Dietary nitrate maintains intestinal epithelia homeostasis in aged mice.

The intestinal tract, which is the primary site of digestion and absorption of nutrients, is one of the most vulnerable organs during aging. Dietary nitrate, which is mainly derived from the diet and absorbed in the intestinal tract, is a key messenger that connecting oral and general health. However, whether dietary nitrate regulates intestinal tract homeostasis remains unclear. Our data revealed that the serum and salivary nitrate levels decreased during mice aging. The functional proteins of the epithelial barrier (E-cadherin, Claudin-1 and Zonula Occludens-1) in the colon tissues decreased during the aging process. Long-term nitrate supplement in drinking water restored the serum and salivary nitrate levels and increased the functional proteins expression of the colon epithelial barrier. Dietary nitrates increase the relative abundance of some intestinal probiotics, particularly those associated with the production of short-chain fatty acids, such as Blautia, Alloprevotella, Butyricicoccus, and Ruminococcaceae, while promoting the butyric acid production in the colon. Moreover, the expression of Sialin (encoded by Slc17a5), which is a nitrate transporter, increased in the colon epithelial cells by nitrate supplementation. The epithelial cell-conditional Slc17a5-knockout mutant mice (K14-cre; Slc17a5fl/fl) revealed that the functional proteins expression of the colon epithelial barrier and the proliferation of PCNA-positive intestinal epithelial cells in the colon crypts was significantly decreased compared with those of the K14-cre; Slc17a5fl/+ mice. Taken together, our findings suggested that nitrate supplementations were associated with the increased expression of colonic epithelial barriers-related proteins and the increased Sialin expression. Nitrate may serve as a potential therapeutic approach in maintaining aged colonic homeostasis.

ALDH3A1 upregulation inhibits neutrophils N2 polarization and halts oral cancer growth.

OBJECTIVES: Tumor-associated neutrophils (TANs) are among the most abundant inflammatory cells in tumor microenvironment (TME). Aldehyde dehydrogenase 3A1 (ALDH3A1) is significantly reduced in oral squamous cell carcinoma (OSCC), ALDH3A1 overexpression suppresses tumorigenesis by inhibiting inflammation. This study investigated the relationship and mechanisms underlying the crosstalk between ALDH3A1 and TANs in OSCC. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence were performed to investigate the abundance of TANs and the expression of ALDH3A1. dHL-60 were induced with tumor-conditioned media and recombinant IL-6/IL-8. The expression of key proteins in PI3K/AKT/NF-κB pathway were detected by RT-PCR and western blot. A xenograft model was utilized to examine the effect of ALDH3A1 on tumorigenicity and polarization of TANs. RESULTS: In patients with OSCC, TANs significantly increased and were associated with a worse prognosis. Additionally, ALDH3A1 negatively correlated with TANs infiltration and especially the N2 phenotype which was the prominent part in OSCC. Furthermore, our study demonstrated that tumor-derived IL-8 drives ALDH3A1-mediated TANs N2 polarization in the TME through PI3K/AKT/NF-κB pathway in vitro and in vivo. CONCLUSION: Our results indicate that TANs can serve as a prognostic biomarker and ALDH3A1 could be a promising therapeutic target for regulating TANs N2 polarization in antitumor therapy.

PANoptosis induced by inflammatory cytokines promotes salivary glands radiation injury.

OBJECTIVE: Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. MATERIALS AND METHODS: Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. RESULTS: Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. CONCLUSIONS: Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.

Deep radiomics-based prognostic prediction of oral cancer using optical coherence tomography.

BACKGROUND: This study aims to evaluate the integration of optical coherence tomography (OCT) and peripheral blood immune indicators for predicting oral cancer prognosis by artificial intelligence. METHODS: In this study, we examined patients undergoing radical oral cancer resection and explored inherent relationships among clinical data, OCT images, and peripheral immune indicators for oral cancer prognosis. We firstly built a peripheral blood immune indicator-guided deep learning feature representation method for OCT images, and further integrated a multi-view prognostic radiomics model incorporating feature selection and logistic modeling. Thus, we can assess the prognostic impact of each indicator on oral cancer by quantifying OCT features. RESULTS: We collected 289 oral mucosal samples from 68 patients, yielding 1,445 OCT images. Using our deep radiomics-based prognosis model, it achieved excellent discrimination for oral cancer prognosis with the area under the receiver operating characteristic curve (AUC) of 0.886, identifying systemic immune-inflammation index (SII) as the most informative feature for prognosis prediction. Additionally, the deep learning model also performed excellent results with 85.26% accuracy and 0.86 AUC in classifying the SII risk. CONCLUSIONS: Our study effectively merged OCT imaging with peripheral blood immune indicators to create a deep learning-based model for inflammatory risk prediction in oral cancer. Additionally, we constructed a comprehensive multi-view radiomics model that utilizes deep learning features for accurate prognosis prediction. The study highlighted the significance of the SII as a crucial indicator for evaluating patient outcomes, corroborating our clinical statistical analyses. This integration underscores the potential of combining imaging and blood indicators in clinical decision-making. TRIAL REGISTRATION: The clinical trial associated with this study was prospectively registered in the Chinese Clinical Trial Registry with the trial registration number (TRN) ChiCTR2200064861. The registration was completed on 2021.

Effect of celecoxib plus standard chemotherapy on cancer prognosis: A systematic review and meta-analysis.

BACKGROUND: Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains uncertain. To assess the association between celecoxib plus standard chemotherapy and cancer prognosis, we conducted a systematic review and meta-analysis of published studies. METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception until July 2022 for randomized controlled trials reporting the prognosis of patients with cancer treated with celecoxib plus standard chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Meta-analysis was performed using Review Manager software version 5.4. The following search terms were used in the databases: ((((celecoxib)) AND ((((((((cancer) OR (carcinoma)) OR (sarcoma)) OR (neoplasms)) OR (tumor)) OR (tumour)) OR (tumors)) OR (tumours))) AND ((survival) OR (mortality))) AND (((Clinical Trials, Randomized) OR (Trials, Randomized Clinical)) OR (Controlled Clinical Trials, Randomized)). RESULTS: Overall, 13 randomized controlled trials, including 8957 patients with cancer, were included in the analysis. Compared to conventional chemotherapy alone, 1-year OS and 1-year PFS rates were not significantly improved with celecoxib adjuvant therapy (OS: p = .38; PFS: p = .65). In addition, no differences were observed between the celecoxib and placebo groups in 3-year overall (p = .98), 3-year progression-free (p = .40), 5-year overall (p = .59), or 5-year progression-free (p = .56) survival rates. An increase in the risk ratio of leukopenia (p = .02) and thrombocytopenia (p = .05) was also observed, suggesting that celecoxib promotes hematologic toxicity. No increased risk of cardiovascular (p = .96) and gastrointestinal (p = .10-.91) events was observed. CONCLUSIONS: The addition of celecoxib to standard chemotherapy did not improve OS or PFS rates of patients with cancer. Additionally, celecoxib can increase hematologic toxicity without increasing the risk of gastrointestinal or cardiovascular reactions. Further randomized controlled trials are necessary to clarify its effects and applications.

Synthesis and Characterization of a New Copolymer Consisting of Polyamide 1210 and Reactive Phosphorus-Nitrogen Flame-Retardant.

The thermal stability and reactivity of organophosphorus flame-retardants play a critical role in synthesizing copolymerized flame-retardant polyamides. Herein, this work successfully synthesizes a flame-retardant CEPPA-DDA salt (CDS) with both good thermal stability and high reactivity by reacting 2-carboxyethyl phenyl phosphonic acid (CEPPA) with 1,12-dodecanediamine (DDA). Flame-retardant polyamide 1210 (FRPA) is further prepared by copolymerizing the CDS, DDA, and sebacic acid (SEA). The test results show that the introduction of CDS can significantly improve the flame-retardant properties of FRPA. Specifically, the flame-retardant polyamide 1210 (FRPA-7) with 7 wt% CDS addition can reach V-0 grade according to UL-94 standard, accompanying limiting oxygen index value of 30.2% and tensile strength of 38.62 MPa. Compared with pure polyamide 1210, the peak heat release rate and total heat release rate of FRPA-7 reduce by 24.11% and 9.40%, respectively. This study provides a simple strategy to prepare flame-retardant polyamides with high flame retardancy and good mechanical properties, which are expected to show great potentials in future industrial applications.

Sialin mediates submandibular gland regeneration ability by affecting polysialic acid synthesis.

OBJECTIVES: Sialin is a multifunctional molecule with a well-described role in physiological equilibrium regulation. The aim of this study was to elucidate the role of sialin in salivary glands regeneration. MATERIALS AND METHODS: Submandibular gland duct ligation/deligation of rat was performed to develop a rat model of submandibular gland regeneration. Phenotype changes were investigated using Western blotting and quantitative real-time polymerase chain reaction, as well as immunohistochemical staining. LV-slc17a5-RNAi vectors were injected into the submandibular glands via retroductal instillation to establish a stable sialin-knockdown model. RESULTS: Submandibular gland tissue structure could completely restore 28 days after duct deligation, when the duct had been ligated for 7 days. The expression of sialin, polysialic acid, and polysialyltransferase IV was significantly increased on Day 0 after duct deligation, and it returned to the level of the control group at Day 28. Moreover, sialin knockdown could weakened gland regeneration by reducing polysialic acid synthesis. Supplementing drinking water with polysialic acid precursors (ManNAc) in drinking water could partially rescue submandibular gland regeneration in sialin-knockdown rats. CONCLUSION: These data indicated that sialin was vital for submandibular gland regeneration which mediated the process of gland regeneration by affecting the polysialic acid synthesis.

ALDH3A1 overexpression in OSCC inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages.

OBJECTIVES: Cancer-related inflammation (CRI) significantly increases the difficulty of treating oral squamous cell carcinoma (OSCC) and remains a major treatment challenge. Our objective was to determine whether tumor ALDH3A1 could attenuate OSCC tumorigenesis by inhibiting tumor-associated macrophages (TAMs) that promoted CRI. MATERIALS AND METHODS: ALDH3A1 in Cal27 cells was overexpressed, and the tumor-conditioned medium (TCM) was collected. We induced THP-1 cells with TCM and recombinant human IL-6. The phosphorylation of STAT3 and the TLR4/TRAF6/TBK1 cascade reaction in TAMs was analyzed using Western blotting, and mitochondrial ROS (mtROS) production was measured using a MitoSox kit. A tumorigenicity assay was performed to examine the tumor volume and weight, and the expression of CD68, CD11b, IL-6, Ki67, and CD31 was analyzed via immunohistochemistry. RESULTS: ALDH3A1 attenuated STAT3 phosphorylation at Ser727 rapidly and mtROS production earlier in TAMs via inhibiting TLR4/TRAF6/TBK1 cascade reaction. MtROS reduction inhibited IL-1ß and IL-8 secretions by NLRP3/caspase-1/IL-1ß/IL-8 pathway. Meanwhile, the inhibition of pro-tumor phenotypes of TAMs, tumor proliferation, and tumor angiogenesis during the process was proved in vivo. CONCLUSION: ALDH3A1 was associated closely with CRI and inhibited CRI regulated by TAMs. This finding may achieve clinical transformation and open new therapeutic options for targeting CRI regulated by TAMs.

Inhibitory effects of circulating natural autoantibodies to CD47-derived peptides on OSCC cells.

OBJECTIVES: Natural autoantibodies serve as an important anti-tumorigenic component in the body. This study was thus designed to investigate whether circulating natural IgG autoantibodies against a cluster of differentiation 47 (CD47) could exert inhibitory effects on oral squamous cell carcinoma (OSCC). SUBJECTS AND METHODS: The expression levels of 13 tumor-targeted genes in three OSCC cell lines were analyzed by qPCR, and CD47 expression in OSCC tissues was also verified with IHC staining. An in-house ELISA was performed to analyze circulating anti-CD47 IgG levels in control subjects, oral benign tumor, and OSCC patients, and to detect anti-CD47 IgG-abundant plasma. Three OSCC cell lines were treated with anti-CD47 IgG-abundant and -deficient plasma, respectively, followed by the analysis of cell proliferation, apoptosis, and invasion/metastasis. RESULTS: The CD47 gene showed the highest expression among 13 genes detected in three OSCC cell lines; its expression was significantly higher in OSCC tissues than adjacent tissues. Plasma anti-CD47 IgG levels showed the differences between control subjects, oral benign tumor, and OSCC patients. Anti-CD47 IgG-abundant plasma could evidently reduce cell viability via suppressing p-AKT expression and inducing cell apoptosis and inhibit the invasion of all three OSCC cell lines. CONCLUSIONS: Natural autoantibodies against CD47 may be a potential agent for OSCC immunotherapy.

Accuracy of Magnetic Resonance Imaging in Evaluating the Depth and Level of Invasion of Buccal Carcinoma: A Prospective Cohort Study.

PURPOSE: This study evaluated the accuracy of magnetic resonance imaging (MRI) in determining the depth and level of invasion of buccal carcinoma. METHODS: Patients with buccal squamous cell carcinoma diagnosed pathologically from July 2016 to December 2019 were included. The depth of invasion (DOI) and level of invasion (LOI) were evaluated by MRI, intraoperative specimens and pathological sections. Statistical analyses were performed using IBM SPSS software version 25.0 (IBM Corp., Armonk, NY). RESULTS: Forty-nine patients were ultimately included. The overall difference in DOI between MRI and pathological sections (DMP) was 5.55 ± 2.40 mm, and T category correlated with the differences in DOI measurement and LOI assessment. The threshold value of DOI by MRI to identify lymph node metastasis was 8.5 mm, and that for overall survival (OS) and disease-specific survival (DSS) was 14.1 mm for both. Buccinator invasion on MRI correlated with OS and DSS. CONCLUSION: Tumors with MRI-derived DOI larger than 8.5 mm deserve simultaneous neck dissection at initial surgery. Buccinator invasion was found to be an independent prognostic factor for buccal carcinoma patients.

Prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with laryngeal squamous cell carcinoma.

OBJECTIVES: We aimed to determine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) in patients with laryngeal squamous cell carcinoma (LSCC). DESIGN AND SETTING: A retrospective analysis of patients with LSCC was conducted in our hospitals. Clinical information, including age, sex, TNM classification and other demographic and clinical data, was acquired and analysed. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan-Meier method and log-rank test. PARTICIPANTS: A total of 147 patients with LSCC were included. RESULTS: According to the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR, PLR and SII were 1.88, 117.36 and 517.64. The analysis revealed NLR, PLR and SII to be independent predictors for OS and PFS (P < .05). CONCLUSIONS: Preoperative NLR, PLR and SII are promising prognostic predictors for patients with LSCC.

Prognosis of Pediatric Patients With Mucoepidermoid Carcinoma of the Parotid Gland.

OBJECTIVE: To summarize the prognosis of pediatric patients with mucoepidermoid carcinoma (MEC) of the parotid gland. METHODS: Pediatric patients with MEC of parotid gland who were surgically treated at the Capital Medical University School of Stomatology from 2000 to 2014 were retrospectively analyzed. Clinical characteristics, pathology reports, and operation records were reviewed and analyzed. RESULTS: In total, 33 patients with an average age of 13.2 years were enrolled. The 5-year overall survival and disease-free survival were 95.8% and 84.4%, respectively. The disease-free survival and overall survival rates were lower in the under-10 age group (75.0 versus 87.7% and 83.3% versus 100%), though no statistically significant difference was found (P = 0.279 and P = 0.075). The patients who underwent complete resection all had a good prognosis without any recurrence or death regardless of whether the cut margin was 1.0 cm, 0.5 cm, or only extracapsular. One patient experienced 3 recurrences within 18 months and eventually died of disease. CONCLUSION: Good outcomes were achieved in pediatric patients with MEC of the parotid gland. Radical resection ensured a good prognosis regardless of the extent of resection. Frequent recurrence in a short period was associated with a poor prognosis. TRIAL REGISTRATION: None.

The impact of age on oral squamous cell carcinoma: A longitudinal cohort study of 2,782 patients.

BACKGROUND: The purposes of this study were to assess the influence of age on oral squamous cell carcinoma patients and sought to analyze the reasons that may contribute to this difference. METHODS: This study enrolled 2,782 patients included 2,443 patients in a retrospective cohort to find the influence of age and 339 patients in a prospective cohort to testify these findings. The patients were divided into young age-group (≤40 years old), moderate age-group (41-75 years old), and advanced age-group (>75 years old). All patients were diagnosed as oral squamous cell carcinoma and were surgically treated in our hospital. Chi-square test, Kaplan-Meier analysis, and Cox proportional-hazards regression model were performed for statistical analysis. RESULTS: Younger patients started smoking (p < 0.001) and drinking (p < 0.001) earlier than the older patients and consumed more tobacco (p = 0.005) and alcohol (p = 0.156). Patients with advanced age had worse outcomes in both recurrence (p = 0.002) and survival (p < 0.001). They also had more severe comorbidity (p < 0.001) and were more likely to receive conservative treatment (p = 0.011). CONCLUSIONS: Compared with young patients, older patients had worse prognosis, and it was related with their more severe comorbidity and received more conservative treatment. Young adults smoking and drinking earlier and heavier than old patients, it may relate with their occurrence of oral squamous cell carcinoma.

Relationship between body mass index and outcomes for patients with oral squamous cell carcinoma.

OBJECTIVE: The purpose of our study was to investigate body mass index (BMI) as a prognostic factor and to examine the relationship between pretreatment BMI and oral squamous cell carcinoma (OSCC) outcomes in northern Chinese patients. METHODS: This retrospective study enrolled 633 patients with OSCC who underwent surgery between 2004 and 2014. RESULTS: Most baseline characteristics (gender, sites, smoking history, comorbidity, hypertension, T stage, clinical features, perineural invasion, flap reconstruction) were differentiated by BMI groups. Overall, the Kaplan-Meier curves indicated no significant relationship between BMI and disease-free survival (DFS) or disease-specific survival (DSS). Interestingly, obese patients exhibited higher risks of recurrence and death than normal-weight patients (DFS: HR: 1.86, 95% CI: 1.16-2.96; DSS: HR: 2.04, 95% CI: 1.08-3.86). However, postoperative complications occurred more frequently in underweight patients than in normal-weight patients. CONCLUSIONS: Obesity may contribute to a higher recurrence rate and a worse prognosis in OSCC patients than in normal-weight patients in northern China. However, underweight patients have a higher risk of postoperative complications.

Nodal Stage: Is It a Prognostic Factor for Submandibular Gland Cancer?

PURPOSE: Submandibular gland cancer is relatively rare. The purpose of this study was to estimate 5-year overall survival (OS) and disease-free survival (DFS) and to identify prognostic factors associated with OS and DFS for submandibular cancer. MATERIALS AND METHODS: The authors implemented a retrospective cohort study and enrolled a sample of patients with submandibular gland cancer. The predictor variables were age, gender, tumor stage, nodal stage, margin status, and extracapsular spread. The outcome variables were 5-year OS and 5-year DFS. Kaplan-Meier methods were used to estimate survival and Cox hazards models were used to identify prognostic variables. RESULTS: The sample was composed of 52 patients with submandibular gland cancer (mean age, 47.4 yr; 51.9% men). The median follow-up was 81 months (range, 11 to 159 months). The 5-year OS and DFS rates were 76.9 and 67.3%, respectively. Fixed mass, positive neck node, and positive margin status were relevant predictors of OS and DFS. Nodal stage was the relevant independent predictor affecting the disease outcome of submandibular gland cancer. CONCLUSION: These results identified several important prognostic factors associated with survival rate in patients with submandibular gland cancer. These prognostic variables include symptoms at presentation, pathologic nodal status, and margin status. These outcomes suggest that heightening vigilance of clinical characteristics for this disease might provide the impetus for improving the survival rate.

MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs.

Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial-mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGFß, downstream protumor factors, and hyaluronan and its cofactor TSG6, which all contribute to the protumor effects of BM-MSCs. The data suggest that iPSC-derived MSCs prepared with the modified protocol are a safer and better alternative to BM-MSCs for therapeutic applications in cancer patients. The protocol is scalable and can be used to prepare the large number of cells required for "off-the-shelf" therapies and bioengineering applications.

Surgery combined with postoperative 125 I seed brachytherapy for the treatment of mucoepidermoid carcinoma of the parotid gland in pediatric patients.

BACKGROUND: This retrospective study was undertaken to analyze the effectiveness and safety of surgery combined with postoperative 125 I seed brachytherapy in the treatment of mucoepidermoid carcinoma (MEC) of the parotid gland with risk factors in pediatric patients. PROCEDURE: From September 2002 to January 2012, 24 patients, ages 5-16 years (mean, 13.2 years; median, 12.3 years), with MEC of the parotid gland were included. Patients with high risk factors received 125 I seed brachytherapy (median actuarial D90, 97 Gy) within 4 weeks following surgery. Radioactivity was 18.5-33.3 MBq per seed and the prescription dose was 60-120 Gy. Overall and disease-free survival rates, local control rate, and distant metastasis were recorded. Radiation-associated late side effects, including dermatitis, hearing loss, thyroid nodules, and secondary malignancy, were also evaluated. RESULTS: During the follow-up period of 5-13.4 years (median, 7.2 years), the overall and disease-free survival rates were all 100%. No patients developed local recurrence, regional/distant metastasis, and no severe radiation-associated complications including the second malignancy were noted. CONCLUSION: Surgery combined with postoperative 125 I seed brachytherapy is effective and safe in the treatment of MEC of the parotid gland in pediatric patients, with no evidence of severe late radiation-related complications. More patients and longer follow-up data are still needed to prove the efficacy of 125 I brachytherapy.

Prognostic Factors Associated With Decreased Survival in Patients With Acinic Cell Carcinoma of the Parotid Gland.

PURPOSE: Acinic cell carcinoma (ACC) of the parotid gland is relatively rare. This study aimed to estimate 5-year survival and to identify prognostic factors associated with survival of ACC of the parotid gland. MATERIALS AND METHODS: Thirty-seven patients with ACC of the parotid gland were included in this retrospective cohort study. They were treated in Beijing Stomatological Hospital from January 2000 to December 2011. Predictor variables, including age, gender, tumor stage, nodal stage, perineural invasion, and margin status, were analyzed. The Cox regression model was used to determine prognostic factors for overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 37 patients, 20 were men (54.1%). Mean age was 42 years (range, 13 to 73 yr). Six patients (16.2%) had T3 or T4 tumors and 5 (13.5%) had positive neck nodes. The 5-year OS and DFS were 86.5 and 78.3%, respectively. Positive margin status was associated with worse OS. Patients older than 60 years with a fixed mass, high-grade tumor and nodal stage, perineural invasion, and angiolymphatic invasion had adverse OS and DFS (P < .05). CONCLUSIONS: The present study identified several important prognostic factors associated with OS and DFS in patients with ACC. These prognostic variables include symptoms at presentation, clinical tumor stage and pathologic nodal status, and histopathology-related factors. All these factors were important in patient therapy and could prolong survival rate.

Prognostic Factors in Malignant Sublingual Salivary Gland Tumors.

PURPOSE: The present study identified the prognostic factors and outcomes for malignant sublingual salivary gland tumors, which are rare. MATERIALS AND METHODS: A retrospective cohort study of patients treated for malignant sublingual salivary gland tumors from 1997 to 2011 was performed. The predictor variables, including age, gender, tumor stage, nodal stage, perineural invasion, margin status, and lymphovascular invasion, were analyzed. The Cox regression model was used to determine the prognostic factors for locoregional recurrence, distant metastasis, and survival. RESULTS: Of the 38 patients, 16 (42.1%) were men. Their mean age was 53 years (range 36 to 75). A total of 11 patients (28.9%) had T3-T4 tumors, and 6 (15.8%) had positive neck lymph nodes. The recurrence rate at 5 years was 18.4%. The distant metastasis rate at 5 years was 23.7%. Multivariable analysis confirmed the independent prognostic importance of patient age, N stage, and limited tongue mobility in locoregional recurrence and mortality at 5 years. CONCLUSIONS: Our results suggest that patient age, N stage, and limited tongue mobility are useful as independent predictors of locoregional recurrence and mortality in patients with malignant sublingual salivary gland tumors.

Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane.

In vivo recycling of nitrate (NO(3)(-)) and nitrite (NO(2)(-)) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate-nitrite-NO balance. More than 25% of the circulating NO(3)(-) is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO(3)(-) to NO(2)(-), which enters circulation and leads to NO generation. The transporters for NO(3)(-) in salivary glands have not yet been identified. Here we report that sialin (SLC17A5), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO(3)(-)/H(+) cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO(3)(-) or sialic acid (SA), but not by Br(-), and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO(3)(-)-induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H(+)-dependent NO(3)(-) conductance. Importantly, adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO(3)(-) secretion in saliva after intake of a NO(3)(-)-rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO(3)(-)/H(+) transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis.