Triple negative breast cancer exhibit increased IL-6 expression compared with matched healthy breast tissue and a strong link between inflammation and cancer progression and metastasis has been reported. We investigated whether doxorubicin-hyaluronan-super-paramagnetic iron oxide nanoparticles (DOX-HA-SPION) would show greater therapeutic efficacy in human triple negative breast cancer cells (TNBC) MDA-MB-231, as was recently shown in drug-sensitive and multidrug-resistant ovarian cancer cells. Therefore, we measured cellular DOX uptake via confocal microscopy; observed morphologic changes: mitochondrial and nuclear changes with electron microscopy, and quantitated apoptosis using FACS analysis after Annexin V and PI staining in MDA-MB-231 cells treated with either DOX alone or DOX-HA-SPION. We also measured both proinflammatory and anti-inflammatory cytokines; IL-6, IL-10 respectively and also measured nitrate levels in the conditioned medium by ELISA. Inaddition, NF-kB activity was measured by luciferase assay. Confocal microscopy demonstrated greater cytoplasmic uptake of DOX-HA-SPION than free DOX. We also demonstrated reduction of Vimentin with DOX-HA-SPION which is significantly less than both control and DOX. DOX-HA-SPION enhanced apoptosis and significantly down regulated both pro-inflammatory mediators IL-6 and NF-kB in comparison to DOX alone. The secretion levels of anti-inflammatory mediators IL-10 and nitrate was not decreased in the DOX or DOX-HA-SPION treatment groups. Our data suggest that DOX-HA-SPION nanomedicine-based drug delivery could have promising potential in treating metastasized and chemoresistant breast cancer by enhancing the drug efficacy and minimizing off-target effects.

Introduction: Cardiovascular disease and not hyperglycemia is the major cause of mortality in patients with diabetes mellitus (DM). Hypertension is particularly burdensome in low income groups, where the prevalence of uncontrolled hypertension is higher than the general population. Federally Qualified Health Centers (FQHCs) provide care for low income and medically underserved populations (both immigrant and non-immigrant population). Objectives: 1) to determine the rate and predictors of Blood Pressure (BP) control in patients with diabetes and hypertension. 2) to identify differences by immigration status in BP control among patients attending FQHCs. Methods: The Office Guidelines Applied to Practice (Office-GAP) study is a cluster randomized trial designed to improve cardiovascular care for minority and low income populations in outpatient clinical settings. Office-GAP intervention included: provider training, patient education in a group visit, and use of Office-GAP checklist and patient decision aids during office visits. We describe baseline patient characteristics (prior to any intervention) in the FQHC sites. Retrospective review was performed of charts of all patients with hypertension, coronary artery disease and or, diabetes mellitus (DM) from September 2010 to December 2012. Hypertension was defined as Systolic BP>140 mmHg (>130 mm Hg in DM patients) and diastolic BP > 90 mmHg (>80 mm Hg in DM patients). A multivariable logistic regression was used to assess the effects of potential predicators on BP control. Results: Of 242 patients identified, 169 had DM, and 166 had hypertension. The mean age was 54.47 ± 11.91 years and 44.39 % were men (99 of 223). Of the total sample, 178 (73.55%, 178 of 242) were non-immigrants, 23.87 % (53 of 222) were covered by Medicaid, 40.99% (91 of 222) by Medicare, 39.19 % (87 of 222) by county outpatient insurance; 33.06% (70 of 242) were Black, 34.71 % (84 of 242) White and 32.23% (78 of 242) formed other races (Hispanics, Somalis, Nepalese). BP control was 36.73% (83 of 226) 95% CI = [30.44, 43.02] and 27.22% (46 of 169) 95% CI = [20.51, 33.93] in total sample and DM patients respectively. BP control among immigrants was 32.2% (19 of 59) 95% CI = [20.28, 44.12] vs. 38.32% (64 of 167) 95% CI = [30.95, 45.69] in non-immigrants. A logistic regression model identify the DM status as the sole significant predictor associated with BP control, with patients without DM having the best BP control (p-value<0.0001). This effect of DM on BP control remained significant even after adjusted for other predictors. Conclusions: We found that significant number of patients attending FQHCs do not have their BP controlled. Immigration status did not play any role in BP control; however BP control among patients with DM was substantially lower than the whole sample. This underscores the urgent need for strategies to improve BP control in FQHCs, particularly among diabetic patients.