Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood, both in human blood samples and in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.

Background Gauging medical education quality has always remained challenging. Many studies have examined predictors of standardized exam performance; however, data sets do not distinguish by institution or curriculum. Our objective is to present a summary of variables associated with the United States Medical Licensing Examination (USMLE) scores, and thus identify institutions (and therefore curriculums) which deviate from trend lines by producing higher USMLE scores despite having lower entrance grade point averages and medical college admissions test (MCAT) scores. Methods Data was obtained from U.S. News and World Report’s 2014 evaluation of allopathic U.S. medical schools. A univariate analysis was performed first for each variable using two sample t-test or Wilcoxon rank sum test for categorical variables, and Pearson or Spearman correlation coefficients for continuous variables. A multivariable linear regression model was developed to identify the factors contributing to USMLE scores. All statistical analyses were two-sided and performed using SAS software version 9.4 (SAS Institute Inc., Cary, NC). Results Univariate analysis reveals a significant association between USMLE Step 1 and 2 scores with medical college admissions test scores, grade point averages, school type (private vs. public), full-time faculty-to-student ratio, National Institute of Health funds, residency director assessment score, peer assessment score, and class size. Of these nine variables, MCAT scores and Step 1 scores display the strongest correlation (corr = 0.72, P < .0001). Multivariable analysis also supports a significant association between MCAT scores and Step scores, meanwhile National Institute of Health funding size demonstrates a negative correlation with USMLE Step 2 scores. Although MCAT scores and National Institute of Health funds are significantly associated with USMLE performance, six outlier institutions were identified, producing higher USMLE scores than trend line predictions. Conclusions Outlier institutions produce USMLE scores that do not follow expected trend lines. Their performance might be explainable by differences in curriculum. Having identified these institutions, their curriculums can be further studied to determine what factors enhance student learning.

No abstract

The ability to multiplex assays in studies of complex cellular mechanisms eliminates the need for repetitive experiments, provides internal controls, and decreases waste in costs and reagents. Here we describe optimization of a multiplex assay to assess apoptosis following a palmitic acid (PA) challenge in an in vitro hypothalamic model, using both fluorescent and luminescent based assays to measure viable cell counts and caspase-3/7 activity in a 96-well microtiter plate format. Following PA challenge, viable cells were determined by a resazurin-based fluorescent assay. Caspase-3/7 activity was then determined using a luminogenic substrate, DEVD, and normalized to cell number. This multiplexing assay is a useful technique for determining change in caspase activity following an apoptotic stimulus, such as saturated fatty acid challenge. The saturated fatty acid PA can increase hypothalamic oxidative stress and apoptosis, indicating the potential importance of assays such as that described here in studying the relationship between saturated fatty acids and neuronal function.