BackgroundThe role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC).MethodsOne hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results.ResultsNSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial–mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction.ConclusionsFOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0700-1) contains supplementary material, which is available to authorized users.
Background—
Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse.
Methods and Results—
Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR− group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR− groups, the MR+ group had more dilated mitral annulus (
P
<0.0001), a reduced annular height to commissural width ratio (AHCWR) (
P
<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (
P
<0.0001), greater leaflet billow volume (
P
<0.0001) and billow height (
P
<0.0001), longer lengths from papillary muscles to coaptation (
P
<0.0001), and more frequent chordal rupture (
P
<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%–20%, and <15%, respectively;
P
=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (
r
2
=0.66,
P
<0.0001). MR severity correlated strongly with leaflet billow volume (
r
2
=0.74,
P
<0.0001) and inversely with AHCWR (
r
2
=0.44,
P
<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1;
P
=0.0004) was strongly associated with significant MR in mitral valve prolapse.
Conclusion—
Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.
MAD is a common anatomic abnormality in MVP. The disjunctive annulus is decoupled functionally from the ventricle, leading to paradoxical annular dynamics with systolic expansion and flattening, and may thus require specific intervention.
The changes in S-100 protein concentration suggest that the brain and/or blood-brain barrier may be more adversely affected during coronary artery surgery with cardiopulmonary bypass than during surgery on the beating heart, but that this may not be reflected in detectable neuropsychologic deterioration at 12 weeks.
Surgery of the descending and thoracoabdominal aorta has been associated with post-operative paraparesis or paraplegia. Different strategies, which can be operative or non-operative, have been developed to minimise the incidence of neurological complications after aortic surgery. This review serves to summarise the current practice of spinal cord protection during surgery of the descending thoracoabdominal aortic surgery. The pathophysiology of spinal cord ischaemia will also be explained. The incidence of spinal cord ischaemia and subsequent neurological complications was associated with (1) the duration and severity of ischaemia, (2) failure to establish spinal cord supply and (3) reperfusion injury. The blood supply of the spinal cord has been extensively studied and the significance of the artery of Adamkiewicz (ASA) being recognised. This helps us to understand the pathophysiology of spinal cord ischaemia during descending and thoracoabdominal aortic operation. Techniques of monitoring of spinal cord function using evoked potential have been developed. Preoperative identification of ASA facilitates the identification of critical intercostal vessels for reimplantation, resulting in re-establishment of spinal cord blood flow. Different surgical techniques have been developed to reduce the duration of ischaemia and this includes the latest transluminal techniques. Severity of ischaemia can be minimised by the use of CSF drainage, hypothermia, partial bypass and the use of adjunctive pharmacological therapy. Reperfusion injury can be reduced with the use of anti-oxidant therapy. The aetiology of neurological complications after descending and thoracoabdominal aortic surgery has been well described and attempts have been made to minimise this incidence based on our knowledge of the pathophysiology of spinal cord ischaemia. However, our understanding of the development and prevention of these complications require further investigation in the clinical setting before surgery on descending and thoracoabdominal aorta to be performed with negligible occurrence of these disabling neurological problems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.