Bmi-1, CD133, Nanog and Oct-4 have been reported as cancer stem cell (CSC) markers in head and neck squamous cell carcinoma (HNSCC). However, the prognostic value of them in HNSCC remains controversial. Hence, this meta-analysis was conducted to access the association between the four CSC markers and survival outcome of HNSCC patients. A total of 22 articles with 27 studies met the inclusion criteria and the combined hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated. Data analysis showed that high expression of CSC markers was associated with poor overall survival (OS) (HR = 1.93; 95% CI: 1.46–2.55, P < 0.001) and disease free survival (DFS) (HR = 4.78; 95% CI: 2.95–7.75, P < 0.001) but not disease specific survival (DSS) (HR = 1.17; 95% CI: 0.74–1.84, P = 0.50) of HNSCC patients. Subgroup analysis indicted that high expression of CD133 (HR = 2.33, 95%CI: 1.42–3.83, P < 0.001), Oct-4(HR = 2.10, 95%CI: 1.36–3.22, P = 0.007) and Nanog (HR = 2.49, 95%CI: 1.66–3.72, P < 0.001) could predict poor OS in HNSCC patients respectively whereas overexpression of Bmi-1 was not related to the reduced OS in HNSCC patients (HR = 1.32, 95%CI: 0.66–2.65, P = 0.43). Therefore, we concluded that CSC markers, especially CD133, Nanog and Oct-4, might be predictive factors in HNSCC patients.

Background Pulpectomy is a technique recommended for treatment of irreversible pulp inflammation or necrosis. Treatment‐related variables and patient factors may affect the prognosis of pulpectomy. Aim To investigate the survival and related predictors associated with failure of pulpectomies performed under general anaesthesia for early childhood caries. Design Dental records of 124 patients, who underwent pulpectomy as part of comprehensive dental treatment under general anaesthesia, were reviewed and assessed. Relapse of pulpitis and periodontal periodontitis were evaluated by clinical examination and periapical film assessment at each follow‐up appointment after original treatment. Results A total of 389 teeth of 124 children were evaluated. By the end of the fourth year, 45% of teeth with pulpitis and 46% of teeth with periapical periodontitis were estimated to relapse; the median (interquartile range) number of years to relapse was 3.5 (3.4‐3.8) and 3.0 (1.8‐3.0) years, respectively. The follow‐up frequency, number of teeth extracted, plaque index, tooth position, type of restoration, pulp status, and quality of root canal filling were observed to have independent effects on relapse. Conclusion Recurrence came earlier in teeth diagnosed with periapical periodontitis than those with pulpitis. Both treatment‐related variables and patient factors could affect the prognosis of pulpectomy.

Chemokine (CC motif) ligand 18 (CCL18) is involved in remodeling of the tumor microenvironment and plays critical roles in oncogenesis, invasiveness, and metastasis. We previously investigated the overexpression of CCL18 in primary oral squamous cell carcinoma (OSCC) tissues and its association with advanced clinical stage in OSCC patients. However, the underlying mechanisms of this CCL18‐derived activity remains unidentified. This study showed exogenous CCL18 increased cell migration and invasion and induced cell epithelial–mesenchymal transition (EMT), and that E‐cadherin, an epithelial marker, decreased and N‐cadherin, a mesenchymal marker, increased, compared to negative control in OSCC cells. Furthermore, we detected that CCL18 induced the acquisition of cancer stem(‐like) cell characteristics in oral cancer cells, but also found a significantly positive correlation between the expression of CCL18 and Bmi‐1 (P < 0.001) in OSCC surgical specimens by immunohistochemistry analysis. The expression of octamer‐binding transcription factor 4 and Bmi‐1 were significantly upregulated, and proportions of aldehyde dehydrogenasehigh+ cells and CD133+ cells were markedly increased in CCL18‐treated cells compared to untreated cells. Sphere formation ability was observably enhanced when cells were continually exposed to high levels of CCL18. Moreover, CCL18 upregulated Slug expression by stimulating the mammalian target of rapamycin (mTOR) signaling pathway in OSCC cell lines. Inhibition of the mTOR pathway by INK128, or Slug knockdown by RNA interference, reversed CCL18‐induced EMT and the stemness response at both molecular and functional levels. In conclusion, our data suggested that CCL18 upregulated Slug expression to promote EMT and stem cell‐like features by activating the mTOR pathway in oral cancer. These findings provide new potential targets for the early diagnosis and treatment of OSCC.

Protein arginine methyltransferase 5 (PRMT5) is an important type II arginine methyltransferase that can play roles in cancers in a highly tissue-specific manner, but its role in the carcinogenesis and metastasis of head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, we detected PRMT5 expression in HNSCC tissues and performed series of in vivo and in vitro assays to investigate the function and mechanism of PRMT5 in HNSCC. We found that PRMT5 was overexpressed in dysplastic and cancer tissues, and associated with lymph node metastasis and worse patient survival. PRMT5 knockdown repressed the malignant phenotype of HNSCC cells in vitro and in vivo . PRMT5 specific inhibitor blocked the formation of precancerous lesion and HNSCC in 4NQO-induced tongue carcinogenesis model, prevented lymph node metastasis in tongue orthotopic xenograft model and inhibited cancer development in subcutaneous xenograft model and Patient-Derived tumor Xenograft (PDX) model. Mechanistically, PRMT5-catalyzed H3R2me2s promotes the enrichment of H3K4me3 in the Twist1 promoter region by recruiting WDR5, and subsequently activates the transcription of Twist1. The rescue experiments indicated that overexpressed Twist1 abrogated the inhibition of cell invasion induced by PRMT5 inhibitor. In summary, this study elucidates that PRMT5 inhibition could reduce H3K4me3-mediated Twist1 transcription and retard the carcinogenesis and metastasis of HNSCC.