| Project/Area Number |
11307026
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | SAPPORO MEDICAL UNIVERSITY |
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Principal Investigator |
WADA Takuro (2002) Sapporo Medical University,school of medicine,asociate professor, 医学部, 助教授 (00244369)
石井 清一 (1999-2001) 札幌医科大学, 医学部, 教授 (20001000)
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| Co-Investigator(Kenkyū-buntansha) |
和田 卓郎 札幌医科大学, 医学部, 助教授 (00244369)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥39,290,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2002: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2001: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2000: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1999: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Keywords | Osteosarcoma / tumor associated antigen / costimulatory signal / tumor immunity / Erb2 receptor protein / Vascular endothelial growth factor / EWS-ETS fusion gene / expression cloning / ヒト骨肉種 / 骨肉種腫瘍抗原 / 接着分子導入細胞ワクチン / BMP-2 / EWS-Flil / G-CSF / 骨肉種 / 転移 / 増殖 / 滑膜肉腫 / 骨肉腫(osteosarcoma) / 血管新生誘導因子(VEGF) / 肺転移(lung metastasis) / 予後(prognosis) / 接着分子(B7-1) / アデノウィルスベクター(adenovirus vector) / ヒト骨肉腫細胞株 / CTL / チロシンキナーゼ受容体蛋白(ErbB2) / 接着因子インテグリン(α5サブユニット) |
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| Research Abstract |
Human osteosarcom associated antigens were identified by using SEREX (serological identification of antigen by recombinant expression cloning) method. Eight candidate genes were identified. They included the genes encoding procollagen type 1 and c-myc binding protein homologue.
Human osteosarcoma associated antigen was identified with expression cloning method. The osteosarcoma cell line (OS2000) and its cytotoxic T-lymphocyte clone (CTL) were used. An HLA-A24 and B55 restricted molecule encoded by 1, 9O0-base pair gene was identified.
B7-1 gene, a member of B7 costimulatory family, was introduced to rat osteosarcoma cells in vivo by using adenovirus vector. Curative immunity against primary osteosarcoma and systemic immunity against pulmonary metastasis was observed. B7-1a molecule induced the most efficacious costimulatory signal among B7 family members.
Expression of ErbB2 gene was compared between the primary and pulmonary metastatic lesions of the same osteosarcoma patients. Loss of
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ErbB2 expression was noted in 14 of 19 patients as the primary tumor became metastatic. In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased level of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival.
Vascular endothelial growth factor (VEGF) expression in untreated ostesarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy. In addition, the pre-therapeutic serum VEGF level reflects tne angiogenic property of primary tumor and has a predictive value on early disease relapse of osteosarcoma.
To identify downstream targets of EWS-ETS fusion protein, we introduced EWS-ETS into a human fibrosarcoma cell line. Tenascin-C is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal EWS-ETS. As Tenascin-C expression is involved in the invasive and malignant phenotype, the oncogenic effect of EWS-ETS may be mediated in part by upregulating of Tenascin-C expression. Less
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