Metastasis by cancer cells relies upon the acquisition of the ability to evade anoikis, a cell death process elicited by detachment from extracellular matrix (ECM). The molecular mechanisms that ECM-detached cancer cells use to survive are not understood. Striking increases in reactive oxygen species (ROS) occur in ECM-detached mammary epithelial cells, threatening cell viability by inhibiting ATP production, suggesting that ROS must be neutralized if cells are to survive ECM-detachment. Here, we report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after ECM-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. Conversely, silencing antioxidant enzyme expression in multiple breast cancer cell lines caused ATP reduction and compromised anchorage-independent growth. Notably, antioxidant enzyme-deficient cancer cells were compromised in their ability to form tumors in mice. In aggregate, our results reveal a vital role for antioxidant enzyme activity in maintaining metabolic activity and anchorage-independent growth in breast cancer cells. Furthermore, these findings imply that eliminating antioxidant enzyme activity may be an effective strategy to enhance susceptibility to cell death in cancer cells that may otherwise survive ECM-detachment. Cancer Res; 73(12); 3704–15. ©2013 AACR.

X-ray Computed Tomography (CT) is one of the most commonly utilized anatomical imaging modalities for both research and clinical purposes. CT combines high-resolution, three-dimensional data with relatively fast acquisition to provide a solid platform for non-invasive human or specimen imaging. The primary limitation of CT is its inability to distinguish many soft tissues based on native contrast. While bone has high contrast within a CT image due to its material density from calcium phosphate, soft tissue is less dense and many are homogenous in density. This presents a challenge in distinguishing one type of soft tissue from another. A couple exceptions include the lungs as well as fat, both of which have unique densities owing to the presence of air or bulk hydrocarbons, respectively. In order to facilitate X-ray CT imaging of other structures, a range of contrast agents have been developed to selectively identify and visualize the anatomical properties of individual tissues. Most agents incorporate atoms like iodine, gold, or barium because of their ability to absorb X-rays, and thus impart contrast to a given organ system. Here we review the strategies available to visualize lung, fat, brain, kidney, liver, spleen, vasculature, gastrointestinal tract, and liver tissues of living mice using either innate contrast, or commercial injectable or ingestible agents with selective perfusion. Further, we demonstrate how each of these approaches will facilitate the non-invasive, longitudinal, in vivo imaging of pre-clinical disease models at each anatomical site.

BACKGROUND:. Surgical site infection (SSI) contributes significantly to postoperative morbidity and mortality and greatly increases the cost of care.OBJ

BACKGROUND: Chronic deep brain stimulation of the rodent lateral cerebellar nucleus (LCN) has been demonstrated to enhance motor recovery following cortical ischemia. This effect is concurrent with synaptogenesis and expression of long-term potentiation markers in the perilesional cerebral cortex. OBJECTIVE: To further investigate the cellular changes associated with chronic LCN stimulation in the ischemic rodent by examining neurogenesis along the cerebellothalamocortical pathway. METHODS: Rats were trained on the pasta matrix task, followed by induction of cortical ischemia and electrode implantation in the contralesional LCN. Electrical stimulation was initiated 6 wk after stroke induction and continued for 4 wk prior to sacrifice. Neurogenesis was examined using immunohistochemistry. RESULTS: Treated animals showed enhanced performance on the pasta matrix task relative to sham controls. Increased cell proliferation colabeled with 5’-Bromo-2’-deoxyuridine and neurogenic markers (doublecortin) was observed in the perilesional cortex as well as bilateral mediodorsal and ventrolateral thalamic subnuclei in treated vs untreated animals. The neurogenic effect at the level of motor cortex was selective, with stimulation-treated animals showing greater glutamatergic neurogenesis but significantly less GABAergic neurogenesis. CONCLUSION: These findings suggest that LCN deep brain stimulation modulates postinjury neurogenesis, providing a possible mechanistic foundation for the associated enhancement in poststroke motor recovery.