OBJECTIVE: To summarize the research progress of rodent models of secondary lymphedema (SL) and provide a reference for selecting appropriate animal models in SL research. METHODS: Recent literature on rodent SL models at home and abroad was comprehensively analyzed, summarizing model categories, development techniques, strengths, and weaknesses. RESULTS: Current research primarily utilizes rats and mice to establish SL models. The main model types include hind limb, forelimb, tail, and head/neck models. The hind limb model is the most frequently employed, typically requiring surgery combined with irradiation to induce stable chronic edema. Forelimb models primarily simulate upper limb lymphedema, but exhibit relatively rapid edema resolution. Tail models offer operational simplicity and are predominantly used for studying acute edema mechanisms and interventions; however, they demonstrate poor clinical relevance. Emerging head/neck models provide a valuable tool for investigating head and neck cancer-associated lymphedema. These models exhibit variations in lymphedema duration, degree of fibrosis, and edema incidences. CONCLUSION Existing models still fall short in faithfully replicating the chronicity, fibrosis, fat deposition, and complex microenvironment characteristic of human chronic lymphedema. Future research must integrate multidisciplinary approaches, optimize model construction strategies, and explore novel modeling approaches to more accurately mimic the human disease and advance SL prevention and treatment research.
Lymphedema/pathology* ; Animals ; Disease Models, Animal ; Rats ; Mice ; Humans ; Head and Neck Neoplasms/complications* ; Rodentia

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a high-molecular-weight protein complex in the cytoplasm, is composed of three core components: the sensor protein NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and the effector protein caspase-1. It plays a critical role in regulating host immune and inflammatory responses. Studies have shown that the NLRP3 inflammasome has increasingly become a focal point in tumor molecular biology field. A growing body of evidence indicates that the increased expression and activation of the NLRP3 inflammasome is closely associated with the pathogenesis of head and neck squamous cell carcinoma (HNSCC) and the tumor microenvironment (TME). It may promote tumor proliferation, invasion, migration, and other biological behaviors through various regulatory mechanisms while influencing tumor immune evasion and therapy resistance, which holds promise as a prognostic biomarker for patients. This review explores the current effect and mechanism of the NLRP3 inflammasome and its signaling pathways in head and neck cancer, providing insights into clinical targeted drug development and molecular immunotherapy.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammasomes/metabolism* ; Head and Neck Neoplasms/pathology* ; Squamous Cell Carcinoma of Head and Neck/metabolism* ; Tumor Microenvironment ; Signal Transduction ; Animals

Objective:To explore the clinical manifestations, diagnosis, treatment, pathological types and prognosis of primary cervical neuroblastoma in children. Methods:The clinical data of 11 children with primary cervical neuroblastoma admitted to the Department of Otolaryngology and Head and Neck Surgery at Shanghai Children's Hospital from April 2015 to April 2022 were retrospectively analyzed. The clinical characteristics, imaging findings, pathological types, treatment methods, and outcomes of these 11 patients were examined in conjunction with a review of the literature. Results:The cohort of 11 neuroblastoma patients ranged in age from 28 days to 88 months （median age: 24 months）, including 3 males and 8 females. Among the 11 patients, 4 had tumors located in the carotid sheath area, 4 in the cervical space, and 3 in the parapharyngeal and retropharyngeal spaces. The clinical manifestations primarily included painless cervical masses and laryngeal stridor. There were 3 cases of primary cervical tumors with cervical lymph node metastasis and 1 case with bone marrow metastasis. Pathological findings revealed neuroblastoma in 8 cases and ganglionic neuroblastoma in 3 cases. In this group, 7 patients underwent surgery combined with chemotherapy, 2 patients received surgery combined with chemoradiotherapy, and 2 patients underwent surgery alone. Surgical resection was performed via a cervical approach in 7 cases, while 3 cases were treated using a transoral endoscopic approach. Additionally, one patient underwent a transoral endoscopic approach initially and a cervical approach subsequently. All patients completed their treatment and were followed up regularly, with follow-up durations ranging from 6 to 79 months （median: 34 months）. Nine patients achieved complete remission, 2 patients achieved partial remission, and none experienced disease progression. Conclusion:Primary cervical neuroblastoma exhibits a high degree of heterogeneity and presents at a younger age, primarily with cervical masses. Compared to external approaches, endoscopy-assisted transoral resection of parapharyngeal tumors offers advantages such as reduced damage to surrounding tissue and no visible neck scars, providing a new method for clinical treatment. Regular follow-up is essential for children with neuroblastoma, along with the establishment of specific disease management protocols and comprehensive care to improve survival quality.
Humans ; Female ; Male ; Neuroblastoma/surgery* ; Child, Preschool ; Infant ; Retrospective Studies ; Child ; Head and Neck Neoplasms/pathology* ; Prognosis

Objective:Paragangliomas （PGLs） are chromaffin cell tumors originating from paraganglia and are classified as neuroendocrine neoplasms.They predominantly occur along the distribution area of the paraganglia, commonly occurring between the ages of 20 and 40, with a slight male predominance.They are most frequently found in the axial regions from the skull base to the pelvic cavity. Paragangliomas in the head and neck region typically lack endocrine functionality and primarily manifest through local mass effects. However, clinical signs and symptoms alone cannot reliably distinguish between metastatic and non-metastatic cases. Clinically apparent metastatic paragangliomas are relatively rare. Herein, we present a case of a paraganglioma located in the region of the jugular foramen with liver, bone, and lymph node metastases, and discuss the treatment and prognosis of head and neck paragangliomas.
Humans ; Head and Neck Neoplasms/pathology* ; Jugular Foramina/pathology* ; Liver Neoplasms/secondary* ; Lymphatic Metastasis ; Paraganglioma/pathology*

OBJECTIVES: This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments. METHODS: The expression of SMAD7 in HNSCC in public databases was studied. Western blot was used to detect the expression of SMAD7 in HNSCC cell lines and normal epithelial cells. The SMAD7 highly expressed HNSCC cell line HSC-4 was silenced, and CCK-8, Transwell assays, and cell scratch experiments were conducted to study the effect of SMAD7 on the biological functions of HSC-4 cells. HNSCC expression profile data were obtained from UCSC xena, and genes related to SMAD7 were selected for gene ontology and Kyoto encyclopedia of genes and genomes gene enrichment analysis, construction of a co-expression gene interaction network, and screening of related cell signaling pathways. Western blot was used to detect the expression changes of proteins in the related cell signaling pathways in HNSCC cells with silenced SMAD7. cBioPortal was utilized to analyze the mutation rate of the SMAD7 gene, and the MethSurv database was used to analyze the methylation level of the SMAD7 gene and its correlation with prognosis. The receiver operating characteristic curve was used to assess the diagnostic value of SMAD7 for HNSCC. TIMER2.0 was used to analyze the correlation between SMAD7 expression and immune cell infiltration. RESULTS: SMAD7 was highly expressed in HNSCC tumor tissues and some cell lines. Silencing the expression of SMAD7 can significantly inhibit the proliferation, migration, and invasion of cancer cells. Silencing SMAD7 can induce the downregulation of vascular cell adhesion molecule 1 (VCAM-1). The bioinformatics analysis showed that the mutation rate of the SMAD7 gene and the methylation level were significantly correlated with the prognosis of patients with HNSCC. The expression of SMAD7 was related to the level of immune cell infiltration in HNSCC. CONCLUSIONS SMAD7 promotes the proliferation, migration, and invasion of HNSCC cells by regulating the expression of VCAM-1. It may be a potential tumor biomarker and therapeutic target for HNSCC.
Humans ; Smad7 Protein/metabolism* ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; Head and Neck Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Computational Biology

Humans ; B7-H1 Antigen/metabolism* ; Squamous Cell Carcinoma of Head and Neck/diagnosis* ; China ; Head and Neck Neoplasms/pathology* ; Consensus ; Biomarkers, Tumor/metabolism* ; Immunotherapy/methods*

Objective:The extranodal extension（ENE） is widely found in head and neck squamous cell carcinoma（HNSCC）, which displays the aggressiveness of the tumor and increasing the risk of local recurrence and distant metastasis, so the ENE often has been used as an important indicator of prognosis and treatment. Although the pathologic and radiologic tests are currently the main diagnostic techniques for ENE, there is still a lack of uniform standards. The article reviews the prognostic value, pathologic and radiologic diagnosis of ENE in HNSCC over the recent years.
Humans ; Head and Neck Neoplasms/pathology* ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/diagnosis* ; Carcinoma, Squamous Cell/diagnosis* ; Extranodal Extension ; Neoplasm Recurrence, Local ; Lymphatic Metastasis

Objective:Head and neck squamous cell carcinoma（HNSCC） is one of the common malignant tumours, and most of them are in locally advanced stages at the time of diagnosis due to the lack of early symptoms, and the prognosis of such patients is still poor. M6A modification is the most common form of RNA modification in eukaryotic organisms, with a wide range of biological functions, and the family of IGF2BPs modulates growth, metastasis, chemotherapy resistance, and other processes of cancer by binding to and stabilizing a wide range of target RNAs through recognition of the m6A locus. The aim of this paper is to review the role and related mechanisms of IGF2BPs in head and neck squamous carcinoma, and to provide new ideas for early diagnosis and precision treatment of HNSCC.
Humans ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Head and Neck Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; RNA-Binding Proteins/genetics* ; Prognosis

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans ; Mouth Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Luteolin/therapeutic use* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; Cell Line, Tumor

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.
Humans ; Squamous Cell Carcinoma of Head and Neck/etiology* ; Retrospective Studies ; Carcinoma, Squamous Cell/pathology* ; Neoplasm Recurrence, Local/pathology* ; Head and Neck Neoplasms ; Antineoplastic Combined Chemotherapy Protocols