Oral submucous fibrosis (OSF) is a potentially malignant disorder. Current studies have shown that chewing areca nut is considered the main cause of OSF, and endothelial-mesenchymal transformation (EndMT) participates in the occurrence and development of the fibrotic lesion. However, the specific molecular mechanisms and treatments remain unclear. Here, we report the mechanism of arecoline-induced EndMT and the importance of this mechanism in OSF, and we also identify potential therapeutics for decreasing OSF incidence. We demonstrate the overexpression of Yes-associated protein (YAP) in human samples and that it was significantly associated with OSF pathologic stage. Arecoline activated YAP by increasing reactive oxygen species levels and inducing the PERK pathway (eukaryotic translation initiation factor 2 alpha kinase 3), resulting in the initiation of EndMT and leading to OSF. Verteporfin, a YAP–TEA domain pathway inhibitor, suppressed EndMT and decreased collagen accumulation, resulting in the alleviation of OSF in mice. These data indicate that arecoline regulates the activity of YAP and highlight an alternative method for treating OSF.
ABSTRACT. Echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangements and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been intensively studied. The objective of this study was to determine the clinicopathological characteristics in genotype-specific subsets of patients with NSCLC to help ensure the optimal identification of patients whose tumors harbor these two driver mutations. The incidence of ALK rearrangements was investigated in 763 NSCLC specimens by immunohistochemistry using a D5F3 antibody, and EGFR mutations were assessed by amplification refractory mutation system (ARMS) in 222 patients with lung adenocarcinoma. Of these, 73 (9.6%) were detected as being ALK-positive; this designation was associated with young age, female gender, never-smokers, lymph node metastasis, and poor tumor differentiation, but not with histology. EGFR mutations were identified in 102 (45.9%) of 222 adenocarcinoma samples, and were more frequent in females and never-smokers. No difference in age was observed. Specifically, we identified several cases of complex EGFR mutations, and concomitant EGFR mutations and ALK rearrangements. These results suggest that young women and never-smokers are at risk for ALK rearrangement. We also identified concomitant mutations of EGFR and rearrangements of ALK in this study.
Introduction Family caregivers of older patients with newly diagnosed lung cancer become responsible for patients’ care, usually without preparation or training in provision of care. Their efforts of care generate caregiving burden, which could deteriorate their quality of life and affect the prognosis of patients. The aims of this study were to examine associations between caregiver burden and quality of life, coping, social support for family caregivers, and to investigate whether coping and social support mediate associations between family caregiver burden and their quality of life. Methods A cross-sectional study was performed at two thoracic surgery wards in one tertiary hospital in Changsha, China from November 2019 to May 2020. This study involved 224 family caregivers of patients aged over 50 years and newly diagnosed with lung cancer. Caregivers-reported outcomes were measured by Zarit caregiver burden interview, simplified coping style questionnaire, social support rating scale, and quality of life family version. Structural equation modeling (SEM) was used to test the hypothesized mediation model. Results SEM indicated a good fit for the mediation model, which explained 49.7% of the variance of quality of life. Higher level of caregivers’ burden was negatively associated with quality of life (r = 0.183, P = 0.042). Coping partially mediated the effect of caregiver burden on quality of life (indirect effect −0.389, P = 0.000). Social support did not mediate the relationship between caregiver burden and quality of life (indirect effect −0.023, P = 0.087). Conclusions Caregivers’ burden of patients with newly diagnosed lung cancer is correlated to quality of life which is partially mediated by coping. Early intervention providing caregivers with positive coping strategies may improve their quality of life.
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