Seventeen patients affected by fibromyalgia syndrome (FMS) (16 females and one male) and 17 matched healthy subjects underwent formal polysomnography, a sleep questionnaire and lung function tests. FMS patients slept significantly less efficiently than the healthy controls (p<0.01), had a higher proportion of stage 1 sleep (mean+/-SD, 21+/-6% versus 11+/-4%; p<0.001), less slow wave sleep (p<0.01) and twice as many arousals per hour of sleep (p<0.001). The respiratory pattern of FMS patients showed a high occurrence of periodic breathing (PB) (15+/-8% of total sleep time) in 15/17 patients, versus 2/17 control subjects. The short length of apnoeas and hypopnoeas did not affect the apnoea/hypopnoea index (5.1+/-3.5 versus 3.2+/-1.6; NS), but FMS patients had a greater number of desaturations per hour of sleep (8+/-5 versus 3+/-3; p<0.01). Pulmonary volumes did not differ between the two groups, but FMS patients had a lower transfer factor of the lung for carbon monoxide (TL,CO (5.8+1 versus 7.7+1 mmol x min(-1) x kPa(-1); p=0.001). PB occurrence correlated with TL,CO (r=-0.62; p=0.01), number of desaturations (r=0.76, p=0.001) and carbon dioxide tension in arterial blood (Pa,CO2) (r=-0.50; p=0.05). Stepwise multiple linear regression analysis showed desaturation frequency (p=0.0001) and TL,CO (p=0.029) to be the best predictors of PB percentage (R2 0.73; p=0.0001). Patients complaining of daytime hypersomnolence had a higher number of tender points, about twice as many arousals per hour and a lower sleep efficiency than patients who did not report this symptom. TL,CO was more impaired and the occurrence of PB was higher. The occurrence of periodic breathing in fibromyalgia syndrome patients, which was previously unreported, and is shown to be linked to a reduction of transfer factor of the lung for carbon monoxide could play a major role in the symptoms of poor sleep of these patients.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug.
Abstract In the present work, we investigated the potential of novel semi‐interpenetrating polymer network (semi‐IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable off‐the‐shelf platforms for 3D cancer cell research. We synthesized semi‐IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long‐term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen‐enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intra‐scaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.
