Ading color to cancer, adenovirus and flow cytometry to identify and capture CTCs

为癌症、腺病毒和流式细胞术着色以识别和捕获 CTC

• 批准号: 8336845
• 负责人: Lyudmila Bazhenova
• 金额: $ 15.22万
• 依托单位: NANOCELLECT BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336845
• 关键词: Adenovirus Vector; Adenoviruses; Aerosols; Affinity Chromatography; Antibodies; Antigens; Biological Assay; Biological Markers; Biology; Biomedical Engineering; Biopsy; Blood; Blood Cells; Blood Circulation; Blood specimen; Cancer Patient; Cardiovascular system; Cell Nucleus; Cell Separation; Cells; Cessation of life; Characteristics; Chimeric Proteins; Clinic; Clinical; Color; Cytosol; Data; Detection; Devices; Diagnosis; Diagnostic; Disseminated Malignant Neoplasm; Doctor of Philosophy; Early identification; Engineering; Epithelial; Evaluation; Flow Cytometry; Fluorescent in Situ Hybridization; Frequencies; Gene Expression Profile; Genetic; Genome; Goals; Growth; Hour; Individual; Invaded; Label; Left; Legal patent; Lesion; Libraries; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mediating; Microfluidics; Microscopy; Molecular; Mutation; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Oncologist; Organ; Pathway interactions; Patients; Phenotype; Primary Neoplasm; Process; Proliferating; Proteins; Reporter; Reporting; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Science; Series; Serotyping; Signal Pathway; Site; Solid Neoplasm; Solutions; Sorting - Cell Movement; Staging; System; Techniques; Technology; Testing; Tissues; Translating; Viral; Viral Vector; Virus; base; cancer cell; cancer therapy; cost; defective adenoviral vector; design; detector; malignant phenotype; micro-total analysis system; microchip; neoplastic cell; novel; novel diagnostics; peripheral blood; point-of-care diagnostics; prognostic; response; selective expression; therapeutic target; tool; tumor; viral detection; voltage; Adenovirus Vector; Adenoviruses; Aerosols; Affinity Chromatography; Antibodies; Antigens; Biological Assay; Biological Markers; Biology; Biomedical Engineering; Biopsy; Blood; Blood Cells; Blood Circulation; Blood specimen; Cancer Patient; Cardiovascular system; Cell Nucleus; Cell Separation; Cells; Cessation of life; Characteristics; Chimeric Proteins; Clinic; Clinical; Color; Cytosol; Data; Detection; Devices; Diagnosis; Diagnostic; Disseminated Malignant Neoplasm; Doctor of Philosophy; Early identification; Engineering; Epithelial; Evaluation; Flow Cytometry; Fluorescent in Situ Hybridization; Frequencies; Gene Expression Profile; Genetic; Genome; Goals; Growth; Hour; Individual; Invaded; Label; Left; Legal patent; Lesion; Libraries; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mediating; Microfluidics; Microscopy; Molecular; Mutation; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Oncologist; Organ; Pathway interactions; Patients; Phenotype; Primary Neoplasm; Process; Proliferating; Proteins; Reporter; Reporting; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Science; Series; Serotyping; Signal Pathway; Site; Solid Neoplasm; Solutions; Sorting - Cell Movement; Staging; System; Techniques; Technology; Testing; Tissues; Translating; Viral; Viral Vector; Virus; base; cancer cell; cancer therapy; cost; defective adenoviral vector; design; detector; malignant phenotype; micro-total analysis system; microchip; neoplastic cell; novel; novel diagnostics; peripheral blood; point-of-care diagnostics; prognostic; response; selective expression; therapeutic target; tool; tumor; viral detection; voltage

"Ad'ing color to cancer: adenovirus & flow cytometry to identify & capture CTCs " NanoSort RESEARCH & RELATED Other Project Information 7. PROJECT SUMMARY We propose a novel technique to identify and capture circulating tumor cels (CTCs) using enginered adenoviruses and sophisticated flow cytometry. Current techniques for detection of CTCs include reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, fluorescence in situ hybridization, and, more recently, microfluidics. Unfortunately, RT-PCR does not distinguish between viable metastatic CTC versus nucleic acids or celular fragments originating from the primary tumor. ! Antibody-based techniques cannot be used for detection of all cancers, but only those cancers that express the most common and well- characterized markers. As such, there is a desperate need to develop new diagnostic agents and tools that not only detect and capture CTCs but also quantify their malignant potential and identify 'up-front' the therapies that are most effective in ablating an individual patient's tumor. Despite the complexity and variability of cancers at a genome scale, a unifying theme is their growth deregulation phenotypes, the so-called hallmarks of cancer, which are conferred by mutations in a relatively small number of key pathways. Rather than focus on detecting individual genetic lesions that are numerous and highly variable between tumors, we propose to create diagnostic viruses that incorporate multiple transcriptional and molecular modules in their genomes to infect and detect a patient's tumor, report its molecular 'hallmarks' and its response to different therapies 'up- front'. Using these agents, the molecular lesions and malignant characteristics of any given tumor wil be rapidly discerned (within 24 hours) and scored via a standardized automated platform. Furthermore, these agents could also be used as reporters to determine rapidly and directly if a patient's tumor is likely to respond to a particular therapy. Our goal is to develop a standardized automated platform that provides point-of-care diagnostics to inform clinical decisions at a level of molecular sophistication and prognostic power that is not possible with any other detection system, biomarkers or correlative gene expression signatures. To achieve this, we will combine transformative new technological platforms developed at the Salk, UCSD, and NanoSort that label tumor cells in different colors based on their acquisition of molecular lesions that dictate malignant progression and response to therapy, facilitating their detection, quantification and isolation using an integrated 'lab-on a chip' flow cytometer. !

“对癌症的颜色：腺病毒和流式细胞仪识别和捕获CTC” 纳米 研究及相关其他项目信息 7。项目摘要 我们提出了一种新型技术，可以使用Enginered识别和捕获循环的肿瘤摄氏（CTC） 腺病毒和复杂的流式细胞仪。当前检测CTC的技术包括反向 转录酶 - 聚合酶链反应（RT-PCR），流式细胞术，荧光原位杂交以及， 最近，微流体学。不幸的是，RT-PCR不能区分可行的转移性CTC 源自原发性肿瘤的核酸或核酸或celular片段。呢基于抗体的技术 不能用于检测所有癌症，但只有那些表达最常见和善良的癌症 特征标记。因此，迫切需要开发新的诊断剂和工具 仅检测和捕获CTC，但也量化其恶性潜力并确定“前期”疗法 最有效地烧毁个体患者的肿瘤。尽管有复杂性和可变性 癌症量表的癌症是一个统一的主题是他们的成长放松调节表型，即所谓的标志 癌症是由相对少量的关键途径中突变赋予的。而不是专注于 检测肿瘤之间众多且高度变化的个体遗传病变，我们建议 创建诊断病毒，将其基因组中的多个转录和分子模块纳入到 感染和检测患者的肿瘤，报告其分子“标志”及其对不同疗法的反应“ 正面'。使用这些药物，任何给定肿瘤的分子病变和恶性特征 迅速辨别（24小时内），并通过标准化的自动化平台得分。此外，这些 代理也可以用作记者，以迅速确定患者的肿瘤是否有反应 进行特定的疗法。我们的目标是开发一个标准化的自动化平台，该平台可提供服务点 以分子成熟和预后能力水平为临床决策告知临床决策的诊断。 在任何其他检测系统，生物标志物或相关基因表达特征中都可能。实现 这，我们将结合Salk，UCSD和Nanosort开发的变革性新技术平台 该标记肿瘤细胞以不同的颜色标记，这些分子病变决定了恶性肿瘤 进展和对治疗的反应，促进其检测，定量和隔离 “实验室芯片”流式细胞仪。呢