Reversal of the estrogen receptor negative phenotype in breast cancer and restoration of antiestrogen response.

Purpose: In breast cancer, the presence of estrogen receptor alpha (ER) denotes a better prognosis and response to antiestrogen therapy. Lack of ERalpha correlates with overexpression of epidermal growth factor receptor or c-erbB-2. We have shown that hyperactivation of mitogen-activated protein kinase (MAPK) directly represses ERalpha expression in a reversible manner.

Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors.

Breast cancer presents as either estrogen receptor alpha (ERalpha) positive or negative, with ERalpha+ tumors responding to antiestrogen therapy and having a better prognosis. By themselves, mRNA expression signatures of estrogen regulation in ERalpha+ breast cancer cells do not account for the vast molecular differences observed between ERalpha+ and ERalpha- cancers. In ERalpha- tumors, overexpression of epidermal growth factor receptor (EGFR) or c-erbB-2, leading to increased growth factor signaling, is observed such that mitogen-activated protein (MAP) kinase (MAPK) is significantly hyperactivated compared with ERalpha+ breast cancer.

Matrix fixed-charge density as determined by magnetic resonance microscopy of bioreactor-derived hyaline cartilage correlates with biochemical and biomechanical properties.

Objective: To use noninvasive magnetic resonance imaging (MRI), biochemical analyses, and mechanical testing of engineered neocartilage grown in a hollow- fiber bioreactor (HFBR) to establish tissue properties, and to test the hypothesis that MRI can be used to monitor biochemical and biomechanical properties of neocartilage.

Methods: Chondrocytes from day 16 embryonic chick sterna were inoculated into an HFBR and maintained for up to 4 weeks with and without exposure to chondroitinase ABC. The fixed-charge density (FCD) of the cartilage was determined using the MRI gadolinium exclusion method.