Organizational Leadership Gender Differences in Medical Schools and Affiliated Universities.

Objective: To compare gender compositions in the leadership of the top 25 medical schools in North America with the leadership of their affiliated university senior leadership and other faculties. Materials and Methods: This retrospective cross-sectional observational study used publicly available gender data from 2018 to 2019 of universities drawn from the U.S. News Best Global Universities for Clinical Medicine Ranking report. Gender compositions in eight leadership tiers from senior leadership to medical school department directors were analyzed. Data analysis included gender compositions by leadership tier and faculty. Results: Male representation is greater at higher leadership tiers, with the largest imbalance being at the level of medical school department heads. The faculty of medicine has more men in leadership positions than the average of the other faculties (p = 0.02), though similar to schools of engineering, business, dentistry, and pharmacy. Across the eight leadership tiers, a significant trend exists between tier and proportions, indicating that male representation was greater at higher tiers (p < 0.001). No correlation was found between a university's leadership gender composition and its ranking. Conclusion: The under-representation of women is greater in medical school leadership than the leadership of their affiliated universities. The faculty of medicine has greater male over-representation than the average of the other faculties.

Patients' understanding of long-term cardiovascular risks and associated health-seeking behaviours after pre-eclampsia.

OBJECTIVE: The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants' knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension. METHODS: We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy. RESULTS: 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p<0.01), and at least one assessment of blood cholesterol (p<0.01), blood glucose (p=0.03) and renal function (p=0.01). Participants who were aware were more likely to be taking antihypertensive medication (24.5% vs 6.6%, p<0.01) since pregnancy, compared with those who were unaware. There were no differences between groups in diet, exercise or smoking habits. CONCLUSION: Among our study cohort, risk awareness was associated with increased health-seeking behaviours. Participants who were aware of their increased risk of cardiovascular disease were more likely to have regular cardiovascular risk factor assessments. They were also more likely to be taking antihypertensive medication.

ChemFOnt: the chemical functional ontology resource.

The Chemical Functional Ontology (ChemFOnt), located at https://www.chemfont.ca, is a hierarchical, OWL-compatible ontology describing the functions and actions of >341 000 biologically important chemicals. These include primary metabolites, secondary metabolites, natural products, food chemicals, synthetic food additives, drugs, herbicides, pesticides and environmental chemicals. ChemFOnt is a FAIR-compliant resource intended to bring the same rigor, standardization and formal structure to the terms and terminology used in biochemistry, food chemistry and environmental chemistry as the gene ontology (GO) has brought to molecular biology. ChemFOnt is available as both a freely accessible, web-enabled database and a downloadable Web Ontology Language (OWL) file. Users may download and deploy ChemFOnt within their own chemical databases or integrate ChemFOnt into their own analytical software to generate machine readable relationships that can be used to make new inferences, enrich their omics data sets or make new, non-obvious connections between chemicals and their direct or indirect effects. The web version of the ChemFOnt database has been designed to be easy to search, browse and navigate. Currently ChemFOnt contains data on 341 627 chemicals, including 515 332 terms or definitions. The functional hierarchy for ChemFOnt consists of four functional 'aspects', 12 functional super-categories and a total of 173 705 functional terms. In addition, each of the chemicals are classified into 4825 structure-based chemical classes. ChemFOnt currently contains 3.9 million protein-chemical relationships and ∼10.3 million chemical-functional relationships. The long-term goal for ChemFOnt is for it to be adopted by databases and software tools used by the general chemistry community as well as the metabolomics, exposomics, metagenomics, genomics and proteomics communities.

Long-term results of robotic-assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy. METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow-up period for all patients were 38 months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively. CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.

Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia.

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7-327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.

Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability.

SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function. Specifically, we used multiplex phospho-flow cytometry to measure variant impact on protein stability, pERK, pGSK3ß, pp38, pCREB, and high-content imaging to examine subcellular localization. We find variants ranging from complete loss-of-function (LoF) to wild-type (WT)-like in their regulation of pERK and pGSK3ß, while all variants retain at least partial ability to dephosphorylate pCREB. Interestingly, our assays reveal that a larger proportion of variants located within the disordered domain of unknown function (DUF) comprising the C-terminal half of SYNGAP1 exhibited higher LoF, compared to variants within the better studied catalytic domain. Moreover, we find protein instability to be a major contributor to dysfunction for only two missense variants, both located within the catalytic domain. Using high-content imaging, we find variants located within the C2 domain known to mediate membrane lipid interactions exhibit significantly larger cytoplasmic speckles than WT SYNGAP1. Moreover, this subcellular phenotype shows both correlation with altered catalytic activity and unique deviation from signaling assay results, highlighting multiple independent molecular mechanisms underlying variant dysfunction. Our multidimensional dataset allows clustering of variants based on functional phenotypes and provides high-confidence, multi-functional measures for making pathogenicity predictions.

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management.

PURPOSE: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027. PATIENTS AND METHODS: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. RESULT: Robust expansion of CAR-T cells along with rapid eradication of CD7+ T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed. CONCLUSIONS: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.

A Hybrid Intrusion Detection Model Combining SAE with Kernel Approximation in Internet of Things.

Owing to the constraints of time and space complexity, network intrusion detection systems (NIDSs) based on support vector machines (SVMs) face the "curse of dimensionality" in a large-scale, high-dimensional feature space. This study proposes a joint training model that combines a stacked autoencoder (SAE) with an SVM and the kernel approximation technique. The training model uses the SAE to perform feature dimension reduction, uses random Fourier features to perform kernel approximation, and then random Fourier mapping is explicitly applied to the sub-sample to generate the random feature space, making it possible to apply a linear SVM to uniformly approximate to the Gaussian kernel SVM. Finally, the SAE performs joint training with the efficient linear SVM. We studied the effects of an SAE structure and a random Fourier feature on classification performance, and compared that performance with that of other training models, including some without kernel approximation. At the same time, we compare the accuracy of the proposed model with that of other models, which include basic machine learning models and the state-of-the-art models in other literatures. The experimental results demonstrate that the proposed model outperforms the previously proposed methods in terms of classification performance and also reduces the training time. Our model is feasible and works efficiently on large-scale datasets.

Recommendations for surgical management of recurrent nasopharyngeal carcinoma during COVID-19 pandemic.

Nasopharyngeal carcinoma is endemic in southern parts of China including Hong Kong. Primary treatment entails radiotherapy ± chemotherapy depending on disease stage at presentation. Surgery is offered as a means of salvage for persistent and recurrent disease. Comprehensive preoperative work-up, careful patient selection, attention to details perioperation and multidisciplinary approach is essential in ensuring optimal outcomes after salvage surgery for recurrent nasopharyngeal carcinoma patients. Since the COVID-19 outbreak, we are faced with unprecedented challenges with priorities of care and resources being shifted to combat the virus. These include patient selection and timing of treatment, while preventing disease transmission to heath care providers. Practices and recommendations made in this document are intended to support safe clinical practice and efficient use of resources during this challenging time.

PathBank: a comprehensive pathway database for model organisms.

PathBank (www.pathbank.org) is a new, comprehensive, visually rich pathway database containing more than 110 000 machine-readable pathways found in 10 model organisms (Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, Escherichia coli and Pseudomonas aeruginosa). PathBank aims to provide a pathway for every protein and a map for every metabolite. This resource is designed specifically to support pathway elucidation and pathway discovery in transcriptomics, proteomics, metabolomics and systems biology. It provides detailed, fully searchable, hyperlinked diagrams of metabolic, metabolite signaling, protein signaling, disease, drug and physiological pathways. All PathBank pathways include information on the relevant organs, organelles, subcellular compartments, cofactors, molecular locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to the rich data contained in public chemical databases such as HMDB or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All PathBank pathways are accompanied with references and detailed descriptions which provide an overview of the pathway, condition or processes depicted in each diagram. Every PathBank pathway is downloadable in several machine-readable and image formats including BioPAX, SBML, PWML, SBGN, RXN, PNG and SVG. PathBank also supports community annotations and submissions through the web-based PathWhiz pathway illustrator. The vast majority of PathBank's pathways (>95%) are not found in any other public pathway database.

Surgical Treatment of Advanced Staged Hypopharyngeal Cancer.

It is not uncommon for patients with hypopharyngeal cancer to present at an advanced stage of disease. Surgical treatment provides a cure for the tumour with immediate relief from obstruction to the airway and the swallowing passage. Careful planning of surgery is important to ensure good outcome of treatment and prevent complications, some of which may be fatal. The shape of the hypopharynx resembles that of a funnel, with a wide circumference above in continuity with the oropharynx, and a small circumference below where it joins with the cervical oesophagus. As a result, while small tumours require the partial removal of the hypopharynx, large tumours, especially those involving the post-cricoid region, warrant a complete, circumferential pharyngectomy. For tumours that invade the cervical esophagus, transcervical approach is still feasible, and this is facilitated by the removal of the manubrium, allowing access to the tumour and resection with clear margins. In the presence of synchronous tumours lower down in the esophagus, pharyngo-laryngo-esophagectomy is indicated. Successful reconstruction of defects after tumour extirpation allows proper wound healing and early delivery of adjuvant radiotherapy. It is also important to ensure quick recovery of the long-term swallowing function. It ranges from the use of the soft tissue flap with skin island that is sutured as a patch to the remnants of the pharyngeal mucosa, to the use of a visceral flap, such as the free jejunal flap, to repair the circumferential pharyngectomy defects. The treatment protocol is personalized according to the extent of the tumour and the characteristics of the patients.

Surgical salvage of recurrent T3 nasopharyngeal carcinoma: Prognostic significance of clivus, maxillary, temporal and sphenoid bone invasion.

BACKGROUND: To study the efficacy of surgery for recurrent T3 nasopharyngeal carcinoma (NPC) and to determine the prognostic significance of various skull base bone invasion. METHOD: Retrospective view of the surgical outcome for recurrent T3 NPC. Kaplan Meier and log rank tests were used to determine the 5-year overall and disease specific survival. Multivariate analysis was used to identify significant independent prognostic factors that affect the surgical outcome. RESULTS: Between 1990 and 2017, 208 patients with recurrent T3 NPC were recruited. Salvage surgery was performed via the endoscopic endonasal approach (n = 22, 10.6%), endoscopic transpterygoid approach (n = 63, 30.3%) and the maxillary swing approach (n = 123, 59.1%). Thirty-eight (18.3%) patients required vascular bypass. The skull base bone involved by the tumours included: maxillary sinus (n = 13), clivus (n = 36), pterygoid process (n = 61), sphenoid sinus (n = 30), petrous part of the temporal bone (n = 42) and a combination of the above (n = 26). The mean follow-up duration was 41.7 months. Multivariate analysis identified tumours involving with both cortexes of the clivus and the lateral wall of the sphenoid sinus, as well as positive bone resection margins as the significant independent prognostic factors for surgical outcome. CONCLUSION: Outcome of surgical salvage is significantly worse for tumours that involve multiple bones at the skull base, particularly when both cortexes of the clivus and the lateral wall of the sphenoid sinus are invaded. Indication of aggressive surgery in such circumstances is controversial.

Real time indocyanin green near infrared lymphangiography for the reduction of drainage volume after neck dissection.

BACKGROUND: To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of drainage after neck dissection. METHODS: Patients with oral cavity squamous cell carcinoma were randomized into Group A (study group) and Group B (control). In the study group, upon the completion of neck dissection, a total of 2.5 mg of ICG was injected submucosally at the four quadrants around the tumour. Another 2.5 mg of ICG was injected subdermally in the groin bilaterally. The neck was screened using Near Infrared fluorescence. The presence of lymphatic leakage was noted and plicated with silk stitches. The total drainage volume of post-operative day 1, day 2 and the total accumulated volume until drain removal was measured. RESULTS: Twenty-two patients (Group A, n = 12; Group B, n = 10) were recruited. All patients in Group A had at least one site of lymphatic leakage identified. One patient in Group B developed chylous fistula and was excluded from analysis. The mean total drain output for day 1 and 2 after surgery, as well as the mean total output before drain removal, were significantly lower in Group A (22.4 ml vs. 86.2 ml [p = .02]; 14.2 ml vs. 72.8 ml [p = .02]; and 58.4 ml vs. 392 ml [p = .01], respectively), allowing earlier drain removal (2.2 days vs. 7.2 days, p = .02). CONCLUSIONS: Intra-operative ICG lymphangiography is useful in the reduction of drainage volume after neck dissection for caners in the head and neck region.

Stage II recurrent nasopharyngeal carcinoma: Prognostic significance of retropharyngeal nodal metastasis, parapharyngeal invasion, and carotid encasement.

BACKGROUND: The purpose of this study was to assess the predictability of the American Joint Committee on Cancer (AJCC) staging system on patients with stage II recurrent nasopharyngeal carcinoma (NPC). METHOD: We conducted a retrospective review of the surgical outcome for patients with recurrent NPC and retropharyngeal lymph node (RLN) metastasis (group I), recurrent NPC and parapharyngeal space (PPS) invasion (group II), and recurrent NPC and internal carotid artery (ICA) encasement (group III). RESULTS: Between 1990 and 2013, 145 patients received an operation for stage II recurrent NPC (group I, n = 62; group II, n = 65; and group III, n = 18). The rate of local tumor recurrence was significantly higher in groups II and III. The rate of systemic metastasis was significantly higher in group III (16.7%). Accordingly, the 5-year overall survival was significantly worse for patients in group III (group I: 81.2%; group II: 68.4%; and group III: 48.5%). CONCLUSION: The significantly worse prognosis of recurrent NPC encasing the ICA warrants an upstage to the T3 classification in the current AJCC staging system.

Three-dimensional endoscopy for endoscopic salvage nasopharyngectomy: Preliminary report of experience.

BACKGROUND: Prospective, observational study to assess the efficacy of salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma (NPC) via the endoscopic endonasal approach using a three-dimensional (3D) high-definition endoscopic system. METHODS: Between 2016 and 2017, 30 patients with recurrent NPC were recruited. Patient demographics, tumor characteristics, and perioperative data were recorded. Instrument ergonomics and perceived advantages were assessed by the operating, assisting, and observing surgeons. RESULTS: The majority (70%) of patients received radiotherapy alone as the initial treatment for NPC, and tumor recurred after a mean interval of 16.8 months. The tumor (T) classifications of the recurrent (R) tumors were: RT1: 46.7%; RT2: 33.3%; and RT3: 20.0%. The mean operative time was 293.3 minutes, and no conversion to open approach was necessary. Internal carotid artery dissection was required in nine patients, and the resection and repair of dura was required in six patients. The most common method of reconstruction was free vastus lateralis flap (46.7%). Microscopically clear resection margins were achieved in 73.3% of patients. The mean hospital stay was 6.8 days. There was no hospital mortality. One patient developed minor secondary hemorrhage, whereas the other developed transient contralateral vocal cord paralysis. On quantitative assessment, surgeons noticed a significant advantage of the 3D system with regard to depth and size perception, anatomy identification, and hand-eye coordination, whereas there was no significant difference in terms of strain sensation and dizziness. CONCLUSION: The 3D high-definition endoscopic system improves the precision of endoscopic nasopharyngectomy, particularly when dissection of the internal carotid artery and dura is required. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1386-1391, 2018.

Transoral robotic total laryngopharyngectomy and free jejunal flap reconstruction for hypopharyngeal cancer.

BACKGROUND: To report on the feasibility of total laryngopharyngectomy and free jejunal flap transfer for patient with hypopharyngeal cancer via the transoral robotic surgery (TORS) approach. MATERIAL AND METHODS: A patient with hypopharyngeal cancer involving the post-cricoid region is used for demonstration of the TORS total laryngopharyngectomy and free jejunal flap reconstruction. RESULTS: The procedure starts with a cruciate incision for terminal tracheostomy. The trachea and cervical esophagus is exposed and transected, making sure that the resection margins are adequate. This is followed by the transoral dissection using the robotic surgical system. The laryngopharyngectomy specimen is delivered and the free jejunal flap is replaced transorally. Jejuno-oesophageal suturing and the microvascular anastomosis are performed through the tracheostomy wound. The remaining pharyngo-jejunal anastomosis is performed transorally via the TORS approach. CONCLUSION: TORS total laryngopharyngectomy and free jejunal flap reconstruction is feasible and provides and alternative option to the traditional transcervical approach.

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis.

BACKGROUND: Programmed cell death protein 4 (PDCD4) is a novel tumor suppressor protein involved in programmed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical significance and prognostic value of PDCD4 in solid tumors. METHODS: A systematic literature review was performed to retrieve publications with available clinical information and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta-analysis Of Observational Studies in Epidemiology group. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's tests. RESULTS: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was significantly associated with the differentiation status of head and neck cancer (OR 4.25, 95% CI 1.87-9.66) and digestive system cancer (OR 2.87, 95% CI 1.84-4.48). Down-regulation of PDCD4 was significantly associated with short overall survival of patients with head and neck (HR: 3.44, 95% CI 2.38-4.98), breast (HR: 1.86, 95% CI 1.36-2.54), digestive system (HR: 2.12, 95% CI 1.75-2.56), and urinary system cancers (HR: 3.16, 95% CI 1.06-9.41). CONCLUSIONS: The current evidence suggests that PDCD4 down-regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be confirmed by large-scale prospective studies.

MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma.

MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC.

Extracranial/intracranial vascular bypass and craniofacial resection: New hope for patients with locally advanced recurrent nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the oncologic outcome and quality of life after surgical treatment of locally advanced (rT3-rT4) recurrent nasopharyngeal carcinoma (NPC) using the staged extracranial/intracranial vascular bypass and combined craniofacial approach. METHODS: We conducted a prospective study. RESULTS: Between 1998 and 2013, 28 patients with rT3 to rT4 tumors were treated with the proposed surgical protocol. Clear resection margin was achieved in 46.4%. The median follow-up was 42.6 months. The rate of local recurrence was 17.8%. The 5-year overall survival was 52%. There was no change in the mean global health system score after the extensive surgery, although the physical functioning scores deteriorated significantly. The most common symptoms experienced by patients were speech and swallowing problems. CONCLUSION: The proposed surgical treatment for locally advanced recurrent NPC was associated with satisfactory local tumor control and survival. Quality of life after surgery was reasonable, although multidisciplinary training was required to maximize the postoperative speech and swallowing function. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1404-E1412, 2016.