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中文摘要
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描述(由申请人提供):通过将复杂的人类疾病小鼠模型与生物发光报告系统相结合,在肿瘤研究中使用小鼠模型产生了一场革命。为量化生物发光信号而优化的高灵敏度成像系统为研究人员提供了实时监测活体哺乳动物体内发生的生物过程的机会,具有高灵敏度和高通量。从这种分子成像方法中获得的信息通常是其他成像方式无法获得的,目前的商业成像系统使用简单,维护成本低廉。Fox Chase癌症中心(FCCC)的许多研究人员目前正在从事或正在开发动物模型,这些模型将需要使用最先进的生物发光成像(BLI)系统。在免疫功能低下的宿主动物中,转基因发光动物或由转染发光基因的细胞系衍生的肿瘤将被成像,以研究动物对治疗反应的分子变化,检测小转移性肿瘤,并在一系列实验中跟踪肿瘤生长。这些实验将比传统的连续牺牲方法使用更少的动物,并为我们提供分子靶向治疗的靶基因表达的实时分析。BLI设备将补充我们现有的小型动物MRI扫描仪(目前FCCC唯一可用的成像方式),购买该设备是我们创建多模式动物成像套件的长期计划的下一步。项目相关性:该提案将展示广泛的临床前研究,包括结肠癌的化疗,前列腺癌原发性和转移性肿瘤联合治疗的作用,蛋白质合成中断的作用,激素相互作用在乳腺癌中的作用,以及由于许多肿瘤类型表现出的血管不良而导致的肿瘤对治疗的抵抗现象。获得的信息将指导研究人员正确使用正在研究的治疗或预防药物,并阐明特定分子事件在肿瘤形成和发展中的作用。
英文摘要
DESCRIPTION (provided by applicant): A revolution in the use of mouse models in oncology research has been created by combining sophisticated mouse models of human disease with bioluminescent reporter systems. Highly sensitive imaging systems optimized for quantifying the bioluminescent signals offer researchers the opportunity to monitor biological processes taking place in a living mammal in real time, with high sensitivity and high throughput. The information gained from this molecular imaging approach is generally unobtainable from other imaging modalities, and current commercial imaging systems are straightforward to use and inexpensive to maintain. A number of investigators at Fox Chase Cancer Center (FCCC) are currently engaged in, or are developing, animal models that will require access to a state-of-the-art bioluminescent imaging (BLI) system. Transgenic luminescent animals, or tumors derived from cell lines transfected with luminescent genes grown in immunocompromised host animals will be imaged to study molecular changes in animals in response to treatment, detect small metastatic tumors, and follow tumor growth in serial experiments. These experiments will use far fewer animals than traditional methods of serial sacrifice, and provide us with a real time assay of target gene expression for molecularly targeted therapies. BLI equipment will complement our existing small animal MRI scanner (currently the only imaging modality available at FCCC), and acquisition of this equipment is the logical next step in our long term plans to create a multi-modal animal imaging suite. Project Relevance: This proposal will present a broad range of preclinical research, including chemotherapy in colon cancer, the role of combination therapies for the treatment of primary and metastatic tumors in prostate cancer, the role of disruptions in protein synthesis, the role of hormone interactions in breast cancer, and the phenomenon of tumor resistance to therapy because of the poor vasculature exhibited by many tumor types. The information gained will guide researchers in the appropriate use of the therapeutic or preventive agents being studied, and elucidate the roles of specific molecular events in tumor formation and development.
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MRI Imaging and Biomarkers for Early Detection of Aggressive Prostate Cancer
MRI Imaging and Biomarkers for Early Detection of Aggressive Prostate Cancer
MRI Imaging and Biomarkers for Early Detection of Aggressive Prostate Cancer
UM Calabresi Clinical Oncology Research Career Development Award
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