Elective neck dissection versus elective neck irradiation in cT3/4N0 maxillary sinus squamous cell carcinoma: a propensity score matching analysis.

BACKGROUND: Maxillary sinus squamous cell carcinoma (MS-SCC) is an infrequent malignancy, and determining the optimal neck management for patients with cT3/4N0 MS-SCC remains a topic of ongoing debate. The purpose of this study was to compare the prognoses and quality of life outcomes of patients who underwent either elective neck dissection (END) or elective neck irradiation (ENI) for cT3/4N0 MS-SCC. METHODS: In this retrospective study, we enrolled patients with surgically treated cT3/4N0 MS-SCC, and the impact of different neck management strategies on regional control and disease-specific survival was compared using propensity score matching. The effect of surgical intervention on quality of life was evaluated using the Mann-Whitney U test. RESULTS: Of the 120 patients included, 36 underwent END. After propensity score matching, our analysis indicated that END did not lead to superior outcomes than ENI, as demonstrated by comparable rates of regional control (p = 0.990) and disease-specific survival (p = 0.999). However, in the 70 returned questionnaires, patients who underwent END reported higher scores in the domains of appearance, chewing, and speech than did patients who underwent ENI. CONCLUSIONS: Our findings suggest that while END and ENI contribute to similar prognoses, END yields superior functional outcomes.

Elective Neck Dissection Improves Regional Control in cN0 Minor Salivary Gland Carcinoma in the Oral Cavity.

PURPOSE: Consensus regarding whether elective neck dissection (END) provides better outcomes than observation in clinically node negative (cN0) minor salivary gland (MSG) carcinoma is lacking. Therefore, this study aimed to compare the impact of END with that of observation on regional control (RC) and overall survival (OS) and to detect the predictors for lymph-node metastasis in oral MSG carcinoma. PATIENTS AND METHODS: A single-institution, retrospective cohort study was designed; it included patients with cN0 oral MSG carcinoma treated at a tertiary teaching hospital between January 2002 and January 2022. The primary predictor variable was END and primary outcome variables were RC and OS. The secondary outcome variable was lymph-node metastasis. Other covariates included demographic and pathologic features, TNM stage, and adjuvant treatment. The Kaplan-Meier method and Cox proportional hazards model were used to determine the effect of END on RC and OS. The chi-squared test and logistic regression models were used to identify independent predictors for lymph-node metastasis. RESULTS: A total of 268 patients (107 men and 161 women) with a mean age of 46.4 ± 15.5 years were included. The 5-year RC rate was statistically different between the observation and END groups (75%; 95% confidence interval [CI], 67%-83; 95% CI, 81%-93%, respectively; P = .014). Cox regression analysis confirmed that END (hazard ratio [HR] 2.395; 95% CI: 1.433-8.275; P = .034) was independently associated with a decreased risk of regional recurrence. The 5-year OS rates for the observation and END groups were 66% (95% CI, 56-76%) and 76% (95% CI, 66-86%), respectively, and the difference was not statistical (P = .057). Occult metastasis occurred in 24.6% of patients. Primary tumor location on the tongue/floor of the mouth (odds ratio [OR], 4.287; 95% CI, 1.773-9.125; P = .011), T3/4 stage (OR, 3.286; 95% CI, 1.228-8.253; P = .021), and high-grade disease (OR, 6.674; 95% CI, 2.199-14.326; P < .001) were independently associated with an increased risk of occult metastasis. CONCLUSIONS: RC was better with END than with observation, but OS was comparable with the two approaches. Primary tumor location on tongue/floor of the mouth, T3/4 stage, and high-grade disease were associated with an increased risk of lymph-node metastasis.

Overexpression of fatty acid desaturase 3 predicts poor prognosis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide, because its discovery time is in the late stage of the disease, so it is important to develop HNSCC biomarkers to achieve the purpose of early detection and treatment. Fatty acid desaturase 3 (FADS3), the third member of the FADS family, is involved in sphingolipid biosynthesis. Here, we for the first time investigated FADS3 expression in HNSCC, as well as its potential biological function, prognostic value and its impact on the immune system. In this study, we used bioinformatics for gene expression analysis, clinicopathological analysis, enrichment analysis, and immune infiltration analysis of The Cancer Genome Atlas (TCGA) datasets. Statistical analysis was done using R. Tumor IMmune Estimation Resource (TIMER) and CIBERSORT were used to analyze the effect of FADS3 on immune responses in HNSCC. Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier (KM) survival analysis, and the Human Protein Atlas (HPA) data were used to validate the results from bioinformatics analysis. Our findings indicate that FADS3 influences HNSCC prognosis. High expression of FADS3 is related to higher lymphatic metastasis, histologic grade, and lymphovascular invasion. Gene set enrichment analysis (GSEA) revealed that FADS3 is related to inhibition of amino acid metabolism. CIBERSORT analysis showed high FADS3 expression correlates with reduced levels of B cells. FADS3 is a marker of HNSCC, and high expression of FADS3 is associated with poor prognosis of HNSCC.

Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts.

OBJECTIVE: The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. METHODS: We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. RESULT: High fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. CONCLUSIONS: These results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis.

[The effect of fluoride on the expression of GRP-78 and caspase-12 in rat ameloblast].

PURPOSE: To study the effect of GRP-78 and caspase-12 on fluoride-induced endoplasmic reticulum stress and apoptosis in rat ameloblast, and explore whether fluoride-induced endoplasmic reticulum stress results in the occurrence of apoptosis. METHODS: The cell activity of ameloblast cultured in various concentrations of fluoride was measured by CCK8 and flow cytometry; Real-time RT-PCR and Western blot were used to analyze the endoplasmic reticulum chaperone GRP-78 and caspase-12 genes and the expression of related proteins. The data was analyzed with SPSS13.0 software package. RESULTS: With the increasing concentration of fluoride, the cell activity of rat ameloblasts decreased gradually, and flow cytometry also showed that the number of apoptosis gradually increased; Real-time RT-PCR and Western blot showed the expression of GRP-78 and caspase-12 increased while the fluoride concentration increased. CONCLUSIONS: Excessive fluoride induces endoplasmic reticulum stress of rat ameloblast, and leads to cell apoptosis.

Fluorosis induces endoplasmic reticulum stress and apoptosis in osteoblasts in vivo.

The present study investigated the effects of fluoride on endoplasmic reticulum (ER) stress (ERS) and osteoblast apoptosis in vivo. Forty-eight Wistar rats were randomly divided into four groups (12/group) and exposed to 0, 50, 100, and 150 mg/L of fluoride in drinking water for 8 weeks, respectively. Peripheral blood samples and bilateral femurs were used to monitor the progression of fluorosis in the animals. Hematoxylin and eosin (H&E) staining of the bone tissues was used to determine the severity of osteofluorosis. The expression of ERS chaperones (glucose-regulated protein 78 (GRP78), X-box binding protein l (XBP1), cysteine aspartate specific protease-12 (caspase-12), and growth arrest and DNA damage-inducible gene 153 (Gadd153/CHOP) was analyzed by immunohistochemistry staining, and osteoblast apoptosis was determined by TUNEL staining and flow cytometry. Accumulation of fluoride in bone was associated with the severity of osteofluorosis. The expression of GRP78, XBP1, caspase-12, and CHOP was increased in a dose-dependent manner. Fluoride-induced apoptosis in osteoblasts was also dose-dependent. High concentrations of fluoride induced ERS and osteoblast apoptosis in vivo. The increased expression of GRP78 and XBP1 increased the adaptation of osteoblasts to ERS to a certain extent. Caspase-12 and CHOP activation was associated with ERS and osteoblast apoptosis.

[Effect of fluoride on the viability and apoptosis of ameloblasts in vitro].

PURPOSE: To evaluate the effect of fluoride on viability of rat ameloblasts in vitro. METHODS: The ameloblasts of rat was exposed to different concentrations of NaF (0, 0.4, 0.8, 1.6, 3.2, 6.4 mmol/L) for 24, 48 and 72 hours. CCK-8 assays were performed to measure the cells proliferation; The morphology of apoptosis was observed by Hoechst 33258 staining and the rate of apoptosis was determined by flow cytometry. The data was analyzed using SPSS 13.0 software package. RESULTS: (1)The proliferation of ameloblasts was increased when concentrations of NaF between 0.4 mmol/L and 0.8 mmol/L, whereas inhibited at 1.6 mmol/L NaF and above. The effects were in time-dependent manner.(2)Cells in the 1.6 mmol/L NaF groups showed unclear karyorrhexis and apoptotic cell morphology. The effects were in concentration-dependent manner. CONCLUSIONS: (1)Fluoride has two-phase effects to ameloblasts: At low doses, it promoted cell proliferation while at high doses it had negative effects. (2)1.6 mmol/L NaF could induce apoptosis of ameloblasts.

[The effect of fluoride on the metabolism of teeth and bone in rats].

PURPOSE: To investigate the effect of fluoride on the metabolism of teeth and bone in rats, and to probe the mechanism of pathogenesis of dental fluorosis. METHODS: A total of 48 Wistar rats were randomly and equally divided into 4 groups including control group (distilled water), low-dose group(NaF,50 mg/L), medium-dose group (NaF,100 mg/L) and high-dose group (NaF, 150 mg/L). After 8 weeks, the rats were sacrificed under anesthesia, and serums were collected. The biochemical technique was used to test serum calcium. Changes in the fluorine content in serums and teeth of each group were analyzed with fluoride ion selective electrode method. Radioimmunoassay was employed to detect the levels of osteocalcin (OC), parathormone (PTH) and calcitonin (CT), respectively. SPSS13.0 software package was used for statistical analysis. RESULTS: The fluorine content in serum and teeth in the fluoride group were significantly higher than that of the control group (P<0.05), and increased with the increasing concentrations (F value was 11.234 and 275.148 respectively, P<0.01). The level of calcium in serum (F=3.906, P<0.05) in the fluoride group was significantly lower than in the control group. The level of PTH and OC in serum in medium and high-dose group were significantly higher than in the control group (P<0.01), with the level of CT in high-dose group decreased significantly (P<0.01). The differences of the level of OC, PTH, CT between groups were significant (F value was 8.548, 3.801 and 5.121 respectively, P<0.05). CONCLUSIONS: Fluoride affects the metabolism of teeth and bone in rats and OC, PTH, CT plays a key role in the pathogenesis of dental fluorosis.

[Effect of fluoride on the expression of endoplasmic reticulum chaperone in ameloblast of rat incisor].

PURPOSE: To investigate the effect of different concentrations of fluoride on the expression of endoplasmic reticulum chaperone, and to explore the mechanism of dental fluorosis in rat. METHODS: Thirty Wistar rats were randomly divided into 3 groups. Immunohistochemistry was used to detect the expression of CRT, GRP78, XBP-1 and caspase-12 in rat incisors. Metamorph microscope images analysis system and SPSS 13.0 software package was used to analyze the data. RESULTS: Typical features of dental fluorosis were found in the fluoride group. Results of immunohistochemistry showed that CRT (F=238.6, P<0.05), GRP78 (F=27.42, P<0.05), XBP-1 (F=139.7, P<0.05) and caspase-12 (F=43.91, P<0.05) were significantly different among the 3 groups. CONCLUSIONS: Excessive fluoride can increase the secretion of CRT, GRP78, XBP-1 and caspase-12 suggest the ameloblasts and in status of endoplasmic reticulum stress and caspase-12 plays an important role during ameloblast apoptosis. Supported by National Natural Science Foundation of China (81072245) and Natural Science Foundation of Liaoning Province (20102278).