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Isolation of cancer stem cells in bone and soft tissue tumors and novel molecular and cellular targeting therapy

Research Project

Project/Area Number 20591765
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionNara Medical University

Principal Investigator

HONOKI Kanya  Nara Medical University, 医学部・医学科, 講師 (40336863)

Co-Investigator(Kenkyū-buntansha) TSUJIUCHI Toshifumi  近畿大学, 理工学部・生命科学科, 教授 (10254492)
Research Collaborator TANAKA Yasuhito  奈良県立医科大学, 医学部・医学科, 教授 (30316070)
TOHMA Yasuaki  奈良県立医科大学, 医学部・医学科, 博士研究員 (60448777)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordssarcoma / cancer stem cell / gene expression / drug resistance / osteosarcoma / mesenchymal stem cell / metastasis / stem cell niche / sarcosphere / DNA repair / INK4a
Research Abstract

The current study indicates that rat and human sarcoma cells contain subpopulation of stem like cells with the formation of 'sarcoshpere'in anchorage-independent, serum starved culture condition, showing higher expression of stemness genes with the ability of self-renewal. Sarcosphere cells show the capacity of resistance to chemo-agents due to the up-regulation of DNA repair enzymes. These results suggest that the chemo-resistance in sarcomas might be caused in part by the presence of stem-like cell populations. These results suggest that targeting sarcoma stem cells could improve the prognosis of sarcoma patients.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (57 results)

All 2011 2010 2009 2008 Other

All Journal Article (30 results) (of which Peer Reviewed: 28 results) Presentation (25 results) Book (2 results)

  • [Journal Article] Mutations and aberrant transcriptions of stk11 (lkb1) gene in rat liver tumors.2011

    • Author(s)
      Wakabayashi N, et al.
    • Journal Title

      Anticancer Res.

      Volume: 31 Pages: 543-547

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of lysophosphatidic acid receptor-3 enhances cell migration in rat lung tumor cells.2011

    • Author(s)
      Hayashi M, et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 405 Pages: 450-454

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of lysophosphatidic acid receptor-5 gene in the acquisition of growth advantage of rat tumor cells.2011

    • Author(s)
      Okabe K, et al.
    • Journal Title

      Mol Carcinog.

      Volume: (E-pub ahead)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance.2010

    • Author(s)
      Honoki K, Fujii H, Kubo A, Kido A, Mori T, Tanaka Y, Tsujiuchi T.
    • Journal Title

      Oncol.Rep 24

      Pages: 501-505

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Do stem-like cells play a role in drug resistance of sarcomas? Expert Rev.2010

    • Author(s)
      朴木寛弥
    • Journal Title

      Anticancer Ther. 10

      Pages: 261-270

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutations of lysophosphatidic acid receptor genes in human osteosarcoma cells.2010

    • Author(s)
      Okabe K, Hayashi M, Fujii M, Honoki K, Mori T, Fukushima N, Tsujiuchi T.
    • Journal Title

      Pathobiology 77(5)

      Pages: 278-282

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hibernoma of the axillary region: a rare benign adipocytic tumor.2010

    • Author(s)
      Honoki K, Morita K, Kasai T, Fujii H, Kido A, Tsukamoto S, Nonomura A, Tanaka Y.
    • Journal Title

      Rare Tumors 2(Epub)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Type 1 neurofibromatosis with a giant intrathoracic lesion : A case report with 25 years of follow-up2010

    • Author(s)
      Tsukamoto S, Kido A, Honoki K, Akahane M, Mii Y, Tanaka Y.
    • Journal Title

      Pathol Res. Pract (Epub ahead)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 骨軟部腫瘍・現況と展望について2010

    • Author(s)
      朴木寛弥
    • Journal Title

      奈良県医師会医学会年報 23

      Pages: 25-31

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutations of lysophosphatidic acid receptor genes in human osteosarcoma cells.2010

    • Author(s)
      Okabe K, et al.
    • Journal Title

      Pathobiology

      Volume: 77 Pages: 278-282

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Allogeneic and autologous stem cell transplantation in advanced small round cell sarcomas.2010

    • Author(s)
      Kido A, et al.
    • Journal Title

      J Orthop Sci.

      Volume: 1 Pages: 690-695

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alterations of the LKB1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.2010

    • Author(s)
      Tajiri M, et al.
    • Journal Title

      Pathobiology

      Volume: 77 Pages: 225-229

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance.2010

    • Author(s)
      Honoki K, et al.
    • Journal Title

      Oncol.Rep.

      Volume: 24 Pages: 501-505

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Do stem-like cells play a role in drug resistance of sarcomas?2010

    • Author(s)
      Honoki K
    • Journal Title

      Expert Rev.Anticancer Ther. 10

      Pages: 261-270

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hibernoma of the axillary region : a rare benign adipocytic tumor2010

    • Author(s)
      Honoki K, et al
    • Journal Title

      Rare Tumors 2(Epub ahead)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type 1 neurofibromatosis with a giant intrathoracic lesion : A casereport with 25 years of follow-up2010

    • Author(s)
      Tsukamoto S, et al
    • Journal Title

      Pathol Res Pract. (Epub)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelioid sarcoma of the forearm arising from perineural sheath of median nerve mimicking carpal tunnel syndrome.2009

    • Author(s)
      Fujii H, Honoki K, Yajima H, Kido A, Kobata Y, Kaji D, Takakura Y.
    • Journal Title

      Sarcoma. (Epub 2009 Apr 14)

      Pages: 595391-595391

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines.2009

    • Author(s)
      Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y.
    • Journal Title

      Int J Oncol 34

      Pages: 1381-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pelvic metastasis of breast synovial sarcoma.2009

    • Author(s)
      Yoshitani K, Kido A, Honoki K, Fujii H, Takakura Y.
    • Journal Title

      J Orthop Sci 142

      Pages: 219-23

    • NAID

      10025587876

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] がん細胞の社会学 ~良・悪性を隔てるもの~2009

    • Author(s)
      朴木寛弥
    • Journal Title

      大阪臨床整形外科医会会報 36

      Pages: 90-93

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutations of LKB1 gene in pancreatic ductal adenocarcinoma induced by N-nitrosobis(2-oxopropyl)amine in hamsters2009

    • Author(s)
      Furukawa M, et al
    • Journal Title

      Anticancer.Res. 29

      Pages: 4047-4050

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelioid sarcoma of the forearm arising from perineural sheath of median nerve mimicking carpal tunnel syndrome2009

    • Author(s)
      Fujii H, et al
    • Journal Title

      Sarcoma (Epub)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines2009

    • Author(s)
      Fujii H, et al
    • Journal Title

      Internatl.J.Oncol. 34

      Pages: 1381-1386

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pelvic metastasis of breast synovial sarcoma2009

    • Author(s)
      Yoshitani K, et al
    • Journal Title

      J.Orthop.Sci 142

      Pages: 219-223

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations of lysophosphatidic acid receptor-1 gene during progression of lung tumors in rats.2009

    • Author(s)
      Yanada T, et al
    • Journal Title

      BBRC 378(Epub)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent mutations of lysophosphatidic acid receptor-1 gene in rat liver tumors.2009

    • Author(s)
      Obo Y, et al
    • Journal Title

      Mutat. Res. 660(Epub)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth inhibition and induction of apoptosis by 3-Methoxyestradiol in rat osteosarcoma and makignant fibrous histiocytoma cell lines.2008

    • Author(s)
      Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y.
    • Journal Title

      In vivo 22

      Pages: 21-26

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epiphyseal preservation and an intercalary vascularized fibular graft with hydroxyapatite composites. Reconstruction in metaphyseal osteosarcoma of the proximal tibia: a case report.2008

    • Author(s)
      Honoki K, Kobata Y, Miyauchi Y, Yajima H, Fujii H, Kido A, Kawamura K, Morishita T, Mii Y, Takakura T
    • Journal Title

      Arch Orthop Trauma Surg 128

      Pages: 189-193

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines

    • Author(s)
      Fujii H, et al
    • Journal Title

      Int. J Oncol. (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelioid sarcoma of the forearm arising from perineural sheath of median nerve mimicking carpal tunnel syndrome

    • Author(s)
      Fujii H, et al
    • Journal Title

      Sarcoma (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 間葉系幹細胞はラット肉腫モデルにおいて腫瘍細胞の早期正着および転移巣形成を促進する2010

    • Author(s)
      朴木寛弥, 他
    • Organizer
      第69回 日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 再発直腸癌における仙骨合併切除の手術適応と手術禁忌に関する文献調査研究2010

    • Author(s)
      城戸顕, 他
    • Organizer
      第69回 日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] コリン欠乏アミノ酸食によるラット寛発がん過程におけるLpa3遺伝子DNAメチル化異常2010

    • Author(s)
      岡部恭子, 他
    • Organizer
      第69回 日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] ニトロソ化合物によるラット拝・肝がん発生におけるLpa5遺伝子発現異常2010

    • Author(s)
      藤井美奈子, 他
    • Organizer
      第69回 日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Possible involvement of stem-like populations with elevated ALDH1 and DNA repair enzymes for drug resistance in human sarcoma2010

    • Author(s)
      Honoki, K, et al
    • Organizer
      56^<th> Orthopedic Research Society Annual Meeting
    • Place of Presentation
      New Orleans, LA USA
    • Year and Date
      2010-03-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cancer stem cell in sarcomas : Role in drug resistance and tumor progression.2010

    • Author(s)
      朴木寛弥
    • Organizer
      BIT's 3^<rd> Annual World Cancer Congress
    • Place of Presentation
      Singapore
    • Related Report
      2010 Final Research Report
  • [Presentation] Possible involvement of stem-like population with elevated ALDH1 and DNA repair enzymes for drug resistance in human sarcoma.2010

    • Author(s)
      Honoki K, Fujii H, Kido A, Tsukamoto S, Tanaka Y, Tsujiuchi T
    • Organizer
      56^<th> Annual Meeting of Orthopedic Research Society
    • Related Report
      2010 Final Research Report
  • [Presentation] 間葉系幹細胞はラット肉腫モデルにおいて腫瘍細胞の早期正着および転移巣形成を促進する2010

    • Author(s)
      朴木寛弥、藤井宏真、藤間保晶、森俊夫、城戸顕、辻内俊文
    • Organizer
      第69回日本癌学会総会
    • Related Report
      2010 Final Research Report
  • [Presentation] がん患者の病的骨折リスク管理を目的とした新しい診療プロトコルの開発2010

    • Author(s)
      城戸顕, 朴木寛弥, 赤羽学, 山崎正晴, 田中康仁
    • Organizer
      第43回日本整形外科学会骨軟部腫瘍学会
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト肉腫幹細胞様細胞はアルデヒドデヒドロゲナーゼ1およびDNA修復酵素を高発現し強い薬剤抵抗性を示す2009

    • Author(s)
      朴木寛弥, 他
    • Organizer
      68^<th>日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-10-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] がん細胞の社会学~良・悪性を隔てるもの2009

    • Author(s)
      朴木寛弥
    • Organizer
      第209回 大阪臨床整形外科医会研修会
    • Place of Presentation
      ANAクラウンプラザホテル大阪
    • Year and Date
      2009-09-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] Human sarcoma cell lines contain drug-resistant shere forming stem-like cell populations with elevated aldehyde dehydrogenase 12009

    • Author(s)
      Honoki, K, et al
    • Organizer
      100^<th> AACR Annual Meeting
    • Place of Presentation
      Denver, CO, USA
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Human sarcoma cell lines contain drug-resistant shere forming stem-like cell populations with elevated aldehyde dehydrogenase 12009

    • Author(s)
      Honoki K, Fujii H, Kubo A, Kido A, Yoshitani K, Mori T, Tsujiuchi T
    • Organizer
      100^<th> Annual Meeting of American Association for Cancer Research
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト肉腫幹細胞様細胞はアルデヒドデヒドロゲナーゼ1およびDNA修復酵素を高発現し強い薬剤抵抗性を示す2009

    • Author(s)
      朴木寛弥, 藤井宏真, 久保篤史、城戸顕, 森俊夫、辻内俊文
    • Organizer
      第68回日本癌学会総会
    • Related Report
      2010 Final Research Report
  • [Presentation] 低濃度ビスフォスフォネート製剤による造骨性肉腫細胞株の局所浸潤能の増強作用2009

    • Author(s)
      城戸顕, 芳谷和洋, 朴木寛弥, 藤井宏真
    • Organizer
      第68回日本癌学会総会
    • Related Report
      2010 Final Research Report
  • [Presentation] イホマイド脳症における危険因子の検討2009

    • Author(s)
      藤井宏真、朴木寛弥、城戸顕、芳谷和洋、高倉義典
    • Organizer
      第82回日本整形外科学会総会
    • Related Report
      2010 Final Research Report
  • [Presentation] がん細胞の社会学~良・悪性を隔てるもの~2009

    • Author(s)
      朴木寛弥
    • Organizer
      第209回大阪臨床整形外科医会研修会
    • Related Report
      2010 Final Research Report
  • [Presentation] Identification of sphere forming chemo-resistant stem-like cells in human Ewing sarcoma HTB166 cell line2008

    • Author(s)
      Honoki, K, et al
    • Organizer
      67^<th> 日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト肉腫細胞における腫瘍幹細胞の単離の試み2008

    • Author(s)
      藤井宏真, 他
    • Organizer
      23th 日本整形外科学会基礎学術集会(パネル・ディスカッション)
    • Place of Presentation
      京都
    • Year and Date
      2008-10-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Stem-like sphere forming cell populations in sarcomas. Implications in chemo-resistance and possible therapeutic targets.2008

    • Author(s)
      Honoki, K, et al
    • Organizer
      8^<th> International Conference of Anti-Cancer Eesearch (Invited speaker)
    • Place of Presentation
      Kos Greece
    • Year and Date
      2008-10-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Human fibrosarcoma cell line HT1080 lacking INK4a-ARF locusgene expression contains sphere forming stem-like cells2008

    • Author(s)
      Honoki, K, et al
    • Organizer
      99^<th> AACR Annual Meeting
    • Place of Presentation
      San Diego, CA USA
    • Year and Date
      2008-04-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] Human fibrosarcoma cell line HT1080lacking INK4a-ARF locus gene expression contains shere forming stem-like cells.2008

    • Author(s)
      Honoki K, Fujii H, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y
    • Organizer
      99^<th> Annual Meeting of American Association for Cancer Research
    • Related Report
      2010 Final Research Report
  • [Presentation] Stem-like sphere forming cell populations in sarcomas. Implications in chemo-resistance and possible therapeutic targets.2008

    • Author(s)
      朴木寛弥, 藤井宏真, 高倉義典, 辻内俊文
    • Organizer
      8^<th> International Conference of Anticancer Research
    • Place of Presentation
      Kos, Greece
    • Related Report
      2010 Final Research Report
  • [Presentation] ユーイング肉腫細胞株HTB166における化学療法抵抗性幹細胞様細胞の単離2008

    • Author(s)
      朴木寛弥, 藤井宏真, 城戸顕, 辻内俊文
    • Organizer
      第67回日本癌学会総会
    • Related Report
      2010 Final Research Report
  • [Presentation] 高純度β-TCPによる良性骨腫瘍の治療2008

    • Author(s)
      宮内義純, 三井宜夫, 森下亨, 朴木寛弥, 城戸顕, 芳谷和洋, 藤井宏真, 高倉義典
    • Organizer
      第41回日本整形外科学会骨軟部腫瘍学会
    • Related Report
      2010 Final Research Report
  • [Book] Cancer Stem Cell Niche : The Role of Mesenchymal Stem Cells in Tumor Microenvironment. In : Cancer Stem Cells (ISBN 978-953-307-1454-5)2011

    • Author(s)
      Honoki K, Fujii H, Tsujiuchi T.
    • Publisher
      INTECH d.o.o., Rijeka, Croatia, in press
    • Related Report
      2010 Final Research Report
  • [Book] Cancer Stem Cells (ISBN 978-953-307-1454-5)2011

    • Author(s)
      Honoki, K., et al.
    • Publisher
      INTECH d.o.o., Rijeka, Croatia(In press)
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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