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Basic research on development of dendritic cell therapy targeting glioma cancer stem cells

Research Project

Project/Area Number 15K10346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKansai Medical University

Principal Investigator

ASAI Akio  関西医科大学, 医学部, 教授 (50231858)

Co-Investigator(Kenkyū-buntansha) 岩田 亮一  関西医科大学, 医学部, 助教 (60580446)
伊藤 量基  関西医科大学, 医学部, 准教授 (70434826)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsグリオーマ / 膠芽腫 / 癌幹細胞 / 樹状細胞 / 免疫抑制 / 免疫治療 / テモゾロミド / がん幹細胞
Outline of Final Research Achievements

Glioblastoma multiforme (GBM) is the most fatal malignant primary brain tumor. GBM contains functional subsets of cells called glioblastoma stem-like cells (GSCs), which are radioresistant and chemoresistant and eventually lead to tumor recurrence. We established GSCs lines and analyzed the expression of immune-associated molecules. GSCs lines were positive for MHC-Ⅰ, which indicated that GSCs can be recognized by T cells. Temozolomide (TMZ) is an oral alkylating agent with established anti-tumor activity in patients with GBM. We focused on the TMZ function and explored its influence on human dendritic cells (DCs) subsets. TMZ suppressed the secretion of IL-10 from DCs. Moreover, the addition of TMZ into peripheral blood mononuclear cells with DCs significantly enhanced the DC mediated ex vivo expansion and expression of cytotoxic molecules in CD8+ T cells. Our present findings suggest that TMZ is a potential anti-tumor reagent suitable for the combination use with DC-vaccine therapy.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 4 results) Book (2 results)

  • [Journal Article] 転移性脳腫瘍とがん幹細胞の関連2018

    • Author(s)
      岩田亮一,丸山正人,大舟晃平,中野洋輔,大江総一,林美樹夫, 吉村晋一,埜中正博,淺井昭雄
    • Journal Title

      Cytometry Research

      Volume: in press

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack2017

    • Author(s)
      Yoshida Y, Wang H, Hiwasa T, Machida T, Takiguchi M, Iwadate Y, et al.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 3 Pages: 8836-8848

    • DOI

      10.1007/s11060-018-2831-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enlarging pediatric ectopic Rathke's cleft cyst in the prepontine cistern: case report.2017

    • Author(s)
      Kamei T, Nonaka M, Uemura Y, Yamanouchi Y, Komori Y, Iwata R, Takeda J, Hashiba T, Yoshimura K, Asai A
    • Journal Title

      J Neurosurg Pediatr

      Volume: 20(5) Issue: 5 Pages: 480-484

    • DOI

      10.3171/2017.6.peds1727

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 5-ALA fluorescence-guided endoscopic surgery for mixed germ cell tumors.2017

    • Author(s)
      Takeda J, Nonaka M, Li Y, Komori Y, Kamei T, Iwata R, Hashiba T, Yoshimura K, Asai A.
    • Journal Title

      J Neurooncol

      Volume: 134(1) Issue: 1 Pages: 119-124

    • DOI

      10.1007/s11060-017-2494-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor.2017

    • Author(s)
      Iwata R, Maruyama M, Ito T, Nakano Y, Kanemura Y, Koike T, Oe S, Yoshimura K, Nonaka M, Nomura S, Sugimoto T, Yamada H, Asai A.
    • Journal Title

      Med Mol Morphol

      Volume: 50(4) Issue: 4 Pages: 211-219

    • DOI

      10.1007/s00795-017-0160-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas2017

    • Author(s)
      Fukushima S, Yamashita S, Kobayashi H, et al.; Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium).
    • Journal Title

      Acta Neuropathologica

      Volume: 133 Issue: 3 Pages: 445-462

    • DOI

      10.1007/s00401-017-1673-2

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of transpulmonary thermodilution monitoring (PiCCO) in patients with neurogenic pulmonary edema and acute obstructive hydrocephalus due to a central neurocytoma: A case report.2017

    • Author(s)
      R Iwata, K Yoshimura, Y Fujita, T Uesaka, H Oshige, A Asai
    • Journal Title

      Interdisciplinary Neurosurgery: Advanced Techniques and Case Management

      Volume: 8 Pages: 57-59

    • DOI

      10.1016/j.inat.2017.01.014

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperperfusion syndrome after clipping of an unruptured aneurysm by transsylvian approach: A Case Repot.2017

    • Author(s)
      R Iwata, K Yoshimura, Y Fujita, T Uesaka, H Oshige, A Asai
    • Journal Title

      Interdisciplinary Neurosurgery: Advanced Techniques and Case Management.

      Volume: 8 Pages: 11-13

    • DOI

      10.1016/j.inat.2017.01.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serine/Threonine kinase MLK4 determines Mesenchymal Identity in Glioma Stem Cells in an NFkB-dependent manner2016

    • Author(s)
      Kim SH, Ezhilarasan R, Chhipa R, Ladner K, Phillips E, Sparks A, Taylor D, Furuta T, Sabit H, Kurozumi K, Kuroiwa T, Akio A, Gallego-Perez1 D, Sulman EP, Cheng S, Lee J, Nakada M, Guttridge D, DasGupta B, Goidts V, Bhat KP, Walker J, Nakano I.
    • Journal Title

      Cancer Cell

      Volume: 29 Issue: 2 Pages: 201-213

    • DOI

      10.1016/j.ccell.2016.01.005

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy2016

    • Author(s)
      Ichimura K, Fukushima S, Nagane M, The Intracranial Berm Cell Tumor Genome Analysis Consortium, et al
    • Journal Title

      Acta Neuropathol

      Volume: Published online: 08 March Issue: 6 Pages: 889-901

    • DOI

      10.1007/s00401-016-1557-x

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 治療後長期間生存している悪性視神経膠腫の1 例.2016

    • Author(s)
      藤原望, 中内正志, 正健一郎, 山田晴彦, 最所千晶, 岩田亮一, 亀井孝昌, 淺井昭雄, 髙橋寛二
    • Journal Title

      臨床眼科

      Volume: 70 Pages: 1473-1478

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.2016

    • Author(s)
      Ichimura K, Nonaka M, Asai A, , Matsutani M, Shibata T, Nishikawa R; Intracranial Germ Cell Tumor Genome Analysis Consortium.
    • Journal Title

      Acta neuropathologica

      Volume: - Pages: 1-13

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Functional expression of inwardly rectifying K+ channel in glioblastoma stem-like cells.2018

    • Author(s)
      Hayashi M, Iwata R, Andharia1 N, Ofune K, Yoshimura K, Nonaka M, Asai A, Matsuda H
    • Organizer
      The Journal of Physiological Sciences 2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of new therapies for glioblastoma multiforme targeting nonselective cation channels.2017

    • Author(s)
      Iwata R, Ofune K, Hayashi M, Yoshimura K, Nonaka M, Matsuda H, Asai A
    • Organizer
      Neuro-Oncology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「グリオーマがん幹細胞に対する非選択性陽イオンチャネルを標的とした治療効果」2017

    • Author(s)
      岩田亮一、大舟晃平、林美樹夫、羽柴哲夫、吉村晋一、埜中正博、松田博子、淺井昭雄
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 「TRP channelを標的とした悪性脳腫瘍の治療法の開発」2017

    • Author(s)
      大舟晃平、岩田亮一、林美樹夫、吉村晋一、埜中正博、松田博子、淺井昭雄
    • Organizer
      第15回がんとハイポキシア研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 「非選択性陽イオンチャネルを標的とした悪性脳腫瘍の治療法の開発」2017

    • Author(s)
      大舟晃平、岩田亮一、林美樹夫、吉村晋一、埜中正博、松田博子、淺井昭雄
    • Organizer
      第49回日本臨床分子形態学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] グリオーマがん幹細胞で発現するICOSLGの機能2017

    • Author(s)
      岩田亮一、大舟晃平、伊藤量基、丸山正人、大江聡一、羽柴哲夫、吉村晋一、埜中正博、山田久夫、淺井昭雄
    • Organizer
      第15回がんとハイポキシア研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 転移性脳腫瘍からのがん幹細胞株樹立2017

    • Author(s)
      岩田亮一, 丸山正人, 中野洋輔, 小池太郎, 大江聡一, 吉村晋一, 埜中正博, 杉本哲夫, 山田久夫, 淺井昭雄
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経内分泌腫瘍の転移脳組織からの癌幹細胞2017

    • Author(s)
      岩田亮一, 丸山正人, 伊藤量基, 中野洋輔, 小池太郎, 大江聡一, 吉村晋一, 埜中正博, 野村昌作, 杉本哲夫, 山田久夫, 淺井昭雄
    • Organizer
      第49回日本臨床分子形態学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト神経膠芽腫由来U87MG細胞から樹立した高い腫瘍形成能を持つスフェロイドはPC3-Secreted Microprotein を高発現する2017

    • Author(s)
      丸山正人, 中野洋輔, 岩田亮一, 加瀬政彦, 杉本哲夫
    • Organizer
      Conbio2017(生命科学系学会合同年次大会:第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 内視鏡下5アミノレブリン酸(5-ALA)蛍光診断(PDD)~連続45症例の検討~.2016

    • Author(s)
      武田純一, 埜中正博, 亀井孝昌, 岩田亮一, 羽柴哲夫, 吉村晋一, 淺井昭雄.
    • Organizer
      第34回日本脳腫瘍学会学術集会.
    • Place of Presentation
      甲府富士屋ホテル、山梨
    • Year and Date
      2016-12-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Effect of Temozolomide on Brain Metastasis of neuroendocrine carcinoma.2016

    • Author(s)
      Ryoichi Iwata, Masato Maruyama, Tomoki Ito, Yoko Fujita, Yoshiyuki Matsuo, Yosuke Nakano, Kunikazu Yoshimura, Masahiro Nonaka, Kiichi Hirota, Shosaku Nomura, Tetsuo Sugimoto, Akio Asai.
    • Organizer
      The 13th Asian Society for Neuro-oncology (ASNO) Meeting.
    • Place of Presentation
      Sheraton on the Park, Sydney, Australia
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Therapeutical Doses of Temozolomide Inhibit IL-10 Production by Dendritic Cells and Enhance the CTL Response.2016

    • Author(s)
      Akio Asai, Ryoichi Iwata, Tomoki Ito, Muneo Inaba, Noriko Katashiba, Kayoko Kibata, Akihiro Tanaka, Shosaku Nomura.
    • Organizer
      The 21st International Conference on Brain Tumor Research and Therapy.
    • Place of Presentation
      Bankoku Shinryokan, Okinawa
    • Year and Date
      2016-04-10
    • Related Report
      2016 Research-status Report
  • [Presentation] グリオーマ癌幹細胞で発現するICOSリガンドを介した免疫制御機構の新展開2015

    • Author(s)
      岩田亮一, 伊藤量基, 稲葉宗夫, 小池太郎, 二宮英樹, 李一, 染野裕美子, 亀井孝昌, 武田純一, 大石哲也, 大重英行, 吉村晋一, 埜中正博, 山田久夫, 野村昌作, 中野伊知郎, 淺井昭雄
    • Organizer
      第33回日本脳腫瘍学会学術集会
    • Place of Presentation
      京都府京都市左京区宝ヶ池グランドプリンスホテル京都
    • Year and Date
      2015-12-06
    • Related Report
      2015 Research-status Report
  • [Presentation] Mesenchymal type Glioma Stem Cell express ICOS Ligand and upregulate Tr1 cells2015

    • Author(s)
      Ryoichi Iwata, Tomoki Ito, Muneo Inaba, Taro Koike, Hideyuki Oshige, Kunikazu Yoshimura, Masahiro Nonaka, Hisao Yamada, Shosaku Nomura, Umberto Dianzani, Ichiro Nakano, Akio Asai
    • Organizer
      the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Onclology
    • Place of Presentation
      San Antonio,Texas, USA San Antonio Marriott Rivercenter
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal type Glioma Stem Cell express ICOS Ligand and upregulate ICOS+IL-10+Tcells2015

    • Author(s)
      岩田亮一, 伊藤量基, 稲葉宗夫, 小池太郎, 大重英行, 吉村晋一, 埜中正博, 山田久夫, 野村昌作, 中野伊知郎, 淺井昭雄
    • Organizer
      第56回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      大阪府枚方市新町関西医科大学枚方新キャンパス
    • Year and Date
      2015-10-03
    • Related Report
      2015 Research-status Report
  • [Presentation] Therapeutical dose of Temozolomide inhibit IL-10 production by dendritic cells and enhance the CTL response2015

    • Author(s)
      Ryoichi Iwata, Tomoki Ito, Muneo Inaba, Noriko Katashiba, Kayoko Kibata, Akihiro Tanaka, Phan Thi Xuan Vien, Hideyuki Oshige, Kunikazu Yoshimura, Takehiro Suyama, Masahiro Nonaka, Shosaku Nomura, Akio Asai
    • Organizer
      ASNO 2015 12th Meeting of the Asian Society for Neuro-Onclology
    • Place of Presentation
      Pasay City Manila, Philippines Sofitel Philippine Plaza Hotel
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal typeのグリーマ癌幹細胞で発現するICOSリガンドは、IL-10産生T細胞を誘導する2015

    • Author(s)
      岩田亮一, 伊藤量基, 稲葉宗夫, 小池太郎, 大重英行, 吉村晋一, 埜中正博, 山田久夫, 野村昌作, 中野伊知郎, 淺井昭雄
    • Organizer
      第25回日本サイトメトリー学会学術集会
    • Place of Presentation
      東京都千代田区神田駿河台ソラシティカンファレンスセンター
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 悪性神経膠腫におけるICOSリガンドを介した腫瘍免疫抑制機序について2015

    • Author(s)
      岩田亮一, 伊藤量基, 小池太郎, 大重英行, 吉村晋一, 埜中正博, 山田久夫, 野村昌作, 中野伊知郎, 淺井昭雄
    • Organizer
      第33回日本脳腫瘍病理学会
    • Place of Presentation
      香川県高松市浜ノ町JRホテルクレメント高松
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Book] 【脳腫瘍学-基礎研究と臨床研究の進歩-】 転移性脳腫瘍 転移性脳腫瘍の治療2016

    • Author(s)
      岩田亮一、淺井昭雄
    • Total Pages
      5
    • Publisher
      日本臨牀
    • Related Report
      2016 Research-status Report
  • [Book] メディカ出版2015

    • Author(s)
      岩田亮一, 淺井昭雄
    • Total Pages
      400
    • Publisher
      中枢神経系感染症、脳神経外科救急ハンドブック 日本脳神経外科救急学会編 改訂第2版
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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