Holistic diagnostics of host during development of cancer

癌症发展过程中宿主的整体诊断

• 批准号: 8333416
• 负责人: David A Lawrence
• 金额: $ 20.41万
• 依托单位: WADSWORTH 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333416
• 关键词: Antibodies; Antigens; Biological; Biological Assay; Biological Markers; Blood; Blood Platelets; Cancer Biology; Cells; Characteristics; Clinical; Complex; Coupled; Cytolysis; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Dimensions; Early Diagnosis; Engineering; Erythrocytes; Evaluation; FDA approved; Female; Flow Cytometry; Fluorescence; Gold; HMGB1 gene; Health Status; Heart; Heat shock proteins; Histology; Image; Immune; Immune Plasma; Immune response; Immunological Diagnosis; Immunology; Individual; Label; Leukocytes; Lymphocyte; Malignant Neoplasms; Mammalian Cell; Measurement; Metals; Microfabrication; Microfluidic Microchips; Microfluidics; Modification; Molecular; Molecular Profiling; Monitor; Mouse Mammary Tumor Virus; Mus; Neoplasm Metastasis; Neurosecretory Systems; Operative Surgical Procedures; Oxidative Stress; Palpable; Particulate; Pathology; Patients; Pattern; Performance; Peripheral Blood Lymphocyte; Phenotype; Physiological; Plasma; Plasma Cells; Procedures; Proteins; Quality Control; Reporting; Research Personnel; Research Project Grants; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Sensitivity and Specificity; Serum; Sorting - Cell Movement; Specificity; Staging; Stress; Surface Plasmon Resonance; System; Technology; Therapeutic Intervention; Time; Tumor Antigens; Water; Whole Blood; Work; biological adaptation to stress; biosignature; body system; cancer diagnosis; cancer surgery; cell separator; cytokine; design; experience; fluorescence imaging; holistic approach; improved; indexing; innovation; innovative technologies; instrument; instrumentation; interest; lymphoblast; male; malignant breast neoplasm; monocyte; neoplastic cell; new technology; novel; outcome forecast; prevent; prognostic; rapid diagnosis; response; sensor; stress protein; tumor

DESCRIPTION (provided by applicant): Our microfluidic Multiplex Immunodiagnostic Tumor Technology (¿MITT), which is able to sort blood components and catch a multitude of analytes, will be used to assess early host changes due to presence of a cancer. The ability to quantify a wide range of constituents from multiple organ systems as well as the cancer, itself, with high sensitivity and specificity will provide a holistic approach to evaluation of the physiological profile of cancer development. We predict that this instrumentation will be a substantial new technology for rapid early diagnosis of circulating tumor cells (CTCs) and of the host response induced by breast cancer. This device will be able to simultaneously quantify soluble analytes in plasma, blood leukocyte subsets and their released products, and CTCs, the critical and key parameter for this proposal. The fabricated chip at the heart of the instrument is able to fractionate blood into plasma, RBC/platelets, leukocytes, and CTCs with use of a micro-pillared array (plasma:cell sorter chip, PCSC) that precedes a grating-coupled surface plasmon resonance (GCSPR) chip capable of GCSPR or GCSP-enhanced fluorescence (GCSPEF) imaging; GCSPEF increases sensitivity approximately two logs, but requires secondary antibodies. The plasma constituents are captured on regions of interest (ROIs) with select antibodies. The plasma constituents will be screened for the host's immune and neuroendocrine response and stress-related proteins as well as tumor-specific antigens. Aim 1 will validate GCSPR/GCSPEF analysis with Luminex analysis and cell quantification by PCSC with flow cytometry. Aim 2 will determine the efficiency by which this technology can detect cancer and unique host biomarker profiles defining health status prior to detection of any palpable tumor. Cancer stage will be assessed by histology after blood assessments; female MMTV-PyMT mice with rapid onset of cancer will be compared to males and MMTV-neu mice as well as FVB controls used to obtain baseline values for blood biomarkers. Captured cells can be further phenotyped for released products or intracellular constituents after lysis. The technology will be optimized for sorting and capturing analytes for the greatest diagnostic and prognostic potential. The quantified profiles will delineate unique biosignatures that determine the characteristics of the host:cancer interaction. This technology will be useful for early cancer diagnosis, and we foresee using the technology to monitor tumor cell dissemination after surgery, tumor reoccurrence, and longitudinal therapeutic interventions.

描述（由申请人提供）：我们的微流体多重免疫诊断肿瘤技术（MITT），能够分选血液成分并捕获多种分析物，将用于评估由于癌症的存在而导致的早期宿主变化。以高灵敏度和特异性量化来自多个器官系统以及癌症本身的广泛成分的能力将提供评估癌症发展的生理特征的整体方法。我们预测，这种仪器将是一个实质性的新技术，用于快速早期诊断循环肿瘤细胞（CTC）和乳腺癌诱导的宿主反应。该设备将能够同时定量血浆中的可溶性分析物、血白细胞亚群及其释放产物，以及CTC，这是该提案的关键和关键参数。在仪器的核心处制造的芯片能够使用微柱阵列（血浆：细胞分选芯片，PCSC）将血液破碎成血浆、RBC/血小板、白细胞和CTC，所述微柱阵列在能够进行光栅耦合表面等离子体共振（GCSPR）或GCSP增强荧光（GCSPEF）成像的GCSPR芯片之前; GCSPEF使灵敏度增加约两个对数，但需要二抗。血浆成分用选择的抗体捕获在感兴趣的区域（ROI）上。将对血浆成分进行宿主免疫和神经内分泌反应和应激相关蛋白以及肿瘤特异性抗原的筛选。目标1将验证采用Luminex分析的GCSPR/GCSPEF分析和采用流式细胞术的PCSC细胞定量。目标2将确定该技术检测癌症的效率，以及在检测任何可触及肿瘤之前定义健康状态的独特宿主生物标志物谱。在血液评估后通过组织学评估癌症分期;将具有快速癌症发作的雌性MMTV-PyMT小鼠与用于获得血液生物标志物的基线值的雄性和MMTV-neu小鼠以及FVB对照进行比较。捕获的细胞可以在裂解后针对释放的产物或细胞内成分进一步表型化。该技术将被优化用于分选和捕获分析物，以获得最大的诊断和预后潜力。量化的概况将描绘确定宿主与癌症相互作用的特征的独特生物特征。这项技术将有助于早期癌症诊断，我们预计将使用该技术来监测手术后肿瘤细胞的传播，肿瘤复发和纵向治疗干预。