Center for 3D Imaging in Cancer Cell Biology

癌细胞生物学 3D 成像中心

• 批准号: 10532377
• 负责人: Denis Wirtz
• 金额: $ 166.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10532377
• 关键词: 3-Dimensional; Address; Advisory Committees; Advocate; Beds; Biomedical Engineering; Blood Vessels; Cells; Cellular biology; Circulation; Communities; Complex; Computational algorithm; Computer software; Cytometry; Detection; Distant; Distant Metastasis; Engineering; Evaluation; Histologic; Human; Image; Imaging Device; Immunofluorescence Immunologic; Invaded; Label; Liver; Malignant - descriptor; Malignant neoplasm of pancreas; Mammary Gland Parenchyma; Mammary Neoplasms; Maps; Methods; Microanatomy; Microscopy; Molecular; Molecular Analysis; Morphology; Mus; Neoplasm Metastasis; Occupational activity of managing finances; Operative Surgical Procedures; Optics; Organoids; Outcome; Pathologic; Pathology; Patients; Phenotype; Physicians; Portal vein structure; Primary Neoplasm; Process; Prognosis; Proteomics; Resected; Resolution; Sampling; Schools; Scientist; Site; Survival Rate; Test Result; Testing; Three-Dimensional Imaging; Tissue Sample; Tissue imaging; Tissues; Venous; Visualization; Wood material; anticancer research; cancer cell; cancer imaging; cell type; cost; data dissemination; deep learning algorithm; experience; imaging modality; immunocytochemistry; insight; large datasets; lymphatic Invasion; malignant breast neoplasm; medical schools; mortality; mouse model; multidisciplinary; multiple omics; novel; pancreatic neoplasm; reconstruction; serial imaging; tool; transcriptomics; tumor; tumor heterogeneity; tumor microenvironment

Project Summary - Overall The mortality rates of breast and pancreatic cancers are intrinsically tied to metastasis. In pancreatic cancer, the 5-year survival rate is only 9% and in ~70% pathological evaluations of the resected tumor, instances of venous invasion are found. Metastasis is a complex multi-step process involving cancer cells, local vasculature, and the surrounding microenvironment at multiple sites. Venous invasion in pancreatic cancer, in which cancer cells gain often invade the portal vein, is an early step in this process and provides the cells a direct path to the liver, the most common site of pancreatic cancer metastasis. As in pancreatic cancer, invasion past normal breast tissue barriers is critically tied to breast cancer outcomes. Most breast tumors can be surgically removed, and so mortality is closely tied to the extent of distant metastasis through lymphovascular invasion. The detection of lymphovascular invasion in a breast tumor correlates with poor prognosis and is not captured in current molecular analyses. The spatial organization of cancer cells, and cellular and stromal components of the tumor microenvironment near and far away from blood vessels is intrinsically three-dimensional, non-symmetric, and highly heterogeneous. In the TECH units of the Johns Hopkins Center for 3D Multiscale Cancer Imaging, we will develop a versatile 3D multiscale imaging method, CODA, which will allow us to probe the phenotypic heterogeneity of tumors from the multi-cm to the micron scale via multiplexing serial imaging. CODA can readily incorporate other imaging modalities to extract high cellular/molecular content from 3D samples. These include immunocytochemistry (CODA+IHC), immunofluorescence (CODA+IF), imaging mass cytometry (CODA+IMC) and spatial transcriptomics/proteomics (CODA+DBiT-seq). These proposed expanded versions of CODA offer a unique opportunity to produce new 3D multi-omic maps of human PDAC and breast tumors near and far from blood vessels. CODA and its integrated versions CODA+X will be tested in the RTB units of the Center in both human/mouse tissue samples and organoids, in breast and pancreatic cancer. Results from these test beds will provide novel mechanistic insights into venous invasion in breast and pancreatic cancer. Exploiting our extensive experience in data dissemination, we will make the large datasets and software produced by our CODA+X platforms and software widely available to the larger cancer research community. The units of the Center will be co-led by Johns Hopkins/Yale engineers, scientists and physicians. Substantial additional support will be provided by the Johns Hopkins U., the JH School of Medicine, the Institute for Convergence, the Department of Pathology, and the Whiting School of Engineering.

项目摘要 - 总体 乳腺癌和胰腺癌的死亡率与转移本质上息息相关。在胰腺癌中 5年生存率仅为9％，在约70％的病理评估中，静脉肿瘤实例 发现入侵。转移是一个复杂的多步骤过程，涉及癌细胞，局部脉管系统和 周围的微环境在多个地点。胰腺癌的静脉侵袭，其中癌细胞获得 通常入侵门静脉，是此过程的早期步骤，并为细胞提供了通往肝脏的直接路径， 胰腺癌转移的最常见部位。与胰腺癌一样，侵入正常乳房组织 障碍与乳腺癌结局密切相关。大多数乳腺肿瘤可以手术切除，因此 死亡率与淋巴血管侵袭的远处转移密切相关。检测 乳腺肿瘤中的淋巴血管浸润与预后不良相关，并且在电流分子中未捕获 分析。癌细胞的空间组织以及肿瘤的细胞和基质成分 附近和远离血管的微环境本质上是三维，非对称和 高度异质。在约翰·霍普金斯（Johns Hopkins）的3D多尺度癌症成像中心的技术单元中 将开发一种多功能的3D多尺度成像方法CODA，这将使我们能够探测表型 通过多重串行成像从多CM到微米尺度的肿瘤的异质性。尾巴很容易 结合其他成像方式，以从3D样品中提取高细胞/分子含量。这些包括 免疫细胞化学（CODA+IHC），免疫荧光（CODA+IF），成像质量细胞术（CODA+IMC） 和空间转录组学/蛋白质组学（CODA+DBIT-SEQ）。这些拟议的扩展版本的尾巴报价 一个独特的机会，可以生产新的3D多摩变图的人类PDAC和乳腺肿瘤附近和远处的乳腺肿瘤 血管。 CODA及其集成版本CODA+X将在中心的RTB单元中进行测试 乳腺癌和胰腺癌中的人/小鼠组织样品和类器官。这些测试床的结果将 提供有关乳腺癌和胰腺癌静脉入侵的新机械洞察力。利用我们的广泛 有数据传播的经验，我们将制造由CODA+X产生的大型数据集和软件 平台和软件广泛可供大型癌症研究界使用。中心的单位将是 由约翰·霍普金斯（Johns Hopkins）/耶鲁大学工程师，科学家和医生共同领导。大量的额外支持将是 由约翰·霍普金斯大学（John Hopkins U.），JH医学院，融合研究所 病理学和惠廷工程学院。