Molecular and pathologic analysis of growth factors on the proliferating activities and metastases in bone and soft tissue sarcomas

生长因子对骨软组织肉瘤增殖活性和转移的影响的分子和病​​理分析

• 批准号: 09470052
• 负责人: TSUNEYOSHI Masazumi
• 金额: $ 8.7万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470052/
• 关键词: bone; soft tissue; sarcoma; metastasis; tumor progression; pathology; molecular biology; growth factor; 軟部デスモイド腫瘍; β-catenin; cyclin D1; APC遺伝子; ABI PRISM 7700; HGF; C-MET; 平滑筋肉腫; P53; MDM2; 癌関連遺伝子; 増殖因子; 骨軟部肉腫

We assessed the biological character of bone and soft tissue tumors by molecular biology technique in addition to clinico-pathologic analysis.1. Malignant transformation : 1) Neurofibroma to malignant peripheral nerve sheath tumor ; abnormal expression of p53 protein, 2) Dermatofibrosarcoma protuberans to fibrosarcoma ; chromosomal abnormality.2. Dedifferentiated chondrosarcoma and dedifferentiated liposarcoma characterized by high grade malignancy : H-ras mutation3. Biological behavior in sarcomas1) Leiomyosarcoma : p53 mutation in 4 dead cases among favorable superficial type. Using Real-Time Semi-quantitative RT-PCR, an increasing level of p53 mRNA associated with an overexpression of p53 protein. 2) Synovial sarcoma : Unfavorable prognostic factors (i) high AJC stage, (ii) large tumor size, (iii) co-expression of HGF/c-MET, (iv) mutation of p53, MDM2, H-ras, beta-catenin. 3) Malignant rhabdoid tumor (i) Immunoexpression of cytokeratin 8 and 18, (ii) Subcellular distribution of cytokeratin and vimentin in rhabdoid cell by three-dimensional imaging, (iii) Genomic abnormality of vimentin and cytokeratin, (iv) Unfavorable prognostic factors : abnormal expression of beta-catenin, p53, hSNF5/INI1 4)Osteosarcoma : Significant nm23, c-MET in metastasis and tumor progression.

结合临床病理分析，采用分子生物学技术评价骨与软组织肿瘤的生物学特性.恶性转化：1）神经纤维瘤至恶性周围神经鞘瘤; p53蛋白表达异常; 2）隆突性皮肤纤维肉瘤至纤维肉瘤;染色体异常.以高度恶性为特征的去分化软骨肉瘤和去分化脂肪肉瘤：H-ras突变3.肉瘤的生物学行为1）平滑肌肉瘤：良性浅表型中4例死亡病例p53突变。采用实时半定量RT-PCR，p53 mRNA水平的增加与p53蛋白的过表达相关。2)滑膜肉瘤：不利的预后因素（i）高AJC分期，（ii）肿瘤大小，（iii）HGF/c-MET共表达，（iv）p53、MDM 2、H-ras、β-连环蛋白突变。3)恶性横纹肌样瘤（i）细胞角蛋白8和18的免疫表达，（ii）通过三维成像的横纹肌样细胞中细胞角蛋白和波形蛋白的亚细胞分布，（iii）波形蛋白和细胞角蛋白的基因组异常，（iv）不利的预后因素：β-连环蛋白、p53、hSNF 5/INI 1的异常表达4）骨肉瘤：在转移和肿瘤进展中显著的nm 23、c-MET。

项目成果

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