Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations ...have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions
intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25-50, 51-75, >75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% OR 1.03 (95% CI: 1.01-1.06) and Breslow index OR 1.28 (95% CI: 1.18-1.46), but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.
Highlights • Obstructive sleep apnea is very prevalent in Marfan syndrome (MFS) patients. • MFS is an inherited disease that affects the connective tissue. • This alteration can modify upper airway ...collapsibility. • A MFS mouse model shows that the critical pressure of the upper airway is increased.
To assess whether noninvasive application of nCPAP is a mechanical stimulus inducing early nasal inflammation.
Prospective controlled animal study.
University laboratory.
32 male Sprague-Dawley rats ...(250-300 g).
The rats were anesthetized and subjected to nCPAP=10 cm H2O and sham-CPAP through a mask for 3 h and 5 h (n=8 each).
After nCPAP or sham, nasal scraping was carried out to detect neutrophils, and septum and dorsal nasal concha were excised to assess gene expression of inflammatory markers by real time PCR. Percentage of neutrophils in nucleated cells in the nasal scrapings was significantly (P = 0.006) higher after 5 h of nCPAP (3.51% +/- 0.73%; m +/- SEM) than in the sham group (1.12% +/- 0.39%). When compared with sham, the mRNA of macrophage inflammatory protein-2 (MIP-2) in nasal tissue was significantly overexpressed after both 3 h (2.28-fold +/- 0.43-fold; P = 0.034) and 5 h (5.56-fold +/-1.88-fold; P = 0.002) of nCPAP=10 cm H2O. No significant changes were found in the gene expressions of tumor necrosis factor-alpha, nerve growth factor and tachykinin-1 receptor.
The compression applied by nCPAP (10 cm H2O, 5 h) on the nasal wall of healthy rats is a mechanical stimulus that triggers an early inflammatory process mediated by MIP-2, resulting in neutrophil extravasation.
Obstructive sleep apnea syndrome (OSA) is a prevalent disease caused by increased collapsibility of the upper airway. OSA induces oxidative stress, inflammation and endothelial dysfunction, with ...important clinical consequences such as neurocognitive alterations and cardiovascular diseases. Although it has been shown that bone marrow-derived stem cells play a protective and reparative function in several diseases involving inflammatory processes and endothelial dysfunction, the data currently available on the potential role of adult stem cells in OSA are scarce. The present review presents recent data on the potential role of bone marrow-derived mesenchymal stem cells (MSC) in OSA. The results obtained in animal models that realistically mimic the events characterizing this sleep breathing disorder strongly support the notion that MSC are mobilized in circulating blood and then activated to play an anti-inflammatory role in OSA.
Relationship Between Sleep Apnea and Cancer Martínez-García, Miguel Ángel; Campos-Rodríguez, Francisco; Almendros, Isaac ...
Archivos de bronconeumología (English ed.)
51, Številka:
9
Journal Article
Recenzirano
Abstract In the light of relationships reported between hypoxemia (tissue hypoxia) and cancer, Abrams et al. concluded in 2008 that sleep apnea-hypopnea syndrome (SAHS) and its main consequence, ...intermittent hypoxia, could be related with increased susceptibility to cancer or poorer prognosis of a pre-existing tumor. This pathophysiological association was confirmed in animal studies. Two large independent historical cohort studies subsequently found that the degree of nocturnal hypoxia in patients with SAHS was associated with higher cancer incidence and mortality. This finding has been confirmed in almost all subsequent studies, although the retrospective nature of some requires that they be considered as hypothesis-generating only. The relationship between sleep apnea and cancer, and the pathophysiological mechanisms governing it, could be clarified in the near future in a currently on-going study in a large group of melanoma patients.
We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model ...(Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.
We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model ...(Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.
We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model ...(Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.
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