Ultrasonographic features of normal parathyroid glands confirmed during thyroid surgery in adult patients.

PURPOSE: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. METHODS: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. RESULTS: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). CONCLUSION: Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Preoperative ultrasonography parathyroid gland mapping can improve identification of normal parathyroid gland during thyroidectomy: A propensity score-matched case-control study.

BACKGROUND: Accurate intraoperative identification of normal parathyroid glands (PTGs) is vital to avoid hypocalcemia post total thyroidectomy. Although ultrasonography (US) has been shown to identify normal PTGs, the significance of preoperative US PTG mapping in this context is not well studied. This study evaluated the impact of preoperative US PTG mapping on intraoperative identification of normal PTGs during total thyroidectomy. METHODS: The study involved 161 consecutive patients who underwent total thyroidectomy between January 2020 and June 2022. These included patients without preoperative US PTG mapping (group 1, n = 91) and those with the mapping (group 2, n = 70). Propensity score matching yielded 61 matched patients from each group. We developed a preoperative US PTG mapping technique combining US identification of normal PTGs with their localization on thyroid CT images. The intraoperative detectability of normal PTGs during thyroid surgery and detectability of normal PTGs by the preoperative US mapping were assessed by the number of PTGs identified per patient and by location. RESULTS: In the matched cohort, group 2 demonstrated a higher median number of identified PTGs (3 vs. 2, p = 0.011), a greater proportion of patients with three or more identified PTGs (65.5% vs. 44.3%, p = 0.018), and a higher ratio of identified to expected PTGs (70.5% vs. 60.2%, p = 0.011) than group 1. In group 2, the median number of normal PTGs identified preoperatively was 3, with at least one identified in 95.7% of patients, two or more in 84.3%, three or more in 52.9%, and four or five in 24.3%. CONCLUSIONS: Preoperative US PTG mapping identified two or more normal PTGs in the majority of adult patients undergoing total thyroidectomy. Those with preoperative mapping showed a higher number of intraoperatively identified normal PTGs, including inferior PTGs, compared to those without. This technique appears to enhance the intraoperative identification of normal PTGs, thereby potentially improving surgical outcomes in total thyroidectomy.

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.

Risk assessment of toxic and hazardous metals in paddy agroecosystem by biochar-for bio-membrane applications.

Toxic and carcinogenic metal (loid)s, such arsenic (As) and cadmium (Cd), found in contaminated paddy soils pose a serious danger to environmental sustainability. Their geochemical activities are complex, making it difficult to manage their contamination. Rice grown in Cd and As-polluted soils ends up in people's bellies, where it can cause cancer, anemia, and the deadly itai sickness. Solving this issue calls for research into eco-friendly and cost-effective remediation technology to lower rice's As and Cd levels. This research delves deeply into the origins of As and Cd in paddy soils, as well as their mobility, bioavailability, and uptake mechanisms by rice plants. It also examines the current methods and reactors used to lower As and Cd contamination in rice. Iron-modified biochar (Fe-BC) is a promising technology for reducing As and Cd toxicity in rice, improving soil health, and boosting rice's nutritional value. Biochar's physiochemical characteristics are enhanced by the addition of iron, making it a potent adsorbent for As and Cd ions. In conclusion, Fe-BC's biomembrane properties make them an attractive option for remediating As- and Cd-contaminated paddy soils. More efficient mitigation measures, including the use of biomembrane technology, can be developed when sustainable agriculture practices are combined with these technologies.

US Features of the Parathyroid Glands: An Intraoperative Surgical Specimen Study.

Purpose: This study aimed to evaluate the US features of the parathyroid glands (PTGs) using surgical specimens of normal PTGs obtained during thyroid surgery. Materials and Methods: This study included 34 normal PTGs from 17 consecutive patients who underwent thyroid surgery between December 2020 and March 2021. All normal PTGs were histologically confirmed by intraoperative frozen-section biopsy for autotransplantation. Surgically resected parathyroid specimens were scanned in sterile normal saline using high-resolution US prior to autotransplantation. The US features of echogenicity (hyperechogenicity or hypoechogenicity), echotexture (homogeneous or heterogeneous), size, and shape (ovoid or round) were retrospectively evaluated. The echogenicity of the three PTGs was compared with that of the thyroid parenchyma of the resected thyroid specimens in two patients. Results: All PTGs showed hyperechogenicity similar to that of gauze soaked in normal saline. Homogeneous hyperechogenicity was observed in 32/34 (94.1%) patients, and the echogenicity of the three PTGs was hyperechoic compared with that of the thyroid parenchyma. The long diameter of the PTGs ranged from 5.1 mm to 9.8 mm (mean, 7.1 mm) and the shape of the PTGs was ovoid in 33/34 (97.1%) patients. Conclusion: The echogenicity of normal PTG specimens was consistently hyperechoic, and the small ovoid homogeneously hyperechoic structure was a characteristic US feature of the PTGs.

ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma.

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens-bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04-0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

Feedback amplification of senolysis using caspase-3-cleavable peptide-doxorubicin conjugate and 2DG.

Therapy-induced senescence (TIS), a common outcome of current cancer therapy, is a known cause of late recurrence and metastasis and thus its eradication is crucial for therapy success. In this study, we introduced a conceptually novel strategy combining radiation-induced apoptosis-targeted chemotherapy (RIATC) with an effective glycolysis inhibitor, 2-deoxy-d-glucose (2DG) to target TIS. RIATC releases cytotoxic payload by amplification, continually increasing TIS, and this can be targeted by 2DG that stimulates an intrinsic apoptotic pathway in senescent cells, the senolysis; the senolytic 2DG also sensitizes cancer cells to chemo/radiation treatment. Anti-tumor efficacy of RIATC was investigated in numerous tumor models, and various cancer types were screened for TIS. Furthermore, in vitro evaluations of molecular markers of senescence, such as senescence-associated ß-galactosidase (SA-ß-Gal) assay, were performed to confirm that TIS was induced by RIATC therapy in MCF-7 cells. The combination therapy with 2DG proved to be effective in MCF-7 tumor-bearing mice that demonstrated feedback amplification of senolysis and successful inhibition of tumor growth. Our findings suggest that RIATC, when given together with 2DG, can overcome therapy-induced senescence and this combination is a promising strategy that enhances the therapeutic benefit of anti-cancer cytotoxic therapy.

Optimisation of high-speed lipidome analysis by nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry: Application to identify candidate biomarkers for four different cancers.

Lipid analysis is a powerful tool that can elucidate the pathogenic roles of lipids in metabolic diseases, and facilitate the development of potential biomarkers. Lipid analysis by large-scale lipidomics requires a high-speed and high-throughput analytical platform. In the present study, a high-speed analytical method for lipid analysis using nanoflow ultrahigh-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (nUHPLC-ESI-MS/MS) was optimised by investigating the effects of column flow rate, pump flow rate, dwell time, initial binary mobile phase composition, and gradient duration on the separation efficiency of standard lipid mixtures. The minimum gradient time for high-speed lipid separation was determined by examining the time-based separation efficiency and spectral overlap of isobaric lipid species during selected reaction monitoring-based quantification of sphingomyelin and a second isotope of phosphatidylcholine, which differ in molecular weight by only 1 Da. Finally, the optimised nUHPLC-ESI-MS/MS method was applied to analyse 200 plasma samples from patients with liver, gastric, lung, and colorectal cancer to evaluate its performance by measuring previously identified candidate lipid biomarkers. About 73% of the reported marker candidates (6 out of 7 in liver, 5/9 in gastric, 4/6 in lung, and 6/7 in colorectal cancer) could be assigned using the optimised method, supporting its use for high-throughput lipid analysis.

High-Speed Screening of Lipoprotein Components Using Online Miniaturized Asymmetrical Flow Field-Flow Fractionation and Electrospray Ionization Tandem Mass Spectrometry: Application to Hepatocellular Carcinoma Plasma Samples.

This study introduces a high-speed screening method for the quantitative analysis of lipoprotein components in human plasma samples using online miniaturized asymmetrical flow field-flow fractionation and electrospray ionization-tandem mass spectrometry (mAF4-ESI-MS/MS). Using an mAF4 channel, high-density lipoproteins and low-density lipoproteins can be fractionated by size at a high speed (<10 min) and directly fed to ESI-MS/MS for the simultaneous screening of targeted lipid species and apolipoprotein A1 (ApoA1). By employing the heated electrospray ionization probe as an ionization source, an mAF4 effluent flow rate of up to a few tens of microliters per minute can be used, which is adequate for direct feeding to MS without splitting the outflow, resulting in a consistent feed rate to MS for stable MS detection. mAF4-ESI-MS/MS was applied to hepatocellular carcinoma (HCC) plasma samples for targeted quantification of 25 lipid biomarker candidates and ApoA1 compared with healthy controls, the results of which were in statistical agreement with the quantified results obtained by nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry. Moreover, the present method provided the simultaneous detection of changes in lipoprotein size and the relative amount. This study demonstrated the potential of mAF4-ESI-MS/MS as an alternative high-speed screening platform for the top-down analysis of targeted lipoprotein components in patients with HCC, which is applicable to other diseases that involve the perturbation of lipoproteins.

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.

Lipidomic signatures of post-hepatectomy liver failure using porcine hepatectomy models.

BACKGROUND: Clinical diagnosis of post-hepatectomy liver failure (PHLF) can only be made on or after the 5th postoperative day. Biomarker for early diagnosis is considered as a critical unmet need. METHODS: Twenty domestic female crossbreed (Yorkshire-landrace and duroc) pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). A comprehensive lipidomic analysis was conducted using sera collected at pre-operation (PO), 14, 30, and 48 h after PH using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Of the 184 quantified lipids, 14 lipids showed significant differences between the two resection groups starting at 30 h after surgery. Four phosphatidylcholine (PC) plasmalogen species (P-16:0/16:0, P-18:0/18:2, P-18:0/20:4, and P-18:0/22:6) and PC 32:2 significantly increased in the 90% PH group while these returned to PO level after 30 h in the 70% PH group, presumably implying the failure markers. In contrast, eight triacylglycerol (TG) species (40:0, 42:1, 42:0, 44:1, 44:2, 46:1, 46:2, and 48:3) and sphingomyelin d18:1/20:0 showed an opposite trend, wherein they significantly decreased in the 90% PH group while these in the 70% PH group were abruptly increased until 30 h but returned to near PO levels at 48 h, implying the recovery markers. Same trends could also be observed in the level of whole lipid classes of PC plasmalogens and TGs, in addition to selected individual lipid species. CONCLUSIONS: Characteristic lipidomic signatures of PHLF could be identified using large animal models. These candidates have a potential to serve as a tool for early diagnosis and may open new paths to the study to overcome PHLF.

Tristetraprolin Posttranscriptionally Downregulates TRAIL Death Receptors.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has attracted attention as a potential candidate for cancer therapy. However, many primary cancers are resistant to TRAIL, even when combined with standard chemotherapy. The mechanism of TRAIL resistance in cancer cells has not been fully elucidated. The TRAIL death receptor (DR) 3'-untranslated region (3'-UTR) is reported to contain AU-rich elements (AREs) that are important for regulating DR mRNA stability. However, the mechanisms by which DR mRNA stability is determined by its 3'-UTR are unknown. We demonstrate that tristetraprolin (TTP), an ARE-binding protein, has a critical function of regulating DR mRNA stability. DR4 mRNA contains three AREs and DR5 mRNA contains four AREs in 3'-UTR. TTP bound to all three AREs in DR4 and ARE3 in DR5 and enhanced decay of DR4/5 mRNA. TTP overexpression in colon cancer cells changed the TRAIL-sensitive cancer cells to TRAIL-resistant cells, and down-regulation of TTP increased TRAIL sensitivity via DR4/5 expression. Therefore, this study provides a molecular mechanism for enhanced levels of TRAIL DRs in cancer cells and a biological basis for posttranscriptional modification of TRAIL DRs. In addition, TTP status might be a biomarker for predicting TRAIL response when a TRAIL-based treatment is used for cancer.

Role of posterior auricular muscle to prevent protruding ear after retroauricular ear surgery.

OBJECTIVE: The posterior auricular muscle (PAM) functions in ear projection in normal position and is severed during the retroauricular approach, and some patients complain of a protruding ear postoperatively. This study was designed to determine whether suturing of the severed PAM reduces pinna projection after the retroauricular approach. METHODS: In a prospective controlled study, we enrolled 91 patients with chronic otitis media, all of who underwent canal wall up mastoidectomy with tympanoplasty via retroauricular approach. They were randomly assigned to the PAM-sutured (n=45) or PAM-non-sutured (n=46) group. Helical-mastoid distance and concho-mastoid angle were measured serially. RESULTS: In both groups, helical-mastoid distance was significantly longer than preoperatively until 1 month postoperatively but was similar to preoperatively by 6 months. Concho-mastoid angle increased significantly until 1 month after surgery in the PAM-non-sutured group but returned to the preoperative value at 6 months postoperatively. In the PAM-sutured group, concho-mastoid angle increased significantly at 3 days postoperatively, was similar to preoperatively at 1 month after surgery, and became narrower than preoperatively at 6 months postoperatively. In both groups, there were significant effects of time on the changes in helical-mastoid distance or concho-mastoid angle. Group assignment did not significantly affect these time-related changes. CONCLUSION: PAM suturing did not affect helical-mastoid distance by 6 months postoperatively, but it did reduce the concho-mastoid angle to below the preoperative value at 6 months. We recommend that PAM be left severed to maintain concho-mastoid angle in the long term when using the retroauricular approach.

Simultaneous Relative Quantification of Various Polyglycerophospholipids with Isotope-Labeled Methylation by Nanoflow Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry.

Herein, we introduce a comprehensive analytical method for the separation and relative quantification of polyglycerophospholipids (PGPLs), including phosphatidylglycerol (PG), bis(monoacylglycero)phosphate (BMP), bis(diacylglycero)phosphate (BDP), Hemi BDP, cardiolipin (CL), monolysocardiolipin (MLCL), and dilysocardiolipin (DLCL), using isotope-labeled methylation (ILM) with nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUHPLC-ESI-MS/MS). Abnormal levels of BMP and CL have been associated with the pathology of lysosomal storage and neurodegenerative diseases. Thus, simultaneous analysis of all PGPLs is important to understand the mechanisms and pathologies of such diseases. In this study, improved separation and MS detection of PGPLs, including their regioisomers, was achieved by the methylation of PGPL. ILM-based relative quantification was applied to lipid extracts from a dopaminergic cell line (SH-SY5Y) treated with drugs commonly used for Parkinson's disease (PD), resulting in the identification of 229 unique PGPLs, including 121 CLs, 71 MLCLs, and 16 Hemi BDP species. The drug treatment induced significant increases in the amount of CLs containing polyunsaturated fatty acyl chains, including 20:4 and 22:6, as well as decreased levels of BMP, Hemi BDP, and BDP species, demonstrating the feasibility of using ILM for the comprehensive and high-speed relative quantification of PGPLs.

Plasma lipid profile comparison of five different cancers by nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry.

A comprehensive lipidomic analysis at the molecular level using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUHPLC-ESI-MS/MS) was performed to elucidate the lipid profiles of patient blood samples from five commonly found cancers (liver, lung, gastric, colorectal, and thyroid), which were then compared with the lipid profiles of healthy controls. From a total of 335 lipids identified and quantified, 50 high abundance lipids showing significant changes (>2-fold and p < 0.01) in at least one of the five cancers (vs. controls) were analysed. Lipid species were found to be significantly associated with more than one type of cancer; the numbers of lipid species found as significantly changed in all five, four, three, two, and one type of cancer were 1, 8, 8, 15, and 17, respectively. Among these, the high abundance phosphatidylethanolamine species, including lysophosphatidylethanolamine and PE plasmalogen, was significantly low in four cancer types, but was high in thyroid cancer. Receiver operating characteristic analysis resulted in the selection of lipids specific to each cancer: liver (four phosphatidylinositols and diacylglycerol 16:1_18:0), gastric (phosphatidylcholine 34:2, 36:3, and 36:4, and lysophosphatidic acid 18:2), lung (lysophosphatidylinositol 16:0, sphingomyelin d18:1/20:0, and triacylglyceride 50:1 and 54:4), and thyroid (lysophosphatidylinositol 18:0 and 18:1). Our results provide a basis for future validation of cancer-specific lipid markers with high diagnostic ability.

p53/BNIP3-dependent mitophagy limits glycolytic shift in radioresistant cancer.

The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradiation showed decreased oxygen consumption and increased glycolysis with compromised mitochondria, corresponding with their enhanced sensitivity to drugs that target glycolysis. In contrast, radioresistant cancer cells with wild-type p53 preserved their primary metabolic profile with intact mitophagic processes and maintained their mitochondrial integrity. Moreover, we identified a previously unappreciated link between p53 and mitophagy, which limited the glycolytic shift through the BNIP3-dependent clearance of abnormal mitochondria. Thus, drugs targeting glycolysis could be used as an alternative strategy for overcoming radioresistant cancers, and the p53 status could be used as a biomarker for selecting participants for clinical trials.

Impact of adenotonsillectomy on urinary storage symptoms in children with sleep-disordered breathing.

OBJECTIVE: To prospectively evaluate the effectiveness of adenotonsillectomy on resolving urinary storage symptoms such as frequency, urgency, and urgency urinary incontinence (UUI) in indicated sleep disordered breathing (SDB) patients. METHODS: We prospectively analyzed changes in storage symptoms and SDB score before and after surgery in 102 children (74 males, 28 females, mean age 8.4 ±â€¯2.8 years) who underwent adenotonsillectomy between July 2011 and Feb 2012. Before and 3 months after surgery, all children and their parents were requested to answer a self-reported SDB scale-questionnaire (22 questions, 0-22 points) and a urinary storage symptoms questionnaire. RESULTS: The prevalence of urgency in the overall patients was 31.2%. After adenotonsillectomy, prevalence of frequency and, urgency in addition to SDB score were significantly decreased (p ≦ 0.001). The prevalence of UUI was also significantly lower (11.6%-7.4%, p < 0.001). Patients with urgency had a significantly higher SDB score than those without (11.4 ±â€¯4.3 vs. 7.8 ±â€¯4.0, p < 0.001). After treatment, there was no difference between these two groups. CONCLUSION: Adenotonsillectomy markedly improved both SDB score and decreased the prevalence of voiding symptoms (frequency, urgency, and UUI). There was a strong correlation between preoperative SDB score and severity of urgency in children with SDB.

EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition.

Radiotherapy is a well-established therapeutic modality used in the treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after radiation treatment. Thus, many studies have attempted to identify effective radiosensitizers. Eph receptor functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains unclear. In the current study, we established a stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and found that EphA3 was expressed predominantly in the radioresistant head and neck cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we found that EphA3 was overexpressed in recurrent laryngeal cancer specimens after radiation therapy. EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study. In conclusion, our results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and plays a crucial role in the development of radioresistance in head and neck cancers by regulating the epithelial mesenchymal transition pathway.

Phosphorylation of PI3K regulatory subunit p85 contributes to resistance against PI3K inhibitors in radioresistant head and neck cancer.

OBJECTIVES: PI3K/Akt/mTOR pathway is commonly activated in most cancers and is correlated with resistance to anticancer therapies such as radiotherapy. Therefore, PI3K is an attractive target for treating PI3K-associated cancers. MATERIAL AND METHODS: We investigated the basal expression and the expression after treatment of PI3K inhibitor or Src inhibitor of PI3K/Akt pathway-related proteins in AMC-HN3, AMC-HN3R, HN30 and HN31 cells by performing immunoblotting analysis. The sensitivity to PI3K inhibitors or Src inhibitor was analyzed by MTT assay and clonogenic assay. To determine the antitumoral activity of combination treatment with PI3K inhibitor and Src inhibitor, we used using xenograft mouse model. RESULTS: We found that PI3K regulatory subunit p85 was predominantly phosphorylated in radioresistant head and neck cancer cell line (HN31), which showed resistance to PI3K inhibitors. Next, we investigated mechanism through which PI3K p85 phosphorylation modulated response to PI3K inhibitors. Of note, constitutive activation of Src was found in HN31 cells and upon PI3K inhibitor treatment, restoration of p-Src was occurred. Src inhibitor improved the efficacy of PI3K inhibitor treatment and suppressed the reactivation of both Src and PI3K p85 in HN31 cells. Furthermore, downregulation of PI3K p85 expression by using a specific siRNA suppressed Src phosphorylation. CONCLUSIONS: Together, our results imply the novel role of the PI3K regulatory subunit p85 in the development of resistance to PI3K inhibitors and suggest the presence of a regulatory loop between PI3K p85 and Src in radioresistant head and neck cancers with constitutively active PI3K/Akt pathway.