2017 Fiscal Year Annual Research Report
Novel treatment for metastatic bone tumors
| Project/Area Number |
16K20042
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| Research Institution | Nagoya City University |
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Principal Investigator |
三輪 真嗣 名古屋市立大学, 大学院医学研究科, 助教 (40753455)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 骨転移 |
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| Outline of Annual Research Achievements |
我々はこれまでに蛍光タンパクで腫瘍を標識することにより腫瘍を可視化させて生体内で観察する技術を確立してきた．また，生体内で腫瘍を可視化させる技術を手術に応用する試みを行っており，本研究ではマウス骨転移モデルを用いて腫瘍の増大，腫瘍再発に対する蛍光ガイド下腫瘍切除術（Fluorescence-guided surgery，以下FGS）の有用性を調査した．
緑色蛍光タンパク（green fluorescent protein: GFP）を発現するヒト前立腺癌細胞PC-3を作成し，25匹のヌードマウスの脛骨に注射することにより骨転移モデルを作成した．注射から1週後，癌胎児性抗原（carcinoembryonic antigen: CEA）に特異的なモノクローナル抗体をDyLight 650で標識して13匹のマウスに尾静脈注射した．12匹のマウスに対して明視野で腫瘍切除術（bright light surgery: BLS）を行い，13匹のマウスに対して蛍光ガイド下で腫瘍切除術（fluorescence-guided surgery: FGS）を行った．術後，毎週蛍光イメージングを行い，腫瘍再発を評価した．FGSは有意に遺残腫瘍を減少させ，継時的イメージングではFGS群の腫瘍再発がわずかであったのに対し，BLS群の腫瘍の急速な増大を認めた．また，FGSは有意に無再発生存率を改善した．この研究から，FGSは前立腺癌骨転移モデルにおいて，遺残腫瘍，腫瘍再発を減少させることが示された．この手法を応用することにより様々な癌腫における遺残腫瘍，腫瘍再発を減少させることができると期待される．
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[Journal Article] Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression2018
Author(s)
Higuchi T, Takeuchi A, Munesue S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Inatani H, Shimozaki S, Kato T, Aoki Y, Abe K, Taniguchi Y, Aiba H, Murakami H, Harashima A, Yamamoto Y, Tsuchiya H
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Journal Title
Cancer Med
Volume: 印刷中
Pages: 印刷中
Peer Reviewed / Open Access
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[Journal Article] Tumor-targeting Salmonella typhimurium A1-R combined with recombinant methioninase and cisplatinum eradicates an osteosarcoma cisplatinum-resistant lung metastasis in a patient-derived orthotopic xenograft (PDOX) mouse model: Decoy, trap and kill chemotherapy moves toward the clinic2018
Author(s)
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Li S, Han Q, Tan Y, Zhao M, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
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Journal Title
Cell Cycle
Volume: 印刷中
Pages: 印刷中
DOI
Peer Reviewed / Open Access
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[Journal Article] Recombinant methioninase in combination with doxorubicin (DOX) overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma2018
Author(s)
spindle-cell sarcoma. Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Murakami T, Kiyuna T, Miyake K, Miyake M, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Singh SR, Eilber FC, Hoffman RM
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Journal Title
Cancer Lett
Volume: 417
Pages: 168～173
DOI
Peer Reviewed
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[Journal Article] Growth of doxorubicin-resistant undifferentiated spindle-cell sarcoma PDOX is arrested by metabolic targeting with recombinant methioninase2018
Author(s)
Igarashi K, Li S, Han Q, Tan Y, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
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Journal Title
J Cell Biochem
Volume: 119
Pages: 3537～3544
DOI
Peer Reviewed
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[Journal Article] Effective Metabolic Targeting of Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models with Recombinant Methioninase2017
Author(s)
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Murakami T, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Hoffman RM
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Journal Title
Anticancer Res
Volume: 37
Pages: 4807-4812
Peer Reviewed
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[Journal Article] Efficacy In Vitro of Caffeine and Valproic Acid on Patient-Derived Undifferentiated Pleomorphic Sarcoma and Rhabdomyosarcoma Cell Lines2017
Author(s)
Igarashi K, Kawaguchi K, Kiyuna T, Murakami T, Miwa S, Nelson SD, Dry SM, Li Y, Singh AS, Kimura H, Hayashi K, Yamamoto N, Tsuchiya H, Eilber FC, Hoffman RM
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Journal Title
Anticancer Res
Volume: 37
Pages: 4081-4084
Peer Reviewed
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[Journal Article] Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone2017
Author(s)
Rosario M, Takeuchi A, Yamamoto N, Hayashi K, Miwa S, Higuchi T, Abe K, Taniguchi Y, Aiba H, Tanzawa Y, Murakami H, Tsuchiya H
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Journal Title
Anticancer Res
Volume: 37
Pages: 749-754
Peer Reviewed
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[Presentation] Deep infection after bone tumor surgery: risk factors and new preventive technology2017
Author(s)
Miwa S, Shirai T, Yamamoto N, Hayashi K, Takeuchi A, Tada K, Kajino Y, Higuchi T, Abe K, Taniguchi Y, Tsuchiya H
Organizer
19th International Society of Limb Salvage General Meeting
Int'l Joint Research
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[Presentation] Deep Infection After Bone Tumor Surgery: Risk Factors And New Preventive Technology2017
Author(s)
Miwa S, Shirai T, Yamamoto N, Hayashi K, Takeuchi A, Tada K, Kajino Y, Higuchi T, Abe K, Taniguchi Y, Tsuchiya H
Organizer
18th EFORT Annual Congress
Int'l Joint Research
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