East Carolina University : Research and Creative Achievement Week 2011
their targeting gene expressions. Modified Vaccinia Ankara as an Oncolytic virus and its use in Pancreatic Cancer, Andrew Freistaedter, Rachel Roper, Gwendolyn Jones, Emmanuel Zervos Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, and it has less than a 5% survival rate over 5 years. Pancreatic tumors over-express the protein mesothelin compared to normal cells, and therefore, mesothelin may be a good tumor target antigen. Our current research focuses on using an improved Modified Vaccinia Ankara (MVA) virus to present mesothelin to the immune system to treat pancreatic tumors in mice. The improved MVA vector is a virus we made that has the poxvirus A35R gene deleted (A35R). The A35R gene inhibits MHC II antigen presentation, and we have shown that its removal improves both B and T lymphocyte responses. Wild-type (normal) and A35R MVA viruses were constructed to express mouse mesothelin. PCR was used to confirm the presence of the mesothelin gene sequence in the recombinant virus and to show its purity from parental MVA. Both Western blot and FACS analysis were used to verify mesothelin protein expression. Our hypothesis is that the A35R virus will be more efficient at stimulating the immune system and protecting from tumors caused by the Panc02 pancreatic adenocarcinoma cell line. MVA does not normally replicate in mammalian cells, but we have found that this virus can kill Panc02 cells, indicating that MVA is also an oncolytic virus for this tumor model. Preliminary results from a one-step growth curve suggest MVA can also replicate in Panc02 cells. Trials are underway in mice to assess the protective efficacy of MVA mesothelin and MVA A35R mesothelin cancer vaccines.
P42
Assessment of perfluorooctanoic acid (PFOA)-induced developmental cardiotoxicity, Qixiao Jiang, Robert Lust, Jamie DeWitt, East Carolina University, Greenville, NC 27858 Perfluorooctanoic acid (PFOA) is widely used as a surfactant and is persistent and widespread in the environment. Concerns of developmental toxicity have been raised by studies that have demonstrated that PFOA is capable of inducing development delays and increases in mortality. This study assessed morphological and functional changes in hearts from chickens developmentally exposed to PFOA. Chicken (Gallus gallus) eggs were air-cell injected prior to incubation (D0), with doses of 0, 0.5, 1 or 2 mg/egg kg in a sunflower oil vehicle. To assess morphology, embryos were removed from eggs and sacrificed on D19. Hearts were collected, formalin-fixed, embedded in paraffin, sectioned at 6 microns, and stained with hematoxylin and eosin (H&E) or for myosin. In H&E stained hearts, right ventricular wall thickness was decreased by 20.15% (P<0.05) in the 1 mg/kg group and by 18.06% in the 2 mg/kg group (P>0.05), relative to controls. Immunohistochemistry against myosin illustrated that the myosin dense layer was significantly thinner in both 1 mg/kg (27.07%, p<0.05) and 2 mg/kg (28.59%, P<0.05) groups. To assess function, one-day-old hatchling chickens were evaluated with cardiac ultrasound. Significant alterations were observed in heart rate, stroke volume and left ventricle morphological parameters. 130
P43