Proteoglycans, particularly hyaluronic acid, play important roles in determining biomechanical properties of tissue oscillation. Future research will likely make these proteins of important therapeutic interest.
A standard method for the empirical rheological characterization of viscoelastic materials was adopted to measure the viscoelastic shear properties of human vocal-fold mucosal tissues (the superficial layer of lamina propria). A parallel-plate rotational rheometer was employed to measure shear deformation of viscoelastic tissue samples, which were deformed between two rigid circular plates rotating in small-amplitude sinusoidal oscillations. Elastic and viscous shear moduli of the samples were then quantified as a function of oscillation frequency (0.01 to 15 Hz) based on shear stresses and strains recorded by the rheometer. Data were obtained from 15 excised human larynges (10 male and 5 female). Results showed that the elastic shear modulus mu and the damping ratio zeta of human vocal-fold mucosa were relatively constant across the range of frequencies observed, while the dynamic viscosity eta decreased monotonically with frequency (i.e., shear thinning). Intersubject differences in mu and eta as large as an order of magnitude were observed, part of which may reflect age-related and gender-related differences. Some molecular interpretations of the findings are discussed.
Results indicated that viscoelastic tissue changes may take place before scar maturation in the scarred vocal fold lamina propria and that, although abundant collagen deposition may influence viscoelastic shear tissue properties, disorganization of collagen and elastin fibers, thick bundle collagen formation, or the interplay of several of these factors might also play a contributing role.
The scaffolding adapter GAB2 maps to a region (11q13-14) commonly amplified in human breast cancer, and is overexpressed in breast cancer cell lines and primary tumors, but its functional role in mammary carcinogenesis has remained unexplored. We found that overexpression of GAB2 (Grb2-associated binding protein 2) increases proliferation of MCF10A mammary cells in three-dimensional culture. Coexpression of GAB2 with antiapoptotic oncogenes causes lumenal filling, whereas coexpression with Neu (also known as ErbB2 and HER2) results in an invasive phenotype. These effects of GAB2 are mediated by hyperactivation of the Shp2-Erk pathway. Furthermore, overexpression of Gab2 potentiates, whereas deficiency of Gab2 ameliorates, Neu-evoked breast carcinogenesis in mice. Finally, GAB2 is amplified in some GAB2-overexpressing human breast tumors. Our data suggest that GAB2 may be a key gene within an 11q13 amplicon in human breast cancer and propose a role for overexpression of GAB2 in mammary carcinogenesis. Agents that target GAB2 or GAB2-dependent pathways may be useful for treating breast tumors that overexpress GAB2 or HER2 or both.
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