Application of a Novel Nanotechnology for Molecular Profiling of Tumor Cellular E

新型纳米技术在肿瘤细胞 E 分子谱分析中的应用

• 批准号: 7643484
• 负责人: EDWARD L. NELSON
• 金额: $ 15.29万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-20 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643484
• 关键词: Address; Adjuvant Chemotherapy; Antibodies; Arts; Be++ element; Behavior; Beryllium; Biological; Biomedical Engineering; Biopsy; Cancer Patient; Cell Line; Cell surface; Cells; Cellular biology; Clinical; Clinical Oncology; Confocal Microscopy; Cytotoxic agent; Detection; Diagnosis; Diagnostic; Dissection; Elements; Epithelial; Epithelium; Evaluation; Excision; Exhibits; Fine needle aspiration biopsy; Flow Cytometry; Future; Gene Expression; Gene Expression Profile; Genetic; Heterogeneity; Histologic; Histology; Immunofluorescence Immunologic; Immunology; Individual; Inflammatory; Lasers; Malignant - descriptor; Malignant Neoplasms; Mammary Neoplasms; Methodology; Methods; Molecular; Molecular Analysis; Molecular Genetics; Molecular Profiling; Molecular Target; Myoepithelial; Myoepithelial cell; Myoepithelioma; Nanotechnology; Neoadjuvant Therapy; Neoplasm Metastasis; Operative Surgical Procedures; Optics; Palliative Care; Patients; Phenotype; Polymers; Population; Primary Neoplasm; Recovery; Relative (related person); Resected; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Slide; Specimen; Stem cells; Surface; Technology; Testing; Therapeutic; Time; Toxic effect; Treatment Efficacy; Tumor Biology; Tumor Tissue; angiogenesis; base; cancer stem cell; clinical application; design; innovation; malignant breast neoplasm; neoplastic cell; novel; optical imaging; outcome forecast; progenitor; prospective; response; stem; therapy resistant; treatment response; treatment strategy; tumor

DESCRIPTION (provided by applicant): Our increasing appreciation of 1) tumor genetic and cellular heterogeneity, 2) the recent descriptions of cancer stem, endothelial progenitor, & myoepithelial cells, among others, and 3) disparate responses to treatment even for histologically similar tumors; raise fundamental questions as to the relative contributions of various tumor cellular subsets to the biologic behavior of a tumor. However, technologies permitting the prospective characterization of discrete tumor cellular elements and recovery of selected viable cells from a tumor have yet to be developed. We have developed a novel nanotechnology consisting of an array of microfabricated SU8 polymer elements that permits the isolation and recovery of individual adherent cells. This advanced nanotechnology combined with multicolor immunofluorescence and advanced confocal microscopy enables us to propose application of this technology to the simultaneous identification, recovery, and evaluation of selected molecular profiles from viable primary adherent cell populations representing the various cellular elements within individual tumors. The HYPOTHESIS for these studies is that the pallet array nanotechnology will permit identification, enumeration, and recovery of the following individual cellular tumor elements: cancer stem, endothelial progenitor, myoepithelial, epithelial, and inflammatory cells leading to the molecular characterization of these cellular subsets within individual tumors and will be tested by pursuing the following Specific Aims: AIM #1. Refine the pallet array for maximum cell capture, detection, and recovery of tumor cellular elements. AIM #2 Apply pallet array to Fine Needle Aspirate (FNA) samples of primary breast tumors to identify and isolate individual cells from discrete tumor cellular elements. AIM #3 Establish feasibility of molecular analysis of recovered individual rare cells, e.g. single cell RT-PCR. These studies represent a convergence of biomedical engineering, advanced laser optics, cell biology, immunology, and clinical oncology and will drive future studies to address fundamental biological and clinical questions.

描述（由申请人提供）：我们对1）肿瘤遗传和细胞异质性，2）最近对癌症干细胞、内皮祖细胞和肌上皮细胞等的描述，以及3）即使对于组织学相似的肿瘤，对治疗的不同反应的认识不断提高;提出了关于各种肿瘤细胞亚群对肿瘤生物学行为的相对贡献的基本问题。然而，允许对离散的肿瘤细胞成分进行前瞻性表征和从肿瘤中回收选定的活细胞的技术还有待开发。我们已经开发了一种新的纳米技术，包括一个阵列的微加工SU 8聚合物元素，允许单独的贴壁细胞的分离和恢复。这种先进的纳米技术与免疫荧光和先进的共聚焦显微镜相结合，使我们能够提出应用这项技术，同时识别，回收和评价选定的分子概况，从活的原代贴壁细胞群体代表各个肿瘤内的各种细胞成分。这些研究的假设是，托盘阵列纳米技术将允许识别、计数和回收以下单个细胞肿瘤成分：癌干细胞、内皮祖细胞、肌上皮细胞、上皮细胞和炎性细胞，从而对单个肿瘤中的这些细胞亚群进行分子表征，并将通过追求以下特定目标进行测试：AIM #1。优化托盘阵列，以最大限度地捕获、检测和回收肿瘤细胞成分。目的#2将托盘阵列应用于原发性乳腺肿瘤的细针抽吸（FNA）样本，以从离散的肿瘤细胞成分中识别和分离单个细胞。目的#3建立回收的单个稀有细胞的分子分析的可行性，例如单细胞RT-PCR。这些研究代表了生物医学工程，先进激光光学，细胞生物学，免疫学和临床肿瘤学的融合，并将推动未来的研究，以解决基本的生物学和临床问题。