Research on the Factor that Determines Susceptibility to Chemotherapy for Musculoskeletal Sarcoma by Genomic/Proteomic Analysis

基因组/蛋白质组分析决定肌肉骨骼肉瘤化疗敏感性的因素

• 批准号: 17591604
• 负责人: KAWAI Akira
• 金额: $ 2.24万
• 依托单位: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591604/
• 关键词: 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

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 … More 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

本研究旨在利用基因组/蛋白质组学分析方法阐明原发性肌肉骨骼肉瘤（包括骨肉瘤、尤文氏肉瘤和胃肠道间质瘤（GIST））的预后因素以及与治疗敏感性相关的因素。该研究的一个特点是阐明基因和蛋白质表达。通过使用实际的临床肌肉骨骼肉瘤，彻底、全面地确定预后和对治疗的敏感性从各种恶性软组织肉瘤和 GIST 的冷冻样本中提取 RNA/蛋白质，并使用 Affymetrix U133 GeneChip 进行详尽的基因表达分析，并根据结果使用荧光二次电泳/质谱进行详尽的蛋白质表达分析。使用基因芯片对恶性软组织肉瘤进行详尽的基因表达分析，我们发现所谓的恶性纤维组织细胞瘤（MFH）可能是细分为几种亚型，表明根据基因表达模式分别分化为平滑肌肉瘤、脂肪肉瘤等的趋势我们还通过详尽的蛋白质表达分析鉴定了具有恶性纤维组织细胞瘤各自组织学类型特征的蛋白质，并报道了原肌球蛋白亚型的表达参与了平滑肌肉瘤亚型的细分，对 GIST 进行了详尽的蛋白质表达分析。我们检测到一种蛋白质的表达水平在术后一年内的早期复发者手臂（预后不良）和两年以上无病生存者手臂（预后良好）之间存在显着差异。基因芯片分析中该蛋白的表达水平也表现出类似的变化，该蛋白称为 pfetin，并且在预后良好组和预后不良组之间也发现了显着差异（p<0.0001）。我们还对原发性肌肉骨骼肉瘤进行了平行的临床和临床病理学研究。

项目成果

Bilateral adrenal gland metastasis from malignant fibrous histiocytoma : Value of [F-18] FDG PET-CT for diagnosis of occult metastases

恶性纤维组织细胞瘤双侧肾上腺转移：[F-18]FDG PET-CT 对隐匿性转移的诊断价值

• 发表时间: 2006
• 期刊: Annals of Nuclear Medicine 20
• 作者: Eisuke Kobayashi;Akira Kawai;Kunihiko Seki;Ukihide Tateishi
• 通讯作者: Ukihide Tateishi

乳癌長管骨骨転移に対する診断と治療

乳腺癌长骨转移的诊断和治疗

• 发表时间: 2005
• 期刊: 整形・災害外科 48
• 作者: 中山ロバート;川井 章
• 通讯作者: 川井 章

整形外科診療実践ガイド

骨科治疗实践指南

• 作者: Misu T;小野寺淳一;Nakashima I.;Lennon VA.;Nakamura M.;Nakashima I.;Nakashima I.;Narikawa K;Matsumoto Y;藤原一男;三須建郎;Nakashima I;藤原一男;斎田孝彦;Fujihara K.;Misu T.;Saida T.;Nakashima I.;Narikawa K;Narikawa K.;Takahashi T.;斎田孝彦;Saida T.;藤原一男
• 通讯作者: 藤原一男

Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas

与软组织肉瘤的组织学分类和分级相对应的蛋白质组学特征

• 发表时间: 2006
• 期刊: Proteomics 6
• 作者: Yoshiyuki Suehara;Tadashi Hasegawa;Akira Kawai;etc
• 通讯作者: etc

下肢悪性骨・軟部腫瘍切除後の歩行能力

下肢恶性骨/软组织肿瘤切除术后步行能力

• 发表时间: 2005
• 期刊: 関節外科 24
• 作者: 川井 章;中山ロバート;中谷文彦
• 通讯作者: 中谷文彦