Intelligent method to predict intensive care unit admission after drainage operation in patients with deep neck space abscess: A multicenter retrospective study.

BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.

Real-time detection of laryngopharyngeal cancer using an artificial intelligence-assisted system with multimodal data.

BACKGROUND: Laryngopharyngeal cancer (LPC) includes laryngeal and hypopharyngeal cancer, whose early diagnosis can significantly improve the prognosis and quality of life of patients. Pathological biopsy of suspicious cancerous tissue under the guidance of laryngoscopy is the gold standard for diagnosing LPC. However, this subjective examination largely depends on the skills and experience of laryngologists, which increases the possibility of missed diagnoses and repeated unnecessary biopsies. We aimed to develop and validate a deep convolutional neural network-based Laryngopharyngeal Artificial Intelligence Diagnostic System (LPAIDS) for real-time automatically identifying LPC in both laryngoscopy white-light imaging (WLI) and narrow-band imaging (NBI) images to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists. METHODS: All 31,543 laryngoscopic images from 2382 patients were categorised into training, verification, and test sets to develop, validate, and internal test LPAIDS. Another 25,063 images from five other hospitals were used as external tests. Overall, 551 videos were used to evaluate the real-time performance of the system, and 200 randomly selected videos were used to compare the diagnostic performance of the LPAIDS with that of laryngologists. Two deep-learning models using either WLI (model W) or NBI (model N) images were constructed to compare with LPAIDS. RESULTS: LPAIDS had a higher diagnostic performance than models W and N, with accuracies of 0·956 and 0·949 in the internal image and video tests, respectively. The robustness and stability of LPAIDS were validated in external sets with the area under the receiver operating characteristic curve values of 0·965-0·987. In the laryngologist-machine competition, LPAIDS achieved an accuracy of 0·940, which was comparable to expert laryngologists and outperformed other laryngologists with varying qualifications. CONCLUSIONS: LPAIDS provided high accuracy and stability in detecting LPC in real-time, which showed great potential for using LPAIDS to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists.

Autophagy and Inflammation: Regulatory Roles in Viral Infections.

Autophagy is a highly conserved intracellular degradation pathway in eukaryotic organisms, playing an adaptive role in various pathophysiological processes throughout evolution. Inflammation is the immune system's response to external stimuli and tissue damage. However, persistent inflammatory reactions can lead to a range of inflammatory diseases and cancers. The interaction between autophagy and inflammation is particularly evident during viral infections. As a crucial regulator of inflammation, autophagy can either promote or inhibit the occurrence of inflammatory responses. In turn, inflammation can establish negative feedback loops by modulating autophagy to suppress excessive inflammatory reactions. This interaction is pivotal in the pathogenesis of viral diseases. Therefore, elucidating the regulatory roles of autophagy and inflammation in viral infections will significantly enhance our understanding of the mechanisms underlying related diseases. Furthermore, it will provide new insights and theoretical foundations for disease prevention, treatment, and drug development.

Network pharmacology-based exploration identified the antiviral efficacy of Quercetin isolated from mulberry leaves against enterovirus 71 via the NF-κB signaling pathway.

Introduction: Mulberry leaf (ML) is known for its antibacterial and anti-inflammatory properties, historically documented in "Shen Nong's Materia Medica". This study aimed to investigate the effects of ML on enterovirus 71 (EV71) using network pharmacology, molecular docking, and in vitro experiments. Methods: We successfully pinpointed shared targets between mulberry leaves (ML) and the EV71 virus by leveraging online databases. Our investigation delved into the interaction among these identified targets, leading to the identification of pivotal components within ML that possess potent anti-EV71 properties. The ability of these components to bind to the targets was verified by molecular docking. Moreover, bioinformatics predictions were used to identify the signaling pathways involved. Finally, the mechanism behind its anti-EV71 action was confirmed through in vitro experiments. Results: Our investigation uncovered 25 active components in ML that targeted 231 specific genes. Of these genes, 29 correlated with the targets of EV71. Quercetin, a major ingredient in ML, was associated with 25 of these genes. According to the molecular docking results, Quercetin has a high binding affinity to the targets of ML and EV71. According to the KEGG pathway analysis, the antiviral effect of Quercetin against EV71 was found to be closely related to the NF-κB signaling pathway. The results of immunofluorescence and Western blotting showed that Quercetin significantly reduced the expression levels of VP1, TNF-α, and IL-1ß in EV71-infected human rhabdomyosarcoma cells. The phosphorylation level of NF-κB p65 was reduced, and the activation of NF-κB signaling pathway was suppressed by Quercetin. Furthermore, our results showed that Quercetin downregulated the expression of JNK, ERK, and p38 and their phosphorylation levels due to EV71 infection. Conclusion: With these findings in mind, we can conclude that inhibiting the NF-κB signaling pathway is a critical mechanism through which Quercetin exerts its anti-EV71 effectiveness.

Nomogram to diagnosis of obstructive sleep apnoea-hypopnoea syndrome in high-risk Chinese adult patients.

INTRODUCTION: Many scales are designed to screen for obstructive sleep apnoea-hypopnoea syndrome (OSAHS); however, there is a lack of an efficiently and easily diagnostic tool, especially for Chinese. Therefore, we conduct a cross-sectional study in China to develop and validate an efficient and simple clinical diagnostic model to help screen patients at risk of OSAHS. METHODS: This study based on 782 high-risk patients (aged >18 years) admitted to the Sleep Medicine department of the Sixth Affiliated Hospital, Sun Yat-sen University from 2015 to 2021. Totally 34 potential predictors were evaluated. We divided all patients into training and validation dataset to develop diagnostic model. The univariable and multivariable logistic regression model were used to build model and nomogram was finally built. RESULTS: Among 602 high-risk patients with median age of 46 (37, 56) years, 23.26% were women. After selecting using the univariate logistic model, 15 factors were identified. We further used the stepwise method to build the final model with five factors: age, BMI, total bilirubin levels, high Berlin score, and symptom of morning dry mouth or mouth breathing. The AUC was 0.780 (0.711, 0.848), with sensitivity of 0.848 (0.811, 0.885), specificity of 0.629 (0.509, 0.749), accuracy of 0.816 (0.779, 0.853). The discrimination ability had been verified in the validation dataset. Finally, we established a nomogram model base on the above final model. CONCLUSION: We developed and validated a predictive model with five easily acquire factors to diagnose OSAHS patient in high-risk population with well discriminant ability. Accordingly, we finally build the nomogram model.

Construction of CpG Delivery Nanoplatforms by Functionalized MoS2 Nanosheets for Boosting Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.

Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI0.8k )-covered MoS2 nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll-like receptor-9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC). It is proved that functionalized nanosheets with medium size display similar CpG loading capacity regardless of low or high PEI0.8k coverage owing to the flexibility and crimpability of 2D backbone. CpG-loaded nanosheets with medium size and low charge density (CpG@MM -PL ) could promote the maturation, antigen-presenting capacity, and proinflammatory cytokines generation of bone marrow-derived dendritic cells (DCs). Further analysis reveals that CpG@MM -PL effectively boosts the TIME of HNSCC in vivo including DC maturation and cytotoxic T lymphocyte infiltration. Most importantly, the combination of CpG@MM -PL and ICB agents anti-programmed death 1 hugely improves the tumor therapeutic effect, inspiring more attempts for cancer immunotherapy. In addition, this work uncovers a pivotal feature of the 2D sheet-like materials in nanomedicine development, which should be considered for the design of future nanosheet-based therapeutic nanoplatforms.

Pattern and prognostic value of lymph node metastasis in sinonasal mucosal melanoma.

OBJECTIVE: To analyze the pattern of lymph node (LN) metastasis and its effect on prognosis in sinonasal mucosal melanoma (SNMM). METHODS: This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) Program data. Survival outcomes were analyzed using the Kaplan-Meier method. Factors were compared between groups using log-rank test and Fisher's exact test, and prognostic factors were screened using the Cox proportional hazards model. Propensity score matching (PSM) was conducted to examine the treatment differences after accounting for sex, age, race, T stage, N stage, and M stage. RESULTS: Level I (57.1%) and level II (53.6%) nodes were the most common sites of lymph node metastasis, followed by level III (17.9%) and IV (17.9%) nodes. T stage, M stage, and tumor size were associated with LN metastasis. The 5-year overall survival rates for patients without and with LN metastasis were 35.2% and 5.3%, respectively. CONCLUSIONS: Level I and II lymph nodes may be the sentinel nodes of SNMM, Advanced T stage and increasing tumor size could promote LN metastasis. LN metastasis may promote distant metastasis and remains an important prognostic factor for patients with SNMM.

Tumor size rather than the thyroid invasion affects the prognosis of parathyroid carcinoma without lymph node or distant metastasis.

PURPOSE: This study aimed to explore the prognostic value of thyroid invasion of parathyroid carcinoma without lymph node or distant metastasis. METHODS: Two hundred and nine cases of parathyroid carcinoma from the SEER (1989-2014) were eligible for this study. A Chi-squared test, t test, X-tile, Kaplan-Meier curves, and multivariate Cox proportional hazard regression were used for analysis. RESULTS: Thyroid invasion, sex, race, age, radiation, and surgery were not significantly associated with cancer-specific survival by multivariate analysis. However, tumor size ≥ 4 cm was significantly associated with worse cancer-specific survival (P < 0.001). CONCLUSION: Thyroid invasion, which was the criterion for T1 and T2 staging criteria of parathyroid carcinoma according to the AJCC, did not affect the prognosis of patients with parathyroid carcinoma without local lymph node or distant metastasis. Our study indicates that a tumor size ≥ 4 cm may be an appropriate indicator of T1 and T2 cancer staging.

Functional analysis of nuclear receptor HR96 gene in Bombyx mori exposed to phoxim.

The nuclear receptor (NRs) gene family functions as ligand-dependent transcription factors in a variety of animals, which participates in a variety of biological processes, such as cell differentiation, metabolic regulation, reproduction, development, insect metamorphosis. In this study, a nuclear receptor HR96 gene in silkworm Bombyx mori (BmHR96) was identified, and the responses of BmHR96 gene to 20-hydroxyecdysone (20E), three insecticides, and two disinfectants were analyzed and its function in phoxim exposure was explored.  Quantitative real-time polymerase chain reaction indicated that the expression of BmHR96 mRNA was the highest in ovary of 5th instar Day 3 silkworm larvae and in silk gland of the wandering stage. The expression patterns of BmHR96 gene in ovary, head, testis, and midgut of different stages were different. After injecting 20E into B. mori, the expression of BmHR96 mRNA had no significant difference compared with control. Three insecticides and two disinfectants were used to treat B. mori, respectively, and it was found that they had different influence patterns on the expression level of BmHR96. siRNA of BmHR96 was injected into silkworm larvae and the expression of BmHR96 was decreased significantly after injecting 72 h. After silencing of BmHR96, B. mori was fed with phoxim-treated leaves. The results showed that the mortality of B. mori after silencing of BmHR96 was significantly higher than the control. Our results indicated that HR96 plays an important role in regulating the stress response of phoxim.

Bacteriological analysis based on disease severity and clinical characteristics in patients with deep neck space abscess.

BACKGROUND: Deep neck space abscess (DNSA) is a serious infection in the head and neck. Antibiotic therapy is an important treatment in patients with DNSA. However, the results of bacterial culture need at least 48 h, and the positive rate is only 30-50%, indicating that the use of empiric antibiotic treatment for most patients with DNSA should at least 48 h or even throughout the whole course of treatment. Thus, how to use empiric antibiotics has always been a problem for clinicians. This study analyzed the distribution of bacteria based on disease severity and clinical characteristics of DNSA patients, and provides bacteriological guidance for the empiric use of antibiotics. METHODS: We analyzed 433 patients with DNSA who were diagnosed and treated at nine medical centers in Guangdong Province between January 1, 2015, and December 31, 2020. A nomogram for disease severity (mild/severe) was constructed using least absolute shrinkage and selection operator-logistic regression analysis. Clinical characteristics for the Gram reaction of the strain were identified using multivariate analyses. RESULTS: 92 (21.2%) patients developed life-threatening complications. The nomogram for disease severity comprised of seven predictors. The area under the receiver operating characteristic curves of the nomogram in the training and validation cohorts were 0.951 and 0.931, respectively. In the mild cases, 43.2% (101/234) had positive culture results (49% for Gram-positive and 51% for Gram-negative strains). The positive rate of cultures in the patients with severe disease was 63% (58/92, 37.9% for Gram-positive, and 62.1% for Gram-negative strains). Diabetes mellitus was an independent predictor of Gram-negative strains in the mild disease group, whereas gas formation and trismus were independent predictors of Gram-positive strains in the severe disease group. The positivity rate of multidrug-resistant strains was higher in the severe disease group (12.1%) than in the mild disease group (1.0%) (P < 0.001). Metagenomic sequencing was helpful for the bacteriological diagnosis of DNSA by identifying anaerobic strains (83.3%). CONCLUSION: We established a DNSA clinical severity prediction model and found some predictors for the type of Gram-staining strains in different disease severity cases. These results can help clinicians in effectively choosing an empiric antibiotic treatment.

Basaloid squamous cell carcinoma of the hypopharynx: an analysis of 213 cases.

PURPOSE: Basaloid squamous cell carcinoma (BSCC) is a rare aggressive variant of squamous cell carcinoma (SCC) with a poor prognosis. No large series of exclusively hypopharyngeal BSCC patients have been previously reported. Therefore, this retrospective population-based study aims to explain the patient demographics, clinicopathologic characteristics, incidence, and survival outcomes of hypopharyngeal BSCC and how it relates to conventional-type SCC. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database registry was queried for patients diagnosed with hypopharyngeal BSCC and conventional-type SCC between 2001 and 2016. RESULTS: The incidence of hypopharyngeal BSCC from 2001 to 2016 was 0.0161 per 100,000 individuals. The BSCC group comprised 213 patients, and the SCC group 7958 patients. The majority of BSCCs were considered high grade (Grade III/IV, 89.58%). Most BSCC patients were diagnosed at an advanced stage (American Joint Committee on Cancer [AJCC] stage IV, 65.38%). The 1-, 5-, and 10-year disease-specific survival (DSS) rates for hypopharyngeal BSCC were 84.10%, 57.40%, and 46.20%, respectively. Multivariate analysis, after adjustment for sex, age, race, tumor location, grade, and AJCC stage, showed that patients with BSCC had significantly better DSS than those with conventional-type SCC. Surgery with radiation contributed to a favorable DSS for BSCC patients in comparison with other treatments. CONCLUSION: This analysis of the largest hypopharyngeal BSCC series indicates a better prognosis for this pathologic type compared with conventional-type hypopharyngeal SCC. Multimodality treatment with surgery and radiation may result in a favorable prognosis for hypopharyngeal BSCC patients.

3D-printed dermis-specific extracellular matrix mitigates scar contraction via inducing early angiogenesis and macrophage M2 polarization.

Scar contraction frequently happens in patients with deep burn injuries. Hitherto, porcine dermal extracellular matrix (dECM) has supplied microenvironments that assist in wound healing but fail to inhibit scar contraction. To overcome this drawback, we integrate dECM into three-dimensional (3D)-printed dermal analogues (PDA) to prevent scar contraction. We have developed thermally gelled, non-rheologically modified dECM powder (dECMp) inks and successfully transformed them into PDA that was endowed with a micron-scale spatial structure. The optimal crosslinked PDA exhibited desired structure, good mechanical properties as well as excellent biocompatibility. Moreover, in vivo experiments demonstrated that PDA could significantly reduced scar contraction and improved cosmetic upshots of split thickness skin grafts (STSG) than the commercially available dermal templates and STSG along. The PDA has also induced an early, intense neovascularization, and evoked a type-2-like immune response. PDA's superior beneficial effects may attribute to their desired porous structure, the well-balanced physicochemical properties, and the preserved dermis-specific ECM cues, which collectively modulated the expression of genes such as Wnt11, ATF3, and IL1ß, and influenced the crucial endogenous signalling pathways. The findings of this study suggest that PDA is a clinical translatable material that possess high potential in reducing scar contraction.

Screening of Tumor Antigens and Construction of Immune Subtypes for mRNA Vaccine Development in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: A growing number of clinical studies have confirmed that mRNA vaccines are effective in the treatment of malignant tumors; however, their efficacy in head and neck squamous cell carcinoma (HNSCC) has not been determined. This study aimed to identify the potential antigens of HNSCC for mRNA vaccine development and further distinguish the immune subtypes of HNSCC to select suitable patients for vaccination. METHODS: We obtained gene expression profiles and corresponding clinical information of HNSCC from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We visualized the genetic alterations of potential antitumor antigens using cBioPortal and obtained the immune gene set from Immport. The correlation between the expression of the identified antigens and the infiltration of antigen-presenting cells was visualized by Tumor Immune Estimation Resource (TIMER). We evaluated the potential biological functions of different samples and described the immune landscape. RESULTS: Increased expression of three potential tumor antigens, CCR4, TMCO1, and SPACA4, associated with superior prognoses and infiltration of antigen-presenting cells, was identified in HNSCC. Three immune subtypes (C1-C3) with different molecular, cellular, and clinical characteristics were defined. Patients with C3 tumor had a better prognosis, representing an immune "cold" phenotype, which may be more suitable for mRNA vaccination. In addition, different immune characteristics were observed among the three immune subtypes, including markers of immune cells, mutation burden, expression of immune checkpoints, and immune modulators. Finally, the immune landscape of HNSCC showed a high degree of heterogeneity between individual patients. CONCLUSION: CCR4, TMCO1, and SPACA4 may be potential antigens for developing mRNA vaccines against HNSCC, especially for patients with C3 tumor. This study could provide a theoretical basis for the development of an mRNA vaccine against HNSCC.

Role of primary tumor resection in patients with metastatic medullary thyroid cancer who have unresectable distant metastases.

BACKGROUND: Whether patients with medullary thyroid carcinoma (MTC) who have unresectable synchronous distant metastases should undergo primary surgical resection (PTR) remains controversial. This study aimed to identify predictive factors associated with the survival of such patients. METHODS: We conducted a retrospective study of patients with MTC who were registered in the Surveillance, Epidemiology, and End Results registry. The overall and cancer-specific mortality rates were assessed using risk-adjusted Cox proportional hazards regression modeling and stratified propensity score matching. RESULTS: One hundred and eight matched patients were assessed. Patients in the PTR group had lower overall mortality than did those in the non-PTR group. The 1-, 3-, and 5-year overall and cancer-specific survival rates in the PTR group were significantly higher. CONCLUSIONS: PTR appears to be the most appropriate intervention for patients with good performance status. Such patients are likely to benefit from surgery and to experience long-term stable disease.

A novel risk score for the prediction of airway management in patients with deep neck space abscess: a multicenter retrospective cohort study.

BACKGROUND: Airway management, including noninvasive endotracheal intubation or invasive tracheostomy, is an essential treatment strategy for patients with deep neck space abscess (DNSA) to reverse acute hypoxia, which aids in avoiding acute cerebral hypoxia and cardiac arrest. This study aimed to develop and validate a novel risk score to predict the need for airway management in patients with DNSA. METHODS: Patients with DNSA admitted to 9 hospitals in Guangdong Province between January 1, 2015, and December 31, 2020, were included. The cohort was divided into the training and validation cohorts. The risk score was developed using the least absolute shrinkage and selection operator (LASSO) and logistic regression models in the training cohort. The external validity and diagnostic ability were assessed in the validation cohort. RESULTS: A total of 440 DNSA patients were included, of which 363 (60 required airway management) entered into the training cohort and 77 (13 required airway management) entered into the validation cohort. The risk score included 7 independent predictors (p < 0.05): multispace involvement (odd ratio [OR] 6.42, 95% confidence interval [CI] 1.79-23.07, p < 0.001), gas formation (OR 4.95, 95% CI 2.04-12.00, p < 0.001), dyspnea (OR 10.35, 95% CI 3.47-30.89, p < 0.001), primary region of infection, neutrophil percentage (OR 1.10, 95% CI 1.02-1.18, p = 0.015), platelet count to lymphocyte count ratio (OR 1.01, 95% CI 1.00-1.01, p = 0.010), and albumin level (OR 0.86, 95% CI 0.80-0.92, p < 0.001). Internal validation showed good discrimination, with an area under the curve (AUC) of 0.951 (95% CI 0.924-0.971), and good calibration (Hosmer-Lemeshow [HL] test, p = 0.821). Application of the clinical risk score in the validation cohort also revealed good discrimination (AUC 0.947, 95% CI 0.871-0.985) and calibration (HL test, p = 0.618). Decision curve analyses in both cohorts demonstrated that patients could benefit from this risk score. The score has been transformed into an online calculator that is freely available to the public. CONCLUSIONS: The risk score may help predict a patient's risk of requiring airway management, thus advancing patient safety and supporting appropriate treatment.

Construction and preliminary identification of a prokaryotic expression single-chain antibody fragments library against Streptococcus pneumoniae from antibody-producing cells in human tonsil.

Tonsillitis is the inflammation of the tonsils due to infection, many patients ultimately have to undergo tonsillectomy. In order to improve the accuracy of diagnosis and even create a new treatment for tonsillitis, we constructed a prokaryotic expression single-chain antibody fragment library against Streptococcus pneumoniae with immunoglobulin heavy chain variable region (VH), κ light chain (Vκ), and λ light chain (Vλ) genes by using human tonsil tissue. Plasmid DNA sequencing showed that single-chain antibodies were complete and constructed correctly. The binding activity of recombinant clones was detected by enzyme-linked immunosorbent assay (ELISA), results showed that the binding activity and specificity of anti-S. pneumoniae single-chain fragment variable (scfv) is proved to be successful. The single-chain antibody may be an attractive strategy for tonsillitis etiologic diagnosis and therapy.

TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway.

Thyroid cancer is commonly seen in the clinic with a rapidly increasing incidence globally. COX-2 overexpression correlates with the pathologic type of thyroid carcinoma, and it has been suggested that COX-2 overexpression is associated with a poor prognosis. However, little is known about its upstream regulatory mechanism. Bioinformatics suggested that transcription factor AP-2 beta (TFAP2B) might specifically bind to the COX-2 promoter, which was confirmed by biotin-labeled COX-2 promoter pulldown and luciferase reporter assays. We performed western blot and immunohistochemical staining to detect the expression of TFAP2B/COX-2 in thyroid cancer tissues (T) and the matched adjacent noncarcinoma tissues (ANT), and investigated the relationship between TFAP2B/COX-2 expression and clinical pathological factors in thyroid cancer patients. Afterward, MTS, colony formation, cell-apoptosis assay, transwell-invasion and scratch assays were performed to examine the proliferation, apoptosis, invasion, and migration of thyroid cancer cells with TFAP2B knocked down or overexpressed. The mouse xenograft experiment was performed to study in vivo the proliferation of thyroid cancer cells with TFAP2B knocked down or overexpressed. We found that TFAP2B bound to the promoter of COX-2 to activate its expression. Western blot and immunohistochemistry showed that TFAP2B/COX-2 was highly expressed in thyroid cancer, and high TFAP2B and COX-2 expression was associated with aggressive clinicopathological features in thyroid cancer. TFAP2B mediated thyroid cancer cell proliferation, apoptosis, invasion, and migration via the COX-2 signaling pathway in vitro and in vivo. TFAP2B bound to the promoter of COX-2 to activate its expression, indicating that TFAP2B is a critical regulatory molecule in the COX-2 signaling pathway that promoted tumor progression in thyroid cancer.

Circulating Glioma Cells Exhibit Stem Cell-like Properties.

: Circulating tumor cells (CTC) are known to be present in the blood of patients with glioblastoma (GBM). Here we report that GBM-derived CTC possess a cancer stem cell (CSC)-like phenotype and contribute to local tumorigenesis and recurrence by the process of self-seeding. Genetic probes showed that mouse GBM-derived CTC exhibited Sox2/ETn transcriptional activation and expressed glioma CSC markers, consistent with robust expression of stemness-associated genes including SOX2, OCT4, and NANOG in human GBM patient-derived samples containing CTC. A transgenic mouse model demonstrated that CTC returned to the primary tumor and generated new tumors with enhanced tumorigenic capacity. These CTCs were resistant to radiotherapy and chemotherapy and to circulation stress-induced cell apoptosis. Single-cell RNA-seq analysis revealed that Wnt activation induced stemness and chemoresistance in CTC. Collectively, these findings identify GBM-derived CTC as CSC-like cells and suggest that targeting Wnt may offer therapeutic opportunities for eliminating these treatment-refractory cells in GBM. SIGNIFICANCE: These findings identify CTCs as an alternative source for in situ tumor invasion and recurrence through local micrometastasis, warranting eradication of systemic "out-of-tumor" CTCs as a promising new therapeutic opportunity for GBM.

PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma.

Angiogenesis is a hallmark of cancer. However, most malignant solid tumors exhibit robust resistance to current anti-angiogenic therapies that primarily target VEGF pathways. Here we report that endothelial-mesenchymal transformation induces glioblastoma (GBM) resistance to anti-angiogenic therapy by downregulating VEGFR-2 expression in tumor-associated endothelial cells (ECs). We show that VEGFR-2 expression is markedly reduced in human and mouse GBM ECs. Transcriptome analysis verifies reduced VEGFR-2 expression in ECs under GBM conditions and shows increased mesenchymal gene expression in these cells. Furthermore, we identify a PDGF/NF-κB/Snail axis that induces mesenchymal transformation and reduces VEGFR-2 expression in ECs. Finally, dual inhibition of VEGFR and PDGFR eliminates tumor-associated ECs and improves animal survival in GBM-bearing mice. Notably, EC-specific knockout of PDGFR-ß sensitizes tumors to VEGF-neutralizing treatment. These findings reveal an endothelial plasticity-mediated mechanism that controls anti-angiogenic therapy resistance, and suggest that vascular de-transformation may offer promising opportunities for anti-vascular therapy in cancer.

Clinical analysis of second primary gingival squamous cell carcinoma after radiotherapy.

INTRODUCTION: Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy. MATERIALS AND METHODS: The data collected included 450 patients diagnosed with gingival squamous cell carcinoma from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a history of radiotherapy for head and neck cancer. We retrospectively analysed the differences in the clinicopathological characteristics and prognosis between sporadic gingival squamous cell carcinoma and radiation-associated gingival carcinoma, with an emphasis on gingival carcinoma. RESULTS: Sporadic gingival squamous cell carcinoma is less likely to have more advanced T stage, and the second primary tumour is more likely to be located in the molar area of the maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The 5-year overall survival of patients with second primary gingival carcinoma was influenced by age distribution, T classification, N classification, clinical TNM stage, histological grade and radiation history in head and neck. Mandibular gingival carcinoma was more likely to have an increased neck lymph node metastasis than maxillary gingival carcinoma (P = 0.001), but there was no significant difference in 5-year overall survival between these two groups (P = 0.828). The main therapy for gingiva carcinoma is surgery or comprehensive treatment based on surgery. CONCLUSIONS: Second primary gingival squamous cell carcinoma after radiotherapy demonstrated particular clinicopathologic features, such as prominent sites and TNM stage; and there was statistically significant difference in 5-year overall survival and prognosis between second primary gingival carcinoma after radiotherapy and sporadic gingival carcinoma.