• CXCR2 EXPRESSING TUMOR CELLS DRIVE VASCULAR MIMICRY IN ANTI-ANGIOGENIC THERAPY RESISTANT GLIOBLASTOMA

      Angara, Kartik Prasad; Department of Biochemistry and Molecular Biology (Augusta University, 7/20/2018)
      Glioblastoma (GBM) is a hypervascular and hypoxic neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation to normalize blood vessels, control abnormal vasculatures and prevent recurrence. The benefits of AAT have been transient and the tumors were shown to relapse faster and demonstrated particularly high rates of AAT-induced therapy resistance due to activation of alternative neovascularization mechanisms. Vascular Mimicry (VM) is the uncanny ability of tumor cells to acquire endothelial-like properties, lay down vascular patterned networks reminiscent of host endothelial blood vessels and served as an irrigation system for the tumors to meet with the increasing metabolic and nutrient demands in the event of the ensuing hypoxia resulting from AAT. In our studies, we have demonstrated that AAT accelerates VM. We observed that Vatalanib (a VEGFR2 tyrosine kinase inhibitor) induced VM vessels are positive for periodic acid-Schiff (PAS) matrix but devoid of any endothelium on the inner side and lined by tumor cells on the outer side. Interestingly, 20-HETE synthesis inhibitor HET0016 significantly decreased GBM tumors through decreasing VM structures both at the core and at the periphery of the tumors. During our extensive studies to understand the tumor-inherent mechanisms of AAT-induced resistance, we identified a crucial chemokine, CXCL8 or IL-8, to be highly upregulated in the GBM tumors treated with AAT. IL-8 has been well established as a highly prevalent cytokine in GBM with potent pro-migratory and pro-angiogenic functions. AAT-treated groups had significantly higher populations of CXCR2+ glioma stem cells and endothelial-like subpopulations and these populations were decreased following treatment with HET0016 and SB225002 (a CXCR2 antagonist). CXCR2+ GBM tumor cells were shown to form VM-like vascular channels carrying functional RBCs. Knocking down CXCR2 led to smaller tumor size in the animals and improperly developed vascular structures without CXCR2+ GBM cells lining them. This confirms our hypothesis that CXCR2+ GBM cells initiate VM and contribute to AAT resistance in GBM. Our present study suggests that HET0016 and SB225002 have potential to target therapeutic resistance and can be combined with other antitumor agents in preclinical and clinical trials.
    • Investigating Student and Faculty Perspectives Related to Predictors of Success: BSN Curriculum and NCLEX-RN Outcomes

      Cosper, Sharon M; Department of Advanced Studies and Innovation (Augusta University, 5/22/2018)
      The literature reports higher patient satisfaction when care is delivered from baccalaureate-prepared nurses (BSN); however, there is a significant shortage of BSN prepared nurses in the country (Schmidt & MacWilliams, 2015; Roa, Shipman, Hooten, & Carter, 2011). For institutions across the nation, there is a lack of understanding as to why certain students struggle academically throughout the program and on the board certification exam. In order to facilitate training, graduation, and success with NCLEX-RN outcomes for these critical healthcare providers, consideration for why students struggle with curriculum and passing the board certification examination is needed. This study utilized a concurrent embedded mixed methods design to gain a greater understanding as to what factors may be contributing to student difficulty. Participants included graduates (n = 75) and faculty (n = 25) within the College of Nursing in a university located in the southeast region of the United States. Data were collected through review of student records, survey responses, focus group participation, and use of the EQ-i 2.0 for descriptive purposes. Results indicate that the BSN GPA, HESI examination scores, and Adult Health II course grades were found to predict performance on the NCLEX-RN. The qualitative findings illuminate categories of external and interpersonal factors contributing to students’ success and first time pass rates on the NCLEX-RN. The themes of Curriculum, Test Methodologies and Preparation, Teaching and Instruction, Balance, Drive, Compassion and Respect, and Critical Thinking were all relevant for consideration to help nursing programs improve the first time pass rates of their graduates on the NCLEX-RN. Further research utilizing methods to understand emotional intelligence and implications for admission as well as successful outcomes on the NCLEX-RN are indicated based on the qualitative findings of this investigation.
    • Investigating Student and Faculty Perspectives Related to Predictors of Success: BSN Curriculum and NCLEX-RN Outcomes

      Callan, Richard S.; Department of Advanced Studies and Innovation (Augusta University, 5/22/2018)
      The literature reports higher patient satisfaction when care is delivered from baccalaureate-prepared nurses (BSN); however, there is a significant shortage of BSN prepared nurses in the country (Schmidt & MacWilliams, 2015; Roa, Shipman, Hooten, & Carter, 2011). For institutions across the nation, there is a lack of understanding as to why certain students struggle academically throughout the program and on the board certification exam. In order to facilitate training, graduation, and success with NCLEX-RN outcomes for these critical healthcare providers, consideration for why students struggle with curriculum and passing the board certification examination is needed. This study utilized a concurrent embedded mixed methods design to gain a greater understanding as to what factors may be contributing to student difficulty. Participants included graduates (n = 75) and faculty (n = 25) within the College of Nursing in a university located in the southeast region of the United States. Data were collected through review of student records, survey responses, focus group participation, and use of the EQ-i 2.0 for descriptive purposes. Results indicate that the BSN GPA, HESI examination scores, and Adult Health II course grades were found to predict performance on the NCLEX-RN. The qualitative findings illuminate categories of external and interpersonal factors contributing to students’ success and first time pass rates on the NCLEX-RN. The themes of Curriculum, Test Methodologies and Preparation, Teaching and Instruction, Balance, Drive, Compassion and Respect, and Critical Thinking were all relevant for consideration to help nursing programs improve the first time pass rates of their graduates on the NCLEX-RN. Further research utilizing methods to understand emotional intelligence and implications for admission as well as successful outcomes on the NCLEX-RN are indicated based on the qualitative findings of this investigation.