Noninvasive assessment of tumor malignancy

肿瘤恶性程度的无创评估

• 批准号: 7479650
• 负责人: Elizabeth Bullitt
• 金额: $ 44.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479650
• 关键词: Address; Affect; Angiography; Animal Model; Basic Science; Biological; Blood Vessels; Blood Volume; Brain; Brain Neoplasms; Carcinoma; Cerebrum; Choroid Plexus Carcinoma; Clinical; Clinical Trials; Data; Development; Ensure; Evaluation; Generic Drugs; Genetically Engineered Mouse; Glioblastoma; Glioma; Goals; Growth; Growth Factor; Histology; Human; Hypervascular; Image; Individual; Lead; Location; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Methods; Microscopic; Modeling; Monitor; Mus; Neoplasm Metastasis; Patients; Perfusion; Permeability; Persons; Physicians; Process; Radiation therapy; Refractory; Research; Resolution; Scientist; Shapes; Solutions; Standards of Weights and Measures; Techniques; Testing; Therapeutic; Therapeutic Agents; Time; Treatment Protocols; Tumor Angiogenesis; Tumor Biology; Tumor Volume; Tumor-Associated Vasculature; Upper arm; Vascular Endothelial Growth Factors; Work; angiogenesis; base; chemotherapeutic agent; design; human subject; image processing; improved; insight; interest; mouse model; novel strategies; pre-clinical; research clinical testing; response; shape analysis; size; therapy development; tumor; tumor growth

DESCRIPTION (provided by applicant): Effective treatment of human brain tumors poses a major challenge. One of the underlying problems is lack of reliable, noninvasive means of assessing tumor malignancy and of assessing treatment response. The current proposal aims to develop and evaluate a new, noninvasive method of assessing tumor activity based upon quantitative, statistical measures of vessel shape determined from magnetic resonance angiograms (MRA). Although we are simultaneously pursuing this approach in human subjects, there are many issues that cannot be readily addressed in human patients since whole-brain histological information is not available. This proposal employs two genetically engineered mouse models in which tumors reliably arise cte novo, in the appropriate anatomical location, with appropriate histology, and with a predictable time course. One model is a glioma that progresses from no tumor to low-grade glioma to grade 3 glioma to glioblastoma. The second model is a heavily vascular choroid plexus carcinoma that mimics the growth of metastatic tumors by producing microscopic foci of malignancy that subsequently grow to large size. This proposal aims to develop and test the proposed method of tumor activity assessment so as: a) to determine whether the new approach can both correctly classify changing tumor grade and predict tumor treatment response under both anti-angiogenic and more generic therapy, b) to compare the ability of the new method to that of more traditional imaging assessment techniques including measurement of tumor volume, perfusion imaging, and permeability imaging, and c) to determine if vessel shape abnormalities as perceived by MRA can be correlated with cancer-induced changes to the vessel wall as evaluated by histology. This proposal addresses a major clinical problem that has been highly refractory to solution by traditional methods. At the same time, the proposed work also addresses important biological questions that could lead to insights into mechanisms of tumor growth. The long term potential of the proposed work includes not only improved means of early clinical evaluation of tumor treatment, but also new methods of developing and testing therapeutic agents in both preclinical animal models and human subjects.

描述（由申请人提供）：人类脑肿瘤的有效治疗提出了重大挑战。根本问题之一是缺乏可靠的、非侵入性的方法来评估肿瘤恶性程度和评估治疗反应。目前的提案旨在开发和评估一种新的无创评估肿瘤活动的方法，该方法基于磁共振血管造影（MRA）确定的血管形状的定量统计测量。尽管我们同时在人类受试者中寻求这种方法，但由于无法获得全脑组织学信息，因此在人类患者中存在许多无法轻易解决的问题。该提案采用了两种基因工程小鼠模型，其中肿瘤可靠地从头开始出现，在适当的解剖位置，具有适当的组织学，并且具有可预测的时间过程。一种模型是神经胶质瘤，其从无肿瘤发展到低级别神经胶质瘤，再到3级神经胶质瘤，再到胶质母细胞瘤。第二种模型是富含血管的脉络丛癌，它通过产生随后生长到大尺寸的微观恶性肿瘤灶来模拟转移性肿瘤的生长。本提案旨在开发和测试所提出的肿瘤活动评估方法，以便：a）确定新方法是否能够正确分类变化的肿瘤等级并预测抗血管生成和更通用疗法下的肿瘤治疗反应，b）将新方法与更传统的成像评估技术（包括肿瘤体积测量、灌注成像和渗透性成像）的能力进行比较，以及c）确定血管形状 MRA 检测到的异常可能与组织学评估的癌症引起的血管壁变化相关。该提案解决了传统方法很难解决的一个主要临床问题。与此同时，拟议的工作还解决了重要的生物学问题，这些问题可能有助于深入了解肿瘤生长的机制。拟议工作的长期潜力不仅包括改进肿瘤治疗早期临床评估的方法，还包括在临床前动物模型和人类受试者中开发和测试治疗药物的新方法。