Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells.

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer.

BACKGROUND: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with H. pylori infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. METHODS: After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. RESULTS: Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. CONCLUSION: We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer.

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model.

Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61-1.03; and RR 0.89; 95% CI 0.70-1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends. The results of this propensity-matched cohort study may not provide a statistically significant association between statin use and a lower risk of HNC recurrence. Further retrospective studies using nationwide claims data and prospective studies are warranted.

Personality traits and emotional status affecting academic achievements of medical students: testifying mediating effect of learning strategies.

PURPOSE: The purpose of this study is to identify possible causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students and to testify mediating effect of learning strategies in these relationships. METHODS: The study subjects are 424 medical students in the academic year of 2020 at the Gyeongsang National University, Jinju, Korea. Using the Multi-dimensional Learning Strategy Test-II, we assessed the students' academic achievements with personality traits, emotional status, and learning strategies. This study employed Structural Equation Modelling to explore the causal relationships among the latent variables. RESULTS: In the path model, personality traits directly affected academic achievements (ß=0.285, p<0.05) and indirectly affected academic achievements via emotional status (ß=0.063, p<0.01) and via learning strategies (ß=0.244, p<0.05), respectively. Further, personality traits indirectly affected academic achievements via emotional status first and learning strategies next (ß=0.019, p<0.05). Personality traits indirectly affected academic achievements through three multiple paths in the model (ß=0.326, p<0.05). Learning strategies partially mediated the relationship between personality traits and academic achievements as well as the relationship between emotional status and academic achievements of medical students. CONCLUSION: Study findings proved constructing the causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students, thus supporting our hypotheses. Early habits of self-regulated learning are essential for the successful academic achievements of medical students. Therefore, medical students should know how to regulate personality traits and control emotional status, significantly affecting learning strategies.

Delayed Horner's Syndrome After Multiple Penetrating Stab Injury of the Neck.

Horner's syndrome is characterized by a triad of symptoms (ipsilateral miosis, ptosis, and anhidrosis) with damage of the sympathetic nervous system. The condition may be congenital or acquired from traumatic conditions including cardiovascular surgery. Horner's syndrome can be also caused by neck trauma especially when cervical vital structures such as blood vessels, the aerodigestive tract, and nerves are disrupted. This report describes a 16-year-old woman with delayed Horner's syndrome who initially presented with internal jugular vein injury caused by multiple penetrating stab injury to the neck. To the best of our knowledge, this is the first reported case of Horner's syndrome resulting from neck trauma of which symptoms were presented after a couple of weeks after initial trauma. Understanding this rare clinical course may help surgeons pay attention to not only early hospital course but also long-term complications of patients with neck trauma.

Two cases of extraluminal migration of fishbones into the thyroid gland and submandibular gland.

Laryngopharyngeal or cervical pain following ingestion of foreign bodies is one of the most frequently encountered emergencies in otolaryngologic practice. Although most of these foreign bodies can be easily removed under laryngoscopic examination without any complications, surgical removal may be required when foreign bodies migrate extraluminally. This report describes two rare cases of ingested fishbones that had migrated, one each to the thyroid gland and submandibular gland. Extraluminal migration fishbones should always be considered in otolaryngologic clinics.

MDM2-dependent Sirt1 degradation is a prerequisite for Sirt6-mediated cell death in head and neck cancers.

Sirt6 is involved in multiple biological processes, including aging, metabolism, and tumor suppression. Sirt1, another member of the sirtuin family, functionally overlaps with Sirt6, but its role in tumorigenesis is controversial. In this study, we focused on cell death in association with Sirt6/Sirt1 and reactive oxygen species (ROS) in head and neck squamous cell carcinomas (HNSCCs). Sirt6 induced cell death, as widely reported, but Sirt1 contributed to cell death only when it was suppressed by Sirt6 via regulation of MDM2. Sirt6 and Sirt6-mediated suppression of Sirt1 upregulated ROS, which further led to HNSCC cell death. These results provide insight into the molecular roles of Sirt6 and Sirt1 in tumorigenesis and could therefore contribute to the development of novel strategies to treat HNSCC.

Therapeutic Effects of Intranasal Tofacitinib on Chronic Rhinosinusitis with Nasal Polyps in Mice.

OBJECTIVES: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA). RESULTS: Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ. CONCLUSION: Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs. LEVEL OF EVIDENCE: N/A. Laryngoscope, 131:E1400-E1407, 2021.

p53-dependent glutamine usage determines susceptibility to oxidative stress in radioresistant head and neck cancer cells.

The manner in which p53 maintains redox homeostasis and the means by which two key metabolic elements, glucose and glutamine, contribute to p53-dependent redox stability remain unclear. To elucidate the manner in which p53 deals with glucose-deprived, reactive oxygen species (ROS)-prone conditions in this regard, two isogenic cancer subclones (HN3R-A and HN3R-B) bearing distinct p53 mutations as an in vitro model of intratumoral p53 heterogeneity were identified. Following cumulative irradiation, the subclones showed a similar metabolic shift to aerobic glycolysis and increasing NADPH biogenesis for cellular defense against oxidative damage irrespective of p53 status. The radioresistant cancer cells became more sensitive to glycolysis-targeting drugs. However, in glucose-deprived and ROS-prone conditions, HN3R-B, the subclone with the original p53 increased the utilization of glutamine by GLS2, thereby maintaining redox homeostasis and ATP. Conversely, HN3R-A, the p53-deficient radioresistant subclone displayed an impairment in glutamine usage and high susceptibility to metabolic stresses as well as ROS-inducing agents despite the increased ROS scavenging system. Collectively, our findings suggest that p53 governs the alternative utilization of metabolic ingredients, such as glucose and glutamine, in ROS-prone conditions. Thus, p53 status may be an important biomarker for selecting cancer treatment strategies, including metabolic drugs and ROS-inducing agents, for recurrent cancers after radiotherapy.

Periostin Plays a Key Role in Radioresistance of Head and Neck Cancer Cells Via Epithelial-to-Mesenchymal Transition.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is an aggressive head and neck malignancy. The aim of this study was to elucidate the role of periostin (POSTN) in the epithelial-to-mesenchymal transition (EMT) process mediating the acquisition of radioresistance in HNSCC. MATERIALS AND METHODS: The expression levels of EMT hallmark genes including POSTN and Erk/Akt signaling pathways were compared between radiosensitive and radioresistant HNSCC cells. RESULTS: POSTN mRNA expression was higher in radioresistant HNSCC cells, and silencing POSTN significantly impaired their invasiveness under the effect of EMT process represented by up-regulation of mesenchymal markers and down-regulation of an epithelial marker. Expression levels of Erk and Akt were higher in radioresistant cells. CONCLUSION: POSTN in association with the Erk and Akt signaling pathways was up-regulated during the EMT process, leading to the conversion of radiosensitive to radioresistant HNSCC cells. POSTN may be a key marker for predicting the radioresistance and therapeutic target of HNSCC.

A rare case of thyroglossal duct cyst extending to the sublingual space: A case report.

RATIONALE: Thyroglossal duct cyst (TGDC) is the most common congenital anomaly of midline neck masses. A thyroglossal duct cyst is especially difficult to diagnose and is treated differently when it appears in the sublingual area. Here, we report a rare case of TGDC extending to the sublingual space. PATIENT CONCERNS: A 42-year-old female presented with a history of neck swelling in the submental region. DIAGNOSIS: The final pathologic diagnosis was a TGDC. INTERVENTIONS: Sistrunk operation was performed. OUTCOMES: Recurrence of the disease has not been seen for the past year. LESSION: Clinical awareness of the thyroglossal duct cyst in the sublingual area or on the oral floor area is important for an accurate diagnosis and the appropriated management.

Endoscope-assisted hairline approach for resecting maxillofacial masses.

The endoscope-assisted hairline approach is becoming a preferred technique in several surgical disciplines because of its advantage of good cosmetic outcomes. However, such operations are not yet standard for benign lesions in the maxillofacial area due to the anatomical complexity of this region. This study describes an endoscope-assisted technique for resecting benign lesions in the maxillofacial area via a hairline approach. The clinical outcomes with this approach were compared to those obtained with the conventional transcutaneous approach. Benign maxillofacial lesions were excised via endoscope-assisted hairline approach in 27 patients and via transcutaneous approach in 28 patients. Clinical outcomes and complications related to the procedures were evaluated; the primary outcome was the efficacy of the procedure and the secondary outcome was cosmetic satisfaction. There were no significant differences with respect to overall demographic characteristics between the groups, although the operation time was longer for the hairline approach (P=0.001). Cosmetic satisfaction showed much better results for the hairline approach (P=0.001). Endoscope-assisted excision of benign maxillofacial lesions via the hairline approach is a feasible method with excellent cosmetic results.

Guidelines for the Surgical Management of Oral Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

Establishment and verification of a mouse model of nasal wound healing.

OBJECTIVES: Poor wound healing as reflected by the development of synechia and osteitis after endoscopic sinus surgery may trigger disease recurrence. Animal models provide insights into the pathogenesis of poor wound healing and may aid in the development of new therapeutics. Here, we established a mouse model of nasal wound healing and confirmed its utility. STUDY DESIGN: Animal study. METHODS: Unilateral intranasal wounds were induced using a small interdental brush in 6-week-old C57BL/6 mice. Forty-five mice were divided into three groups (each n = 15): one control and two experimental groups (intranasal vs. intraperitoneal dexamethasone). Mice were sacrificed on days 2, 14, and 28 after injury (each n = 5). Serial changes in nasal wound histopathology were described, and intergroup differences were analyzed. RESULTS: On day 2, mucosal detachment, hemorrhage, and exudate were observed. On day 14, synechiae featuring neo-osteogenesis (bone lacunae, osteoblasts, and multinucleated osteoclasts) between the septum and the maxilloturbinate were prominent, followed by wound maturation on day 28: fewer lacunae and smaller osteoblasts. Macrophages were evident only on day 2, and lymphocytes were predominant on day 28. The amount of exudate on day 2 and the synechial area on day 28 were significantly reduced in mice that received dexamethasone systemically compared with control mice, with similar trends in those treated intranasally. CONCLUSION: Our mouse model of nasal wound healing was characterized by the development of bony synechia and neo-osteogenesis, not soft-tissue synechia. The model may be useful in the assessment of novel therapeutics to prevent those wounds. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E266-E271, 2019.

Not CD68 but stabilin-1 expression is associated with the risk of recurrence in patients with oral cavity squamous cell carcinoma.

BACKGROUND: This study's aim was to identify CD68 and stabilin-1 expressions and their prognostic implications in patients with oral cavity cancer (OCC). METHODS: Stabilin-1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin-1 expression levels and their effect on prognostic factors and survival. RESULTS: Fifty-four patients' data were analyzed. CD68 and stabilin-1 expressions were positively correlated (P = .008). CD68 and stabilin-1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin-1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence-free nor OCC-specific survival. CONCLUSION: CD68 and stabilin-1 expressions in OCC were positively correlated. Stabilin-1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed.

Transoral Dermoid Cyst Excision: A Multicenter Prospective Observational Study.

OBJECTIVE: Transoral surgery is becoming a preferred technique because it does not leave any scar after surgery. However, transoral surgery for a dermoid cyst of the oral cavity is not standardized yet, due to the anatomic complexity of this region. The aim of this study was to evaluate the safety and efficacy of a transoral dermoid cyst excision. STUDY DESIGN: Multicenter prospective observational study. SETTING: University hospital. SUBJECTS AND METHODS: This study was designed as a 4-year prospective multicenter evaluation of dermoid cyst excisions within the floor of mouth. Clinical outcomes and complications related to procedures were evaluated among patients. The primary outcome was the efficacy of the procedure, and the secondary outcome was cosmetic satisfaction of each procedure. RESULTS: Twenty-one patients underwent transoral dermoid cyst excisions, and 22 underwent transcervical excisions. In the transoral surgery group, the mean size of the dermoid cyst was 5.35 cm (95% CI, 4.79-5.91), and in the transcervical surgery group, it was 6.19 cm (95% CI, 5.67-6.71). There was no significant differences with respect to overall demographic characteristics between the groups. However, the duration of the operation was shorter with the transoral group than with the transcervical group ( P = .001), and cosmetic satisfaction was much better in the transoral group ( P < .001). CONCLUSION: Transoral dermoid cyst excision is a potentially safe and effective method that can lead to easy and quick removal of an oral cavity dermoid cyst, with excellent cosmetic outcomes.

Ultrasonography-guided core needle biopsy of cervical lymph nodes for diagnosing head and neck lymphoma compared with open surgical biopsy: Exploration for factors that shape diagnostic yield.

PURPOSE: This study was conducted to compare the diagnostic yields of Ultrasonography-guided core needle biopsy (USG-CNB) and open surgical biopsy (OSB) in head and neck (HN) lymphoma and to identify the factors that shape USG-CNB diagnostic yield. MATERIALS AND METHODS: All consecutive patients who were diagnosed with HN lymphoma in our hospital were analyzed. The frequencies with which these first-line procedures yielded a sample that permitted histological confirmation of lymphoma were determined. To identify the factors that shape the diagnostic yield of USG-CNB, the patients in whom USG-CNB was and was not sufficiently confirmatory were compared in terms of demographics, computed tomography (CT) and pathological findings. RESULTS: In total, 83 patients underwent USG-CNB (n = 26, 31.3%) or OSB (n = 57, 68.7%) for confirming lymphoma. USG-CNB yielded a fully sufficient diagnosis in 18 (69.2%) patients. By contrast, OSB yielded a confirmative diagnosis in 56 (98.2%) patients. Maximal standardized uptake value (SUVmax) of targeted LN on positron emission tomography-CT (PET-CT) in confirmatively diagnosed subjects was much higher than deferred counterparts (22.9 ±â€¯13.4 vs. 10.1 ±â€¯5.2, p = 0.017), however, there was no significant difference in other parameters associated with the first-line USG-CNB diagnostic success. CONCLUSIONS: First-line USG-CNB was less frequently successful than OSB for diagnosing HN lymphoma involving cervical LN. Mean SUVmax of LN on PET-CT in confirmatively diagnosed subjects was higher than deferred counterparts on USG-CNB.

No-Scar Transoral Thyroglossal Duct Cyst Excision in Children.

BACKGROUND: No-scar transoral thyroglossal duct cyst (TGDC) excision is a newly developed treatment for TGDC, but limited information is available regarding the clinical outcomes in children. The aim of this study was to evaluate the safety, efficacy, and effects of transoral TGDC excision in children. METHODS: Forty-four children <10 years of age received operative treatment for TGDC from January 2013 to December 2014, and follow-up was performed over 24 months. Clinicopathologic, surgical, and follow-up data were collected and analyzed. The primary outcome variable was feasibility of the procedure, and the secondary outcome was patient's cosmetic satisfaction after each operation. RESULTS: Twenty-one patients underwent transoral TGDC excision, and 21 patients underwent conventional excision. No significant differences were observed between the two groups in terms of the overall patient and operation factors. However, the rate of identifying the thyroglossal duct during transoral excision was superior to that during conventional excision (p < 0.05), and cosmetic satisfaction was much better in the transoral TGDC excision group (p < 0.001). CONCLUSION: No-scar transoral TGDC excision in children is a potentially safe and effective methodology that can achieve easy removal of the thyroglossal duct and excellent cosmetic outcomes.

Tracheobronchial foreign body removal in infants who had very small airways: A prospective clinical trial.

BACKGROUND AND AIMS: Tracheobronchial foreign body aspiration is a life-threatening emergency. Using a rigid bronchoscope with optical forceps is the most effective method for foreign body removal. However, occasionally for some infants these instruments could not be used, as they may be too large for their small airways. Here, they present the apnea technique with only an optical forceps for foreign body removal in infants with very small airways. METHODS: Foreign bodies were removed using only an optical forceps for infants who had very small diameter airways. After general anesthesia, the suspension laryngoscope was set just above the vocal cord, and the inserted ventilation tube was pulled out, followed by a new one being inserted through the suspension laryngoscope and placed at the trachea. With the oxygen saturation at 100%, we pulled out the ventilation tube and inserted the optical forceps with an endoscope. After that, the foreign body was removed by the optical forceps. RESULTS: The foreign body removal using only an optical forceps is technically feasible for an infant. The mean operation time was 40.33 ± 8.06 min, and the hospital stay was 2.25 ± 0.62 days. When we pulled out the ventilation tube, the O2 saturation mean time (apnea time) was 106.25 ± 14.30 sec. In 12 infants, the foreign body was removed completely without a need for a second procedure. CONCLUSIONS: The apnea technique for the removal of foreign body from the airway, using only an optical forceps with an endoscope, is useful in infants who had very small airways.