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Kiemen, A.

Publications and source records attributed to Kiemen, A..

2 recordsLinked to original sources

Deep Learning Identification of Stiffness Markers in Breast Cancer

While essential to our understanding of solid tumor progression, the study of cell and tissue mechanics has yet to find traction in the clinic. Determining tissue stiffness, a mechanical property known to promote a malignant phenotype in vitro and in vivo, is not part of the standard algorithm for the diagnosis and treatment of breast cancer. Instead, clinicians routinely use mammograms to identify malignant lesions and radiographically dense breast tissue is associated with an increased risk of developing cancer. Whether breast density is related to tumor tissue stiffness, and what cellular and non-cellular components of the tumor contribute the most to its stiffness are not well understood. Through training of a deep learning network and mechanical measurements of fresh patient tissue, we create a bridge in understanding between clinical and mechanical markers. The automatic identification of cellular and extracellular features from hematoxylin and eosin (H&E)-stained slides reveals that global and local breast tissue stiffness best correlate with the percentage of straight collagen. Global breast tissue mechanics correlate weakly with the percentage of blood vessels and fibrotic tissue, and non-significantly with the percentage of fat, ducts, tumor cells, and wavy collagen in tissue. Importantly, the percentage of dense breast tissue does not directly correlate with tissue stiffness or straight collagen content.

cancer biology

Multi-compartment tumor organoids

Organoid cultures are widely used because they preserve many features of cancer cells in vivo. Here, we developed high-throughput oil-in-water droplet microtechnology to generate highly uniform, small-volume, multi-compartment organoids. Each organoid culture features a microenvironmental architecture that mimics both the basement membrane and stromal barriers. This matrix architecture, which allows accessing both proliferative and invasive features of cancer cells in a single platform, has profound effect on observed drug responsiveness and tumor progression that correlate well with in vivo and clinical outcomes. The method was tested on multiple types of cancer cells including primary cells and immortalized cell lines, and we determined our platform is suitable even for cells of poor organoid-forming ability. These new organoids also allow for direct orthotopic mouse implantation of cancer cells with unprecedented success.

cancer biology