Cystic fibrosis (CF) is the most common lethal recessive genetic disease of the Caucasian population. Although reports of cancer frequency in CF have emphasized an elevated observed-to-expected ratio of 6.5 for digestive tract cancers, these studies also show a significantly decreased observed-to-expected ratio for other malignancies including breast cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an ATP channel. We found that heterozygous and homozygous CFTR knockout mice had elevated blood ATP concentrations. Elevated extracellular ATP is known to inhibit tumor growth in vivo and in vitro. Using double mutant mice created by F2 generation crosses of CFTR knockout and nude mice, we observed reduced breast tumor implantability in CFTR homozygous nude animals. Decreased tumor growth rate was observed in both CFTR heterozygous and homozygous nude animals. Extracellular ATP reduced human breast tumor cell growth rate in vitro, and a breast tumor transfected with human CFTR that had high extracellular ATP concentrations in vitro correspondingly had a slower growth rate in vivo. The results suggest that both CFTR heterozygosity and homozygosity suppress breast cancer growth and that elevated extracellular ATP can account for this phenomenon.
Objectives:The prevalence of Psoriatic Arthritis (PsA) is the same in men and women, however, the latter experience a higher burden of disease and are affected more frequently by polyarthritis. Here, we performed an early PsA cohort analysis to assess sex-related differences in demographics, disease characteristics and evolution over 1 year including applied treatment strategies. Methods:Our study is embedded in the Dutch south-west Early Psoriatic Arthritis cohoRt. We described patient characteristics and treatment decisions. For the comparison across sexes and baseline and 1 year follow up, appropriate tests depending on the distribution were used. Results:273 men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly higher tender joint count, a higher disease activity, higher levels of pain and lower functional capacity. Although minimal disease activity (MDA) rates increased over time for both sexes, MDA remained significantly more prevalent among men at one year (58.1% vs 35.7%, p<0.00). Initially, treatment strategies were similar in both sexes with Methotrexate being the most frequently used drug during the first year. Women received Methotrexate for a shorter period [196(93-364) vs 306(157-365), p<0.00] and therefore received a lower cumulative dose compared to men. Retention time was shorter for all DMARDs and women had a delayed start on b-DMARDs. Conclusion:After 1 year of standard-of-care treatment women didn’t surpass their baseline disadvantages. Despite the overall improvement, they still presented higher disease activity, higher levels of pain and lower functional capacity score than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in early PsA patients.
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