Melanoma-related costs by disease stage and phase of management in Ireland.

BACKGROUND: Management options for the treatment of melanoma have expanded in recent years. In an era of promising, but expensive novel pharmacological treatments, robust stage-specific melanoma-related cost estimates are necessary to support budgetary planning, evaluation of cost-effectiveness and to contribute to the investment case for prevention. METHODS: A detailed decision model, describing the melanoma care pathway (by disease stage) from diagnosis, through treatment and follow-up was developed over a 5-year time frame from the perspective of the Irish healthcare system. The model was populated with real-world data from the National Cancer Registry Ireland. Uncertainty was explored using one-way and probabilistic sensitivity analysis. RESULTS: The cost of managing a case of melanoma diagnosed at Stage IV (€122 985) was more than 25 times more expensive than managing a case diagnosed at Stage IA (€4269). Total costs were sensitive to the choice of immunotherapeutic and targeted drug, duration of treatment and proportion of patients receiving immunotherapy agents. CONCLUSIONS: The rising incidence of melanoma and high cost of new novel therapies presents an immediate challenge to cancer control and public health globally. This study highlights the cost differential between early and late detection and the potential return on investment for prevention versus high-cost treatment.

Transfection efficiency and toxicity of polyethylenimine in differentiated Calu-3 and nondifferentiated COS-1 cell cultures.

In the present study, we evaluated polyethylenimine (PEI) of different molecular weights (MWs) as a DNA complexing agent for its efficiency in transfecting nondifferentiated COS-1 (green monkey fibroblasts) and well-differentiated human submucosal airway epithelial cells (Calu-3). Studying the effect of particle size, zeta potential, presence of serum proteins or chloroquine, it appeared that transfection efficiency depends on the experimental conditions and not on the MW of the PEI used. Comparing transfection efficiencies in both cell lines, we found that PEI was 3 orders of magnitude more effective in COS-1 than in Calu-3 cells, because Calu-3 cells are differentiated and secrete mucins, which impose an additional barrier to gene delivery. Transfection efficiency was strongly correlated to PEI cytotoxicity. Also, some evidence for PEI-induced apoptosis in both cell lines was found. In conclusion, our results indicate that PEI is a useful vector for nonviral transfection in undifferentiated cell lines. However, results from studies in differentiated bronchial epithelial cells suggest that PEI has yet to be optimized for successful gene therapy of cystic fibrosis (CF).