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OBJECTIVES: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. MATERIAL AND METHODS: We studied the variation of extracellular parameters--such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture"--pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. RESULTS: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. CONCLUSIONS: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation.

Positron emission tomography/computed tomography introduction in the clinical management of patients with suspected recurrence of ovarian cancer: a cost-effectiveness analysisAim of this study was to evaluate the economic impact of the introduction of positron emission tomography/computed tomography (PET/CT) in the early detection of recurrent ovarian cancer through a cost-effectiveness analysis of different diagnostic strategies. Thirty-two consecutive patients with suspected ovarian cancer recurrence, studied by both contrast enhanced abdominal CT and PET/CT, were retrospectively included in the study. Three different diagnostic strategies were evaluated and compared: (1) CT only or baseline strategy; (2) PET/CT for negative CT or strategy A; (3) PET/CT for All or strategy B. For each one, expected costs, avoided surgery and incremental cost-effectiveness ratio (ICER) were calculated to identify the most cost-effective strategy. The number of positive patients increased from baseline strategy (20/32) to strategy A and B (30/32 and 29/32 respectively). Positron emission tomography/computed tomography reoriented physician choice in 31% and 62% of patients (strategies A and B respectively). Strategy A is dominated by strategy B, which is more expensive (2909 Euro vs. 2958 Euro), but also more effective (3 cases of surgery avoided) and presents an ICER of 226.77 Euro per surgery avoided (range: 49.50-433.00 Euro). Positron emission tomography/computed tomography introduction in this population is cost-effective and allowed to redirect the clinical management of patients towards more appropriate therapeutic choices.

AIM: The aim of this study was to evaluate the economic impact of the introduction of positron emission tomography (PET) in the clinical management of patients with known or suspected lung cancer through a cost-effectiveness analysis of different diagnostic strategies. METHODS: In Italy, 75 patients with known or suspected lung cancer were included in the study. Three different diagnostic strategies were compared: 1) baseline or traditional strategy, i.e. computed tomography (CT) alone; 2) strategy A, i.e. PET for indefinite CT; 3) strategy B, i.e. PET for all. For each strategy expected costs and life expectancy, as measured by life year saved (LYS), were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated to identify the most effective strategy. RESULTS: Compared to the baseline strategy, the introduction of PET changed the clinical management in 40% of cases in strategy A and in 51% of cases in strategy B, with an optimization of the clinical management. Costs of strategy A (2 735.42 Euro) and strategy B (2 984.52 Euro) were, respectively, 8% and 18% higher than the baseline strategy (2 534.81 Euro). LYS was 2.04 and 2.64 for strategy A and B, which were, respectively, 4% and 35% higher than the baseline strategy (1.96 LYS). The ICERs were 2 507.63 Euro/LYS and 415.17 Euro/LYS for strategy A and B, respectively. Strategy A is dominated by strategy B, which is more expensive, but also more effective. CONCLUSION: In Italy, the introduction of PET in the clinical management of all patients with known or suspected lung cancer previously evaluated with CT is cost-effective and allows to gain 2.64 life years at an annual cost of about 415 Euro.

In the present study, we investigated the effect of the interaction of electromagnetic radiation with human keratinocytes (HaCaT)at low frequency. HaCaT cells were exposed to a sinusoidal magnetic field at a density of 2 mT (50 Hz)These cells are a good model for studying interaction of non-ionising radiation, because they are totally open to electromagnetic waves and also because they are resistant to both mechanical and thermal stimuli. We performed scanning microscopy which showed modification in shape and morphology in exposed cells. This modification is related to differential actin distribution as revealed by phalloidin fluorescence analysis. Moreover, 50 Hz exposed cells show increased clonogenic capacity, as well as increased cellular growth as showed by clonogenicity assays and growth curves. Indirect immunofluorescence analysis using a fluorescent antibody against involucrin and b4 integrin differentiation and adhesion markers respectively, revealed an increase of involucrin expression and segregation of b4 integrin in the cell membrane in 50 Hz exposed cells, suggesting that a higher percentage of the exposed cells shows a modified pattern of adhesion and differentiation markers. We also present evidence that electromagnetic field (EMF) exposure of HaCaT cells can interfere with protein kinase activity. Our observations confirm the hypothesis that electromagnetic fields, at 50 Hz may modify cell membrane morphology and interfere with initiation of the signal cascade pathway, and cellular adhesion.