Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits cancer cell proliferation and tumor formation, including in nasopharyngeal carcinoma (NPC), which we proved in a previous study. However, whether rapamycin affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we found regions of CD44-positive cancer cells co-expressing the stem cell biomarker OCT4, suggesting the presence of CSCs. Following this, we used double-label immunohistochemistry to identify whether the mTOR signaling pathway was activated in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC cells and secondary tumors in BALB/c nude mice. Interestingly, we found that rapamycin inhibited mTOR signaling in addition to simultaneously downregulating the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor size and weight both in vitro and in vivo. Collectively, we confirmed for the first time that CSC properties are reduced and invasion potential is restrained in response to mTOR signaling inhibition in NPC. This evidence indicates that the targeted inhibition of CSC properties may provide a novel strategy to treat cancer.
Abstract. An increasing amount of evidence demonstrates that epithelial-mesenchymal transition (EMT) is important in tumor invasion and metastases. The cell-cell adhesion molecule N-cadherin and the Wnt/β-catenin cascade protein β-catenin are two biomarkers of EMT. The present study aimed to measure the expression levels of N-cadherin and β-catenin in samples from patients with nasopharyngeal carcinoma (NPC) and evaluate their prognostic significance. N-cadherin and β-catenin mRNA was evaluated using reverse transcription-quantitative polymerase chain reaction in 26 NPC tissue samples and 8 nasopharyngeal epithelium samples. Protein expression of N-cadherin and β-catenin was also detected using immunohistochemistry in 128 archival NPC paraffin-embedded specimens. Finally, associations between clinical pathological parameters and prognostic values in NPC were evaluated. The results demonstrated that both the mRNA and protein levels of N-cadherin and β-catenin were significantly increased in NPC tissues compared with the controls. Enhanced expression of N-cadherin and β-catenin protein was strongly correlated with the status of lymph node metastasis and clinical stages in patients with NPC. Notably, high expression of N-cadherin and β-catenin proteins was significantly correlated with lower overall survival (OS) rate in patients with NPC. Finally, multivariate analysis demonstrated that expression of N-cadherin protein and clinical stages were independent prognostic factors for patients with NPC. Therefore, the present study demonstrated that N-cadherin and β-catenin expression may be used as potential prognostic biomarkers for patients with NPC.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a group of multifactorial and heterogeneous disorders with a significant economic strain on society, likely made up of different endotypes, each with a unique pathomechanism. In addition to the traditional clinical measures, there is a recognized need for reliable biomarkers to provide predictive information regarding diagnosis, endotypes, treatment responses, and future risk of recurrence. Fueled by the advances in basic research, various biomarkers have been explored in recent years. Biomarkers of CRSwNP can originate from a variety of sources, including nasal secretions, nasal biopsies, exhaled breath, and peripheral blood. In this review, we aim to summarize the existing and emerging biomarkers available for the evaluation and management of CRSwNP. Currently, eosinophil count in nasal mucosa has proved particularly valuable for endotyping, assessing disease severity, and predicting steroid responsiveness and surgical outcomes. Blood eosinophilia may be used as a surrogate for tissue eosinophilic inflammation, whereas its utility remains limited. Type 2 cytokines, such as IL-4, IL-5, and IL-13, and IgE have been identified as potential therapeutic targets. Moreover, matrix metalloproteinases (MMP)-9 is linked to healing quality after sinus surgery. Nasal nitric oxide (nNO) appears to fill the niche as a noninvasive measure for sinus ostial patency. In addition, recent data have shown some promising biomarkers involved in corticosteroid resistance and olfactory dysfunction. However, rigorous validation using large cohort studies is necessary before these biomarkers can be mainstreamed into clinical practice.
Six eligible articles were reviewed. The pooled MDs of PTA differences was 3.42 (95% CI = 0.17-6.67, p = .04) and the pooled ORs of recovery rate was 2.05 (95% CI = 1.38-3.03, p = .0003), which indicated that ITS treatment yielded better PTA improvement than SST. Sub-group analyses based on the initial hearing loss were also conducted; however, the difference was insignificant according to our analysis results (p = .82 for PTA improvement and p = .26 for recovery rate).
Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a heterogeneous disorder that can be classified into either eosinophilic or noneosinophilic endotypes. However, the immunological mechanisms of each remain unclear. The purpose of the present study was to compare and analyze inflammatory signatures of eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). Cytokine antibody array was used to identify inflammatory mediators that were differentially expressed among ECRSwNP, NECRSwNP, and control groups. Then, bioinformatics approaches were conducted to explore biological functions and signaling pathways. In addition, pairwise correlation analyses were performed among differential levels of inflammatory mediators and tissue eosinophil infiltration. The results showed that nine mediators were significantly up-regulated in ECRSwNP, including eotaxin-2, eotaxin-3, CCL18, IL-4, IL-5, IL-10, IL-12p70, IL-13, and IL-15. Bioinformatics analysis indicated that these mediators were mainly enriched in leukocyte chemotaxis and proliferation, JAK-STAT cascade, asthma, and Th1 and Th2 cell differentiation. Furthermore, seven mediators were identified to be significantly up-regulated in NECRSwNP, including CCL20, resistin, transforming growth factor (TGF)-β2, triggering receptor expressed on myeloid cells 1 (TREM-1), CD14, glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), and lipocalin-2. These mediators were closely associated with LPS responses, neutrophil chemotaxis and migration, and IL-17 signaling pathway. In addition, pairwise correlation analyses indicated that differential levels of inflammatory mediators in ECRSwNP and NECRSwNP were broadly correlated with each other and with tissue eosinophil infiltration. In conclusion, we found that ECRSwNP and NECRSwNP exhibited different patterns of inflammatory signatures. These findings may provide further insights into heterogeneity of CRSwNP.
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