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.

乳腺癌是现代社会的一种致命疾病，治疗方法有限。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，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类型的癌症有效。表观遗传景观乳腺肿瘤分化的显微成像（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分化的开始有关。这个快速通道项目的第一阶段将证明在标准的二维培养中使用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，使用基于免疫标记的MIEL-BTD版本。第二阶段将开发遗传编码表观遗传探针（GEEPs）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检测将用于新型乳腺癌治疗方法的合同研究。IC-200 SIM将同时面向学术和制药癌症研究人员销售。

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.