<p> Most of the colon cancer patient tumors progress to metastases, despite undergoing surgical resection or adjuvant chemotherapy. Predicting which patients will progress to metastases has been extremely challenging. There is an urgent need to identify early novel prognostic biomarkers that can early on predict the patient outcome. Vitamin C has been shown to have a pro-oxidant effect on cancer that enhances tumor growth and survival. Vitamin C is transported into mammalian cells via two isoforms of sodium-dependent vitamin C transporters (SVCTs), SVCT1 and SVCT2. The expression and clinical implications of SVCTs in tumor tissues could help us investigate its prognostic value in predicting patient outcome. In this report, we performed immunohistochemistry to determine SVCT1 and SVCT2 expression on primary tumors of 178 colon cancer patients. Colon cancer cells selectively expressed SVCT2 but not SVCT1. Moreover, poorly differentiated and metastatic tumors correlated with higher SVCT2 expression. Furthermore, increased SVCT2 expression was associated with shorter progression-free survival in patients with no or little lymph node invasion. We confirmed that SVCT2 could be an early stage prognostic biomarker that can predict colon cancer disease progression and survival.</p><p>

<p> Endothelial cells play a vital role in the normal physiology of the vasculature. The cerebrovascular region is highly populated by endothelial cells with distinct morphology and functions. However, endothelial cells are also a vital region in the pathophysiology of the vasculature, such as aneurysm formation, due to reactive oxygen species (ROS) production. To study the effects of glucose and flow on ROS production in brain arterial endothelial cells, ROS production was measured. This thesis is divided into three parts: glucose effect on ROS, flow effect on ROS, and glucose effect on flow-induced ROS. Previous endothelial cultures were provided by Joeseph Moran-Guiati and Jason Kushner. The effect of high glucose on static endothelial cells was shown to increase ROS production as compared to the effect of normal glucose. Under chronic treatment of endothelial cells with high flow, ROS production was significantly greater that in endothelial cells under chronic treatment of normal flow. High glucose was shown to exacerbate the high flow response. These studies provide insight to a possible connection between intracranial aneurysm formation and a major risk factor, Diabetes Mellitus.</p>