Abstract P4-07-10: Epithelial mesenchymal transition associated with high miR-221 and integrin {beta}6 leads to poor prognosis in hormone receptor positive HER2 negative breast cancers

Breast cancer progression is associated with systemic effects such as functional limitation, sarcopenia and cachexia. These effects are manifested as muscle weakness, body pain or depletion of skeletal muscle mass. Over a quarter of 2.8 million breast cancer patients in the United States experience a precachexia to cachexia syndrome. It has been reported that cancer-induced cytokines activate NF-κB, which promotes cancer progression, metastasis, and chemoresistance. These cytokines could potentially induce NF-kB in skeletal muscle, impair skeletal muscle function, and cause functional limitations. Therefore, NF-κB inhibitors could serve dual purpose of inhibiting cancer progression and reducing functional limitations. In present study, we usedMMTV-PyMT transgenic mammary tumor model to test therapeutic effects of the NF-κB inhibitor, Diaminomethylparthenolide (DMAPT), an orally bioavailable NF-kB inhibitor. We observed deteriorating physical and functional conditions in PyMT+ mice with the progression of mammary tumor.Compared to wildtype mice, PyMT+ mice with mammary tumors showed decreased fat mass and grip strength, both are markers of functional limitations. Treatment with DMAPT (100mg/kg, 5 times/week, orally), starting at 8 week-old prior to mammary tumor occurrence, delayed mammary tumor onset and slowed tumor growth rates compared to vehicle treatment. Consequently, DMAPT-treated mice showed lower systemic effects of mammary tumors on grip strength and alterations ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research