Genomic Assessment of Clinical Variability in OGS

OGS 临床变异的基因组评估

• 批准号: 7113696
• 负责人: Michael J Yaszemski
• 金额: $ 51.64万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113696
• 关键词: Internet; clinical research; gene expression; genetic markers; genetic polymorphism; genetic screening; human therapy evaluation; human tissue; image processing; laser capture microdissection; microarray technology; molecular biology information system; molecular cloning; molecular oncology; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer surgery; neoplasm /cancer therapy; nucleic acid sequence; osteosarcoma; outcomes research; polymerase chain reaction; postoperative state; preoperative state

DESCRIPTION (provided by applicant): The diagnosis of osteogenic sarcoma (OGS) is determined by the histological appearance and anatomical location of the tumor. Despite improvements in the clinical, morphological and imaging tools used to classify OGS and the introduction of neoadjuvant chemotherapy, patients with the same histological diagnosis often experience markedly different clinical outcomes. Clearly, classification using current diagnostic techniques does not adequately capture the variability in chemotherapy response and in metastatic frequency, or the unpredictable mortality that characterizes disease progression in patients with this tumor. The current tumor biology literature indicates that clinical variability in histologically similar tumors is due to the frequent inability of current diagnostic and staging criteria to characterize the biological variability inherent in distinct molecular subgroups of tumors. Thus, there is a great need for tools that, by identifying molecularly homogeneous subgroups of OGS, will assist in developing more effective interventions. Recently published studies show that multivariate analysis of the multigene signatures generated by expression profiling (from DNA-arrays) will "cluster" tumors with clinically distinct phenotypes (i.e. distinct molecular subgroups) from groups of histologically identical tumors. These studies have established that expression profiling based on tumor-specific genes is significantly more effective in identifying prognostic determinants of tumor behavior than expression profiling based on randomly-chosen genes, or profiling based on genes where expression does not change between normal and tumor cells. We submit that DNA-arrays containing OGS-specific genes will generate multigene signatures that are informative for clustering osteogenic sarcomas into clinically distinct molecular subgroups, and we propose in this application to develop such DNA-array-based tools for treatment of OGS. Our strategy is, first, to identify genes (molecular markers) which are "tumor specific" for OGS and to use these genes as probes in a custom DNA-array (OGS-chip); second, to validate the ability of this OGS-chip to generate multigene signatures and, by multivariate analysis, bin OGS tumor samples into clinically distinct clusters; and, finally, to use these multigene signatures to prospectively predict clinical characteristics of OGS.

描述（由申请人提供）：骨肉瘤（OGS）的诊断取决于肿瘤的组织学外观和解剖位置。尽管用于OGS分类的临床、形态学和影像学工具有所改进，新辅助化疗的引入，但具有相同组织学诊断的患者通常会经历明显不同的临床结局。显然，使用当前诊断技术的分类 不能充分捕捉化疗反应和转移频率的变异性，或这种肿瘤患者疾病进展的不可预测的死亡率。目前的肿瘤生物学文献表明，组织学相似肿瘤的临床变异性是由于目前的诊断和分期标准经常无法 表征肿瘤不同分子亚组固有的生物学变异性。因此，有一个很大的需要的工具，通过确定分子同质亚组的OGS，将有助于制定更有效的干预措施。最近发表的研究表明，通过表达谱分析（来自 DNA阵列）将从组织学上相同的肿瘤组中“聚类”具有临床上不同的表型（即不同的分子亚组）的肿瘤。这些研究已经确定，基于肿瘤特异性基因的表达谱在识别肿瘤行为的预后决定因素方面比基于随机选择的基因的表达谱或基于表达在正常细胞和肿瘤细胞之间不改变的基因的表达谱显著更有效。 我们提出，含有OGS特异性基因的DNA阵列将产生多基因标记，这些标记为成骨肉瘤聚类成临床上不同的分子亚组提供信息，并且我们在本申请中提出开发这种基于DNA阵列的工具， 治疗OGS。我们的策略是，首先，这些基因对OGS具有“肿瘤特异性”，并将这些基因用作定制DNA阵列中的探针，第二，验证该OGS芯片产生多基因签名的能力，并通过多变量分析将OGS肿瘤样品分入临床上不同的簇;最后，使用这些多基因标记来前瞻性地预测OGS的临床特征。

项目成果

Cellular uptake of gold nanoparticles directly cross-linked with carrier peptides by osteosarcoma cells.

• DOI: 10.1007/s10856-008-3588-x
• 发表时间: 2009-01
• 期刊: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
• 影响因子: 3.7
• 作者: Mandal, Deendayal;Maran, Avudaippan;Yaszemski, Michael J.;Bolander, Mark E.;Sarkar, Gobinda
• 通讯作者: Sarkar, Gobinda

Osteoblastic and osteolytic human osteosarcomas can be studied with a new xenograft mouse model producing spontaneous metastases.

• DOI: 10.1080/07357900802491477
• 发表时间: 2009-05
• 期刊: Cancer investigation
• 影响因子: 2.4
• 作者: Yuan J;Ossendorf C;Szatkowski JP;Bronk JT;Maran A;Yaszemski M;Bolander ME;Sarkar G;Fuchs B
• 通讯作者: Fuchs B

Preferential expression of the secreted and membrane forms of tumor endothelial marker 7 transcripts in osteosarcoma.

骨肉瘤中肿瘤内皮标志物 7 转录物的分泌型和膜型优先表达。

• 发表时间: 2009
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Halder,Chandralekha;Ossendorf,Christian;Maran,Avudaiappan;Yaszemski,Michael;Bolander,MarkE;Fuchs,Bruno;Sarkar,Gobinda
• 通讯作者: Sarkar,Gobinda