RESUMO
Background: Multiple sclerosis (MS) places a considerable financial burden on the society. However, data quantifying the contemporary cost burden in France are lacking. Objective: This cost-of-illness study aimed to estimate the direct and indirect costs associated with MS in France. Methods: Between October 2020-November 2020, 208 French adults with a confirmed diagnosis of MS were recruited via MSCopilot® (a new MS self-assessment digital solution) and several MS patient networks. Indirect costs were estimated using a combination of top-down and bottom-up approaches. Direct costs were retrieved from Assurance Maladie (i.e. national system of health insurance) publications. Out-of-pocket expenses (OOPEs) incurred by MS patients were also reported. All costs were expressed in 2020. Data from the survey were extrapolated to the overall French MS population. Results: MS exerted an annual cost burden of 2.7 billion on the French society (indirect costs: 1.3 billion; direct costs: 1.4 billion). Mean annual costs were 27,164.7 per-patient, with indirect and direct costs accounting for 48.1% and 51.9% of the total annual costs, respectively. OOPEs contributed over 90 million to the total annual costs. Conclusions: MS imposes a substantial cost burden on the French society, with approximately half of the total annual costs driven by indirect costs.
RESUMO
Voltage-gated Na+ channels (VGSCs) are highly expressed in several types of carcinomas including breast, prostate and lung cancers as well as in mesothelioma and cervical cancers. Although the VGSCs activity is considered crucial for the potentiation of cancer cell migration and invasion, the mechanisms responsible for their functional expression and regulation in cancer cells remain unclear. In the present study, the role of the small GTPase RhoA in the regulation of expression and function of the Nav1.5 channel in the breast cancer cell lines MDA-MB 231 and MCF-7 was investigated. RhoA silencing significantly reduced both Nav1.5 channel expression and sodium current indicating that RhoA exerts a stimulatory effect on the synthesis of an active form of Nav1.5 channel in cancer cells. The inhibition of Nav1.5 expression dramatically reduced both cell invasion and proliferation. In addition, a decrease of RhoA protein levels induced by Nav1.5 silencing was observed. Altogether, these findings revealed: i) the key role of the small GTPase RhoA in upregulation of Nav1.5 channel expression and tumor aggressiveness, and ii) the existence of a positive feedback of Nav1.5 channels on RhoA protein levels.