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: 8530181
• 负责人: David A Lawrence
• 金额: $ 19.45万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8530181
• 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 Circulating Cells; 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)：我们的微流控多路免疫诊断肿瘤技术(？MITT)能够对血液成分进行分类并捕获多种分析物，将用于评估由于癌症存在而导致的早期宿主变化。能够以高灵敏度和特异度量化来自多个器官系统的各种成分以及癌症本身，将为评估癌症发展的生理学特征提供一种全面的方法。我们预测，这种仪器将是一项重要的新技术，用于快速早期诊断循环中的肿瘤细胞(CTCs)和乳腺癌引起的宿主反应。该设备将能够同时定量血浆中的可溶性分析物、血液白细胞亚群及其释放的产品，以及CTCs，这是这项提议的关键参数。仪器核心制造的芯片能够利用微柱阵列(等离子体：细胞分类芯片，PCSC)将血液分离为血浆、红细胞/血小板、白细胞和CTCs，该阵列领先于能够进行GCSPR或GCSPEF成像的光栅耦合表面等离子共振(GCSPR)芯片；GCSPEF将灵敏度提高约两个对数，但需要二次抗体。血浆成分用精选抗体捕获在感兴趣区(ROI)上。将对血浆成分进行筛选，以了解宿主的免疫和神经内分泌反应、应激相关蛋白以及肿瘤特异性抗原。目的1用Luminex分析验证GCSPR/GCSPEF分析，用流式细胞术验证PCSC细胞定量。目标2将确定这项技术检测癌症的效率，以及在检测到任何可触及的肿瘤之前定义健康状况的独特宿主生物标志物概况。癌症分期将在血液评估后通过组织学进行评估；癌症快速发作的雌性MMTV-PYMT小鼠将与雄性MMTV-neu小鼠以及用于获得血液生物标志物基准值的FVB对照组进行比较。捕获的细胞可以在裂解后进一步对释放的产物或细胞内成分进行表型鉴定。该技术将针对分类和捕获分析物进行优化，以实现最大的诊断和预测潜力。量化的图谱将描绘出独特的生物签名，这些签名决定了宿主的特征：癌症相互作用。这项技术将有助于癌症的早期诊断，我们预计将使用该技术监测手术后肿瘤细胞的扩散、肿瘤复发和纵向治疗干预。