Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

Introduction.Despite an increase in the rigor of entry-level Doctor of Physical Therapy (DPT) program admission, programs still struggle with student retention and success. The purpose of this study was to examine demographic and preadmission factors predictive of first year and overall program success in an entry-level public physical therapist education program.Subjects.Retrospective data from 473 DPT students at the Texas Woman’s University in Houston, TX, who entered the program between 2010 and 2018.Methods.This study included the following predictor variables: last 60 hours undergraduate (UG) grade point average (GPA), UG math/science GPA, overall UG GPA, science/nonscience major, Graduate Record Examination (GRE) component scores, GRE summed score (GRE-S), size and type of UG institution (dichotomized), gender, age, and personal grit score. Success in the program was measured by first-semester GPA, cumulative third-semester GPA, final program GPA, three-tiered ranking of academic and clinical education (CE) standing, completion of first-year program, and completion of the entire 3-year program.Results.First-year program success (first-semester GPA, cumulative third-semester GPA, and first-year completion) was predicted by age, overall UG GPA, GRE-S, and all GRE components. GRE scores and UG GPA when entered together predicted 45.8% of the first-year GPA. Overall program success was predicted by UG GPA, GRE-S, and all GRE components. GRE-S and UG GPA when entered together predicted 34.8% of final program GPA. Academic standing was predicted by multiple predictors, whereas CE performance was only predicted by 2 components of the GRE and GRE-S. When comparing students who completed the program versus those who did not, significant differences were found in all GRE components and overall UG GPA. Receiver-operating-characteristics analysis was used to determine cutoff scores for the GRE and overall UG GPA, which best predict first-year and program retention.Conclusion.Admissions committees of DPT should analyze their program-specific data to better guide their admissions decisions. Overall UG GPA and GRE continue to be strong predictors of physical therapist program success. In order to increase retention rates, DPT programs should consider additional resources for students who may be at risk.