Objective:To investigate the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues and analyze their expression levels in relation to clinical features and prognosis. Methods:From January 1, 2019, to December 31, 2019, 69 cases of nasopharyngeal carcinoma tissues and adjacent non-cancerous tissues were collected from patients treated at Yunnan Cancer Hospital. Immunohistochemistry was employed to detect the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues. The Kaplan-Meier method was used to predict survival time, and the clinicopathological features were evaluated using the log-Rank test. Results:The positive expression rates of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were 87.0% and 84.5%, respectively. Compared to adjacent normal tissues, the expression levels of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were significantly increased （P<0.05）. Furthermore, the expression of NFAT5 and IGF1R was positively correlated with T stage, N stage, skull base invasion, and cranial nerve palsy （P<0.05）. The overexpression of NFAT5 and IGF1R significantly affected the survival rate of patients with nasopharyngeal carcinoma and was negatively correlated with prognosis （P<0.05）. Conclusion:In nasopharyngeal carcinoma tissues, overexpression of NFAT5 and IGF1R is observed, which is closely linked to clinical features and patient outcomes. These markers may serve as valuable indicators for predicting the prognosis of nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/metabolism* ; Prognosis ; Female ; Receptor, IGF Type 1/metabolism* ; Male ; Transcription Factors/metabolism* ; Middle Aged ; Survival Rate ; Adult ; Neoplasm Staging

Objective:This study explored the effect of nanoparticle-encapsulated curcumin on the highly expressed multidrug resistance gene 1 （MDR1） in a human low-differentiated nasopharyngeal carcinoma cell line （CNE2）. Methods:Curcumin/chitosan deoxycholic acid nanoparticles were prepared, and the cells were subjected to different treatments: radiotherapy, empty carriers, curcumin, and curcumin-loaded nanoparticles. Cell survival was analyzed using the clonogenic assay, and assessments of apoptosis, MDR1 levels, and miR593 levels were conducted. Results:The cell survival fractions in the curcumin group and the curcumin-loaded nanoparticles group were significantly reduced. Notably, higher apoptosis rates were observed in cells treated with curcumin or curcumin-loaded nanoparticles compared to those that received only radiotherapy. Moreover, a decreased MDR1 level was noted in both the curcumin group and the curcumin-loaded nanoparticles group, with further reduction in MDR1 expression observed in the nanoparticle group （P<0.05）. Enhanced expression of miR593 was found in the curcumin group and the curcumin-loaded nanoparticles group, with a relatively higher level in the nanoparticle group （P<0.05）. Curcumin encapsulated in nanoparticles exhibited a stronger radiosensitizing effect. The combination of curcumin and radiotherapy effectively inhibited nasopharyngeal carcinoma （NPC） tumor growth, suppressed MDR1 expression, and enhanced miR593 levels. After inhibiting miR593, MDR1 expression increased. The radiosensitizing effect of curcumin-loaded nanoparticles was regulated by miR593 rather than being triggered by MDR1. Conclusion:Curcumin-loaded nanoparticles mediated enhanced expression of miR593, which in turn inhibited the transcription and translation of the MDR1 gene, thereby reducing the radioresistance of NPC and effectively restraining its growth.
Humans ; Curcumin/pharmacology* ; Nasopharyngeal Neoplasms/pathology* ; Nasopharyngeal Carcinoma ; Nanoparticles ; Cell Line, Tumor ; Apoptosis/drug effects* ; MicroRNAs ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism* ; Cell Survival

Objective:To explore the correlation between ferroptosis-related proteins SLC7A11, GPX4, ACSL4 and the radiosensitivity and prognosis of nasopharyngeal carcinoma. And to investigate the potential of these proteins as molecular markers for predicting the radiosensitivity of nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted on 52 cases of nasopharyngeal carcinoma （nasopharyngeal carcinoma group） and 20 cases of chronic nasopharyngiti s（control group）. The relevant clinical data were reviewed, and paraffin-embedded tissue blocks were collected for study. The expressions of SLC7A11, GPX4, and ACSL4 in pathological specimens were detected by immunohistochemical staining. The expression differences of ferroptosis-related proteins between the nasopharyngeal carcinoma group and the control group were analyzed. The nasopharyngeal carcinoma group was further divided based on the protein expression levels into high and low expression subgroups for SLC7A11, GPX4, and ACSL4. Subsequently, a differential analysis of clinical data and survival analysis was conducted for each of these subgroups. Finally, logistic regression analysis was performed to identify the factors influencing radiotherapy resistance in nasopharyngeal carcinoma. Results:①The differential analysis revealed that, compared to the control group, the nasopharyngeal carcinoma group exhibited significantly higher expression of SLC7A11 and GPX4, and lower expression of ACSL4 （P<0.05）. ②Notably, the proportion of patients displaying radioresistance was higher in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups （P<0.05）. However, the proportion of radioresistance in the ACSL4 high expression group was lower than that in the ACSL4 low expression group （P<0.05）. Survival analysis indicated that the 5-year overall survival rate was lower in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups（P<0.05）. However, the 5-year overall survival rate of the ACSL4 high expression group was higher than that of the ACSL4 low expression group（P<0.05）. ③logistic regression analysis showed that SLC7A11 and GPX4 was an independent risk factor for radioresistance in patients with nasopharyngeal carcinoma（P<0.05）. Conclusion:Nasopharyngeal carcinoma tissues over-express SLC7A11, GPX4, and under-express ACSL4. Over-expression of SLC7A11 and GPX4 are independent risk factors for radioresistance in patients with nasopharyngeal carcinoma. The inhibition of ferroptosis may be related to the occurrence, progression and radioresistance of nasopharyngeal carcinoma. Detection of the expression of SLC7A11, GPX4, and ACSL4 has guiding significance for the evaluation of radiosensitivity and prognosis of patients with nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/pathology* ; Coenzyme A Ligases/metabolism* ; Radiation Tolerance ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Prognosis ; Long-Chain-Fatty-Acid-CoA Ligase ; Retrospective Studies ; Ferroptosis ; Male ; Female ; Middle Aged

Objective:To investigate the anatomic origin of juvenile nasopharyngeal angiofibroma（JNA） through radiologic analysis of tumor invasion patterns, providing insights into tumor etiology and surgical recurrence prevention. Methods:This retrospective cohort study included primary JNA cases at the Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University from March 2015 to September 2024. All patients underwent preoperative high-resolution CT（HRCT） scans, and some underwent enhanced magnetic resonance imaging. The study retrospectively analyzed the patients' imaging data to examine tumor invasion into the pterygopalatine fossa and the vidian canal. These sites were categorized into non-invaded, partially invaded, and completely invaded for the pterygopalatine fossa and the vidian canal. The study analyzed the proportions of invasion at these sites to further speculate on the origin of JNA. Results:A total of 105 JNA patients were included in the study. Among them, 100% of the patients had complete tumor invasion in the pterygopalatine fossa. For the vidian canal, the proportions of complete invasion, partial invasion, and non-invasion were 54.3%, 27.6%, and 18.1%, respectively. As the staging of JNA tumors increased, the proportion of vidian canal invasion also increased. Conclusion:Our evidence suggests that the pterygopalatine fossa, rather than the vidian canal, might be the likely origin of JNA, which is enlightening for the study of the etiological mechanisms of JNA.
Humans ; Nasopharyngeal Neoplasms/pathology* ; Retrospective Studies ; Angiofibroma/pathology* ; Neoplasm Invasiveness ; Pterygopalatine Fossa/pathology* ; Female ; Magnetic Resonance Imaging ; Male ; Tomography, X-Ray Computed ; Adolescent

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Carcinoma, Small Cell ; Nasopharynx/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Nasopharyngeal Neoplasms/pathology*

OBJECTIVES: Peripheral whole blood cell counts have been used as prognostic indicators for various cancers, but their predictive value in nasopharyngeal carcinoma remain unclear. This study aims to evaluate the prognostic significance of the pretreatment hemoglobin×lymphocyte/monocyte ratio (HLMR) in non-recurrent, non-metastatic NPC patients undergoing definitive radiotherapy. METHODS: Clinical and follow-up data from 805 NPC patients who completed definitive radiotherapy or chemoradiotherapy were retrospectively analyzed. Pretreatment hemoglobin, lymphocyte count, and monocyte count were collected to calculate HLMR. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off value of HLMR. Patients were then classified into high and low HLMR groups. The association between HLMR and clinicopathological characteristic was assessed using chi-square tests. Independent prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified using Cox proportional hazards models. A nomogram was constructed based on the independent predictors to estimate patient survival rates, and internal validation was performed using a validation cohort. RESULTS: The ROC curve identified 605.5 as the optimal HLMR cut-off value for predicting 5-year survival. Multivariate Cox regression analysis revealed that T stage (HR=1.886, 95% CI 1.331 to 2.673, P<0.001), N stage (HR=2.021, 95% CI 1.267 to 3.225, P=0.003), Eastern Cooperative Oncology Group (ECOG) score (HR=3.991, 95% CI 1.257 to 12.677, P=0.019), concurrent chemoradiotherapy regimen (HR=0.338, 95% CI 0.156 to 0.731, P=0.006), and HLMR (HR=0.648, 95% CI 0.460 to 0.912, P=0.013) were independent prognostic factors for OS. A nomogram including T stage, N stage, and HLMR in the training cohort was constructed to predict 3-, 5-, and 7-year OS, with a C-index of 0.713. The area under the curves for predicting 3-, 5-, and 7-year OS were 0.744, 0.665, and 0.682, respectively. Calibration curves showed good agreement between predicted and observed survival rates. The above results were further confirmed in the validation cohort. CONCLUSIONS Pretreatment HLMR may serve as a promising prognostic biomarker for patients with nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/mortality* ; Prognosis ; Hemoglobins/analysis* ; Nasopharyngeal Neoplasms/pathology* ; Monocytes/cytology* ; Female ; Male ; Retrospective Studies ; Middle Aged ; Adult ; Aged ; Nomograms ; Chemoradiotherapy ; ROC Curve

Objective:To investigate the effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its molecular mechanism. Methods:①Western blot assay was used to detect the expression levels of HSP27 and p-HSP27 in CNE1 and CNE2 cells of nasopharyngeal carcinoma. Inhibited the phosphorylation of HSP27, Transwell assay detected the metastasis ability of nasopharyngeal carcinoma cells. ②Nasopharyngeal carcinoma cell lines（CNE2-OE1 and CNE2-OE2） overexpressing phosphorylated and dephosphorylated mutants of HSP27 were synthesized, empty vector transfected CNE2 cells（CNE2-NC） were used as controls. The proliferation ability of the three groups of cells was detected by CCK8, and the expression levels of CyclinD1, Bax and Bcl-2 were detected by Western blot. Transwell was used to detect the migration and invasion ability of cells, and Western blot was used to detect the expression levels of E-cadherin, Vimentin, MMP2 and MMP9. Results:The expression level of HSP27 in CNE2 was higher than that of CNE1 cells, while the expression level of p-HSP27 was opposite. After inhibition of HSP27 phosphorylation, the invasion and migration ability of CNE1 cells decreased significantly, with no significant change in CNE2 cells. Compared with CNE2-NC, the growth rate of CNE2-OE1 decreased, and the growth rate of CNE2-OE2 increased. The expression level of CyclinD1 was down-regulated in CNE2-OE1 and higher in CNE2-OE2. The expression level of Bax in CNE2-OE1 was increased, while the expression of Bcl-2 was decreased. There was no significant change in the expression of Bax and Bcl-2 in CNE2-OE2. Compared with CNE2-NC, the migration ability of CNE2-OE1 was enhanced and the invasion ability was weakened, while the migration ability of CNE2-OE2 was weakened and the invasion ability was enhanced. There was no significant difference in the expression levels of E-cadherin was decreased in CNE2-OE1 and increased in CNE2-OE2. There was no significant difference in the expression levels of Vimentin among the three groups. The expression levels of MMP2 and MMP9 were up-regulated in CNE2-OE2, and slightly down-regulated in CNE2-OE1. Conclusion:HSP27 and p-HSP27 were differentially expressed in different nasopharyngeal carcinoma cells, and the metastasis ability of nasopharyngeal carcinoma was not only related to the expression level of HSP27, but also related to the level of p-HSP27. The p-HSP27 inhibited CNE 2 cell proliferation and promoted their apoptosis. As p-HSP27 plays different roles in different stages of nasopharyngeal carcinoma metastasis, it can increase the migration ability of CNE2 cells and reduce its invasion ability. p-HSP27 may induce EMT changes in CNE2 by down-regulating E-cadherin, thus promoting CNE2 migration, and may inhibit CNE2 invasion by down-regulating MMPs expression.
Humans ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/pathology* ; Cell Movement ; HSP27 Heat-Shock Proteins/metabolism* ; Phosphorylation ; Neoplasm Metastasis ; Matrix Metalloproteinase 9/metabolism* ; Neoplasm Invasiveness ; Matrix Metalloproteinase 2/metabolism* ; Heat-Shock Proteins/metabolism* ; Cyclin D1/metabolism* ; Molecular Chaperones/metabolism* ; Cadherins/metabolism*

The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.
Humans ; Animals ; Mice ; Cisplatin/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Nasopharyngeal Carcinoma/drug therapy* ; Mice, Nude ; Nasopharyngeal Neoplasms/pathology* ; Tumor Microenvironment

Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/pathology* ; Carcinoma/surgery* ; Neoplasm Recurrence, Local/therapy* ; Treatment Outcome

Objective:To investigate the surgical approach for the resection of juvenile nasopharyngeal angiofibroma（JNA） under nasal endoscopy. Methods:The clinical data of 87 patients undergoing endoscopic resection of nasopharyngeal fibroangioma were retrospectively analyzed. We classified JNA according to tumor site, size, invasion scope and anatomic position relationship between tumor and midline of pupil. Three endoscopic surgical approaches were selected according to the classification, and the postoperative symptoms, complications and recurrence were investigated and analyzed. Results:The tumor resection rate of 87 cases by nasal endoscopic surgery was 100%. Thirty-five cases were approached through the middle nasal passage（small tumors located in the nasal sinuses and pterygopalatine fossa）, forty-five cases were approached through the lateral wall of the nasal cavity（tumor invaded the pterygopalatine fossa but did not exceed the midline of the pupil） , and seven cases were approached via the lateral wall of nasal cavity + ipsilateral anterior wall of maxillary sinus（tumor invaded the infratemporal fossa beyond the midline of pupil or invaded the cavernous sinus and the middle cranial fossa epidural）, Postoperative patients with nasal congestion, nasal bleeding, headache, dizziness, vision loss and other symptoms showed varying degrees of improvement. No surgical death or intracranial infection occurred. The postoperative follow-up was 6-78 months, and the recurrence rate was 3.44%. Conclusion:Endoscopic resection of nasopharyngeal fibroangioma is the main treatment method for JNA. Selecting suitable endoscopic approach to resect JNA, To maximize the advantage of nasal endoscopic equipment according to the inherent anatomical space of the human nasal cavity, In order to achieve the purpose of JNA resection, reduce intraoperative and postoperative complications, reduce the recurrence rate and improve the prognosis.
Humans ; Angiofibroma/pathology* ; Retrospective Studies ; Nasopharyngeal Neoplasms/pathology* ; Endoscopy/methods* ; Prognosis