Effect of back-up head-elevated position during drug-induced sleep endoscopy in obstructive sleep apnea patients.

PURPOSE: This study aimed to evaluate the difference of upper airway collapse between the back-up head-elevated position (a 45° upward inclination) and supine position to better elucidate the role of back-up head-elevated position in reductions of obstructive sleep apnea (OSA) severity. METHODS: From August 2016 to May 2019, 198 patients aged between 18 and 70 years were recruited in this study prospectively. Drug-induced sleep endoscopy (DISE) findings were recorded with the patients first placed in the supine position then into the back-up head-elevated position with a 45° upward inclination. RESULTS: From the supine to back-up head-elevated position, a significant decrease in the severity of collapse was observed in velum anteroposterior collapse and velum concentric collapse (p < 0.001 and p < 0.001, respectively), which was more predominant in patients with mild OSA than in patients with moderate to severe OSA. On the other hand, there was no significant improvement of any other collapse at the level of oropharynx, tongue base, or epiglottis when the position was shifted from the supine into back-up head-elevated position. CONCLUSIONS: The back-up head-elevated position with a 45° upward inclination improved upper airway obstruction during DISE in velum anteroposterior collapse and velum concentric collapse. The proportion of patients with amelioration of upper airway collapse was much higher in patients with mild OSA than in patients with moderate to severe OSA. The back-up head-elevated position may be a reasonable alternative to traditional positional therapy for certain subgroups of patients with OSA.

Dynamic tongue base thickness measured by drug-induced sleep ultrasonography in patients with obstructive sleep apnea.

BACKGROUND/PURPOSE: The aim of this study was to determine the value of drug-induced sleep ultrasonography (DISU) for evaluating tongue base thickness (TBT) from the awake state to drug-induced sleep, to further understand the impact of dynamic changes in TBT in obstructive sleep apnoea (OSA) patients. METHODS: From May 2017 to May 2018, thirty patients with OSA were prospectively recruited. Sleep was induced with propofol via use of a target-controlled infusion (TCI) system. The depth of sedation was monitored by the bispectral (BIS) index with BIS levels ranging from 50 to 70. The dynamic change in the tongue base from the awake state to drug-induced sleep was recorded. The correlation between TBT in the awake state and in drug-induced sleep with OSA severity was analysed. RESULTS: The mean TBT in drug-induced sleep was significantly greater than that in the awake state (66.2 ± 4.8 mm vs 61.6 ± 4.6 mm, P < 0.001). TBT in drug-induced sleep was more correlated with AHI compared to TBT in the awake state (r = 0.50 vs r = 0.40). This study showed that TBT in drug-induced sleep had the largest AUC (Area Under the Curve) in the ROC (Receiver Operating Characteristics) analysis (0.875), providing a cut-off point of 63.20 mm with 95% sensitivity for diagnosis of moderate versus severe OSA. CONCLUSION: Our findings validate the use of DISU in objectively assessing the tongue base collapse in OSA patients. It provides a convenient and non-invasive way to evaluate the upper airway changes in OSA patients in the future.

A preclinical evaluation of thiostrepton, a natural antibiotic, in nasopharyngeal carcinoma.

Background Thiostrepton, a natural antibiotic, has recently been shown to be a potential anticancer drug for certain cancers, but its study in nasopharyngeal carcinoma (NPC) is still limited. The aims of this study were to investigate the anticancer effect of thiostrepton on NPC cells and to explore its underlying mechanism. Methods The effects of thiostrepton on the proliferation, migration, and invasion of NPC cells were investigated by a WST-1 assay, wound healing assay, and cell invasion assay, respectively. Microarrays were conducted and further analyzed by Ingenuity Pathways Analysis (IPA) to determine the molecular mechanism by which thiostrepton affects NPC cells. Results Our results showed that thiostrepton reduced NPC cell viability in a dose-dependent manner. Thiostrepton inhibited the migration and invasion of NPC cells in wound healing and cell invasion assays. The microarray data analyzed by IPA indicated the top 5 ingenuity canonical pathways, which were unfolded protein response, NRF2-mediated oxidative stress response, retinoate biosynthesis I, choline biosynthesis III, and pancreatic adenocarcinoma signaling. Conclusion Thiostrepton effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. Thiostrepton may be a potential therapeutic agent for treating NPC in the future.

Role of rhinomanometry in the prediction of therapeutic positive airway pressure for obstructive sleep apnea.

BACKGROUND: This study was conducted to evaluate the relationship between nasal resistance in different posture and optimal positive airway pressure (PAP) level. Other potential factors were also assessed for possible influence on PAP pressure. METHODS: Forty- three patients diagnosed with obstructive sleep apnea (OSA) were prospectively recruited in this study. Nasal resistance was assessed by active anterior rhinomanometry in a seated position and then in a supine position at pressures of 75, 150, and 300 pascal. The factors correlating with PAP pressure were analyzed, including nasal resistance and patients' clinical data. RESULTS: Univariate analysis revealed that PAP pressure was correlated to nasal resistance in the supine position at 75 and 150 pascal (SupineNR75 and SupineNR150) (P = 0.019 and P = 0.004 in Spearman's correlation coefficient analysis), but not correlated to nasal resistance in the seated position at different pressures or in the supine position at 300 pascal. The multiple linear regression analysis revealed that both SupineNR150 and body mass index (BMI) significantly predicted PAP pressure (ß = 0.308, p = 0.044; ß = 0.727, p = 0.006). The final PAP pressure predictive model was: PAP pressure = 0.29 BMI + 2.65 SupineNR150 + 2.11. CONCLUSIONS: Nasal resistance in the supine position measured at 150 pascal may provide valuable information regarding optimal PAP pressure. Rhinomanometry should be included in the treatment algorithm of OSA patients when PAP therapy is considered.

The comparison of multilevel surgery (hyoid myotomy and suspension with uvulopalatopharyngoplasty) with CPAP in moderate to severe OSAS patients.

PURPOSE: The study aimed to determine the efficacy of multilevel surgery (hyoid myotomy and suspension with uvulopalatopharyngoplasty) and continuous positive airway pressure (CPAP) for the treatment of moderate to severe obstructive sleep apnea syndrome (OSAS) and to clarify whether our surgical protocol could be as effective as CPAP. METHODS: We conducted a case series study comparing the effects of multilevel surgery and CPAP in the same subjects to minimize the influence of confounding factors. Fifteen subjects were enrolled with a pretreatment apnea-hypopnea index (AHI) ≥ 15. RESULTS: Both CPAP and multilevel surgery could improve the AHI and oxygen desaturation index (ODI). The median AHI for baseline, CPAP and surgery were 38.9, 1.2 and 12.6, respectively (p < 0.001). The medina ODI for baseline, CPAP and surgery were 34.8, 0.9 and 7.2, respectively (p < 0.001). However, the results indicated CPAP as the more efficacious treatment modality compared with multilevel surgery. Moreover, CPAP not only decreased N1 sleep but also had beneficial effects on blood pressure control, whereas multilevel surgery did not have any significant difference. CONCLUSION: CPAP is efficacious in improving OSAS severity, oxygen desaturation, sleep stage, and blood pressure control; while hyoid myotomy and suspension with uvulopalatopharyngoplasty are only efficacious in improving OSAS severity and oxygen desaturation. This study suggested that CPAP is the first choice when considering treatment of OSAS, especially in patients with hypertension or other cardiovascular diseases.

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

PURPOSE: The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). METHODS: A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. RESULTS: A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. CONCLUSIONS: By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

Drug-induced sleep endoscopy in children with Prader-Willi syndrome.

PURPOSE: Review drug-induced sleep endoscopy (DISE) findings in children with Prader-Willi syndrome (PWS) and correlate the patterns of airway collapse with apnea-hypopnea index (AHI) and body mass index (BMI). METHODS: A total of nine children with PWS underwent DISE. DISE findings were recorded using the VOTE classification system. The relationship between different patterns of airway collapse with AHI and BMI was analyzed. RESULTS: The majority of children with PWS were found to have multilevel obstruction (six out of nine children, 66.6 %). The velum was the most common site of obstruction (nine out of nine children, 100 %). All of the patients had positional obstructive sleep apnea (OSA). Patients with partial or complete anterior-posterior tongue base collapse were associated with a significantly higher AHI (P = 0.016) compared to patients with no anterior-posterior tongue base collapse. Apart from tongue base collapse, no other patterns of airway collapse showed a consistent association with AHI in our results. No patterns of airway collapse showed a significant association with BMI in our study. CONCLUSIONS: In our study, partial or complete anterior-posterior tongue base collapse was associated with higher AHI values in children with PWS. Therefore, careful attention should be addressed to the management of tongue base collapse. Positional therapy could be a potential treatment for patients with PWS since it may alleviate the severity of tongue base collapse.

Safety of outpatient airway dilation for adult laryngotracheal stenosis.

OBJECTIVES: To evaluate the safety of outpatient airway dilation for adult patients with subglottic or tracheal stenosis. METHODS: The records of patients treated with airway dilation between October 2003 and September 2013 were reviewed. Outcomes of patients who underwent dilation as inpatients versus outpatients were compared. Emergency room visits, readmissions, and 3 or more primary care physician visits within 30 days postoperatively were specifically evaluated. Postoperative hemorrhage, airway edema, recurrent laryngeal nerve paralysis, reintubation, tracheostomy, tracheal rupture, pneumomediastinum, pneumothorax, acute respiratory distress, or death were also reviewed. RESULTS: One hundred fourteen dilations performed in 53 patients with airway stenosis were included. Outpatient dilation was performed in 93 (82%); 21 (18%) underwent the procedure in the inpatient setting. Complications were low among both inpatient and outpatient groups (10% vs 1%, P=.09). No complications occurred during the overnight stay of the inpatient group. CONCLUSIONS: Outpatient airway dilation is a safe and feasible procedure. It can be routinely performed on an ambulatory basis.

Transcutaneous Laryngeal Ultrasound for Assessing Hyaluronic Acid Status in Patients Undergoing Injection Laryngoplasty.

OBJECTIVE: Injection laryngoplasty (IL) with hyaluronic acid (HA) is an effective treatment for patients with glottic insufficiency. The duration of HA maintenance in the vocal fold remains unknown. In this study, transcutaneous laryngeal ultrasound (TLUS) was used to evaluate the absorption and migration of HA after IL. Subsequent management might be provided based on the TLUS finding. METHODS: Patients diagnosed with unilateral vocal fold paralysis (UVFP) or vocal fold atrophy were recruited. All patients underwent IL with HA in an office-based setting along with TLUS to monitor the status of HA. The schedule of TLUS included assessments before and after IL until non-visualization. RESULTS: The study population comprised 38 women and 17 men. Of the patients, 54.1% underwent IL for UVFP, whereas 45.9% underwent IL for vocal fold atrophy. Multivariate Cox regression analysis for factors affecting HA absorption revealed that the cause of injection was the most important independent predictor (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.03-4.46; p = 0.040). The duration of HA maintenance was significantly longer in patients with UVFP than in those with vocal fold atrophy (8.77 vs. 4.70 months, HR, 2.33; 95% CI, 5.47-8.18; p = 0.002). CONCLUSION: TLUS is an objective assessment method for patients undergoing IL with HA. Subsequent tailor-made management could be offered based on the TLUS findings during follow-up. For patients at high risk of upper respiratory tract infection or who are intolerant to flexible nasopharyngoscopy, TLUS can be used as an alternative tool to evaluate the condition of the glottis after IL with HA. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

Antipsychotic drug trifluoperazine as a potential therapeutic agent against nasopharyngeal carcinoma.

BACKGROUND: Trifluoperazine (TFP) is a typical antipsychotic primarily used to treat schizophrenia. In this study, we aimed to evaluate whether TFP can be used as a therapeutic agent against nasopharyngeal carcinoma (NPC) and identify its underlying molecular mechanisms. METHODS: We used NPC-TW01, TW03, TW04, and BM to assess the anticancer effects of TFP by using cytotoxicity, wound healing, colony formation, and cell invasion assays. An in vivo animal study was conducted. RNA sequencing combined with Ingenuity Pathways Analysis was performed to identify the mechanism by which TFP influences NPC cells. RESULTS: Our data revealed that TFP decreased NPC cell viability in a dose-dependent manner. The invasion and migration of NPC tumor cells were inhibited by TFP. An in vivo study also demonstrated the anticancer effects of TFP. RNA sequencing revealed several anticancer molecular mechanisms following TFP administration. CONCLUSIONS: The antipsychotic drug TFP could be a potential therapeutic regimen for NPC treatment.

Survival analyses of different treatment modalities and clinical stage for hypopharyngeal carcinoma.

Objective: We investigated the effects of different treatment modalities and clinical stage for hypopharyngeal carcinoma (HPC) patients. Methods: Between February 2004 and December 2012, 167 HPC patients were reviewed. We calculated overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS), regional failure-free survival (RFFS), and distant metastasis failure-free survival (DMFFS) using the Kaplan-Meier method and compared various survival outcomes between definitive chemoradiotherapy (CRT) and surgery-based therapy (SBT). Results: There were no significant differences in baseline characteristics between SBT (n = 102) and definitive CRT (n = 65) groups. The 5-year rates of OS (59.7% vs. 24.0%, p < 0.0001) and PFS (49.9% vs. 22.6%, p = 0.0002) were significantly better in patients who received SBT than in those who received definitive CRT. The SBT group also obtained better LFFS (p < 0.0001), RFFS (p = 0.0479), and DMFFS (p = 0.0110). We did similar analyses by different T-classification (T1-2, T3, and T4) and found that SBT had better OS (p < 0.0001 and p = 0.0020), PFS (p < 0.0001 and p = 0.0513), LFFS (p = 0.0002 and p = 0.0075), RFFS (p = 0.1949 and p = 0.0826), and DMFFS (p = 0.0248 and p = 0.0436) in the T4 and T1-2 subgroups but similar OS (p = 0.9598), PFS (p = 0.5052), RFFS (p = 0.9648), and DMFFS (p = 0.8239) in T3 patients. Analyses by different overall stages revealed no differences between definitive CRT and SBT for stage III patients but significantly better results for stage IV patients who received SBT. Conclusions: SBT can obtain significant survival benefits when compared with definitive CRT for the whole cohort of patients. Definitive CRT has similar survival outcomes compared with SBT only for T3 tumors or overall stage III disease.

A preliminary study on the role of inherited prothrombotic risk factors in Taiwanese patients with sudden sensorineural hearing loss.

Sudden sensorineural hearing loss (SSHL) is a disease with unknown etiology. Recently, several studies revealed that some inherited prothrombotic risk factors are associated with SSHL in western populations. The objective of this study was to investigate the roles of the two most common genetic prothrombotic factors, the factor V Leiden G1691A and prothrombin G20210A in Taiwanese patients with SSHL. Twenty-four patients diagnosed with SSHL of more than 30 dB on average pure tone audiometry (PTA) and thirty-six healthy subjects without a history of hearing loss were enrolled in this study. Genomic DNA was isolated from peripheral blood leukocytes and the single nucleotide polymorphisms (SNPs) genotyping of factor V Leiden G1691A and prothrombin G20210A were analyzed using the TaqMan genotyping assays. Neither factor V Leiden G1691A nor prothrombin G20210A was detected in SSHL patients or in the control subjects. Both the patient group and the control group exhibited wild-type V Leiden 1691GG and wild-type prothrombin 20210GG. In conclusion, the factors V Leiden G1691A and prothrombin G20210A do not seem to play any role in Taiwanese patients with SSHL. Further studies with a large series of patients are needed to identify other possible candidate genes in order to elucidate the pathogenesis of SSHL.

Association Between Breathing Route, Oxygen Desaturation, and Upper Airway Morphology.

OBJECTIVES/HYPOTHESIS: This study aimed to assess the role of capnography in objectively evaluating breathing routes during drug-induced sleep endoscopy (DISE) and further elucidate the relationship between breathing route, obstructive sleep apnea (OSA) severity, and DISE findings. STUDY DESIGN: Prospective observational study. METHODS: Nighty-five patients with established OSA were recruited for this study from May 2017 to May 2019. DISE was performed in the operating room. Sedation was maintained with propofol using a target-controlled infusion system and the depth of sedation was monitored based on the bispectral index. The breathing routes, which included oral breathing, oronasal breathing, and nasal breathing, were detected using capnography. DISE findings were recorded using the VOTE (velum, oropharynx, base of tongue, and epiglottis) classification. RESULTS: Patients with mouth breathing were associated with increased OSA severity, worse oximetric variables, and higher body mass index in comparison with those with other breathing routes. Mouth breathing was associated with a higher degree and higher prevalence of lateral pharyngeal wall collapse and tongue base collapse during DISE. CONCLUSIONS: Mouth breathing was significantly associated with worse oxygen desaturation and increased degree of upper airway collapse. Therefore, patients with mouth breathing during propofol-based intravenous anesthesia should be carefully monitored. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E659-E664, 2021.

The correlation between drug-induced sleep endoscopy findings and severity of obstructive sleep apnea.

OBJECTIVE: This study aimed to assess the relationship between anthropometric data, drug-induced sleep endoscopy (DISE) findings, and severity of obstructive sleep apnea (OSA). METHODS: From August 2016 to August 2017, a total of 147 surgically naïve adult patients with OSA underwent DISE. Factors that were analyzed included anthropometric data and DISE findings. RESULTS: When anthropometric data and DISE findings were analyzed with AHI by univariate analysis, the results showed that Epworth Sleepiness Scale (ESS), body mass index (BMI), neck circumference, concentric collapse of the velum, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were considered potentially independent predictors (p = 0.024, p < 0 .001, p < 0 .001, p < 0.001, p < 0.001, p < 0 .001, respectively, by Spearman correlation). When all important factors were evaluated in a stepwise multiple linear regression analysis, BMI, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were identified as significant predictors for the severity of OSA. The final model was listed as below: AHI score = 2.19 BMI + 7.56 Oropharynx/Lateral degree + 8.23 Tongue base/ Anterior-Posterior degree - 40.59. CONCLUSION: By analyzing anthropometric data and DISE findings with AHI score, the results indicated that BMI, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were important factors associated with the severity of OSA.

Nasal Obstruction as a Potential Factor Contributing to Hypoxemia in Obstructive Sleep Apnea.

PURPOSE: This study aimed to evaluate the correlation between nasal resistance and oxygen desaturation to better elucidate the role of nasal obstruction in the pathophysiology of obstructive sleep apnea (OSA). PATIENTS AND METHODS: Eighty-eight OSA patients aged between 22 and 77 years were enrolled in this study. Nasal resistance was measured at pressures of 75, 150, and 300 Pa, with the patients first in the seated position than in the supine position. Relationships between the oximetric variables and nasal resistance in the seated and supine positions were analyzed. RESULTS: From seated to supine position, a statistically significant increase in nasal resistance was observed at pressures of 75 and 150 Pa (p=0.001 and p=0.006, respectively). Significant positive correlations were noted between nasal resistance in the supine position at 75 Pa (SupineNR75) and oximetry variables, including oxygen desaturation index (ODI, p=0.015) and the percentage of total time with oxygen saturation level lower than 90% (T < 90%, p=0.012). However, significant positive correlations existed only in moderate to severe OSA when the study group was further divided into two subgroups (mild vs moderate to severe OSA). Body mass index (ß = 0.476, p<0.001) and SupineNR75 (ß = 0.303, p=0.004) were identified as independent predictors for increased ODI. CONCLUSION: Nasal resistance in the supine position measured at 75 Pa significantly correlated with the severity of oxygen desaturation. Therefore, nasal obstruction may play an important role in the pathophysiology of hypoxemia in OSA patients, especially in patients with moderate to severe OSA.

Role of drug-induced sleep endoscopy in evaluation of positional vs non-positional OSA.

BACKGROUND: The study aimed to evaluate the anatomical differences between positional and non-positional OSA, and to identify the potential predictors for distinguishing between these two types of OSA. METHODS: A cross-sectional study of 230 consecutive patients with OSA undergoing DISE (Drug-induced Sleep Endoscopy) was carried out at a tertiary academic medical center. The factors correlating with positional and non-positional OSA were analyzed, including clinical characteristics, polysomnography data, and DISE findings. RESULTS: Univariate analysis revealed that non-positional dependency was correlated with a higher BMI (p < 0.001), neck circumference (p < 0.001), modified Mallampati score (p = 0.003), AHI (p < 0.001), degree of velum concentric collapse (p = 0.004), degree of oropharyngeal lateral wall collapse (p < 0.001), and degree of tongue base anteroposterior collapse (p = 0.004). Multivariate analysis revealed that oropharyngeal lateral wall collapse (OR = 1.90, p = 0.027) was the only anatomical factor significantly predicted non-positional dependency in OSA patients. AHI (OR = 1.04, p < 0.001), although significant, made only a marginal contribution to the prediction of non-positional dependency. CONCLUSIONS: Oropharyngeal lateral wall collapse was identified as the only anatomical predictor for non-positional dependency in OSA patients. Therefore, further treatment modalities should address the distinct anatomical trait between positional and non-positional OSA.

Polyethylene Glycol-Coated Graphene Oxide Loaded with Erlotinib as an Effective Therapeutic Agent for Treating Nasopharyngeal Cancer Cells.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan, and radiation therapy combined with or without chemotherapy is its mainstay treatment. Although it is highly sensitive to radiotherapy, local recurrence and distant metastasis remain difficult unsolved problems. In recent years, graphene oxide (GO) has been found to be a promising novel anticancer drug carrier. Here, we present our designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as a drug carrier, which was loaded with erlotinib and showed promising anticancer effects on NPC cells. METHODS: The effects of GO-PEG-erlotinib on the proliferation, migration, and invasion of NPC cells were investigated by WST-8 assay, wound healing assay, and invasion assay, respectively. RNA sequencing was conducted and analyzed to determine the molecular mechanisms by which GO-PEG-erlotinib affects NPC cells. RESULTS: Our results showed that GO-PEG-erlotinib reduced NPC cell viability in a dose-dependent manner and also inhibited the migration and invasion of NPC cells. The RNA sequencing revealed several related molecular mechanisms. CONCLUSION: GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be a potential therapeutic agent for treating NPC in the future.

Podoplanin, a Potential Therapeutic Target for Nasopharyngeal Carcinoma.

INTRODUCTION: The role of podoplanin (PDPN) in nasopharyngeal carcinoma (NPC) is still unknown. The aims of this study were to investigate the expression and role of PDPN in NPC cells. MATERIALS AND METHODS: Immunofluorescence staining and functional tests were used to determine the effects of PDPN knockdown by siRNA in TW01 NPC cells. Microarray analysis was conducted to identify genes regulated by PDPN. The molecular mechanism of PDPN on NPC cells was further determined by Ingenuity Pathways Analysis (IPA). RESULTS: PDPN was expressed in most TW01 NPC cells. PDPN knockdown by siRNA decreased NPC cell proliferation, migration, and invasion. The microarray data showed 63 upregulated genes and 12 downregulated genes following PDPN knockdown. The top 5 most upregulated genes analyzed by IPA were IFI27, IFI44L, IFI6, OAS1, and TRIM22, and the most relevant pathway was the interferon signaling pathway. CONCLUSIONS: To the best of our knowledge, this is the first report to show that knocking down PDPN leads to suppression of NPC cell proliferation, migration, and invasion. Our results suggest that PDPN may serve as a potential chemotherapeutic target for NPC treatment in the future.

Second primary malignancies in squamous cell carcinomas of the tongue and larynx: an analysis of incidence, pattern, and outcome.

BACKGROUND: Head and neck cancer patients have a higher risk of developing a second primary malignancy (SPM) than the general population. This study was conducted to identify the characteristics of SPM and its impact on survival in patients with squamous cell carcinoma of the tongue (TSCC) and larynx (LSCC). METHODS: A retrospective study was conducted of 538 patients who were treated by surgery primarily for TSCC (n = 146) and LSCC (n = 392) from 1990 to 2000. The incidence, site, and overall survival of SPMs were evaluated. RESULTS: Seventy-seven patients developed SPM during the follow-up period (median, 73 months), including 18 (12%) with TSCC and 59 (15%) with LSCC. Fifty-six percent of SPMs of the TSCC group appeared in the oral cavity. Among the SPMs of LSCC patients, 54% developed in the lung (31%) and larynx (24%). The 5-year overall survival after the diagnosis of SPM in the head and neck was 39%, compared to 29% for SPM in other areas (p = 0.010). CONCLUSION: SPMs after treatment of TSCC and LSCC are similar in incidence but distinct in pattern. SPMs within the head and neck are associated with a better prognosis than those outside this area.