2004 Fiscal Year Final Research Report Summary
Genetic aberrations in the metastatic process and its control -mouse sarcoma and human sarcoma cells-
| Project/Area Number |
13470306
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KANAMORI Masahiko Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Orthopedics, Associate Professor, 医学部, 助教授 (20204547)
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| Co-Investigator(Kenkyū-buntansha) |
OHMORI Kazuo Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Orthopedics, Assistant Professor, 附属病院, 助手 (80303238)
KAWAGUCHI Makoto Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Pathology, Assistant Professor, 医学部, 助手 (50204699)
GEJO Ryuichi Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Orthopedics, Assistant Professor, 医学部, 助手 (00359712)
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| Project Period (FY) |
2001 – 2004
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| Keywords | fibrosarcoma / metastasis / gene analysis / sarcoma / genomic hybridization |
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| Research Abstract |
Genomic analysis of the mouse sarcoma and its differentiation and apoptotic therapy
Genomic analysis of a high-metastatic clone established from poorly differentiated murine sarcoma (HM-RCT), in which a tumor was spontaneously developed in a C3H/He mouse, was used. HM-RCT expressed enhanced POU domain (class 2, associating factor 1), adenylate cyclase 7, procollagen type III (a), A kinase anchor protein 4 and Ehm (expressed on high-metastatic cells) and 11 expressed sequence tags (ESTs), compared with the original clone of RCT. However, 18 specific genes and 14 ESTs were underexpressed in HM-RCT. Moreover, we investigated the effects of angiogenesis inhibitor TNP-470, dibutyryl cyclic AMP and hyperthermia on tumor growth and differentiation for the mouse sarcoma cells.
Genomic analysis of the human sarcoma
Genetic instability analyzed by comparative genomic hybridization method (CGH) were identified in human sarcomas. Seven clones showed high-level amplification in all osteosarcomas. They were 1Qtel10 (1qtel), WHSC1(4p16.3), CCND3(6p21), MTAP(9p21.3), INSR(19p13.2), CCNE1(19q12), and PCNT2(21qtel). Of these clones, CCND3 and MTAP also showed high-level amplification in aggressive giant cell tumors, whereas 1Qtel10 and MTAP showed high amplification in chondrosarcoma. NRSA(1p13.2) and RAF1(3q25), which were commonly low in aggressive bone tumors, were lost in osteosarcomas. Thus, the present pilot study suggests that array-based genome-wide CGH could powerful means to detect genetic instability and gene aberrations that are reflected to the progression and outcome of human sarcomas.
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