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2013 Fiscal Year Final Research Report

Treatment strategy and analysis of progression mechanism of musculoskeletal tumors using fluorescent imaging

Research Project

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Project/Area Number 23390360
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

TSUCHIYA Hiroyuki  金沢大学, 医学系, 教授 (40227434)

Co-Investigator(Renkei-kenkyūsha) YAMAMOTO Norio  金沢大学, 医薬保健学総合研究科, 特任教授 (90332668)
SHIRAI Toshiharu  京都府立医科大学, 大学院・医学研究科, 講師 (20397186)
HAYASHI Katsuhiro  金沢大学, 大学病院, 助教 (80507054)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords骨・軟部腫瘍学
Research Abstract

Fluorescent labeled osteosarcoma cell line was transplanted in nude mice and harvested in lung metastasis to obtain higher metastatic cell line. The more metastatic potential, the more PAI -1 and u-PA levels increased. We previously reported that caffeine-assisted chemotherapy. We found caffeine affects tumor cells through various pathways, such as PTEN, AKT, NF-kB, and ERK activities. Modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by fluorescent ubiquitination-based cell cycle indicator in the nucleus. Caffeine overcame the cell-cycle arrest induced by cisplatinum, thereby increasing its efficacy. Theobromine, a caffeine derivative, was investigated as a new anti-cancer effect. It elevates intracellular cAMP levels and inhibits cell proliferation. Surgical navigation for bone and soft tissue tumor in mouse and human was also performed using ICG and near-infrared fluorescent imaging.

  • Research Products

    (52 results)

All 2014 2013 2012 2011

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (28 results) (of which Invited: 9 results)

  • [Journal Article] Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B2014

    • Author(s)
      Sugimoto N, Miwa S, Hitomi Y, Nakamura H, Tsuchiya H, Yachie A
    • Journal Title

      Nutr Cancer

      Volume: 66(3) Pages: 419-23

    • DOI

      10.1080/01635581.2013.877497

    • Peer Reviewed
  • [Journal Article] A novel method to apply osteogenic potential of adipose derived stem cells in orthopaedic surgery2014

    • Author(s)
      Fang X, Murakami H, Demura S, Hayashi K, Matsubara H, Kato S, Yoshioka K, Inoue K, Ota T, Shinmura K, Tsuchiya H
    • Journal Title

      PLoS One

      Volume: 9(2) Pages: e88874

    • DOI

      10.1371/journal.pone.0088874

    • Peer Reviewed
  • [Journal Article] Imaging UVC-induced DNA damage response in models of minimal cancer2013

    • Author(s)
      Miwa S, Yano S, Hiroshima Y, Tome Y, Uehara F, Mii S, Efimova EV, Kimura H, Hayashi K, Tsuchiya H, Hoffman RM
    • Journal Title

      J Cell Biochem

      Volume: 114(11) Pages: 2493-9

    • DOI

      10.1002/jcb.24599

    • Peer Reviewed
  • [Journal Article] Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy2013

    • Author(s)
      Miwa S, Yano S, Tome Y, Sugimoto N, Hiroshima Y, Uehara F, Mii S, Kimura H, Hayashi K, Efimova EV, Fujiwara T, Tsuchiya H, Hoffman RM
    • Journal Title

      J Cell Biochem

      Volume: 114(11) Pages: 2454-60

    • DOI

      10.1002/jcb.24593

    • Peer Reviewed
  • [Journal Article] Single Cell Time-lapse Imaging of Focus Formation by the DNA Damage-Response Protein 53BP1 after UVC Irradiation of Human Pancreatic Cancer Cells2013

    • Author(s)
      Miwa S, Tome Y, Yano S, Hiroshima Y, Uehara F, Mii S, Kimura H, Hayashi K, Tsuchiya H, Bouvet M, Efimova EV, Hoffman RM
    • Journal Title

      Anticancer Res

      Volume: 33 Pages: 1373-7

    • Peer Reviewed
  • [Journal Article] Diagnosis and treatment of low-grade osteosarcoma : experience with nine cases2013

    • Author(s)
      Hayashi K, Tsuchiya H, Yamamoto N, Shirai T, Nishida H, Takeuchi A, Kimura H, Miwa S, Inatani H, Okamoto H, Yamada S, Ikeda H, Sawada-Kitamura S, Nojima T, Ooi A, Otsuka T
    • Journal Title

      Int J Clin Oncol

    • DOI

      10.1007/s10147-013-0592-z

    • Peer Reviewed
  • [Journal Article] Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities2013

    • Author(s)
      Shimozaki S, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Inatani H, Kato T, Tsuchiya H
    • Journal Title

      J Orthop Sci

      Volume: 19(1) Pages: 156-63

    • DOI

      10.1007/s00776-013-0487-x

    • Peer Reviewed
  • [Journal Article] Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft2013

    • Author(s)
      Miwa S, Takeuchi A, Ikeda H, Shirai T, Yamamoto N, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Igarashi K, Tsuchiya H
    • Journal Title

      PLoS One

      Volume: 8(8) Pages: e71362

    • DOI

      10.1371/journal.pone.0071362

    • Peer Reviewed
  • [Journal Article] Chemotherapy for osteosarcoma - where does it come from? What is it? Where is it going?2013

    • Author(s)
      Yamamoto N, Tsuchiya H
    • Journal Title

      Expert Opin Pharmacother

      Volume: 14(16) Pages: 2183-93

    • DOI

      10.1517/14656566.2013.827171

    • Peer Reviewed
  • [Journal Article] Innovative antimicrobial coating of titanium implants with iodine2012

    • Author(s)
      Tsuchiya H, Shirai T, Nishida H, Murakami H, Kabata T, Yamamoto N, Watanabe K, Nakase J
    • Journal Title

      J Orthop Sci

      Volume: 5 Pages: 595-604

    • DOI

      10.1007/s00776-012-0247-3

    • Peer Reviewed
  • [Journal Article] Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes2012

    • Author(s)
      Yamamoto N, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Inatani H, Shimozaki S, Kitamura S, Tsuchiya H
    • Journal Title

      Anticancer Res

      Volume: 32 Pages: 1821-5

    • Peer Reviewed
  • [Journal Article] Histological study on liquid nitrogen-treated tumor-bearing bone of the proximal femur excised eight years after transplantation2012

    • Author(s)
      Yamamoto N, Inatani H, Shirai T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Igarashi K, Shimozaki S, Kato T, Tsuchiya H
    • Journal Title

      Low Temp Med

      Volume: 38 Pages: 5-8

    • Peer Reviewed
  • [Journal Article] Imaging the inhibition by anti-β1 integrin antibody of lung seeding of single osteosarcoma cells in live mice2012

    • Author(s)
      Kimura H, Tome Y, Momiyama M, Hayashi K, Tsuchiya H, Bouvet M, Hoffman RM
    • Journal Title

      Int J Cancer

      Volume: 131 Pages: 2027-33

    • DOI

      10.1002/ijc.27475

    • Peer Reviewed
  • [Journal Article] A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma2012

    • Author(s)
      Miwa S, Taki J, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Ooi A, Tsuchiya H
    • Journal Title

      Journal of Surgical Oncology

      Volume: 106 Pages: 273-9

    • DOI

      10.1002/jso.23074

    • Peer Reviewed
  • [Journal Article] Caffeine induces apoptosis by inhibiting Akt/mTOR/S6K, NF-κB and MAPK pathways in osteosarcoma cell2012

    • Author(s)
      Miwa S, Sugimoto N, Yamamoto N, Shirai T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Igarashi K, Yachie A, Tsuchiya H
    • Journal Title

      Anticancer Research

      Volume: 32 Pages: 3643-9

    • Peer Reviewed
  • [Journal Article] TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors2012

    • Author(s)
      Miwa S, Nishida H, Tanzawa Y, Takeuchi A, Yamamoto N, Hayashi K, Kimura H, Tsuchiya H
    • Journal Title

      PLoS ONE

      Volume: 926

    • DOI

      10.1371/annotation/7c0f14e6-cfba-4f5f-b93d-1a149eaeec96

    • Peer Reviewed
  • [Journal Article] Uncultured adipose-derived regenerative cells promote peripheral nerve regeneration2012

    • Author(s)
      Suganuma S, Tada K, Hayashi K, Takeuchi A, Sugimoto N, Ikeda K, Tsuchiya H
    • Journal Title

      J Orthop Sci

      Volume: 18 Pages: 145-51

    • DOI

      10.1007/s00776-012-0306-9

    • Peer Reviewed
  • [Journal Article] Basic science and clinical frontiers of sarcoma treatment2011

    • Author(s)
      Tsuchiya H
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Pages: 82-83

    • DOI

      10.1007/s10147-011-0219-1

    • Peer Reviewed
  • [Journal Article] Tumor imaging with multicolor fluorescent protein expression2011

    • Author(s)
      Yamamoto N, Tsuchiya H
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Pages: 84-91

    • DOI

      10.1007/s10147-011-0201-y

    • Peer Reviewed
  • [Journal Article] High-grade undifferentiated pleomorphic sarcoma of pelvis treated with curettage and bone graft after complete remission following caffeine-potentiated chemotherapy2011

    • Author(s)
      Tsuchiya H
    • Journal Title

      J Orthop Sci

      Volume: 16 Pages: 476-481

    • DOI

      10.1007/s00776-011-0056-0

    • Peer Reviewed
  • [Journal Article] Comparison of Cancer-Cell Seeding, Viability and Deformation in the Lung, Muscle and Liver, Visualized by Subcellular Real-time Imaging in the Live Mouse2011

    • Author(s)
      Hayashi K, Kimura H, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Kishimoto H, Hasegawa A, Bouvet M, Hoffman RM
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 3665-72

    • Peer Reviewed
  • [Journal Article] Potentiation of the antitumor effect of calcium phosphate cement containing anticancer drug and caffeine on rat osteosarcoma2011

    • Author(s)
      Tanzawa Y, Tsuchiya H, Shirai T, Nishida H, Hayashi K, Takeuchi A, Kawahara M, Tomita K
    • Journal Title

      J Orthop Sci

      Volume: 16 Pages: 77-84

    • DOI

      10.1007/s00776-011-0045-3

    • Peer Reviewed
  • [Journal Article] Use of (99m)Tc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma : comparison with (201)Tl scintigraphy and angiography2011

    • Author(s)
      Miwa S, Shirai T, Taki J, Sumiya H, Nishida H, Hayashi K, Takeuchi A, Ooi A, Tsuchiya H
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Pages: 373-8

    • DOI

      10.1007/s10147-011-0194-6

    • Peer Reviewed
  • [Journal Article] Caffeine activates tumor suppressor PTEN in sarcoma cells2011

    • Author(s)
      Miwa S, Sugimoto N, Shirai T, Hayashi K, Nishida H, Ohnari I, Takeuchi A, Yachie A, Tsuchiya H
    • Journal Title

      Int J Oncol

      Volume: 39 Pages: 465-72

    • DOI

      10.3892/ijo.2011.1051

    • Peer Reviewed
  • [Presentation] Biological reconstruction in tumor surgery2013

    • Author(s)
      土 屋弘行
    • Organizer
      Annual Meeting of Hellenic Association of Orthopaedic Surgery and Traumatology
    • Place of Presentation
      DIVANI CARAVEL HOTEL (Greece)
    • Year and Date
      20131002-05
    • Invited
  • [Presentation] 骨腫瘍2013

    • Author(s)
      土屋弘行
    • Organizer
      日本小児整形外科学会
    • Place of Presentation
      京都府立医科大学青蓮会館(京都)
    • Year and Date
      20130824-25
    • Invited
  • [Presentation] Invasion and metastasis : from basics to real-time imaging2013

    • Author(s)
      土屋弘行
    • Organizer
      European Musculoskeletal Oncology Society Meeting
    • Place of Presentation
      Swedish Exhibition and Congress Center (Sweden)
    • Year and Date
      20130611-13
    • Invited
  • [Presentation] 悪性骨軟部腫瘍再建術の未来2013

    • Author(s)
      土屋弘行
    • Organizer
      日本整形外科学会学術集会
    • Place of Presentation
      リーガロイヤルホテル広島(広島)
    • Year and Date
      20130523-26
    • Invited
  • [Presentation] 骨軟部腫瘍学の進歩2013

    • Author(s)
      土屋弘行
    • Organizer
      東日本整形外科災害外科学会
    • Place of Presentation
      軽井沢プリンスホテル(長野)
    • Year and Date
      2013-09-21
    • Invited
  • [Presentation] 骨腫瘍における機能再建術2013

    • Author(s)
      土屋弘行
    • Organizer
      第9回整形外科アップデートセミナー
    • Place of Presentation
      東京ドームホテル(東京)
    • Year and Date
      2013-07-27
    • Invited
  • [Presentation] 骨肉腫に対する挑戦2013

    • Author(s)
      土屋弘行
    • Organizer
      平成25年度十全同窓会新任教授就任記念講演会
    • Place of Presentation
      十全講堂(金沢)
    • Year and Date
      2013-07-06
    • Invited
  • [Presentation] Progress of osteosarcoma treatment : Ultimate conservative surgery in conjunction with caffeine-potentiated chemotherapy2012

    • Author(s)
      Tsuchiya H
    • Organizer
      17th World Congress on Advances in Oncology and 15th International Symposium on Molecular Medicine
    • Place of Presentation
      Creta Maris Hotel (Greece)
    • Year and Date
      20121011-13
    • Invited
  • [Presentation] 患肢温存手術の動向-そして未来へ2012

    • Author(s)
      土屋弘行
    • Organizer
      第119回中部日本整形外科災害外科学会特別講演
    • Place of Presentation
      福井市フェニックスプラザ(福井)
    • Year and Date
      20121005-06
  • [Presentation] Update of Caffeine-potentiated chemotherapy for osteosarcoma2012

    • Author(s)
      Tsuchiya H
    • Organizer
      The 9th Asia Pacific Muscloskeletal Tumor Society Meeting
    • Place of Presentation
      Hilton Kualarunpul (Malaysia)
    • Year and Date
      20120907-09
  • [Presentation] Multicenter study of caffeine-potentiated chemotherapy for bone and soft tissue sarcoma2012

    • Author(s)
      Hayashi K, Tsuchiya H, et al
    • Organizer
      9th Asian Pacific Musculoskeletal Tumor Society (APMSTS)
    • Place of Presentation
      Hilton Kualarunpul (Malaysia)
    • Year and Date
      20120906-09
  • [Presentation] Anti-β1 integrin antibody inhibits osteosarcoma lung seeding and metastasis2012

    • Author(s)
      Kimura H, Tsuchiya H, et al
    • Organizer
      9th Asian Pacific Musculoskeletal Tumor Society (APMSTS)
    • Place of Presentation
      Hilton Kualarunpul (Malaysia)
    • Year and Date
      20120906-09
  • [Presentation] 腫瘍外科医の限りなき挑戦2012

    • Author(s)
      土屋弘行
    • Organizer
      第45回日本整形外科学会骨軟部腫瘍学術集会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      20120714-15
  • [Presentation] Effect of anti-β1 integrin antibody on lung seeding of osteosarcoma cells in live mice visualized by single-cell in vivo imaging2012

    • Author(s)
      Kimura H, Tsuchiya H, et al
    • Organizer
      2012 Annual Meeting of American Society of Clinical Oncology (ASCO)
    • Place of Presentation
      McCormick Place (USA)
    • Year and Date
      20120601-05
  • [Presentation] ここまで来た骨腫瘍再建術2012

    • Author(s)
      土屋弘行
    • Organizer
      第85回日本整形外科学会学術総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      20120517-20
  • [Presentation] 骨軟部腫瘍学の現状2012

    • Author(s)
      土屋弘行
    • Organizer
      第46回東海地区整形外科教育研修会
    • Place of Presentation
      ミッドランドホール(名古屋)
    • Year and Date
      2012-10-20
    • Invited
  • [Presentation] 骨軟部腫瘍の最先端2012

    • Author(s)
      土屋弘行
    • Organizer
      第7回斯整会骨軟部腫瘍検討会特別講演会
    • Place of Presentation
      東急ホテル(名古屋)
    • Year and Date
      2012-08-18
  • [Presentation] 骨腫瘍の再建術 : 過去・現在・未来2011

    • Author(s)
      土屋弘行
    • Organizer
      第7回つくば運動器セミナー
    • Place of Presentation
      オークラフロンティアホテルつくば (茨城県)
    • Year and Date
      2011-12-02
  • [Presentation] 抗β1 インテグリン抗体は骨肉腫細胞の肺への接着および肺転移の発生を抑制する2011

    • Author(s)
      木村浩明, 土屋弘行, 他
    • Organizer
      第26回日本整形外科学会基礎学術集会
    • Place of Presentation
      ベイシア文化ホール(群馬県)
    • Year and Date
      2011-10-21
  • [Presentation] 肉腫細胞の可視化モデルを用いた肉腫転移機構の解明2011

    • Author(s)
      林克洋, 土屋弘行, 他
    • Organizer
      第26回日本整形外科学会基礎学術集会
    • Place of Presentation
      ベイシア文化ホール(群馬県)
    • Year and Date
      2011-10-20
  • [Presentation] Real-time imaging of single cancer-cell dynamics of lung metastasis International Society of Limb2011

    • Author(s)
      Kimura H, Tsuchiya H, et al
    • Organizer
      Salvage/Musculoskeletal Tumor Society Combined Meeting
    • Place of Presentation
      China National Convention Center (China)
    • Year and Date
      2011-09-18
  • [Presentation] Benefit of caffeine-potentiated chemotherapy for high-grade soft tissue sarcoma International2011

    • Author(s)
      Takeuchi A, Tsuchiya H, et al
    • Organizer
      Society of Limb Salvage/Musculoskeletal Tumor Society Combined Meeting
    • Place of Presentation
      China National Convention Center (China)
    • Year and Date
      2011-09-17
  • [Presentation] Comparison of Sarcoma Cell Seeding, Viability and Deformation in the Lung, Muscle and Liver, Visualized by Subcellular Real-Time Imaging in the Live Mouse2011

    • Author(s)
      Hayashi K, Tsuchiya H, et al
    • Organizer
      International Society of Limb Salvage/Musculoskeletal Tumor Society Combined Meeting
    • Place of Presentation
      China National Convention Center (China)
    • Year and Date
      2011-09-17
  • [Presentation] 腫瘍外科医の挑戦2011

    • Author(s)
      土屋弘行
    • Organizer
      第20回近整会夏季研究会(招待講演)
    • Place of Presentation
      ホテルシーガルてんぽーざん大阪(大阪府)
    • Year and Date
      2011-08-27
  • [Presentation] 蛍光蛋白を用いたがん細胞のin vivo 動態イメージング2011

    • Author(s)
      山本憲男, 土屋弘行, 他
    • Organizer
      第44回日本整形外科学会 骨・軟部腫瘍学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-07-15
  • [Presentation] 蛍光蛋白発現がん細胞を用いた肺転移形成のリアルタイムイメージング2011

    • Author(s)
      木村浩明, 土屋弘行, 他
    • Organizer
      第44回日本整形外科学会 骨・軟部腫瘍学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-07-15
  • [Presentation] A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma2011

    • Author(s)
      Miwa S, Tsuchiya H, et al
    • Organizer
      American Society of Clinical Oncology Annual Meeting
    • Place of Presentation
      Mc Cormick place (USA)
    • Year and Date
      2011-06-05
  • [Presentation] Anti-β1 integrin antibody inhibits osteosarcoma lung seeding and metastasis2011

    • Author(s)
      Kimura H, Tsuchiya H, et al
    • Organizer
      102th Annual meeting of American Association for Cancer Research
    • Place of Presentation
      Orange county convention center (USA)
    • Year and Date
      2011-04-04

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Published: 2015-06-25  

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