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: 8900235
• 负责人: Ivan Pedrosa
• 金额: $ 29.39万
• 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 2018-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8900235
• 关键词: Age; Aggressive behavior; Area; Behavior; Blood; Blood Vessels; Blood flow; Cancer Center; Cellularity; Cessation of life; Characteristics; Clinical; Collaborations; Data; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance 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 biomarker; 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）：横断面成像的常规使用导致肾细胞癌（RCC）的年龄调整发病率显着增加。然而，这并没有转化为癌症特异性死亡的减少，表明可能存在对小型、潜在惰性肾肿瘤的过度治疗。因此，有人建议对小肿瘤进行肾细胞癌的主动监测。然而，这些肿瘤的自然史仍然未知。血管生成和肿瘤坏死与肾细胞癌的预后和转移潜力相关。 VHL 基因失活、HIF 上调和 VEGF 过度表达构成了与 RCC 相关的血管生成增强的分子基础。动脉自旋标记 (ASL) 是一种磁共振成像 (MRI) 方法，通过操纵流入动脉血的信号来测量血流量。 ASL 血流量与 RCC 中的血管分布密切相关。通过弥散加权成像 (DWI) 测量的肾细胞癌表观弥散系数 (ADC) 与病理学上的肿瘤细胞构成相关。我们试图确定肾细胞癌体内血管和扩散 MRI 测量值，这些测量值与促进血管生成和缺氧的空间共同注册分子改变相关，并预测攻击行为。各种基于组织的分析与体内肿瘤灌注和缺氧变化的空间同步可能有助于开发更强大的成像生物标志物来预测肾细胞癌的生物学行为。如果成功，这些成像生物标志物将立即应用于临床实践，并将有助于选择患者进行主动监测。