Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

Analgesic effect of a lidocaine-ropivacaine mixture for extraction of impacted mandibular third molars: a randomized controlled trial.

OBJECTIVES: The painless postoperative period can be significantly prolonged by using long-acting local anesthetics such as ropivacaine, though these local anesthetics are known for their slower onset of action. To compensate for this, a mixture of short-onset (e.g., lidocaine) and long-acting local anesthetics is used. However, the efficacy of such an anesthetic cocktail has not been elucidated in the field of oral and maxillofacial surgery. MATERIALS AND METHODS: To address the research purpose, this prospective randomized controlled trial included 56 patients scheduled for impacted mandibular third molar extraction. All patients received the inferior alveolar nerve block (IANB) using either 2% lidocaine with epinephrine or a 1:1 mixture of 2% lidocaine with epinephrine and 0.75% ropivacaine. RESULTS: Patients anesthetized using the lidocaine-ropivacaine mixture showed significantly prolonged postoperative analgesia and pain control than those anesthetized using lidocaine only. CONCLUSIONS: IANB using a lidocaine-ropivacaine mixture can provide prolonged postoperative anesthesia and pain control with extraction of mandibular third molars. CLINICAL RELEVANCE: This method can be a noteworthy addition to existing methods of local anesthesia for the extraction of mandibular third molars. Trial registration number University Hospital Medical Information Network (No. UMIN000044315).

Association of health behaviors, dietary habits, and oral health with weight gain after 20 years of age in community-dwelling Japanese individuals aged 40 years and older: a cross-sectional study.

OBJECTIVES: This cross-sectional study investigated the factors associated with weight gain ≥ 10 kg after 20 years of age in the general Japanese population, with a focus on the number of teeth. MATERIALS AND METHODS: We included individuals aged ≥ 40 years from Yamagata prefecture, Japan from 2017-2021. A postal survey was conducted using a self-administered questionnaire; 5,940 participants were included in the final analysis. The questionnaire included items on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake. A multivariate logistic regression analysis was used to identify independent associations between weight gain ≥ 10 kg after 20 years of age and various parameters; adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Less than 20 teeth, male sex, drinking habit frequency, eating very fast or fast, and a higher frequency of eating-away-from-home were significant factors associated with weight gain ≥ 10 kg after 20 years of age; individuals with < 20 versus > 20 teeth exhibited a 1.35-fold higher OR (95% CI 1.15-1.59; p < 0.01). CONCLUSIONS: Our results suggest that having < 20 teeth may affect weight gain ≥ 10 kg after 20 years of age. However, owing to the cross-sectional study design, causality could not be determined. Therefore, maintaining healthy lifestyle behaviors to avoid tooth loss may also affect weight gain ≥ 10 kg after 20 years of age. CLINICAL RELEVANCE: Having < 20 teeth has the potential to affect long-term weight gain after 20 years of age.

Reconstruction After Hemimandibulectomy With a Plate and Soft-Tissue Free Flap Followed by a Titanium Mesh and Particulate Cancellous Bone and Marrow Harvested From Bilateral Posterior Ilia: A Case Report.

A particulate cancellous bone and marrow (PCBM) graft combined with titanium (Ti-) mesh tray has become one of the most popular mandibular reconstruction methods. The technique has been applied to the mandibular discontinuity defects after segmental mandibulectomy. To the best of our knowledge, there are no reports on using the technique after hemimandibulectomy, during which a wide mandibular resection, including the condyle, is performed. Here, we first report a case of mandibular reconstruction after hemimandibulectomy, using a plate and soft-tissue free flap, followed by a Ti-mesh and PCBM harvested from the bilateral posterior ilia, which was successful. This case report first revealed how bone resorption occurred clinically in mandibular reconstruction using PCBM and Ti-mesh tray after hemimandibulectomy. We also revealed the high predictability of the mandibular reconstruction using PCBM and Ti-mesh tray after hemimandibulectomy. Our report also provides a guiding principle to overcome the limitation of mandibular reconstruction using PCBM and Ti-mesh tray after hemimandibulectomy. However, our manuscript has limited evidence, being a case report.

Evaluation of effects of perioperative oral care intervention on hospitalization stay and postoperative infection in patients undergoing lung cancer intervention.

PURPOSE: This retrospective study investigated the effect of perioperative oral care intervention on postoperative outcomes in patients undergoing lung cancer resection, in terms of the length of postoperative hospital stay and the incidence of postoperative respiratory infections. METHODS: In total, 585 patients underwent lung resection for lung cancer, 397 received perioperative oral care intervention, whereas the remaining 188 did not. This study retrospectively investigated the demographic and clinical characteristics (including postoperative complications and postoperative hospital stay) of each group. To determine whether perioperative oral care intervention was independently associated with either postoperative hospital stay or postoperative respiratory infections, multivariate analysis, multiple regression analysis, and multivariate logistic regression analysis were conducted. RESULTS: Parameters significantly associated with a prolonged postoperative hospital stay in lung cancer surgery patients were older age, postoperative complications, increased intraoperative bleeding, more invasive operative approach (e.g., open surgery), and lack of perioperative oral care intervention (standard partial regression coefficient (ß) = 0.083, p = 0.027). Furthermore, older age and longer operative time were significant independent risk factors for the occurrence of postoperative respiratory infections. Lack of perioperative oral care intervention was a potential risk factor for the occurrence of postoperative respiratory infections, although not statistically significant (odds ratio = 2.448, 95% confidence interval = 0.966-6.204, p = 0.059). CONCLUSION: These results highlight the importance of perioperative oral care intervention prior to lung cancer surgery, in order to shorten postoperative hospital stay and reduce the risk of postoperative respiratory infections.

High Parity Is an Independent Risk Factor for Tooth Loss in Women: A Community-Based Takahata Study in Japan.

Risk factors for tooth loss have been widely examined previously. However, no previous study has comprehensively investigated the risk factors, including lifestyle-related specific factors (parity, oral health habits, and socioeconomic status), for fewer than 20 teeth among women in the general population in Japan. This cross-sectional study explored the association of these risk factors, especially parity, with having fewer than 20 teeth among Japanese women. A self-reported questionnaire including items on lifestyle-related risk factors (parity, oral health, diet [e.g., alcohol and sucrose consumption]) and socioeconomic status was sent by post to female residents (age ≥ 40 years) of Takahata town, Yamagata Prefecture, in 2005. Multivariate logistic regression analysis including 3,854 eligible participants was performed to investigate the association between various factors (including parity) and having fewer than 20 teeth. The results indicated that, compared with nulliparous women, women with two, three, and four completed pregnancies had 2.485-, 2.844-, and 4.305-fold increased risk of having fewer than 20 teeth, respectively. Our study is the largest-scale study of the general female population in Japan and the first study to comprehensively investigate risk factors (parity, oral health status, and socioeconomic status) for fewer than 20 teeth. We thus found that higher parity, especially, two or more, was independent risk factors for having less than 20 teeth among Japanese women. In conclusion, the present study emphasizes the importance of good oral health habits in women, especially, during pregnancy and in the postpartum period, to maintain 20 or more teeth.

Discrimination of oral squamous cell carcinoma from oral lichen planus by salivary metabolomics.

OBJECTIVE: This study was conducted to distinguish salivary metabolites in oral squamous cell carcinoma (OSCC) from those in oral lichen planus (OLP) to identify practical biomarkers for the discrimination of OSCC from OLP. SUBJECTS AND METHODS: Whole unstimulated saliva samples were collected from patients with OSCC (n = 34) and OLP (n = 26). Hydrophilic metabolites in the saliva samples were comprehensively analysed by capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC from OLP. RESULTS: Fourteen metabolites were found to be significantly different between the OSCC and OLP groups. Among them, indole-3-acetate and ethanolamine phosphate were used to develop the MLR model. The combination of these two metabolites showed a high area under the receiver operating characteristic curve (0.856, 95% confidential interval: 0.762-0.950; p < .001) for discriminating OSCC from OLP. CONCLUSIONS: We identified salivary metabolites for discerning between OSCC and OLP, which is clinically important for detecting the malignant transformation of OLP by both dentists and oral surgery specialists. Our candidate salivary metabolites show potential for non-invasive screening of OSCC versus OLP.

Evaluation of a Semi-Solidifying Liquid Formula for Nasogastric Tube Feeding After Oral and Maxillofacial Surgery.

PURPOSE: The aim of this retrospective study was to evaluate a semi-solidifying liquid formula for nasogastric tube (NGT) feeding after oral and maxillofacial surgery. MATERIALS AND METHODS: In total, 42 patients who underwent oral and maxillofacial surgery for malignant tumors, benign tumors, jaw reconstruction, or jaw fractures received postoperative NGT feeding for nutritional control between 2013 and 2019. Of these patients, 21 received a liquid diet (liquid group; administration rate, 100 mL/hour) and 21 received a semi-solidifying liquid formula (semisolid group [SSG]; administration rate, 400 mL/hour; Mermed Plus; Terumo, Tokyo, Japan). We retrospectively evaluated the complications of NGT feeding in both groups. RESULTS: During the course of NGT feeding, the incidence of abdominal pain (P = .022), rate of probiotic prescription for diarrhea (P = .012), and Bristol stool form scale score (P = .014) were significantly lower in the SSG than in the liquid group. The maximum defecation frequency per day was also lower in the SSG, although the difference was not significant (P = .069). CONCLUSIONS: Overall, the semi-solidifying formula was associated with a higher administration rate and a lower incidence of gastrointestinal complications. These findings will help oral and maxillofacial surgeons in the selection of appropriate diets for postoperative NGT feeding.

Association between presence of 20 or more natural teeth and all-cause, cancer-related, and cardiovascular disease-related mortality: Yamagata (Takahata) prospective observational study.

BACKGROUND: Several studies have surveyed the relationship between the presence of ≥ 20 natural teeth and mortality. However, very few have evaluated this association over a long-term follow-up of more than ten years within a large population in Japan. This study aimed to prospectively confirm the associations between mortality and the presence of ≥ 20 natural teeth within a community-based population in Japan. METHODS: A prospective observational study including 2208 participants aged ≥ 40 years was conducted in Takahata Town, Japan, between May 2005 and December 2016. All participants answered a self-administered questionnaire to provide their background characteristics, including their number of teeth. The participants were classified into two categories based on their self-reported number of teeth (< 20 and ≥ 20 teeth). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional-hazards regression model to assess risk factors for all-cause, cancer-, and cardiovascular disease-related mortality. RESULTS: The total follow-up period was 131.4 ± 24.1 months (mean ± SD). After adjusting for covariates, the risk of all-cause mortality was significantly higher in the group with < 20 teeth than in those with ≥ 20 teeth (HR = 1.604, 95% CI 1.007-2.555, p = 0.047). However, the risk of cancer- and cardiovascular disease-related mortalities was not statistically significant between the two groups. CONCLUSION: In this study, participants with < 20 teeth had a significantly higher risk of all-cause mortality, although the difference was borderline significant. These results emphasize the importance of having ≥ 20 natural teeth for a healthy life expectancy.

Comparison of Complications With Semisolid Versus Liquid Diet Via Nasogastric Feeding Tube After Orthognathic Surgery.

PURPOSE: The aim of this retrospective study was to compare the effectiveness of nasogastric tube (NGT) feeding of a semisolid diet versus a liquid diet after orthognathic surgery. PATIENTS AND METHODS: The orthognathic surgery patients were relatively young and generally healthy, without severe medical disease. Of the patients, 26 received liquid feeding (liquid diet group [LG], with an administration rate of 100 mL/hour), 30 received semisolid feeding at a high administration rate (semisolid diet-rapid administration group [SSRAG], 200 to 500 mL/hour), and 33 received semisolid feeding at a slower rate (semisolid diet-slow administration group [SSSAG], 100 mL/hour). We retrospectively investigated the complications of NGT feeding in each group. RESULTS: The incidence of diarrhea was clearly lower in the SSRAG than in the LG. Among patients with lower-gastrointestinal tract symptoms, stool form scale scores and maximum defecation frequency per day were significantly lower in the SSRAG than in the LG (P = .001 for both). Rapid administration of a semisolid diet via an NGT resulted in fewer complications and shorter feeding times for orthognathic surgery patients. CONCLUSIONS: The rapid administration of a semisolid diet via an NGT should decrease the complications of NGT feeding and improve the quality of the perioperative period for patients. The findings of this study will help clinicians select NGT diets for relatively young, healthy patients, such as orthognathic surgery patients.

Risk factors for tooth loss in community-dwelling Japanese aged 40 years and older: the Yamagata (Takahata) study.

OBJECTIVES: The aim of the present study was to investigate comprehensively the risk factors, including some lifestyle-associated factors, oral health habits, and socioeconomic status, for having less than 20 teeth in cross-sectional study in the general population of Japan. MATERIALS AND METHODS: The survey population was the general population of individuals aged greater than or equal to 40 years in Takahata town, Japan in 2005. A postal survey with a self-administered questionnaire was distributed, and 7542 participants were entered into the final statistical analysis. The self-administered questionnaire contained items regarding some lifestyle-associated factors, oral health, and dietary intake, including alcohol and sucrose consumption. To confirm the independent association between the number of teeth and several parameters, a multivariate logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A low educational status, no dental check-ups, low frequency of brushing, older age, and smoking habit were independent risk factors for less than 20 teeth. A low educational status was a particularly significant risk factor for less than 20 teeth (OR = 1.352, 95% CI = 1.125-1.624). CONCLUSION: These results emphasize the importance of good oral health habits, such as frequent tooth brushing, routine dental check-ups, and no smoking, and indicate that more appropriate and compulsory education regarding oral health is needed to lessen the education level-derived differences in oral health. CLINICAL RELEVANCE: Poor oral health habits and low educational status are the independent risk factors for having less than 20 teeth.

Identification of salivary metabolites for oral squamous cell carcinoma and oral epithelial dysplasia screening from persistent suspicious oral mucosal lesions.

OBJECTIVE: To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML). SUBJECTS AND METHODS: Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML. RESULTS: Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760-0.982; p < 0.001) to discriminate OSCC/OED from PSOML. CONCLUSIONS: This is the first study to identify salivary metabolites that discriminate OSCC/OED from PSOML rather than from healthy controls. The profiles of salivary metabolites were significantly different between OSCC/OED and PSOML. The ability to discriminate OSCC/OED from PSOML is important for dentists who are not oral surgery specialists. These salivary metabolites showed potential for non-invasive screening to discriminate OSCC/OED from PSOML. CLINICAL RELEVANCE: Salivary metabolites in this study showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.

Fewer teeth are a risk factor for being underweight in community-dwelling Japanese aged 40 years and older: The Yamagata (Takahata) Study.

OBJECTIVE: The aim of the present study was to investigate comprehensively, the risk factors for underweight in cross-sectional study in the general population of Japan. METHODS: The survey population was the general population of individuals aged >40 years in Takahata town, Japan in 2005. A postal survey in the form of a self-administered questionnaire was distributed, and 6084 individuals were entered into the final statistical analysis. The self-administered questionnaire contained items regarding lifestyle, oral health status, socio-economic status and dietary intake. To examine the independent relationships between an underweight status and several parameters, a multivariate logistic regression analysis was used to estimate adjusted odds ratios (ORs). RESULTS: The number of teeth, age, alcohol consumption, hypertension, spousal status, smoking habit, appetite, body weight at 20 years of age, habit of going out and physical activity were independently associated with an underweight status compared with the normal weight group. Individuals with fewer than 10 teeth were especially more likely to be underweight than individuals with more than 20 teeth (OR = 1.956, 95% CI = 1.261-3.035). CONCLUSION: This study showed an independent association between the number of teeth and an underweight status, indicating that fewer teeth can increase the risk of being underweight.

NAP1L1 regulates NF-κB signaling pathway acting on anti-apoptotic Mcl-1 gene expression.

Nuclear factor-κB (NF-κB) participates in apoptosis signaling pathway under various pathophysiological conditions. It exerts transcriptional control on the anti-apoptotic Bcl-2 family, such as Bcl-2, Bcl-xl, and Mcl-1, which act on the mitochondrial outer membrane. Previously, we described that NF-κB is negatively regulated by diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates a lipid second messenger diacylglycerol. DGKζ downregulation enhances inhibitors of NF-κB α (IκBα) degradation and p65 subunit phosphorylation, leading to enhanced NF-κB transcriptional activity. Transcriptional machinery is tightly regulated by assembly/disassembly and modification of nucleosomal components. Of those, the human NAP1-like protein (NAP1L) family functions in the transport, assembly/disassembly of nucleosome core particles. We previously identified NAP1L1 and NAP1L4 as novel DGKζ binding partners, but the mechanism by which NAP1Ls are involved in NF-κB signaling pathway remains unclear. Here we show that knockdown of NAP1L1 suppresses IκBα degradation and nuclear transport of p65 subunit after treatment with TNF-α stimulation, leading to attenuation of the NF-κB transcriptional activity, whereas NAP1L4 knockdown remains silent. Moreover, ChIP assay reveals that NAP1L1 knockdown attenuates p65 binding to the Mcl-1 promoter after TNF-α stimulation. This attenuation leads to reduced expression of anti-apoptotic Mcl-1, thereby decreasing the mitochondrial membrane potential and subsequent apoptosis after treatment with TNF-α and CHX. Collectively, results of this study suggest that NAP1L1 downregulation renders the cell vulnerable to apoptotic cell death through attenuation of NF-κB transcriptional activity on the anti-apoptotic Mcl-1 gene.

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells.

The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion, and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). As a result, recent studies suggest that the exocyst complex may be involved in several diseases such as kidney disease, neuropathogenesis, diabetes, and cancer. In this review, we focus on the diverse functions and cellular signaling pathways of the exocyst complex in various tumors. J. Cell. Physiol. 232: 939-957, 2017. © 2016 Wiley Periodicals, Inc.

Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection.

The aim of this study is to evaluate the effect of duration after meals for saliva collections for oral cancer detection using metabolomics. Saliva samples were collected from oral cancer patients (n = 22) and controls (n = 44). Saliva from cancer patients was collected 12 h after dinner, and 1.5 and 3.5 h after breakfast. Control subjects fasted >1.5 h prior to saliva collection. Hydrophilic metabolites were analyzed using capillary electrophoresis mass spectrometry. Levels of 51 metabolites differed significantly in controls vs. oral cancer patients at the 12-h fasting time point (P < 0.05). Fifteen and ten metabolites differed significantly at the 1.5- and 3.5-h time points, respectively. The area of under receiver operating characteristic curve for discriminating oral cancer patients from controls was greatest at the 12-h fasting time point. The collection time after meals affects levels of salivary metabolites for oral cancer screening. The 12-h fasting after dinner time point is optimal. This study contributes to design of saliva collection protocols for metabolomics-based biomarker discovery.

Downregulation of diacylglycerol kinase ζ enhances activation of cytokine-induced NF-κB signaling pathway.

The transcription factor NF-κB family serves as a key component of many pathophysiological events such as innate and adaptive immune response, inflammation, apoptosis, and oncogenesis. Various cell signals trigger activation of the regulatory mechanisms of NF-κB, resulting in its nuclear translocation and transcriptional initiation. The diacylglycerol kinase (DGK) family, a lipid second messenger-metabolizing enzyme in phosphoinositide signaling, is shown to regulate widely various cellular processes. Results of recent studies suggest that one family member, DGKζ, is closely involved in immune and inflammatory responses. Nevertheless, little is known about the regulatory mechanism of DGKζ on NF-κB pathway in cytokine-induced inflammatory signaling. This study shows that siRNA-mediated DGKζ knockdown in HeLa cells facilitates degradation of IκB, followed by nuclear translocation of NF-κB p65 subunit. In addition, DGKζ-deficient MEFs show upregulation of p65 subunit phosphorylation at Serine 468 and 536 and its interaction with CBP transcriptional coactivator upon TNF-α stimulation. These modifications of p65 subunit might engender enhanced NF-κB transcriptional reporter assay of DGKζ knockdown cells. These findings provide further insight into the regulatory mechanisms of cytokine-induced NF-κB activation.

Nuclear Translocation of p65 is Controlled by Sec6 via the Degradation of IκBα.

Nuclear factor-κB (NF-κB) is an inducible transcription factor that mediates immune and inflammatory responses. NF-κB pathways are also involved in cell adhesion, differentiation, proliferation, autophagy, senescence, and protection against apoptosis. The deregulation of NF-κB activity is found in a number of disease states, including cancer, arthritis, chronic inflammation, asthma, neurodegenerative diseases, and heart disease. The 90 kDa ribosomal S6 kinase (p90RSK) family, which is serine/threonine kinases, is phosphorylated by extracellular signal-regulated kinase1/2 (ERK1/2) and is related to NF-κB pathways. Our previous studies revealed that Sec6, a component of the exocyst complex, plays specific roles in cell-cell adhesion and cell cycle arrest. However, the mechanism by which Sec6 regulates the NF-κB signaling pathway is unknown. We demonstrated that Sec6 knockdown inhibited the degradation of IκBα and delayed the nucleus-cytoplasm translocation of p65 in HeLa cells transfected with Sec6 siRNAs after treatment with tumor necrosis factor alpha (TNF-α). Furthermore, the binding of p65 and cAMP response element binding protein (CREB) binding protein (CBP) or p300 decreased and NF-κB related genes which were inhibitors of NF-κB alpha (IκBα), A20, B cell lymphoma protein 2 (Bcl-2), and monocyte chemoattractant protein-1 (MCP-1) were low in cells transfected with Sec6 siRNAs in response to TNF-α stimulation. Sec6 knockdown decreased the expression of p90RSKs and the phosphorylation of ERK or p90RSK1 at Ser380 or IκBα at Ser32. The present study suggests that Sec6 regulates NF-κB transcriptional activity via the control of the phosphorylation of IκBα, p90RSK1, and ERK.

Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells.

Sec6 and Sec8, which are components of the exocyst complex, has been concerned with various roles independent of its role in secretion, such as cell migration, invadopodia formation, cytokinesis, glucose uptake, and neural development. Given the vital roles of the exocyst complex in cellular and developmental processes, the disruption of its function may be closely related to various diseases such as cancer, diabetes, and neuronal disorders. Malignant peripheral nerve sheath tumors (MPNSTs) have high malignant potential and poor prognosis because of aggressive progression and metastasis. To date, no chemotherapeutic agents have been validated for MPNSTs treatment because how MPNSTs are resistant to chemotherapeutic agents remains unknown. This study demonstrates that combination of doxorubicin and sorafenib induces apoptosis in MPNST cells through downregulation of B cell lymphoma protein 2 (Bcl-2), Bcl-2-related protein long form of Bcl-x (Bcl-xl), and myeloid cell leukemia 1 (Mcl-1). Moreover, both Sec6 and Sec8 levels decreased after treatment with doxorubicin and sorafenib and were found to be associated with Bcl-2 and Mcl-1 expressions, but not Bcl-xl. Although Sec8 was found to be involved in the regulation of both Bcl-2 and Mcl-1 at the mRNA level, Sec6 regulated Bcl-2 at the mRNA level and the binding affinity of F-box and WD repeat domain containing 7 and Mcl-1, thereby controlling Mcl-1 at the protein level. Bcl-2 or Mcl-1 mRNA suppression by Sec6 or Sec8 depletion resulted in significant changes in nuclear factor-kappa B, cAMP response element, and p53 transcriptional activity. These results suggest that Sec6 and Sec8 are therapeutic target molecules in MPNST.

Angioleiomyoma of the tongue: a case report and review of the literature.

Angioleiomyoma (AL) is a benign tumor derived from smooth muscle. The overwhelming majority of ALs occur in the uterus, gastrointestinal tract, or skin; AL of the oral cavity is infrequent, and AL of the tongue is particularly rare. The present report describes a case of AL of the tongue that resulted in a good outcome. We also review the literature with a special emphasis on the etiology of ALs. It is generally agreed that minor trauma, venous stasis, and hormonal changes are etiological factors for AL. The roles of estrogen and progesterone have been particularly emphasized, and the expression of progesterone receptors (PRs) and estrogen receptors (ERs) has been recently evaluated in some cases of AL. To our knowledge, the presence of PRs and ERs has only been evaluated in seven cases of AL arising in different regions of the body including the oral cavity. This is the first report to demonstrate negative expression of both receptors in an AL of the oral cavity. Further study and additional cases are needed to elucidate the influence of PRs and ERs in AL of the oral cavity.