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Tumor-selective high LET and high RBE particles can overcome the radiation-resistant glioma stem cells

Research Project

Project/Area Number 23390355
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOsaka Medical College

Principal Investigator

MIYATAKE Shin-Ichi  大阪医科大学, 医学部, 教授 (90209916)

Co-Investigator(Kenkyū-buntansha) KAWABATA Shinji  大阪医科大学, 医学部, 講師 (20340549)
MICHIUE Hiroyuki  岡山大学, 医歯薬総合研究科, 助教 (20572499)
KUROIWA Toshihiko  大阪医科大学, 医学部, 教授 (30178115)
KAJIMOTO Yoshinaga  大阪医科大学, 医学部, 教授 (30224413)
KIRIHATA Mitsunori  大阪府立大学, 21世紀科学研究機構, 教授 (60128767)
MASUNAGA Shin-ichirou  京都大学, 原子炉実験所, 教授 (80238914)
ONO Koji  京都大学, 原子炉実験所, 教授 (90122407)
中村 英夫  熊本大学, 医学部附属病院, 講師 (30359963)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywordshigh LET / BNCT / glioma stem cell / 放射線抵抗性 / 癌幹細胞 / 放射線 / X線 / 粒子線 / グリオーマ幹細胞 / 高LET粒子線 / ほう素中性子捕捉療法 / 高LET放射線治療
Research Abstract

GSLC were induced from GBM cell line A172. The phenotypes of GSLCs were confirmed by stem cell markers. These cells were irradiated with 60Co gamma rays or reactor neutron beams. Under neutron beam irradiation, high-LET proton particles can be produced. Radiosensitivity was assessed by a CFA, and the DNA double-strand breaks (DSBs) were assessed by gamma-H2AX focus assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and express neural stem cell markers, Sox2 and Musashi, abundantly in comparison with their parental cells. GSLCs were significantly more radioresistant to gamma rays than their parental cells, but neutron beams overcame this resistance. Twenty-four hours after irradiation with gamma rays, there were significantly fewer gamma-H2AX foci in A172 GSLCs than in their parental cultured cells, while there was no apparent difference following neutron beam irradiation. High-LET radiation can overcome the radioresistance of GSLCs.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (48 results)

All 2014 2013 2012 2011

All Journal Article (26 results) (of which Peer Reviewed: 18 results,  Open Access: 2 results) Presentation (22 results) (of which Invited: 9 results)

  • [Journal Article] High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation2014

    • Author(s)
      Hirota Y, Masunaga SI, Kondo N, Kawabata S, Hirakawa H, Yajima H, Fujimori A, Ono K, Kuroiwa T, Miyatake SI
    • Journal Title

      J Radiat Res

      Volume: 55(1) Pages: 75-83

    • Related Report
      2013 Final Research Report
  • [Journal Article] The roles of Platelet-Derived Growth Factors and their receptors in brain radiation necrosis2014

    • Author(s)
      Miyata T, Toho T, Nonoguchi N, Furuse M, Kuwabara H, Yoritsune E, Kawabata S, Kuroiwa T, and Miyatake S
    • Journal Title

      Radiation Oncology

      Volume: 9 Pages: 51-51

    • Related Report
      2013 Final Research Report
  • [Journal Article] Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients : four cases2014

    • Author(s)
      Miyatake SI, Kawabata S, Hiramatsu R, Furuse M, Kuroiwa T, Suzuki M
    • Journal Title

      Radiat Oncol

      Volume: 9(1) Pages: 6-6

    • Related Report
      2013 Final Research Report
  • [Journal Article] High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation2014

    • Author(s)
      Hirota Y, Masunaga S, Kondo N, et al. 計10名
    • Journal Title

      J Radiat Res

      Volume: 55(1) Issue: 1 Pages: 75-83

    • DOI

      10.1093/jrr/rrt095

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The roles of platelet-derived growth factors and their receptors in brain radiation necrosis2014

    • Author(s)
      Miyata T, Toho T, Nonoguchi N, Furuse M, Kuwabara H, Yoritsune E, Kawabata S, Kuroiwa T, and Miyatake S
    • Journal Title

      Radiation Oncology

      Volume: 9 Issue: 1 Pages: 51-59

    • DOI

      10.1186/1748-717x-9-51

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases2014

    • Author(s)
      Miyatake SI, Kawabata S, Hiramatsu R, Furuse M, Kuroiwa T, Suzuki M.
    • Journal Title

      Radiation Oncology

      Volume: 9 Issue: 1 Pages: 6-11

    • DOI

      10.1186/1748-717x-9-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases2013

    • Author(s)
      Miyatake SI, Furuse M, Kawabata S, Maruyama T, Kumabe T, Kuroiwa T, Ono K
    • Journal Title

      Neuro Oncol

      Volume: 15(6) Pages: 650-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET Motomasa Furuse2013

    • Author(s)
      Naosuke Nonoguchi, Shinji Kawabata, Erina Yoritsune, Masatsugu Takahashi, Taisuke Inomata, Toshihiko Kuroiwa and Shin-Ichi Miyatake
    • Journal Title

      Bevacizumab Treatment for Jpn J Clin Oncol

      Volume: 43(3) Pages: 337-41

    • Related Report
      2013 Final Research Report
  • [Journal Article] Boron neutron capture therapy for recurrent high-grade meningiomas2013

    • Author(s)
      Kawabata S, Hiramatsu R, Kuroiwa T, Ono K, Miyatake SI
    • Journal Title

      J Neurosurg

      Volume: 119(4) Pages: 837-44

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map2013

    • Author(s)
      Hiramatsu R, Kawabata S, Furuse M, Miyatake S, Kuroiwa T
    • Journal Title

      Radiat Oncol

      Volume: 8(1) Pages: 192-192

    • Related Report
      2013 Final Research Report
  • [Journal Article] Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.2013

    • Author(s)
      Shin-Ichi Miyatake, Motomasa Furuse, Shinji Kawabata, Takashi Maruyama,
    • Journal Title

      Neuro Oncol

      Volume: 15 Issue: 6 Pages: 650-655

    • DOI

      10.1093/neuonc/not020

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bevacizumab Treatment for Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET2013

    • Author(s)
      Motomasa Furuse, Naosuke Nonoguchi, Shinji Kawabata1, Erina Yoritsune, Masatsugu Takahashi, Taisuke Inomata, Toshihiko Kuroiwa and Shin-Ichi Miyatake
    • Journal Title

      Jpn J Clin Oncol

      Volume: 43 Issue: 3 Pages: 337-341

    • DOI

      10.1093/jjco/hys231

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boron neutron capture therapy for recurrent high-grade meningiomas.2013

    • Author(s)
      Kawabata S, Hiramatsu R, Kuroiwa T, Ono K, Miyatake SI.
    • Journal Title

      J Neurosurg

      Volume: 119 Issue: 4 Pages: 837-844

    • DOI

      10.3171/2013.5.jns122204

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map2013

    • Author(s)
      Hiramatsu R, Kawabata S, Furuse M, Miyatake S, Kuroiwa T
    • Journal Title

      Radiation Oncology

      Volume: 8 Issue: 1 Pages: 192-200

    • DOI

      10.1186/1748-717x-8-192

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.2013

    • Author(s)
      Shin-Ichi Miyatake
    • Journal Title

      Neuro Oncol

      Volume: 印刷中

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.2013

    • Author(s)
      Sun Wei
    • Journal Title

      Photodiagnosis Photodyn Ther

      Volume: 10 Issue: 1 Pages: 42-50

    • DOI

      10.1016/j.pdpdt.2012.06.003

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boron neutron capture therapy for recurrent high-grade meningiomas2013

    • Author(s)
      Shinji Kawabata
    • Journal Title

      J Neurosurg

      Volume: 印刷中

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 症候性脳放射線壊死の診断と治療2013

    • Author(s)
      宮武伸一
    • Journal Title

      脳神経外科

      Volume: 41 Pages: 197-208

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 脳j放射線壊死の成因と治療 -高度医療(第3項先進医療)の申請2012

    • Author(s)
      宮武伸一
    • Journal Title

      脳神経外科ジャーナル

      Volume: 21 Pages: 472-479

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The distribution of vascular endothelial growth factor-producing cells in clinical radiation necrosis of the brain. - Pathological consideration of their potential roles2011

    • Author(s)
      Nonoguchi N
    • Journal Title

      J Neuro-Oncol

      Volume: 105 Issue: 2 Pages: 423-431

    • DOI

      10.1007/s11060-011-0610-9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II clinical study of boron neutron capture therapy combined with X-ray radiotherapy/temozolomide in patients with newly diagnosed glioblastoma multiforme-Study design and current status report2011

    • Author(s)
      Kawabata S
    • Journal Title

      Appl Radiat

      Volume: 69 Issue: 12 Pages: 1796-1799

    • DOI

      10.1016/j.apradiso.2011.03.014

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced expression of coproporphyrinogen oxidase in malignant brain tumors : CPOX expression and 5-ALA. induced fluorescence2011

    • Author(s)
      Kenkichi Takahashi, Naokado Ikeda, Naosuke Nonoguchi他7名
    • Journal Title

      Neuro-Oncology

      Volume: 13 Issue: 11 Pages: 1234-43

    • DOI

      10.1093/neuonc/nor116

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Application of a novel boronated porphyrin (H2OCP) as a dual sensitizer for both PDT and BNCT2011

    • Author(s)
      Hiramatsu R
    • Journal Title

      Lasers in Surgery & Medicine

      Volume: 43 Issue: 1 Pages: 52-58

    • DOI

      10.1002/lsm.21026

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Computed tomography imaging of transferrin targeting liposomes encapsulating both boron and iodine contrast agents by convection-enhanced delivery to F98 rat glioma for boron neutron capture therapy2011

    • Author(s)
      Miyata S, Kawabata S, Hiramatsu R, Doi A, Ikeda N, Yamashita T, Kuroiwa T, Kasaoka S, Maruyama K, Miyatake S.
    • Journal Title

      Neurosurgery

      Volume: 68巻 Issue: 5 Pages: 1380-1387

    • DOI

      10.1227/neu.0b013e31820b52aa

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases2011

    • Author(s)
      Furuse M
    • Journal Title

      J Neuro-Oncol

      Volume: 102 Issue: 3 Pages: 471-475

    • DOI

      10.1007/s11060-010-0333-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-l-phenylalanine in CCS-bearing animal models2011

    • Author(s)
      Ando T
    • Journal Title

      Appl Radiat

      Volume: 69 Pages: 1721-1724

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 悪性脳腫瘍に対するホウ素中性子捕捉療法の現状と未来2013

    • Author(s)
      宮武伸一
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      宮崎
    • Year and Date
      2013-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Bevacizumab for progressive radiation necrosis with the nuclear medicine diagnosis : institutional results and ongoing nation-wide clinical trial2013

    • Author(s)
      Miyatake S
    • Organizer
      SNO meeting
    • Place of Presentation
      San Fransisco
    • Year and Date
      2013-11-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 「症候性脳放射線壊死の核医学的診断とベバシズマブの静脈内投与による治療」薬事承認を目指した多施設共同研究2013

    • Author(s)
      宮武伸一, 他16 名
    • Organizer
      第3項先進医療 JASTRO 2013
    • Place of Presentation
      青森
    • Year and Date
      2013-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 薬事承認を目指した多施設共同研究, 第3項先進医療「症候性脳放射線壊死の核医学的診断とベバシズマブの静脈内投与による治療」日本脳神経外科学会2013

    • Author(s)
      宮武伸一, 他16 名
    • Organizer
      第72回学術総会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-18
    • Related Report
      2013 Final Research Report
  • [Presentation] 症候性脳放射線壊死に対する診断と治療2013

    • Author(s)
      宮武伸一
    • Organizer
      第72回日本医学放射線学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-04-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 症候性脳放射線壊死の核医学的診断とベバシズマブの静脈内投与による治療」薬事承認を目指した多施設共同研究、第3項先進医療2013

    • Author(s)
      宮武伸一、寺坂俊介、井内俊彦、別府高明、荒川芳輝、田部井勇助、成田善孝、中村英夫、坪井康次、永根基雄、古瀬元雅、三輪和弘、杉山一彦、阿部竜也、武笠晃丈、寺崎瑞彦、隈部俊宏
    • Organizer
      JASTRO 2013
    • Place of Presentation
      青森
    • Related Report
      2013 Annual Research Report
  • [Presentation] 症候性脳放射線壊死に対する診断と治療2013

    • Author(s)
      宮武伸一
    • Organizer
      第72回日本医学放射線学会総会 教育講演
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 悪性脳腫瘍に対するホウ素中性子捕捉療法の現状と未来2013

    • Author(s)
      宮武伸一
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      Munbai, India
    • Related Report
      2013 Annual Research Report
  • [Presentation] 薬事承認を目指した多施設共同研究、第3項先進医療2013

    • Author(s)
      宮武伸一、寺坂俊介、井内俊彦、別府高明、荒川芳輝、田部井勇助、成田善孝、中村英夫、坪井康次、永根基雄、古瀬元雅、三輪和弘、杉山一彦、阿部竜也、武笠晃丈、寺崎瑞彦、隈部俊宏
    • Organizer
      日本脳神経外科学会 第72回学術総会シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Bevacizumab for progressive radiation necrosis with the nuclear medicine diagnosis:2013

    • Author(s)
      Miyatake S
    • Organizer
      SNO meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Boron neutron capture therapy for malignant brain tumors, current status and future prospects.2013

    • Author(s)
      Miyatake S
    • Organizer
      The 7th Pan-pacific Neurosurgery Congress
    • Place of Presentation
      Hilton Waikoloa Village,Waikoloa,Hawaii,USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 症候性脳放射線壊死に対する 診断と治療2013

    • Author(s)
      宮武伸一
    • Organizer
      第72回日本医学放射線学会総会 教育講演
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] High LET-irradiation can overcome radioresistance of glioma stem-like cells which are radioresistant with low LET-irradiation.2012

    • Author(s)
      Yuki Hirota
    • Organizer
      15th ICNCT
    • Place of Presentation
      筑波国際会議場(茨城県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Glioms stem-like cellsに対するLow-LETおよびHigh-LET放射線の感受性検定2012

    • Author(s)
      弘田祐己
    • Organizer
      日本分子脳神経外科学会
    • Place of Presentation
      熊本市国際交流会館(熊本県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] High LET放射線を用いたGlioma stem like cellsに対するLow LET放射線抵抗性の克服2012

    • Author(s)
      弘田祐己
    • Organizer
      日本脳神経外科学会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腫瘍細胞選択的粒子線治療「ホウ素中性子捕捉療法」2012

    • Author(s)
      宮武伸一
    • Organizer
      第32回日本脳神経外科コングレス総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] PET Imaging, Using Amino-acid Tracer for the Analysis of Tumor and Brain Molecular Metabolism.2012

    • Author(s)
      宮武伸一
    • Organizer
      第30回日本脳腫瘍病理学会,ランチョンセミナー
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 症候性脳放射線壊死に対するベバシズマブの静脈内投与による治療(高度医療評価制度の利用)2011

    • Author(s)
      宮武伸一
    • Organizer
      第20回日本定位放射線学会シンポジウム
    • Place of Presentation
      ウインク愛知(愛知県)
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 高度医療(第3項先進医療)「症候性脳放射線壊死に対する核医学的診断とベバシズマブの静脈内投与による治療」について2011

    • Author(s)
      宮武伸一
    • Organizer
      第8回日本中性子捕捉療法学会学術大会
    • Place of Presentation
      徳島大学(徳島県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高度医療(第3項先進医療)「症候性脳放射線壊死に対する核医学的診断とベバシズマブの静脈内投与による治療」について。2011

    • Author(s)
      宮武伸一
    • Organizer
      第70回日本脳神経外科学会学術総会シンポジウム
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 高度医療(第3項先進医療)「症候性脳放射線壊死に対する核医学的診断とベバシズマブの静脈内投与による治療」について。2011

    • Author(s)
      宮武伸一
    • Organizer
      第51回日本核医学会学術総会ワークショップ
    • Place of Presentation
      つくば国際会議場(茨城県)
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 脳腫瘍の放射線治療に伴う脳壊死―機序と対策―2011

    • Author(s)
      宮武伸一
    • Organizer
      第24回日本放射線学会学術総会 シンポジウム
    • Place of Presentation
      神戸ポートピアホテル(兵庫県)
    • Related Report
      2011 Annual Research Report
    • Invited

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Published: 2011-04-06   Modified: 2019-07-29  

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