Date of Award
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.
Sykelyk, Alexander, "Combined treatment of human tumour cells with adenovirus dl1520 and melphalan as a strategy to enhance cancer therapy" (2010). Digitized Theses. 3733.