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Aptamer Based Technology for Molecular Analysis of Leukemia

基于适体的白血病分子分析技术

基本信息

批准号：
8223244
负责人：
Ying Li
金额：
$ 29.49万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8223244
关键词：
Acute Promyelocytic Leukemia Acute T Cell Leukemia Acute leukemia Affinity Antibodies Aptamer Technology Biological Markers Blood Flow Cytometry Bone Marrow Burkitt Lymphoma Cancer cell line Cell Line Cell physiology Cell surface Cells Characteristics Chromosome abnormality Classification Clinical Clinical Medicine Color Coupled Cultured Cells Cytogenetics DNA DNA biosynthesis Diagnosis Disease Dysmyelopoietic Syndromes Evaluation Evolution Face Flow Cytometry Formalin Goals Hematopoietic Human body Image Analysis Individual Knowledge Laboratories Life Ligands Lymphoma Malignant Neoplasms Membrane Proteins Methodology Methods Modeling Molecular Molecular Analysis Molecular Diagnosis Molecular Probes Molecular Profiling Monitor Monoclonal Antibodies Normal Cell One-Step dentin bonding system Patients Pharmaceutical Preparations Phenotype Physicians Protein Tyrosine Kinase Proteins Research Design Residual Neoplasm Residual Tumors Resources Role Single-Stranded DNA Specificity Specimen Surface Syndrome Technology Testing Time Translating Treatment Protocols Tumor Tissue aptamer base cancer cell cancer therapy cancer type chromosome 5q loss clinical practice disease diagnosis effective therapy experience improved leukemia leukemia/lymphoma molecular marker neoplastic cell novel peripheral blood response tool tumor

项目摘要

DESCRIPTION (provided by applicant): Today, millions of people are living with cancer or have had cancer. To provide effective treatments for a particular type of cancer, cancers should be classified according to their molecular characteristics. The molecular characteristics of individual tumors can be used to tailor treatment regimens, monitor the response to treatment, and to detect residual diseases. The major goal of this proposal is to develop a panel of aptamers as novel molecular probes for molecular profiling of leukemia cells. The biggest advantage of the aptamer- based technology is the unique cell-based selection process, Cell- SELEX (Systematic Evolution of Ligands by Exponential enrichment), used in the proposed studies. A group of cell-specific aptamers can be selected using a subtraction strategy in a relatively short period without even knowing which target molecules are present on the cell surface. Once specific aptamers are selected, we can begin to profile tumor cells without identifying each individual target proteins. These types of studies cannot be done with other types of technologies used for proteonomic studies. Also, not only can the selected aptamers be used as molecular probes for molecular profiling, but they can be used as tools for identifying new biomarkers expressed by tumor cells or other cells in disease status. The stability and easy synthesis of DNA-aptamer probes will have many more advantages than antibodies in making microarrays for proteonomic molecular profiling. Thus, aptamer technology holds a promise to overcome the challenges in current molecular profiling of normal or tumor cells. We begin our studies with well-characterized leukemia cell lines to develop the cell-based SELEX methodologies. We are then going to use patients' leukemia specimens or tumor tissue sections to select aptamers that can recognize patients' leukemia cells or formalin-fixed tumor cells. The developed strategies using leukemia cell lines or lymphoma tumor sections should easily be applied to other cancer cell lines or clinical specimens. By the completion of this project, we will have produced panels of aptamer probes for different types of leukemias. With flow cytometry or tools of imaging analysis, the cell-specific aptamers are valuable probes for molecular diagnosis and classification of tumors, as well as for the evaluation of the effects of drugs on cancer cells, which in turn will improve the diagnosis and therapy of cancers. This project is to use cell-based SELEX methodologies for developing novel DNA aptamer probes that can recognize patients' leukemia or lymphoma cells. The cell-specific aptamers are valuable probes for molecular diagnosis and classification of tumors, as well as for the evaluation of the effects of drugs on cancer cells, which in turn will improve the diagnosis and therapy of cancers.

描述(申请人提供)：今天，数以百万计的人患有癌症或患有癌症。为了对特定类型的癌症提供有效的治疗，癌症应该根据它们的分子特征进行分类。单个肿瘤的分子特征可用于定制治疗方案、监测治疗反应和检测残留疾病。这项提议的主要目标是开发一组适体，作为白血病细胞分子图谱的新型分子探针。基于适体的技术最大的优势是在拟议的研究中使用了独特的基于细胞的选择过程，Cell-SELEX(指数浓缩配体的系统进化)。使用减法策略可以在相对较短的时间内选择一组细胞特异性适配子，甚至不需要知道细胞表面存在哪些靶分子。一旦选择了特定的适配子，我们就可以开始分析肿瘤细胞，而不需要识别每个单独的靶蛋白。这些类型的研究不能用用于蛋白质组学研究的其他类型的技术来完成。此外，所选择的适体不仅可以用作分子图谱的分子探针，还可以用作识别肿瘤细胞或其他处于疾病状态的细胞表达的新生物标记物的工具。DNA适体探针的稳定性和易于合成将比抗体在制作蛋白质组分子图谱的微阵列方面具有更多的优势。因此，适体技术有望克服目前正常或肿瘤细胞分子图谱中的挑战。我们从具有良好特性的白血病细胞系开始研究，以开发基于细胞的SELEX方法。然后，我们将使用患者的白血病样本或肿瘤组织切片来选择能够识别患者白血病细胞或福尔马林固定的肿瘤细胞的适体。利用白血病细胞系或淋巴瘤肿瘤切片开发的策略应该很容易应用于其他癌细胞系或临床标本。到这个项目完成时，我们将生产出针对不同类型白血病的适体探针面板。通过流式细胞术或图像分析工具，细胞特异性适配子是肿瘤分子诊断和分类以及评估药物对癌细胞的作用的有价值的探针，这反过来将改善癌症的诊断和治疗。该项目将使用基于细胞的SELEX方法来开发能够识别患者白血病或淋巴瘤细胞的新型DNA适体探针。细胞特异性适配子是肿瘤分子诊断和分类的有价值的探针，也是评价药物对癌细胞作用的有价值的探针，这反过来将改善癌症的诊断和治疗。