Targeted inhibition of EG-1 blocks breast tumor growth

EG-1 is a gene product that is significantly elevated in human breast cancer tissues. Previously, we have shown that EG-1 overexpression stimulates cellular proliferation both in vitro and in vivo. Here, we ask whether this molecule can be targeted for experimental therapeutic purpose. siRNA lentivirus and polyclonal antibodies were designed to suppress EG-1 expression. These agents were then used in cell culture proliferation assays and breast tumor xenograft models. Serum and urine from breast cancer patients were also analyzed for the presence of EG-1 peptide. We report here for the first time that endogenous EG-1 can be targeted to inhibit breast tumor growth. This inhibition, whether delivered via siRNA lentivirus or polyclonal antibody, resulted in decreased cellular proliferation in culture and smaller xenografts in mice. The effects were shown in both ER (estrogen receptor)-positive human breast cancer MCF-7 cells, as well as in ER-negative MDA-MB-231 cells. Furthermore, we detected soluble EG-1 in serum and urine of breast cancer patients. These observations demonstrate that EG-1 is relevant to human breast cancer, and is a molecular target worthy of translational efforts into effective breast cancer therapy.     

Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.     

Adipocytokines and VLDL metabolism: independent regulatory effects of adiponectin, insulin resistance, and fat compartments on VLDL apolipoprotein B-100 kinetics?

We investigated the relationship of plasma adipocytokine concentrations with VLDL apolipoprotein B (apoB)-100 kinetics in men. Plasma adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured using enzyme immunoassays and insulin resistance by homeostasis model assessment (HOMA) score in 41 men with BMI of 22-35 kg/m(2). VLDL apoB kinetics were determined using an intravenous infusion of 1-[(13)C]leucine, gas chromatography-mass spectrometry, and compartmental modeling. Visceral and subcutaneous adipose tissue mass (ATM) were determined using magnetic resonance imaging, and total ATM was measured by bioelectrical impedance. In univariate regression, plasma adiponectin and leptin concentrations were inversely and directly associated, respectively, with plasma triglyceride; HOMA score; and visceral, subcutaneous, and total ATMs. Conversely, adiponectin and leptin were directly and inversely correlated, respectively, with VLDL apoB catabolism and HDL cholesterol concentration (P < 0.05). Resistin, IL-6, and TNF-alpha were not significantly associated with any of these variables. In multivariate regression, adiponectin was the most significant predictor of plasma VLDL apoB concentration (P = 0.001) and, together with total or subcutaneous ATM, was an independent predictor of VLDL apoB catabolism (P < 0.001); HOMA score was the most significant predictor of VLDL apoB hepatic secretion (P < 0.05). Leptin was not an independent predictor of VLDL apoB kinetics. In conclusion, plasma VLDL apoB kinetics may be differentially controlled by adiponectin and insulin resistance, with adiponectin regulating catabolism and insulin resistance regulating hepatic secretion in men. Total body fat may also independently determine the rate of VLDL catabolism, but leptin, resistin, IL-6, and TNF-alpha do not have a significant effect in regulating apoB kinetics.     

The use of oxytocin in nipple fluid aspiration

It has been shown that early detection of breast cancer saves lives. Recently there has been increasing interest in nipple aspirate fluid as a potential avenue for breast cancer diagnosis. One major challenge regarding studies of nipple aspirate fluid is the ability to obtain adequate samples. Here we describe the use of nasal oxytocin in a group of volunteer women in order to increase the yield of nipple aspirate fluid.     

Systemic lupus erythematosus with celiac disease: a report of five cases

Systemic lupus erythematosus and celiac disease (CD) are rarely reported in combination. We report five cases seen over a 4-year period. The two conditions occurred concomitantly in one patient, whereas the CD antedated the lupus in one patient and postdated the lupus in the remaining three patients. Villous atrophy on duodenal biopsy specimens with a favorable response to a gluten-free diet was noted in all five patients. Only four patients had positive serological tests for CD and only three had abdominal symptoms.