TOPIC 382 - THE MICROSCOPIC IMAGING OF EPIGENETIC LANDSCAPE BREAST TUMOR DIFFERENTIATION (MIEL-BTD) ASSAY: A HIGH THROUGHPUT SCREEN TO IDENTIFY NOVEL THERAPEUTICS FOR BREAST CANCER.

主题 382 - 表观遗传景观乳腺肿瘤分化 (MIEL-BTD) 测定的显微成像：用于鉴定乳腺癌新疗法的高通量筛选。

• 批准号: 10030948
• 负责人: PATRICK MCDONOUGH
• 金额: $ 29.99万
• 依托单位: VALA SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2020-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10030948
• 关键词: 18 year old; 3-Dimensional; African American; Agriculture; Animals; Antibodies; Area; Biological Assay; Biological Markers; Breast; Breast Cancer Cell; Breast Cancer cell line; Breast Epithelial Cells; Caseins; Cattle; Cell Culture Techniques; Cell Cycle; Cell Line; Cell Nucleus; Cell division; Cells; Chemicals; Cultured Cells; Data; Data Analyses; Development; Devices; Dexamethasone; Dimensions; Disease; ERBB2 gene; Epigenetic Process; Epithelial Cells; Epithelium; Estradiol; Exposure to; Female; Fluorescent in Situ Hybridization; Genetic Variation; Glioblastoma; Glucocorticoids; Goat; Growth; Hand; Histones; Hormones; Human; Image; Image Analysis; In Vitro; Individual; Insulin; Label; Laboratories; Ligands; Light; Lighting; Lipids; Location; Logic; MCF7 cell; MDA-MB-468; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Messenger RNA; Methods; Microscope; Milk Proteins; Modeling; Modernization; Modification; Myoepithelial; Neurons; Nuclear; Operative Surgical Procedures; Pathway interactions; Pattern; Personal Communication; Pharmacologic Substance; Phase; Phenotype; Phosphotransferases; Positioning Attribute; Procedures; Process; Production; Prolactin; Proteins; Protocols documentation; Publishing; Reproducibility; Research; Research Contracts; Research Personnel; Resolution; Rodent; Running; SKBR3; Sampling; Scanning; Science; Side; Societies; Solid; Stains; Stimulus; Structure; Tamoxifen; Testing; Therapeutic; Therapeutic Agents; Three-Dimensional Image; Time; Tretinoin; Tumor Initiators; Undifferentiated; Vial device; Work; base; cancer type; cell type; density; digital; epigenetic marker; expectation; experience; experimental study; high throughput screening; interest; knock-down; lactogenesis; malignant breast neoplasm; mammary epithelium; microscopic imaging; milk fat globule; milk production; neoplastic cell; novel; novel therapeutics; precursor cell; targeted treatment; time use; tumor

Breast cancer is a deadly disease in modern society with limited therapeutics options. Tumor malignancy is likely due to tumor-initiating cells that are relatively undifferentiated. This project will develop an assay to identify chemical compounds that encourage differentiation of breast tumor cells, a strategy that has proven effective for other cancer types. The Microscopic Imaging of Epigenetic Landscape Breast Tumor Differentiation (MIEL-BTD) assay will utilize Vala Sciences’ Structured Illumination Microscope (IC200-SIM) to quantify changes in the patterns of histone tags within the nucleus, associated with the initiation of differentiation of breast epithelium towards milk production. Phase I of this Fast-Track project will demonstrate feasibility utilizing MCF7 cells (representative of ER+ lumenal breast tumor), SKBR-3 cells (HER2/neu+) and MDA-MB-468 (triple negative) breast tumor cells, in standard, 2-D cultures using a version of the MIEL-BTD based upon immunolabeling. Phase II will develop genetically-encoded epigenetic probes (GEEPs) and tumor spheroid (3-D) culture models. SIM and image analysis methods will be developed for increased resolution of sub-nuclear patterns of epigenetic markers. The MIEL-BTD assay will be utilized in contract research for discovery of novel breast cancer therapeutics. The IC-200 SIM will be marketed to both academic and pharmaceutical cancer researchers.

乳腺癌是现代社会中的一种致命疾病，治疗选择有限。肿瘤恶性可能是由于相对未分化的肿瘤起始细胞。该项目将开发一种检测方法，以识别促进乳腺肿瘤细胞分化的化合物，这一策略已被证明对其他癌症类型有效。表观遗传景观乳腺肿瘤分化的显微成像（MIEL-BTD）试验将利用Vala Sciences的结构化照明显微镜（IC 200-SIM）来量化细胞核内组蛋白标签模式的变化，与乳腺上皮细胞向乳汁产生分化的起始相关。该快速通道项目的I期将证明使用基于免疫标记的MIEL-BTD版本在标准2-D培养物中使用MCF 7细胞（ER+管腔乳腺肿瘤的代表）、SKBR-3细胞（HER 2/neu+）和MDA-MB-468（三阴性）乳腺肿瘤细胞的可行性。第二阶段将开发遗传编码的表观遗传探针（GEEP）和肿瘤球体（3-D）培养模型。将开发SIM和图像分析方法，以提高表观遗传标记的亚核模式的分辨率。MIEL-BTD检测将用于合同研究，以发现新型乳腺癌治疗方法。 IC-200 SIM将面向学术和制药癌症研究人员销售。