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Pancreatic ductal adenocarcinomas (PDAs) are characterized by a robust fibroinflammatory response. We show here that this desmoplastic reaction generates inordinately high interstitial fluid pressures (IFPs), exceeding those previously measured or theorized for solid tumors, and induces vascular collapse, while presenting substantial barriers to perfusion,(More)
BACKGROUND Stromal-epithelial interactions are of particular significance in breast tissue as misregulation of these interactions can promote tumorigenesis and invasion. Moreover, collagen-dense breast tissue increases the risk of breast carcinoma, although the relationship between collagen density and tumorigenesis is not well understood. As little is(More)
Subfailure damage in ligaments was evaluated macroscopically from a structural perspective (referring to the entire ligament as a structure) and microscopically from a cellular perspective. Freshly harvested rat medial collateral ligaments (MCLs) were used as a model in ex vivo experiments. Ligaments were preloaded with 0.1 N to establish a consistent point(More)
Ligaments display time-dependent behavior, characteristic of a viscoelastic solid, and are nonlinear in their stress-strain response. Recent experiments (25) reveal that stress relaxation proceeds more rapidly than creep in medial collateral ligaments, a fact not explained by linear viscoelastic theory but shown by Lakes and Vanderby (17) to be consistent(More)
Evidence for the potent influence of stromal organization and function on invasion and metastasis of breast tumors is ever growing. We have performed a rigorous examination of the relationship of a tumor-associated collagen signature-3 (TACS-3) to the long-term survival rate of human patients. TACS-3 is characterized by bundles of straightened and aligned(More)
Cells generate mechanical force to organize the extracellular matrix (ECM) and drive important developmental and reparative processes. Likewise, tumor cells invading into three-dimensional (3D) matrices remodel the ECM microenvironment. Importantly, we previously reported a distinct radial reorganization of the collagen matrix surrounding tumors that(More)
The goal of this study was to characterize the viscoelastic behavior of the rabbit medial collateral ligament (MCL) at multiple levels of strain (between 0% and approximately 5%) and their corresponding stresses (between 0 and approximately 55 MPa) for stress relaxation and creep, respectively. We hypothesized that in the rabbit MCL the rate of stress(More)
BACKGROUND Mammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma. Despite the strong clinical correlation, breast density has not been causally linked to tumorigenesis, largely because no animal model has existed for studying breast tissue density. Importantly, regions of high breast density are associated(More)
Mammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma, yet the associated molecular mechanisms remain largely unknown. Importantly, regions of high breast density are associated with increased stromal collagen and epithelial cell content. We set out to determine whether increased collagen-matrix density, in(More)