| Project/Area Number |
13671508
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
MYOUI Akira Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10263261)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASE Takanobu Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00283755)
UEDA Takafumi Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00324773)
YOSHIKAWA Hideki Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60191558)
HASHIMOTO Nobuyuki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50324752)
TOMITA Tetsuya Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30283766)
鳥塚 之嘉 大阪大学, 医学系研究科, 助手 (20324775)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | bone metastasis / osteosarcoma / tyrosine kinase / MAP kinase / insuline-like growth factor / cadherin / organ-specific metastasis / NF-kB / 骨肉腫 / 転移性肺腫瘍 / VCP / アポトーシス / パルテノライド / 臓器特異性 / 微小環境 / 遺伝子発現 / 転移性骨腫瘍 / 破骨細胞 / 肺転移 / 増殖因子 / 低分子G蛋白 / 血管新生因子 |
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| Research Abstract |
1. Mechanisms of cancer metastasis to bone and its experimental treatment
Role of Src tyrosine kinase, insulin-like growth factor, NF-kB and cadherin-11 in the development of cancer metastasis to bone was investigated. Elevated Src tyrosine kinase activity and overexpression of insulin-like growth factor receptor and cadherin-11 were revealed to increase the metastatic capacity of cancer cells in experimental model of bone metastasis. Inhibition of NF-kB activation reduced bone metastasis. FR167653, a specific inhibitor of p38 MAP kinase, was tested for the ability to inhibit breast cancer metastasis to bone but did not inhibit bone metastasis.,
2. Mechanisms of lung metastasis of osteosarcoma and its experimental treatment
Organ-specific metastasis was tested by injecting mouse Dunn osteosarcoma cells into tail vein of mouse with ectopically implanted organs. Osteosarcoma cells preferentially metastasized to ectopic lung tissue. Conditioned media of lung organ culture stimulated osteosarcoma cell growth and conditioned media of alveolar epithelial cells upregulated VEGF expression of osteosarcoma cells. Highly metastatic subclone of Dunn osteosarcoma cells constitutively expressed VCP and eventually exhibited constitutive activation of NF-kB. Parthenolide, an inhibitor of NF-kB, specifically inhibited lung metastasis of osteosarcoma cells.
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