Point-of-care AI-enhanced novice echocardiography for screening heart failure (PANES-HF).

The increasing prevalence of heart failure (HF) in ageing populations drives demand for echocardiography (echo). There is a worldwide shortage of trained sonographers and long waiting times for expert echo. We hypothesised that artificial intelligence (AI)-enhanced point-of-care echo can enable HF screening by novices. The primary endpoint was the accuracy of AI-enhanced novice pathway in detecting reduced LV ejection fraction (LVEF) < 50%. Symptomatic patients with suspected HF (N = 100, mean age 61 ± 15 years, 56% men) were prospectively recruited. Novices with no prior echo experience underwent 2-weeks' training to acquire echo images with AI guidance using the EchoNous Kosmos handheld echo, with AI-automated reporting by Us2.ai (AI-enhanced novice pathway). All patients also had standard echo by trained sonographers interpreted by cardiologists (reference standard). LVEF < 50% by reference standard was present in 27 patients. AI-enhanced novice pathway yielded interpretable results in 96 patients and took a mean of 12 min 51 s per study. The area under the curve (AUC) of the AI novice pathway was 0.880 (95% CI 0.802, 0.958). The sensitivity, specificity, positive predictive and negative predictive values of the AI-enhanced novice pathway in detecting LVEF < 50% were 84.6%, 91.4%, 78.5% and 94.1% respectively. The median absolute deviation of the AI-novice pathway LVEF from the reference standard LVEF was 6.03%. AI-enhanced novice pathway holds potential to task shift echo beyond tertiary centres and improve the HF diagnostic workflow.

Impact of COVID-19 pandemic early response measures on myocardial infarctions and acute cardiac care in Singapore.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics.

On the removal efficiency of copper ions in wastewater using calcined waste eggshells as natural adsorbents.

Eggshells offer many advantages as adsorbents, such as affordability without special preparations other than pulverization and calcination. However, the manufacturing industry generally has a severe problem with high concentrations of heavy metals in wastewater. The purpose of this study was to use eggshell byproducts and calcined eggshell treatment for the adsorption of copper in an aqueous solution. The reaction time, metal concentration, adsorbent dose, temperature, and pH were evaluated using primary factors followed by the response surface method (RSM) to investigate the optimum conditions for eggshell byproducts and calcined eggshell adsorption treatment. The results of the one-factor-at-a-time experiment showed that the optimal adsorption rate was obtained from treatment at 24 h, 25 mg/L, 10 mg, and 25 °C. In addition, the effect of pH on the adsorption rates of eggshells and eggshells with membrane were detected at pH values of 5 and 5.9 and found to be 95.2, 90.5, and 73.3%. The reaction surface experiment showed that the best adsorption rate reached 99.3% after calcination at 900 °C for 2 h and a 20 min reaction. The results showed that eggshells, eggshell membranes, eggshells with membrane, and calcined eggshells could be applied to remove copper ions from industrial wastewater. The adsorption capacity of the calcined eggshell is better than that of the non-calcined eggshell and has good neutrality in acidic industrial wastewater. Therefore, it is convenient and practical for practical production and application. Likewise, this study conveys promising findings in the context of improving wastewater treatment based on a circular economy approach to waste reuse in the food industry and represents a valuable direction for future research.

Expression of Thymic Stromal Lymphopoietin in Immune-Related Dermatoses.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Quantitative analysis and prediction of urban heat island intensity on urban-rural gradient: A case study of Shanghai.

Urbanization causes enormous land use/land cover (LULC) changes, which have become significant drivers of land surface temperature (LST) change in rapidly urbanizing city, and the changes in LULC subsequently increase the LST to form urban heat island (UHI). This paper first identified the spatial distribution pattern of the LULC changes and surface urban heat island intensity (SUHII) in the study area in recent 20 years based on Landsat TM/OLI data. And later, the relationship between the distribution of impervious surface (IS) and vegetable coverage (VC) and SUHII was analyzed quantitatively. Then, the land cover and land surface temperature (LST) in Shanghai in 2027 under three development modes were simulated and predicted based on FLUS model and geospatial analysis. The results showed that (1) Regional land cover and LST had obvious differences in gradient distribution from urban to rural areas, and the outer ring road (Ring3) was an obvious dividing line; (2) the proportion of IS and VC were significantly positively (|R| > 0.695) and negatively (|R| > 0.328) correlated with LST; (3) under the three different scenario development models, the ecological space protection model effectively regulated the SUHII, which was 15.91% less than the SUHII in 2017 (34% inside Ring3 and 14% outside Ring3). The results could provide a reference for the rational allocation of urban land and landscape optimization in reducing SUHII` in typical urbanized areas.

Acute lethal and sublethal effects of four insecticides on the lacewing (Chrysoperla sinica Tjeder).

The lacewing, Chrysoperla sinica, is an important predatory insect, which plays an important role in the integrated pest management of agroforestry pests. However, the extensive use of insecticides negatively affects C. sinica. The acute toxicity, risk level, and, sublethal effects on growth and production, predation ability, protective enzyme activity and genotoxicity of four insecticides: indoxacarb, emamectin benzoate, imidacloprid and lambda-cyhalothrin to C. sinica were studied. The results showed that all four insecticides had lethal toxicity to larvae of C. sinica. Among them, emamectin benzoate had the highest toxicity with LC50 value of 7.41 mg/L. The insecticides also had different effects on the growth and reproduction of C. sinica, of which lambda-cyhalothrin had the greatest impacts. Even at a very low LC1 concentration (3.37 mg/L), it had strong impacts on the growth, reproduction and predatory ability of C. sinica. The four insecticides also caused a decrease in the predatory ability of the lacewing, of which lambda-cyhalothrin had the greatest effect. During the larval stage, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were significantly decreased by the four insecticides. At the pupal and adult stages, the effects of the four insecticides on the activities of protective enzymes were different, and the activities of SOD, CAT and POD decreased or increased. Indoxacarb and lambda-cyhalothrin exposure induced DNA damage in the haemocytes of C. sinica and produced obvious genotoxicity. These results provide important scientific basis for the rational use of these insecticides and the protection and utilization of lacewing.

Two rare cases of synchronous and metachronous colonic metastases in patients with advanced gastric cancer.

BACKGROUND: Patients with advanced gastric cancer (GC) may ultimately die because GC mostly leads to synchronous or metachronous metastasis. However, colonic metastasis of GC is extremely rare. According to a PubMed search of papers published from May 1968 to March 2017, only 21 patients with GC (10 patients from 10 case reports and 11 patients from a retrospective study) have been found to have colonic metastasis. In this report, we present two cases of synchronous and metachronous colonic metastases of advanced GC. CASE PRESENTATION: Two patients with advanced GC received a diagnosis of colonic metastasis based on colonoscopic findings and computed tomography images, and the diagnosis was confirmed through pathological immunohistochemical analysis. Herein, we describe the management and outcomes of these metastases. CONCLUSIONS: Submucosal swelling and segmental bowel wall thickening observed through colonoscopy in patients with advanced GC might indicate colonic metastasis.

Specificity protein 1-modulated superoxide dismutase 2 enhances temozolomide resistance in glioblastoma, which is independent of O6-methylguanine-DNA methyltransferase.

Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants derived from MGMT-negative GBM clinical samples and cell lines were studied, revealing there to be increased specificity protein 1 (Sp1) expression associated with reduced reactive oxygen species (ROS) accumulation following TMZ treatment. Analysis of gene expression databases along with cell studies identified the ROS scavenger superoxide dismutase 2 (SOD2) as being disease-related. SOD2 expression was also increased, and it was found to be co-expressed with Sp1 in TMZ-resistant cells. Investigation of the SOD2 promoter revealed Sp1 as a critical transcriptional activator that enhances SOD2 gene expression. Co-treatment with an Sp1 inhibitor restored the inhibitory effects of TMZ, and decreased SOD2 levels in TMZ-resistant cells. This treatment strategy restored susceptibility to TMZ in xenograft animals, leading to prolonged survival in an orthotopic model. Thus, our results suggest that Sp1 modulates ROS scavengers as a novel mechanism to increase cancer malignancy and resistance to chemotherapy. Inhibition of this pathway may represent a potential therapeutic target for restoring treatment susceptibility in GBM.

Remote monitoring of patients with cardiac implantable electronic devices: a Southeast Asian, single-centre pilot study.

INTRODUCTION: Remote monitoring of cardiac implantable electronic devices (CIED) has been shown to improve patient safety and reduce in-office visits. We report our experience with remote monitoring via the Medtronic CareLink(®) network. METHODS: Patients were followed up for six months with scheduled monthly remote monitoring transmissions in addition to routine in-office checks. The efficacy of remote monitoring was evaluated by recording compliance to transmissions, number of device alerts requiring intervention and time from transmission to review. Questionnaires were administered to evaluate the experiences of patients, physicians and medical technicians. RESULTS: A total of 57 patients were enrolled; 16 (28.1%) had permanent pacemakers, 34 (59.6%) had implantable cardioverter defibrillators and 7 (12.3%) had cardiac resynchronisation therapy defibrillators. Overall, of 334 remote transmissions scheduled, 73.7% were on time, 14.5% were overdue and 11.8% were missed. 84.6% of wireless transmissions were on time, compared to 53.8% of non-wireless transmissions. Among all transmissions, 4.4% contained alerts for which physicians were informed and only 1.8% required intervention. 98.6% of remote transmissions were reviewed by the second working day. 73.2% of patients preferred remote monitoring. Physicians agreed that remote transmissions provided information equivalent to in-office checks 97.1% of the time. 77.8% of medical technicians felt that remote monitoring would help the hospital improve patient management. No adverse events were reported. CONCLUSION: Remote monitoring of CIED is safe and feasible. It has possible benefits to patient safety through earlier detection of arrhythmias or device malfunction, permitting earlier intervention. Wireless remote monitoring, in particular, may improve compliance to device monitoring. Patients may prefer remote monitoring due to possible improvements in quality of life.

[Effect of Rapamycin on Expression of Survivin and Caspase-3 and Its Influence on K562 Cell Ultrastructure].

OBJECTIVE: To investigate the effect of rapamycin on the expression of survivin and caspase-3 at mRNA level in K562 cells and the influence of rapamycin on K562 cell ultrastructure. METHODS: The effects of rapamycin at various concentration on K562 cell proliferation were analyzed by CCK8; the morphological characteristics of K562 cells was observed by transmission electron microscopy; the expression of survivin and caspase-3 at mRNA level in K562 cells treated with rapamycin was detected by RT-PCR. RESULTS: The proliferation of K562 cells was significantly inhibited by rapamycin. The apoptosis level of K562 cells increased with increase of rapamycin concentration, the expression of survivin at mRNA level decreased with increase of rapamycin concentration (P < 0.05). The expression of caspase-3 at mRNA level increased with increase of rapamycin concentration. CONCLUSION: Rapamycin can prornote K562 cell apoptosis through up-regulating caspase-3 level and reduceing survivin level.

STMN1 overexpression correlates with biological behavior in human cutaneous squamous cell carcinoma.

Stathmin 1 (STMN1) is an important molecule in regulating cellular microtubule dynamics and promoting microtubule depolymerization in interphase and late mitosis. Evidences showed that STMN1 was up-regulated in many cancers, but there was no report about the roles of STMN1 in human cutaneous squamous cell carcinoma (cSCC). Here, we confirmed significant upregulation of STMN1 in cSCC tissues and cell lines compared with non-tumor counterparts. STMN1 upregulation was associated with the proliferation, migration, invasion and apoptosis of cSCC cells. The results suggested that STMN1 may play an important role in the development and tumor progression of cSCC.

Electrophysiologic monitoring correlates of recurrent laryngeal nerve heat thermal injury in a porcine model.

OBJECTIVES/HYPOTHESIS: Thermal injury to the recurrent laryngeal nerve (RLN) may not be visually apparent and may go unrecognized intraoperatively. This study aimed to investigate the heat thermal tolerance of RLN and evaluate the electrophysiologic correlates of electromyographic (EMG) signal change during an acute RLN heat damage. STUDY DESIGN: Prospective porcine model with continuous intraoperative neuromonitoring (CIONM). METHODS: Ten pigs (20 RLNs) undergoing CIONM had their EMG tracings recorded and correlated with heated normal saline (NS) irrigation of varying temperature and duration. RESULTS: In the initial pilot study, the EMG was without change during incremental heated NS irrigation (40/45/50/55 °C for 60 seconds), but adverse EMG combined events (CE) (amplitude decrease with a concordant latency increase) occurred and degraded to loss of signal (LOS) (by 17.5 ± 1.3 seconds) when the temperature was elevated to 60 °C (n = 4). Another 16 RLNs were evaluated to further compare the EMG pattern after various degrees of thermal stress (60/70 °C for 30/20 seconds). Electromyographic recordings showed CEs and LOS in all RLNs, and only six of eight RLNs with 60 °C exposure showed slight EMG amplitude recovery (16%-35%) after 20 minutes. None of the injured nerve segments were visually apparent, but all were detectable by IONM. CONCLUSION: Sixty degrees Celsius is a critical temperature to cause RLN thermal injury. Continuous intraoperative neuromonitoring can be used as a tool for the early detection of acute thermal stress and may guide use of energy-based devices during thyroid procedures. LEVEL OF EVIDENCE: N/A.

Expression and Function of HAX-1 in Human Cutaneous Squamous Cell Carcinoma.

HAX-1 is an anti-apoptotic factor and overexpressed in many types of cancers. However, the functional role of HAX-1 in human cutaneous squamous cell carcinoma (cSCC) remains unclear. Our aim was to investigate the expression of HAX-1 in cSCC and its relationship with the development of cSCC. HAX-1 expression in cSCC tissues and in-vitro cell models were evaluated by real-time quantitative PCR (RT-qPCR), Western blot and immunohistochemistry. And the RNAi strategy was used to observe the relationship of HAX-1 and cSCC in A431 cells. The mRNA and protein level of HAX-1 were significantly higher in cSCC compared with normal tissue. There were significant differences in thickness (P=0.014), differentiation (P=0.027) and TNM stages (P=0.007). After knockdown the expression of HAX-1 by siRNA, the proliferation and the motility of A431 cell was inhibited obviously, and the apoptosis of A431 cells were induced too. HAX-1 may be a risk factor for patients with cSCC. As a potential tumor promoter in cSCC, HAX-1 may be a novel potential therapeutic target for cSCC treatment and deserves further investigation.

Postoperative wound infection after posterior spinal instrumentation: analysis of long-term treatment outcomes.

PURPOSE: Postoperative spinal implant infection (PSII) places patients at risk for pseudarthrosis, correction loss, spondylodiscitis, adverse neurological sequelae, and even death; however, prognostic factors that predict long-term treatment outcomes have not been clearly investigated. In addition, few studies concerning the feasibility of reconstructing the failed spinal events have been published. METHODS: We performed a cohort study of 51 patients who contracted PSII in the posterolateral thoracolumbar region at a single tertiary center between March 1997 and May 2007. Forty-seven patients (92.2 %) had one or more medical problems. Isolated bacterial species, infection severity, treatment timing, and hosts' defense response were evaluated to assess their relationship with management outcomes. The use of implant salvage, or removal subsequent with a revision strategy depended on the patient's general conditions, infection control, and implant status for fusion. RESULTS: The most common infective culprit was Staphylococcus spp. found in 35 of 60 (58.3 %) isolates, including 20 methicillin-resistant species. Gram-negative bacilli and polymicrobial infection were found significantly in patients presenting early-onset, deep-site infection and myonecrosis. Prompt diagnosis and aggressive therapy were responsible for implant preservation in 41 of 51 cases (80.4 %), while implant removal noted in 10 cases (19.6 %) was attributed to delayed treatment and uncontrolled infection with implant loosening, correction loss, or late infection with spondylodesis. The number of employed debridements alone was not significantly correlated with successful implant preservation. Delayed treatment for infection >3 months significantly led to implant removal (p < 0.05) and a higher number of failed spinal events. Patients with significant comorbidities, malnutrition, severe trauma, neurological deficits, long-level instrumentation, and delayed treatment had poor outcomes. Sixteen patients (31.4 %) exhibited probable nonunion or pseudarthrosis, and eight symptomatic patients among them underwent successful revision surgery. CONCLUSIONS: Retention of the mechanically sound implants in early-onset infection permits fusion to occur, while delayed treatment, severe malnutrition and multiple comorbidities will most likely result in a lack of effectiveness in eradicating the infecting pathogens. Restoring optimal physiological conditions is imperative in high-risk patients to allow for further healing. When loosened screws cause peridiscal erosion and incapacitating motion pain, premature implant removal possibly results in failed fusion and correction loss. Reconstruction for a failed spinal event is feasible following infection control.

Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance.

BACKGROUND: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. RESULTS: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. CONCLUSIONS: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.

Xanthogranulomatous prostatitis: a rare entity resembling prostate adenocarcinoma with magnetic resonance image picture.

Granulomatous prostatitis, characterized by chronic granulomatous inflammation in the prostate, is rare. Xanthogranulomatous prostatitis is an even rarer granulomatous inflammation. We present a 74-year-old man who presented with lower urinary tract symptoms and elevated prostate specific antigen. A transrectal ultrasonography-guided prostate biopsy was performed, and pathological results showed foamy macrophage and inflammatory cell infiltrates, which were a distinctive feature of xanthogranulomatous prostatitis. We also present the characteristics of magnetic resonance imaging in xanthogranulomatous prostatitis which has never been previously described.

Indicators associated with coronary atherosclerosis in metabolic syndrome.

BACKGROUND: Metabolic factors associated with coronary atherosclerosis (CA) in metabolic syndrome (MetS) remain unclear. METHODS: A total of 550 consecutive subjects without documented coronary artery disease who received contrast-enhanced coronary computed tomography angiography were analyzed. CA was defined as coronary artery calcification (CAC) scores >0 or, zero CAC score combining noncalcified plaques within the proximal third segment of major coronary arteries. Metabolic factors and novel atherosclerotic biomarkers including high-sensitive C-reactive protein (hs-CRP) and adiponectin were measured. MetS was recognized according to the ethnicity-specific National Cholesterol Educational Program Adult Treatment Panel III, 2001. RESULTS: After adjusted with novel atherosclerotic biomarkers, MetS was significantly associated with CA Odds ratio [OR], 2.88; 95% confidence interval [CI], 1.88 to 4.42; p<0.001). Subgroup analysis revealed that fasting blood glucose ≥ 110 mg/dl/diabetes mellitus in non-MetS subjects (OR, 1.40; 95%CI, 1.08 to 1.82; p<0.05) and total cholesterol (TC)/high density lipoprotein-cholesterol (HDL-C) ≥ 4.2 in MetS subjects (OR, 4.44; 95%CI, 1.93 to 10.20; p<0.001) were independently associated with CA. Both indicators were significantly associated with increased serum hs-CRP and reduced adiponectin levels in all subjects. CONCLUSIONS: MetS is independently associated with CA after adjustment of atherosclerotic biomarkers. TC/HDL-C ≥ 4.2 in MetS and fasting blood glucose ≥ 110 mg/dl/diabetes mellitus in non-MetS subjects are independent indicators of CA, suggesting the potential difference in pathophysiology of CA.

Ectomesenchymal chondromyxoid tumor of tongue.

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare entity of the dorsal tongue first described in 1995. Herein, we report a rare case of lingual ECMT in a 41-year-old man. Patient presented with an asymptomatic, small nodule (0.5 cm in diameter) in the anterior tongue. The pathological findings showed uni-lobular proliferation of fusiform cells, arranged in net-like sheets or swirls, in a chondromyxoid background. The tumor cells were immunoreactive for S-100 and glial fibrillary acidic protein (GFAP), but negative for epithelial markers. Familiarity with this entity helps pathologists make a correct diagnosis.

Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo.

PURPOSE: Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently accounts for the tumorigenesis in head and neck cancer. To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells. EXPERIMENTAL DESIGN: The in vitro antitumor effect of BGT226 was determined in various cancer cell lines. Animal models were also applied to examine drug potency. The inhibitory ability of BGT226 on the PI3K/AKT/mTOR signaling pathway was analyzed. RESULTS: The growth inhibition assay revealed that BGT226 was active against all tested cancer cell lines. Cross-resistance was not observed in the cisplatin-resistant cell line. The activation of the AKT/mTOR signal cascade was suppressed by BGT226 in a concentration- and time-dependent manner. Flow cytometric analysis revealed an accumulation of cells in the G(0)-G(1) phase with concomitant loss in the S-phase. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and the analysis of caspase 3/7 and PARP indicated that BGT226 induced cancer cell death through an apoptosis-independent pathway. BGT226 induced autophagy as indicated by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3-methyladenine, inhibited the BGT226-induced autophagy and led to the retrieval of colony survival. In a xenografted animal model, BGT226 significantly delayed tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase and the presence of autophagosome formation. CONCLUSIONS: These data indicate that BGT226 is a potential drug in the treatment of head and neck cancer.