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Novel Strategy of Gene Therapy for Musculoskeletal Sarcoma-Targeting Intratumoral Spread of Viral Vectors

Research Project

Project/Area Number 21591920
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAGANO Satoshi  鹿児島大学, 医歯学総合研究科, 助教 (50373139)

Co-Investigator(Kenkyū-buntansha) KOMIYA Setsuro  鹿児島大学, 医歯学総合研究科, 教授 (30178371)
SETOGUCHI Takao  鹿児島大学, 医歯学総合研究科, 特任准教授 (40423727)
KAMIZONO Junichi  鹿児島大学, 医学部歯学部付病院, 医員 (30444897)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords癌 / 遺伝子治療 / ウイルスベクター / 骨軟部腫瘍 / 遺伝子
Research Abstract

We generated a novel survivin-responsive Surv. m-CRA-OCp, which is regulated by the survivin promoter and cancer/tissue-specific osteocalcin promoter, and demonstrated reduced toxicity to normal tissues, while maintaining its anticancer effects. Significant contribution of matrix-metalloproteinase-14 on vascular invasion and metastasis of breast cancer is shown. We analyzed hedgehog pathway in osteosarcoma and showed that inhibition of GLI2 may represent an effective therapeutic approach for patients with osteosarcoma.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (59 results)

All 2011 2010 2009 Other

All Journal Article (28 results) (of which Peer Reviewed: 28 results) Presentation (29 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses : implications for the generation of ideal m-CRAs2011

    • Author(s)
      Horikawa Y, Wang Y, Nagano S, Kamizono J, Ikeda M, Komiya S, Kosai KI.
    • Journal Title

      Cancer Gene Ther

      Volume: 18(10) Issue: 10 Pages: 724-33

    • DOI

      10.1038/cgt.2011.44

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors2011

    • Author(s)
      Perentes JY, Kirkpatrick ND, Nagano S, Smith EY, Shaver CM, Sgroi D, Garkavtsev I, Munn LL, Jain RK, Boucher Y.
    • Journal Title

      Cancer Res

      Volume: 71(13) Pages: 4527-38

    • URL

      http://cancerres.aacrjournals.org/content/71/13/4527.long

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR12011

    • Author(s)
      Matsunoshita Y, Ijiri K, Ishidou Y, Nagano S, Yamamoto T, Nagao H, Komiya S, Setoguchi T.
    • Journal Title

      PLoS One

      Volume: 6(1)

    • NAID

      120005342569

    • URL

      http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016234

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of GLI2 in the growth of human osteosarcoma2011

    • Author(s)
      Nagao H., Ijiri K., Hirotsu M., Ishidou Y., Yamamoto T., Nagano S., Takizawa T., Nakashima K., Komiya S., and Setoguchi T.
    • Journal Title

      The Journal of Pathology

      Volume: 224 Issue: 2 Pages: 169-79

    • DOI

      10.1002/path.2880

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth2011

    • Author(s)
      Kawabata N, Ijiri K, Ishidou Y, Yamamoto T, Nagao H, Nagano S, Maeda S, Komiya S, Setoguchi T.
    • Journal Title

      Int J Oncol

      Volume: 399 Pages: 899-906

    • DOI

      10.3892/ijo.2011.1076

    • NAID

      120005342568

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of GOLPH3 and GOLPH3L in the proliferation of human rhabdomyosarcoma2011

    • Author(s)
      Kunigou O., Nagao H., Kawabata N., Ishidou Y., Nagano S., Maeda S., Komiya S., and Setoguchi T.
    • Journal Title

      Oncology Reports

      Volume: 5 Pages: 1337-42

    • DOI

      10.3892/or.2011.1413

    • NAID

      120005342567

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical implications of determination of safe surgical margins by using a combination of CT and 18FDG-positron emission tomography in soft tissue sarcoma2011

    • Author(s)
      Yokouchi M, Terahara M, Nagano S, Arishima Y, Zemmyo M, Yoshioka T, Tanimoto A, Komiya S.
    • Journal Title

      BMC Musculoskelet Disord

      Volume: 12 Pages: 166-166

    • URL

      http://www.biomedcentral.com/1471-2474/12/166

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combination of ultrasound and bubble liposome enhance the effect of doxorubicin and inhibit murine osteosarcoma growth2011

    • Author(s)
      Ueno Y, Sonoda S, Suzuki R, Yokouchi M, Kawasoe Y, Tachibana K, Maruyama K, Sakamoto T, Komiya S.
    • Journal Title

      Cancer Biol Ther

      Volume: 12(4) Pages: 270-7

    • URL

      http://www.landesbioscience.com/journals/cbt/article/16259/

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical implications of determination of safe surgical margins by using a combination of CT and 18FDG-positron emission tomography in soft tissue sarcoma2011

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

      BMC Musculoskelet Disord

      Volume: 12(on-line) Pages: 166-166

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bilobular calcifying fibrous pseudotumor in soleus muscle : a case report2011

    • Author(s)
      Shinohara N, et al
    • Journal Title

      J Med Case Reports

      Volume: 5(on-line) Pages: 487-487

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer cell-associated MT1-MMP promotes blood vessel invasion and distant metastasis in triple-negative mammary tumors2011

    • Author(s)
      Perentes JY, et al
    • Journal Title

      Cancer Res

      Volume: 71 Pages: 4527-4538

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of GLI2 in the growth of human osteosarcoma.2011

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

      J.Pathol.

      Volume: (On-line publication)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR12011

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

      PLoS One.

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Senescence of chondrocytes in aging articular cartilage : GADD45β mediatesp21 expression in association with C/EBPβ in senescence-accelerated mice.2011

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

      Pathol Res Pract.

      Volume: 207 Pages: 225-231

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gadd45β expression in chondrosarcoma : a pilot study for diagnostic and biological implications in histological grading.2010

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

      Diagn.Pathol.

      Volume: 13 Pages: 69-69

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of Notch pathway molecules in oral squamous cell carcinoma.2010

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

      Int J Oncol.

      Volume: 36 Pages: 817-822

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 成人発症骨肉腫の治療における化学療法の意義2010

    • Author(s)
      永野聡, ほか
    • Journal Title

      整形外科と災害外科

      Volume: 59 Pages: 242-245

    • NAID

      10026059928

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ependymal cyst in the conus medullaris2010

    • Author(s)
      Nagano S., et al
    • Journal Title

      J Clin Neurosci 17

      Pages: 272-273

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Smoothened as a new therapeutic target for human osteosarcoma2010

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

      Mol Cancer 9

      Pages: 5-5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High Mobility Group Box 1 Is Upregulated After Spinal Cord Injury and Is Associated With Neuronal Cell Apoptosis2010

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

      Spine 26(On line publication)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mazabraud's syndrome with solitary myxoma and monostotic fibrous dysplasia2010

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

      J Orthop Sci 15(On line publication)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth2010

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

      Int J Oncol 23

      Pages: 677-84

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells2009

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

      Br J Cancer 101

      Pages: 2030-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation2009

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

      Br J Cancer 100

      Pages: 1957-65

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathway2009

    • Author(s)
      Taniguchi N, et al
    • Journal Title

      Proc Natl Acad Sci U S A 106

      Pages: 6817-22

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress deprivation from the patellar tendon induces apoptosis of fibroblasts in vivo with activation of mitogen-activated protein kinases2009

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

      J Biomech 42

      Pages: 2611-5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GADD45beta enhances Col10a1 transcription via the MTK1/MKK3/6/p38 axis and activation of C/EBPbeta-TAD4 in terminally differentiating chondrocytes2009

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

      J Biol Chem 285

      Pages: 8395-407

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retinal astrocyte differentiation mediated by leukemia inhibitory factor in cooperation with bone morphogenetic protein 22009

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

      Int J Dev Neurosci 27

      Pages: 685-90

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト骨肉腫におけるGLI2の機能解析2011

    • Author(s)
      中村俊介、瀬戸口啓夫、永尾宗子、永野聡、小宮節郎
    • Organizer
      第122回西日本整形・災害外科学会
    • Place of Presentation
      熊本市
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 後腹膜発生のCastleman's diseaseの1例2011

    • Author(s)
      海江田英泰, ほか
    • Organizer
      第122回西日本整形・災害外科学会
    • Place of Presentation
      熊本市
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨巨細胞腫に対する治療方法の検討2011

    • Author(s)
      篠原直弘, ほか
    • Organizer
      第122回西日本整形・災害外科学会
    • Place of Presentation
      熊本市
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒト骨肉腫におけるGLI2の強発現とGLI2をターゲットにした骨肉腫治療の可能性2011

    • Author(s)
      永尾宗子、小宮節郎、瀬戸口啓夫
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2011-07-28
    • Related Report
      2011 Final Research Report
  • [Presentation] 神経鞘腫の診断におけるPET, T1シンチの有用性-粘液型肉腫との比較2011

    • Author(s)
      永野聡, ほか
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Hedgehogシグナル制御による横紋筋肉腫の腫瘍増殖抑制効果2011

    • Author(s)
      川畑直也, ほか
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 横紋筋肉腫におけるGOLPH3遺伝子の高発現とその機能解析2011

    • Author(s)
      救仁郷修, ほか
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] FDG-PETを用いた軟部肉腫新規切除縁設定法2011

    • Author(s)
      寺原幹雄, ほか
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗腫瘍薬投与後のEGR1発現上昇と骨肉腫細胞浸潤抑制2011

    • Author(s)
      松野下幸弘, ほか
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨肉腫の患肢温存率に影響する因子の検討2010

    • Author(s)
      永野聡, ほか
    • Organizer
      第120回 西日本整形・災害外科学会
    • Place of Presentation
      佐賀市、佐賀県
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 三次元細胞培養を用いた腫瘍内遺伝子治療ベクター感染効率の解析2010

    • Author(s)
      永野聡、Boucher Y、小宮節郎
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都市、京都府
    • Year and Date
      2010-10-14
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 骨肉腫を多因子で特異標的かつ効果的に治療する革新的な増殖制御型アデノウイルス薬の開発2010

    • Author(s)
      堀川良治、永野聡、神囿純一、池田美奈子、小宮節郎、小戝健一郎
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都市、京都府
    • Year and Date
      2010-10-14
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 骨肉腫における切断術症例の検討2010

    • Author(s)
      永野聡、横内雅博、寺原幹雄、中島隆之、善明美千久、有島善也、小宮節郎
    • Organizer
      第43回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      新宿区、東京都
    • Year and Date
      2010-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 脂肪腫と高分化型脂肪肉腫の鑑別診断におけるMRI所見と血管密度の有用性2010

    • Author(s)
      永野聡, ほか
    • Organizer
      第43回日本整形外科学会 骨・軟部腫瘍学術集会
    • Place of Presentation
      千代田区、東京都
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨肉腫における切断術症例の検討2010

    • Author(s)
      永野聡, ほか
    • Organizer
      第43回日本整形外科学会 骨・軟部腫瘍学術集会
    • Place of Presentation
      新宿区、東京都
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tumor cell death-inducing Pretreatments Improves Distribution and Efficacy of Oncolytic Virus in Solid tumors2010

    • Author(s)
      Nagano S, Komiya S, Boucher Y.
    • Organizer
      The 20th Japanese-Korean Combined Orthopaedic Symposium
    • Place of Presentation
      指宿市、鹿児島県
    • Year and Date
      2010-06-04
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Significance of Chemotherapy for Treatments on Osteosarcoma in Adult Patients2010

    • Author(s)
      Nagano S, et al
    • Organizer
      The 20th Japanese-Korean Combined Orthopaedic Symposium
    • Place of Presentation
      指宿市、鹿児島県
    • Year and Date
      2010-06-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Functional analysis of EGR1 and its up-regulation using anti-tumor agents2010

    • Author(s)
      Matsunoshita Y., Setoguchi T., Kunigou O., Hirotsu M., Komiya S.
    • Organizer
      56th Annual Meeting of Orthopedic Research Society
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-03-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Smoothend as a new therapeutic target of osteosarcoma2010

    • Author(s)
      Kunigou O., et al
    • Organizer
      56^<th> Annual Meeting of Orthopedic Research Society
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Functional analysis of EGR1 and its up-regulation using anti-tumor agents2010

    • Author(s)
      Matsunoshita Y., et al
    • Organizer
      56^<th> Annual Meeting of Orthopedic Research Society
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] アポトーシス誘導型の前治療はoncolytic virusの腫瘍内拡散と抗腫瘍効果を向上させる2009

    • Author(s)
      永野聡、小宮節郎、Boucher Y.
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report
  • [Presentation] アポトーシス誘導型の前治療は oncolytic virus の腫瘍内拡散と抗腫瘍効果を向上させる2009

    • Author(s)
      永野聡, ほか
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhibition of Notch pathway prevents osteosarcoma growth by regulation of cell cycle2009

    • Author(s)
      Setoguchi T., Tanaka M., Komiya S.
    • Organizer
      15 th meeting of European CanCer Organisation(ECCO)
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2009-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Inhibition of Notch pathway prevents osteosarcoma growth by regulation of cell cycle2009

    • Author(s)
      Setoguchi T., et al
    • Organizer
      15th meeting of European CanCer Organisation(ECCO)
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2009-09-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Improved distribution and efficacy of oncolytic virus in solid tumors by apoptosis-inducing pretreatments2009

    • Author(s)
      Nagano S., Komiya S., Boucher Y.
    • Organizer
      15 th meeting of European CanCer Organisation(ECCO)
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2009-09-21
    • Related Report
      2011 Final Research Report
  • [Presentation] Improved distribution and efficacy of oncolytic virus in solid tumors by apoptosis-inducing pretreatments2009

    • Author(s)
      永野聡, ほか
    • Organizer
      15th meeting of European CanCer Organisation(ECCO)
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2009-09-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] 固形腫瘍の細胞密度と細胞外マトリックスの制御による新しいoncolytic遺伝子治療2009

    • Author(s)
      永野聡、Boucher Y、小宮節
    • Organizer
      第42回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-07-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 固形腫瘍の細胞密度と細胞外マトリックスの制御による新しい oncolytic 遺伝子治療2009

    • Author(s)
      永野聡, ほか
    • Organizer
      第42回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-07-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 成人発症骨肉腫の治療成績2009

    • Author(s)
      永野聡, ほか
    • Organizer
      第42回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-07-15
    • Related Report
      2009 Annual Research Report
  • [Book] バイオプシーの進め方、整形外科基本手技2011

    • Author(s)
      永野聡、小宮節郎
    • Publisher
      文光堂
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2018-02-02  

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