Project/Area Number |
17591604
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Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East |
Principal Investigator |
KAWAI Akira National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, National Cancer Center and Research Center for Innovative Oncology, Hospital East, Researcher (90252965)
|
Co-Investigator(Kenkyū-buntansha) |
KONDO Tadashi National Cancer Center and Research Center for Innovative Oncology, Project Leader (30284061)
ICHIKAWA Hitoshi National Cancer Center and Research Center for Innovative Oncology, Project Leader (30201924)
HASEGAWA Tadashi School of Medicine, Sapporo Medical University, Professor (40281167)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | Bone and soft tissue sarcoma / Gene expression analysis / Two dimensional difference gel electrophoresiS / prognostic factor / malignant fibrous histiocytoma / GIST / osteosarcoma / 骨肉腫 / 悪性骨軟部腫瘍 / 網羅的遺伝子発現解析 / フェチン / 抗がん剤感受性 |
Research Abstract |
This research is aimed to clarify prognostic factors and factors related to the treatment susceptibility of primary musculoskeletal sarcoma including osteosarcoma, Ewing's sarcoma and gastrointestinal stromal tumor (GIST) using genomic/proteomic analytical methods. A feature of the research was to clarify gene and protein expression that determined the prognosis and susceptibility to treatment exhaustively and integratively by using actual clinical musculoskeletal sarcoma samples. RNA/protein were extracted from frozen samples of various malignant soft tissue sarcomas and GISTs, and exhaustive gene expression analyses were carried out using Affymetrix U133 GeneChip and exhaustive protein expression analyses using fluorescence secondary electrophoresis/mass spectrometry. Based on the results of the exhaustive gene expression analyses of malignant soft tissue sarcomas using GeneChip, we found that so-called malignant fibrous histiocytoma (MFH) could be subclassified into several subtypes
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that suggested a tendency to respectively differentiate into leiomyosarcoma, liposarcoma, etc. depending on the gene expression pattern. We also identified proteins that featured respective histological types of malignant fibrous histiocytoma by exhaustive protein expression analysis, and reported that the expression of tropomyosin subtype was involved in the subclassification of leiomyosarcoma into its subtypes. As a result of exhaustive protein expression analyses of GISTs, we detected a protein that was significantly different in its expression levels between the arm of early relapsers within one year after surgery (poor prognosis), and the arm of disease-free survivals for over two years (good prognosis). The mRNA that encoded this protein demonstrated similar changes in its expression levels also in the GeneChip analysis. This protein is called pfetin, and a significant difference (p<0.0001) was also found between the good prognosis and the poor prognosis arms in the antipfetin antibody immunostaining and Western blotting using GIST surgery samples. We also conducted parallel clinical and clinicopathologic research of primary musculoskeletal sarcoma. Less
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