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Full-Text Articles in Chemistry
Comparative Study Of Multicellular Tumor Spheroid Formation Methods And Implications For Drug Screening, Maria F. Gencoglu, Lauren E. Barney, Christopher L. Hall, Elizabeth A. Brooks, Alyssa D. Schwartz, Daniel C. Corbett, Kelly R. Stevens, Shelly Peyton
Comparative Study Of Multicellular Tumor Spheroid Formation Methods And Implications For Drug Screening, Maria F. Gencoglu, Lauren E. Barney, Christopher L. Hall, Elizabeth A. Brooks, Alyssa D. Schwartz, Daniel C. Corbett, Kelly R. Stevens, Shelly Peyton
Chemical Engineering Faculty Publication Series
Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Multicellular tumor spheroids (MCTS) are a popular method for three-dimensional (3D) cell culture, because they capture some aspects of the dimensionality, cell–cell contact, and cell–matrix interactions seen in vivo. Many approaches exist to create MCTS from cell lines, and they have been used to study tumor cell invasion, growth, and how cells respond to drugs in physiologically relevant 3D microenvironments. However, there are several discrepancies in the observations made of cell behaviors when comparing …
Sorafenib Resistance And Jnk Signaling In Carcinoma During Extracellular Matrix Stiffening, Thuy V. Nguyen, Marianne Sleiman, Timothy Moriarty, William G. Herrick, Shelly Peyton
Sorafenib Resistance And Jnk Signaling In Carcinoma During Extracellular Matrix Stiffening, Thuy V. Nguyen, Marianne Sleiman, Timothy Moriarty, William G. Herrick, Shelly Peyton
Chemical Engineering Faculty Publication Series
Tumor progression is coincident with mechanochemical changes in the extracellular matrix (ECM). We hypothesized that tumor stroma stiffening, alongside a shift in the ECM composition from a basement membrane-like microenvironment toward a dense network of collagen-rich fibers during tumorigenesis, confers resistance to otherwise powerful chemotherapeutics. To test this hypothesis, we created a high-throughput drug screening platform based on our poly(ethylene glycol)-phosphorylcholine (PEG-PC) hydrogel system, and customized it to capture the stiffness and integrin-binding profile of in vivo tumors. We report that the efficacy of a Raf kinase inhibitor, sorafenib, is reduced on stiff, collagen-rich microenvironments, independent of ROCK activity. Instead, …