Non-invasive Physiologic Predictors of Aggressiveness in Renal Cell Carcinoma

肾细胞癌侵袭性的非侵入性生理预测因子

• 批准号: 8705896
• 负责人: Ivan Pedrosa
• 金额: $ 28.62万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705896
• 关键词: Age; Aggressive behavior; Area; Behavior; Biological Markers; Blood; Blood Vessels; Blood flow; Cancer Center; Cellularity; Cessation of life; Characteristics; Clinical; Collaborations; Data; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Funding; Gene Expression; Geographic Distribution; Grant; Heterogeneity; Histopathologic Grade; Histopathology; Hypoxia; Image; Incidence; Indolent; Intervention; Israel; Kidney Neoplasms; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Medical center; Methods; Molecular; Molecular Analysis; Molecular Profiling; Monitor; Natural History; Necrosis; Neoplasm Metastasis; Nephrectomy; Nuclear Grade; Outcome; Pathologic; Pathology; Patients; Perfusion; Phenotype; Physiological; Proteins; Protocols documentation; Qualifying; Renal Cell Carcinoma; Renal carcinoma; Research; Risk; Sampling; Signal Transduction; Specimen; Spin Labels; Staging; Surface; Tissues; Translating; Tumor Angiogenesis; United States National Institutes of Health; Up-Regulation; VHL Gene Inactivation; Variant; Vascular Endothelial Growth Factors; Von Hippel-Lindau Syndrome; Xenograft procedure; angiogenesis; base; clinical practice; cohort; experience; imaging modality; in vivo; outcome forecast; patient population; prognostic; success; tumor; tumor progression; two-dimensional

DESCRIPTION (provided by applicant): The routine use of cross-sectional imaging has resulted in a significant increase in the age-adjusted incidence of renal cell carcinoma (RCC). However, this has not translated into a decrease in cancer specific deaths, suggesting the possible over treatment of small, potentially indolent renal tumors. Thus, active surveillance of RCC has been proposed for small tumors. However, the natural history of these tumors remains unknown. Angiogenesis and tumor necrosis correlate with prognosis and metastatic potential in RCC. Inactivation of the VHL gene, HIF upregulation, and VEGF over- expression form the molecular basis of the enhanced angiogenesis associated with RCC. Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method for measuring blood flow by manipulating the signal from inflowing arterial blood. ASL blood flow correlates tightly to vascularity in RCC. The apparent diffusion coefficient (ADC) in RCC, measured with diffusion-weighted imaging (DWI), correlates with tumor cellularity at pathology. We seek to identify vascular and diffusion MRI measures in RCC in vivo that correlate to spatially-co-registered molecular alterations promoting angiogenesis and hypoxia and predict aggressive behavior. The spatial synchronization of various tissue-based analyses with in vivo alterations in tumor perfusion and hypoxia may help develop more robust imaging biomarkers to predict the biologic behavior of RCC. If successful, these imaging biomarkers will be immediately applicable to clinical practice and will help selecting patients for active surveillance.

描述（由申请人提供）：常规使用横断面成像导致肾细胞癌（RCC）年龄调整后的发生率显着增加。然而，这尚未转化为癌症特异性死亡的减少，这表明可以治疗小小的潜在腹部肾脏肿瘤。因此，已经提出了针对小肿瘤的RCC的主动监测。但是，这些肿瘤的自然史仍然未知。血管生成和肿瘤坏死与RCC的预后和转移潜力相关。 VHL基因，HIF上调和VEGF过度表达的失活形成了与RCC相关的增强血管生成的分子基础。动脉自旋标记（ASL）是一种磁共振成像（MRI）方法，用于通过操纵动脉血液中的信号来测量血流。 ASL血流与RCC中的血管紧密相关。通过扩散加权成像（DWI）测量的RCC中的明显扩散系数（ADC）与病理学的肿瘤细胞相关。我们试图在体内RCC中确定与空间注册的分子改变相关的血管和扩散MRI测量，从而促进了血管生成和缺氧并预测攻击行为。各种基于组织的分析的空间同步随肿瘤灌注和缺氧的体内改变可能有助于开发更健壮的成像生物标志物，以预测RCC的生物学行为。如果成功，这些成像生物标志物将立即适用于临床实践，并将帮助选择患者进行主动监测。