマント期にT細胞応答抵抗性癌細胞が新たに出現する。2012

    • Author(s)
      岡野慎士 他2名
    • Organizer
      日本癌学会
    • Place of Presentation
      ロイトン札幌、さっぽろ芸文館(札幌市)
    • Related Report
      2012 Research-status Report
  • [Book] Effects of metronomic chemotherapy on immunity, in “Metronomic chemotherapy” (eds) Bocci G, Francia G.2014

    • Author(s)
      Mamoru Harada
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Remarks] 島根大学医学部免疫学ホームページ

    • URL

      http://www.med.shimane-u.ac.jp/immunology/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 島根大学医学部 免疫学講座

    • URL

      http://www.med.shimane-u.ac.jp/immunology/

    • Related Report
      2013 Research-status Report
  • [Remarks] 島根大学医学部免疫学ホームページ

    • URL

      http://www.med.shimane-u.ac.jp/immunology/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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