The IVACS section once again held our annual student competition. We are always pleased to give the students and post-doctoral fellows an opportunity to present and are frequently surprised and impressed with their presentation skills. Each participant presented an oral talk lasting approximately 15 minutes. We had a good participation with five competitors this year. Each participant gave an excellent talk which generated lots of questions. A cash award was given for first, second and third place. First place went to Breanne Cuddington, second place to Taylor Lavallie, and third place to Debora Esposito. We extend congratulations to all the participants and thanks to our judges, Brad Upham, Bill Smith and Lia Campbell.
Submitted by Lia Campbell
First Place
Breanne Cuddington
Characterization of Bovine Herpesvirus Type 1 as a Novel Oncolytic Virus
Oncolytic viruses are an attractive avenue of cancer therapy due to the absence of toxic side effects often seen in current treatment modalities. HSV-1 has been studied extensively as an oncolytic virus due to the many advantages it possesses for use in virotherapy; however, there are also a number of disadvantages to this approach. To this end, we are interested in evaluating BHV-1 as an oncolytic herpesvirus. A preliminary screen measuring both virus replication and cellular viability showed that BHV-1 is cytotoxic to various human immortalized and transformed cell lines, while being relatively restricted in normal primary cells in vitro. In addition, the NCI60 panel of human cancer cell lines has been screened with BHV-1. Results of the screen show that 94% of tumour cell lines were permissive to BHV-1 with 79% showing a decrease in cellular viability. These results suggest that BHV-1 holds promise as a broad spectrum oncolytic vector that is able to infect tumour cells from a variety of histological origins. In contrast to many oncolytic viruses, cellular sensitivity does not correlate with type I IFN signaling. Furthermore, non-permissive cell lines are susceptible to infection with wild type HSV-1, which utilizes the same cellular receptors as BHV-1 for viral adsorption and penetration, indicating that the block to BHV-1 infection occurs downstream of entry. However, it is not yet known which mechanisms dictate cellular sensitivity to BHV-1 infection. Additional studies will evaluate the factors determining permissivity to BHV-1 infection, the mechanism of cell death in permissive cell types, and the in vivo tumour killing ability of BHV-1. In the future, these results will contribute to optimizing effectiveness of BHV-1 for use in the oncolytic platform as an ideal cancer therapy. These studies will also provide important insights into the mechanisms that govern virus-host interactions which are crucial for understanding how viruses cause disease and for the development of clinically relevant antiviral treatments.
Breanne Cuddington. Department of Pathology and Molecular Medicine, Institute for Infectious Disease Research, McMaster University, Hamilton, ON, CANADA. In Vitro Cellular and Developmental Biology, 48:S32, 2012
Second Place
Taylor Lavallie
Evaluation of Aurora kinase B as a Potential Therapeutic Target for Human Liposarcoma
In 2012 it is estimated that 11,280 new cases of soft tissue sarcomas will be diagnosed in the United States and 3,900 Americans will die due to soft tissue sarcomas. Liposarcoma represents one of the most common types of soft tissue sarcomas. Current chemotherapeutic options for sarcomas include ifosfamide and doxorubicin; however, these drugs have not significantly increased survival rates for patients with sarcoma. In a pilot study we recently demonstrated that Aurora kinase B is overexpressed in intermediate and high grade soft tissue sarcomas compared to normal tissues. The goal of this research was to investigate Aurora kinase B expression in cultured human adipocytes versus the SW-872 human liposarcoma cell line, and to determine the effects of an Aurora kinase B inhibitor, AZD1152, on cellular proliferation. To evaluate Aurora kinase B expression, human mesenchymal stem cells were differentiated into adipocytes, and differentiation was assessed by oil red O staining and by examining the expression of the late differentiation marker, peroxisome proliferator-activated receptor gamma. Expression of Aurora-kinase B mRNA was evaluated by RT-PCR and was found to be increased in the SW-872 liposarcoma cells compared to the mesenchymal stem cells or the differentiated adipocytes. Treatment of the SW-872 liposarcoma cells with AZD1152 (0 – 300 nM) resulted in a growth inhibition and the presence of multi-nucleated cells. These studies suggest that Aurora kinase B may represent a novel chemotherapeutic target for human liposarcoma.
Taylor Lavallie. Biomedical Sciences Program, Midwestern University, 555 31st Street, Downers Grove, IL 60515. In Vitro Cellular and Developmental Biology, 48:S33, 2012
Third Place
Deborah Esposito
Homobrassinolide Enhances Myogenic Potential of Satellite Muscle Cells
Muscle satellite cells are widely accepted as the resident stem cells of skeletal muscle, supplying myoblasts for growth, homeostasis and repair. Activation of these cells in response to muscle mechanical change or injury involves activation of the muscle-specific transcription networks. Here we present evidence suggesting that oral administration of brassinosteroid to rat resulted in upregulation of muscle-specific genes to ensure proper expression during muscle fiber hypertrophy observed in the previous study. Gene expression profiling revealed that two groups of myogenic transcription factors MyoD and Pax3/7, calcineurin (Cnaa), adrenergic alpha-1d receptor (Adra1d), and androgen receptor (Ar) transcripts were increased in muscle of the treated animals fed either standard chow or high protein diet. Animals consuming standard diet showed a moderate increase in muscle atrophy/remodeling-related signaling that was abolished by high-protein diet. In L6 rat myoblast lineage cells, brassinosteroid treatment accelerated differentiation, expression of structural proteins, and fusion into multinucleated myotubes. Taken together, our results suggest that therapeutic modulation of myogenic activity by brassinosteroid could represent a viable future approach for repairing damaged muscle.
Deborah Esposito. Plants for Human Health Institute, NC State University, 600 Laureate Way, Kannapolis, NC 28081 and Rutgers University, Plant Biology Department, 59 Dudley Road, New Brunswick, NJ 08901. In Vitro Cellular and Developmental Biology, 48:S31, 2012
