Date of Award


Degree Type


Degree Name

Master of Science


Physiology and Pharmacology


Dr. James Koropatnick


Oncolytic adenoviruses exploit tumour-specific properties to selectively kill tumor cells. Anti-tumour effects of combined treatment with adenovirus dll 520 (selective for p53-deficient cells) and chemotherapy are well documented. It was hypothesized that combined treatment of dll 520 and melphalan would be more effective than established dh 520-chemotherapy combinations. Colourimetric- based cell viability assays and flow cytometric analysis of cell death were used to assess anti-tumour effects of combined treatments. Melphalan-mediated changes in coxsackievirus and adenovirus receptor (CAR) mRNA and protein levels were assessed using RT-PCR and immunoblot, respectively. Melphalan enhanced the anti-proliferative effects of dll 520 better than cisplatin and paclitaxel. Combined dl1520-melphalan treatment resulted in greater-than- additive cell death. Upregulation of CAR mRNA and protein after melphalan treatment was observed, although at concentrations higher than assayed for melphalan-mediated changes in dll 520 sensitivity. Combining dll 520 with melphalan has potential to afford enhanced therapeutic benefit compared to an established chemotherapy-dl1520 combination for treatment of cancer.



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