ABSTRACT
Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.
Subject(s)
Animals , Humans , Mice , B7-H1 Antigen/metabolism , Carcinoma, Squamous Cell , Cell Line, Tumor , Feedback , Head and Neck Neoplasms , Mouth Neoplasms , Protein Kinase C , STAT1 Transcription Factor , Squamous Cell Carcinoma of Head and NeckABSTRACT
Objective To investigate the clinical effect of three -line anastomosed nasal septum surgery combined with low-temperature plasma radiofrequency ablation in the treatment of patients with moderate -severe perennial allergic rhinitis ( PAR) with nasal septum deviation .Methods 72 patients with moderate -severe PAR with nasal septum deviation were selected as study objects .The patients were divided into two groups according to the random number table method ,with 36 cases in each group .The control group underwent three -line anastomosis and septoplasty .The study group received three -line anastomosed nasal septum surgery combined with low temperature plasma radiofrequency ablation.Before treatment,1 year after treatment,the saccharin clearance time and nasal resistance, symptom score were observed .And the clinical efficacy ,postoperative complications were compared between the two groups .Results Before treatment ,the saccharin clearance time ,nasal resistance and symptom scores between the two groups had no statistically significant differences (all P>0.05).After treatment for 1 year,the saccharin clearance time,nasal resistance and symptom scores of the two groups were all decreased compared with before treatment .The saccharin clearance time and nasal resistance in the study group were (16.03 ±2.72)min and (0.31 ±0.09)kPa· L-1· S-1,respectively,which were lower than those in the control group [(17.15 ±2.85)min,(0.44 ±0.10)kPa·L-1· S-1] (t=2.467,5.798,all P<0.05).The scores of runny nose,sneezing,nasal itching and nasal congestion in the study group were (0.74 ±0.18)points,(1.01 ±0.25)points,(0.62 ±0.13)points and (0.79 ±0.16)points, respectively,which were lower than those in the control group [(1.21 ±0.31)points,(1.33 ±0.43)points,(0.99 ± 0.22)points and (1.18 ±0.34)points] (t=7.867,3.860,8.688,6.227,all P<0.05).Overall,the clinical effect of the study group was significantly better than taht of the control group (Z=-3.181,P<0.05).The total effective rate of the study group was 94.44%,which was significantly higher than 63.89%of the control group (χ2 =10.189, P<0.05).Different degrees of short -term olfactory decline,nasal obstruction were observed in both two groups ,after corresponding treatment ,the symptoms disappeared .No serious complications such as nasal septum perforation ,atrophic rhinitis,and loss of smell occurred in all patients .Conclusion Three -line anastomosed nasal septum surgery combined with low-temperature plasma radiofrequency ablation in the treatment of patients with moderate -severe PAR and nasal septal deviation can effectively correct the abnormal nasal structure ,significantly relieve the symptoms of patients,with high safety and clinical efficacy ,it is worthy of clinical promotion and application .
ABSTRACT
Polymorphonuclear neutrophil leukocyte (PMN) is an important member of the human immune cells. Recentyears, the recognition of the PMN function and the relationship between PMN and periodontitis have been updated. Besidesthe pathogens killing and phagocytosis, PMN also play an important role in immunoregulation and proresolving. The maintaining of PMN homeostasis is an intricate process and the precondition of defense function, which involves activation, adhesion, recruitment, apoptosis and efferocytosis. The regulatory mechanism of PMN homeostasis called neutrophil rheostat, it works through several cytokines and cells. Any factors that break the homeostasis will result in the damage of host immunity,and may relate to the occurrence of periodontitis. Moreover, PMN dysfunction, because of host factors or microorganism factors, is closely related to periodontitis, especially those associated with systemic diseases and gene defect.