It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(-) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.
BackgroundHuman mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell‐based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair.Methods and ResultsWe isolated and grew hMSCs from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation‐ and fibrosis‐related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSCs induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSCs from atrium and epicardial fat and minimal after transplantation of hMSCs from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor‐α secretion from hMSCs and posttransplantation left ventricular remodeling and dysfunction.ConclusionsBecause of their proinflammatory properties, hMSCs from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.
The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment.
In this work we present the first parameterizations of the global occurrence rate and chemical influence of Blue Jets, a type of transient luminous event taking place in the stratospheric region above thunderclouds. These parameterizations are directly coupled with five different lightning parameterizations implemented in the Whole Atmosphere Community Climate Model (WACCM4). We have obtained a maximum Blue Jet global occurrence rate of about 0.9 BJ per minute. The geographical occurrence of Blue Jets is closely related to the chosen lightning parameterization. Some previously developed local chemical models of Blue Jets predicted an important influence onto the stratospheric concentration of N2O, NOx, and O3. We have used these results together with our global implementations of Blue Jets in WACCM4 to estimate their global chemical influence in the atmosphere. According to our results, Blue Jets can inject about 3.8 Tg N2O‐N/year and 0.07 Tg NO‐N/year near the stratosphere, where N2O‐N and NO‐N stand for the mass of nitrogen atoms in N2O and NO molecules, respectively. These production rates of N2O and NOx could have a direct impact on, for example, the acidity of rainwater or the greenhouse effect. We have found that Blue Jets could also slightly contribute to the depletion of stratospheric ozone. In particular, we have estimated that the maximum difference in the concentration of O3 at 30 km of altitude between simulations with and without Blue Jets can be about −5% in equatorial and polar regions.
The Erbium laser provides very accurate tissue ablation and allows the sculpturing of the hypertrophied areas, offering good cosmetic results, with a very short healing period as shown in our study.
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