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.

乳腺癌是现代社会的一种致命疾病，治疗选择有限。肿瘤恶性可能是由于肿瘤起始细胞相对未分化所致。该项目将开发一种检测方法来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显微成像 (MIEL-BTD) 检测将利用 Vala Sciences 的结构照明显微镜 (IC200-SIM) 来量化细胞核内组蛋白标签模式的变化，这些变化与乳腺上皮向产奶分化的启动相关。该快速通道项目的第一阶段将展示在标准二维培养物中使用基于免疫标记的 MIEL-BTD 版本的 MCF7 细胞（ER+ 腔内乳腺肿瘤的代表）、SKBR-3 细胞（HER2/neu+）和 MDA-MB-468（三阴性）乳腺肿瘤细胞的可行性。第二阶段将开发基因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亚核模式的分辨率。 MIEL-BTD 测定将用于发现新型乳腺癌疗法的合同研究。 IC-200 SIM 将向学术和药物癌症研究人员销售。