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1.
Cancer Control ; 30: 10732748221148912, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36592162

RESUMO

BACKGROUND: We aimed to investigate the determinant factors of anti-PD-1 therapy outcome in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, we included 64 patients with recurrent/metastatic NPC. The association of patients' characteristics, C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) with survival benefit of anti-PD-1 therapy were analyzed using Cox regression models and Kaplan-Meier analyses. Patients were divided based on the median value of CRP, NLR or LDH into different subgroups. RESULTS: At a median follow-up time of 11.4 months (range: 1-28 months), median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, .18-3.6) and 15 months (95% CI, 10.9-19.1) months, respectively. Pretreatment metastases numbers was significant predictor of PFS (HR = 1.99; 95% CI 1.10-3.63; P = .024) and OS (HR = 2.77; 95% CI 1.36-5.61; P = .005). Baseline LDH level was independent predictor of OS (HR = 7.01; 95% CI 3.09-15.88; P < .001). Patients with LDH level >435 U/L at the baseline had significantly shorter PFS and OS compared to patients with LDH level ≤435 U/L (median PFS: 1.7 vs 3.5 months, P = .040; median OS: 3.7 vs 18.5 months, P < .001). Patients with non-durable clinical benefit (NDB) had significantly higher LDH level at the baseline compared to patients who achieved durable clinical benefit (DCB) (P = .025). Post-treatment levels of CRP, LDH, and NLR were decreased compared to baseline in patients with DCB (P = .030, P = .088, and P = .066, respectively), whereas, there was a significant increase in post-treatment level of LDH compared with baseline in patients with NDB (P = .024). CONCLUSIONS: LDH level at the baseline was an independent predictor of OS and pretreatment metastases numbers was a significant predictor of PFS and OS.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Lactato Desidrogenases , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
2.
J Int Med Res ; 51(1): 3000605221147187, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36597379

RESUMO

Brain metastasis of nasopharyngeal carcinoma (NPC) is a rare event with limited research. In this report, we discuss the details of a case of brain metastasis from NPC that presented with a solitary, cystic lesion in the frontal lobe. We also reviewed the related literature published in the last 20 years. We analyzed the patient's clinical characteristics, which indirectly suggested hematogenous spread rather than a cerebrospinal fluid route. Although there are no standard treatments for brain metastasis of NPC, previous studies reported that combined surgery and radiotherapy was a good treatment option, with long survival. Our patient achieved intracranial complete response after the combination of conventional chemoradiotherapy and novel immunotherapy. This treatment option could be useful in future similar cases.


Assuntos
Neoplasias Encefálicas , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Indução de Remissão , Quimiorradioterapia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundário
3.
Indian J Pathol Microbiol ; 66(1): 159-161, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656230

RESUMO

SMARCB1 deficient sinonasal carcinomas are rare neoplasms, classified under sinonasal undifferentiated carcinomas by the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. It is characterized immunohistochemically by loss of SMARCB1(INI1) expression. We are reporting the case of a 63-year-old man who was evaluated for nasal stuffiness of 3 months duration in another hospital where a radiological evaluation showed a polypoidal soft tissue lesion in the right maxillary sinus extending to the right nasal cavity and spheno-ethmoidal sinus. He underwent excision biopsy which was reported as non- keratinizing nasopharyngeal carcinoma. He was referred to our center with residual disease in spheno-ethmoidal recess for which radiotherapy was given. After completion of radiotherapy, the primary site had no residual disease, but while on follow-up he developed left sided neck nodes within 4 months of completion of treatment. Excision of the lesion was done and histopathological and immunohistochemical analysis revealed it to be metastasis from SMARCB1 deficient sinonasal carcinoma and not nasopharyngeal carcinoma as diagnosed from the other center. This case is being reported to highlight the diagnostic challenge associated with this rare entity.


Assuntos
Carcinoma , Neoplasias do Seio Maxilar , Neoplasias Nasofaríngeas , Masculino , Humanos , Pessoa de Meia-Idade , Proteína SMARCB1/genética , Proteína SMARCB1/análise , Neoplasias do Seio Maxilar/diagnóstico , Neoplasias do Seio Maxilar/genética , Neoplasias do Seio Maxilar/metabolismo , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/metabolismo , Biópsia , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise
4.
Indian J Ophthalmol ; 71(1): 303-305, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588259

RESUMO

A 40-year-old male presented with reduced vision in the right eye for one week. He had a history of nasopharyngeal carcinoma for which 34-Gy radiation was administered. The best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/20 in the left eye. Anterior segment examination suggested a bilateral early posterior subcapsular cataract. Fundoscopy revealed bilateral localized telangiectasia and macular edema in the right eye. Diagnosis of bilateral extremely delayed onset radiation retinopathy with right eye macular edema was made. Three doses of intravitreal bevacizumab injection were administered in the right eye. The patient was lost to follow-up due to COVID-19 and presented with recurrence.


Assuntos
COVID-19 , Edema Macular , Neoplasias Nasofaríngeas , Doenças Retinianas , Masculino , Humanos , Adulto , Edema Macular/diagnóstico , Inibidores da Angiogênese , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/tratamento farmacológico , Controle de Doenças Transmissíveis , Bevacizumab , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Doenças Retinianas/tratamento farmacológico , Injeções Intravítreas , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico
5.
Radiat Oncol ; 18(1): 15, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681832

RESUMO

BACKGROUND: The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups. METHODS: The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables. RESULTS: After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein-Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort. CONCLUSIONS: The novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Nasofaríngeas/patologia , Herpesvirus Humano 4/genética , DNA Viral , Tomada de Decisão Clínica
6.
BMC Med Imaging ; 23(1): 15, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698156

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) is commonly used for the diagnosis of nasopharyngeal carcinoma (NPC) and occipital clivus (OC) invasion, but a proportion of lesions may be missed using non-enhanced MRI. The purpose of this study is to investigate the diagnostic performance of synthetic magnetic resonance imaging (SyMRI) in differentiating NPC from nasopharyngeal hyperplasia (NPH), as well as evaluating OC invasion. METHODS: Fifty-nine patients with NPC and 48 volunteers who underwent SyMRI examination were prospectively enrolled. Eighteen first-order features were extracted from VOIs (primary tumours, benign mucosa, and OC). Statistical comparisons were conducted between groups using the independent-samples t-test and the Mann-Whitney U test to select significant parameters. Multiple diagnostic models were then constructed using multivariate logistic analysis. The diagnostic performance of the models was calculated by receiver operating characteristics (ROC) curve analysis and compared using the DeLong test. Bootstrap and 5-folds cross-validation were applied to avoid overfitting. RESULTS: The T1, T2 and PD map-derived models had excellent diagnostic performance in the discrimination between NPC and NPH in volunteers, with area under the curves (AUCs) of 0.975, 0.972 and 0.986, respectively. Besides, SyMRI models also showed excellent performance in distinguishing OC invasion from non-invasion (AUC: 0.913-0.997). Notably, the T1 map-derived model showed the highest diagnostic performance with an AUC, sensitivity, specificity, and accuracy of 0.997, 96.9%, 97.9% and 97.5%, respectively. By using 5-folds cross-validation, the bias-corrected AUCs were 0.965-0.984 in discriminating NPC from NPH and 0.889-0.975 in discriminating OC invasion from OC non-invasion. CONCLUSIONS: SyMRI combined with first-order parameters showed excellent performance in differentiating NPC from NPH, as well as discriminating OC invasion from non-invasion.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nasofaringe , Curva ROC , Hiperplasia/patologia , Estudos Retrospectivos
7.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677874

RESUMO

Distant metastasis remains the primary cause of treatment failure and suggests a poor prognosis in nasopharyngeal carcinoma (NPC). Epithelial-mesenchymal transition (EMT) is a critical cellular process for initiating a tumor invasion and remote metastasis. Our previous study showed that the blockage of the stromal interaction molecule 1 (STIM1)-mediated Ca2+ signaling blunts the Epstein-Barr virus (EBV)-promoted cell migration and inhibits the dissemination and lymphatic metastasis of NPC cells. However, the upstream signaling pathway that regulates the STIM1 expression remains unknown. In this follow-up study, we demonstrated that the miRNA-185-5p/STIM1 axis is implicated in the regulation of the metastatic potential of 5-8F cells, a highly invasive NPC cell line. We demonstrate that the knockdown of STIM1 attenuates the migration ability of 5-8F cells by inhibiting the epidermal growth factor receptor (EGFR) phosphorylation-induced switch from E- to N-cadherin in vitro. In addition, the STIM1 knockdown inhibited the locoregional lymphatic invasion of the 5-8F cells in mice. Furthermore, we identified miRNA-185-5p as an upstream regulator that negatively regulates the expression of STIM1. Our findings suggest that the miRNA-185-5p/STIM1 axis regulates the invasiveness of NPC cell lines by affecting the EGFR activation-modulated cell adhesiveness. The miRNA-185-5p/STIM1 axis may serve as a potentially effective therapeutic target for the treatment of NPC.


Assuntos
Infecções por Vírus Epstein-Barr , MicroRNAs , Neoplasias Nasofaríngeas , Animais , Camundongos , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Infecções por Vírus Epstein-Barr/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4 , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica/genética , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Humanos
8.
Curr Oncol ; 30(1): 1000-1009, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36661725

RESUMO

(1) Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) maintained nutritional status and improved survival of patients with locally advanced nasopharyngeal carcinoma (LA-NPC). However, the role of PEG in patients' quality of life (QoL) is still controversial. We aimed to investigate the effect of PEG on the QoL of patients with LA-NPC without progression. (2) Methods: Patients with LA-NPC between 1 June 2010 and 30 June 2014 in Fujian Cancer Hospital were divided into PEG and non-PEG groups. The QoL Questionnaire core 30 (QLQ-C30), incidence of adverse effects, weight, and xerostomia recovery were compared between the two groups of patients without progression as of 30 June 2020. (3) Results: No statistically significant difference in the scores of each QLQ-C30 scale between the two groups (p > 0.05). The incidence of xerostomia was higher in the PEG group than in the non-PEG group (p = 0.044), but the association was not seen after adjusting for gender, age, T, and N stage (OR: 0.902, 95%CI: 0.485-1.680). No significant difference in the incidence of other adverse effects as well as in weight and dry mouth recovery (p > 0.05). (4) Conclusion: PEG seems not to have a detrimental effect on long-term Qol, including the self-reported swallowing function of NPC patients without progressive disease.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Xerostomia , Humanos , Carcinoma Nasofaríngeo , Qualidade de Vida , Estudos Transversais , Gastrostomia/efeitos adversos , Xerostomia/etiologia , Neoplasias Nasofaríngeas/terapia
9.
Hum Exp Toxicol ; 42: 9603271221150248, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607163

RESUMO

BACKGROUND: MicroRNA-3612 (miR-3612) is considered a tumor suppressor in different cancers. Nonetheless, its function in nasopharyngeal carcinoma (NPC) has yet to be uncovered. METHODS: NPC cells and tissues were tested by means of reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting to quantify the expressions of miR-3612 and Thrombospondin 1 (THBS1). Cell Counting Kit-8 (CCK-8) and scratch experiments were carried out to evaluate the migration and proliferation of NPC cells. NPC cell adhesion was also assessed. The predicted interaction of miR-3612 with THBS1 was verified by means of a luciferase reporter assay. In vivo experiments were also conducted to examine how miR-3612 overexpression affects in vivo tumorigenicity. Lastly, phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway status was assessed via western blotting. RESULTS: MiR-3612 was downregulated in NPC cells and tissues, whereas THBS1 expression showed an opposite trend. The MiR-3612 mimic inhibited the NPC cell proliferation, adhesion, and migration and also inactivated the PI3K/AKT signaling pathway. Furthermore, miR-3612 mimic also hampered NPC tumorigenesis in vivo. MiR-3612 targeted THBS1 and downregulated THBS1 expression. THBS1 offset the miR-3612-overexpression-induced repression of the migration, adhesion, and proliferation of NPC cells via the activation of the PI3K/AKT pathway. CONCLUSION: MiR-3612 retarded NPC cell migration, adhesion, and proliferation by targeting THBS1 and inactivating the PI3K/AKT signaling pathway. This provides a novel therapeutic approach for NPC intervention.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/patologia , Trombospondina 1/genética , Trombospondina 1/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica
10.
Artigo em Chinês | MEDLINE | ID: mdl-36603862

RESUMO

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.


Assuntos
Forâmen Jugular , Neoplasias Nasofaríngeas , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Nasofaríngeo , Recidiva Local de Neoplasia , Endoscopia/métodos , Neoplasias Nasofaríngeas/cirurgia
11.
J Transl Med ; 21(1): 11, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624463

RESUMO

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. METHODS: This was a large­scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10- 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy. CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients. TRIAL REGISTRATION NUMBER:  Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .


Assuntos
Canais de Cálcio , Estudo de Associação Genômica Ampla , Neoplasias Nasofaríngeas , Humanos , Quimiorradioterapia , Variação Genética , Genótipo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Canais de Cálcio/genética
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(1): 63-69, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36631017

RESUMO

Objective To investigate whether miR-141-3p promote the migration of CNE-2 human nasopharyngeal carcinoma (NPC) cells by regulating vimentin. Methods Real-time quantitative PCR was used to detect the expression of miR-141-3p in NPC tissues and adjacent tissues and the expression level of vimentin was detected by immunohistochemical staining and Western blot analysis. Real-time quantitative PCR and Western blot were used to screen 5-8F, CNE-2, HNE1 human NPC cell lines with the highest relative expression of miR-141-3p. Real-time quantitative PCR and Western blot analysis were used together to verify the relationship between miR-141-3p and vimentin expression. Small interfering RNA (si-miR-141-3p) was used to down-regulate miR-141-3p of CNE-2 cells. MTT assay tested the proliferating inhibition rate of CNE-2 cells. TranswellTM chamber assay was performed to detect cell invasion and migration and Western blot analysis to detect the expression of vimentin. Results Compared with the paracancerous tissues, the expression of miR-141-3p and vimentin in NPC tissues increased significantly. Compared with NP69 cells, the expressions of miR-141-3p and vimentin increased significantly in CNE-2 cells. The down-regulation of miR-141-3p in CNE-2 cells has induced significant decrease of cell invasion and migration capabilities, cell proliferation capabilities, as well as vimentin protein expression. Conclusion miR-141-3p can enhance the proliferation and migration of CNE-2 cells by promoting vimentin expression.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Vimentina/genética , Vimentina/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética
13.
Theranostics ; 13(2): 458-471, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632221

RESUMO

Nasopharyngeal carcinoma (NPC) is a diverse cancer with no well-defined tumor antigen, associated with oncogenic Epstein-Barr Virus (EBV), and with usually late-stage diagnosis and survival <40%. Current radiotherapy and chemotherapy have low effectiveness and cause adverse effects, which calls for the need of new therapy. In this regard, adoptive immunotherapy using γδ T cells has potential, but needs to be coupled with butyrophilin 2A1 and 3A1 protein expression to achieve tumoricidal effect. Methods: Human γδ T cells were expanded (with Zol or PTA) and used for cytotoxicity assay against NPC cells, which were treated with the EBV EBNA1-targeting peptide (L2)P4. Effect of (L2)P4 on BTN2A1/BTN3A1 expression in NPC cells was examined by flow cytometry and Western blot. An NPC-bearing NSG mice model was established to test the effectiveness of P4 and adoptive γδ T cells. Immunofluorescence was performed on NPC tissue sections to examine the presence of γδ T cells and expression of BTN2A1 and BTN3A1. EBV gene expression post-(L2)P4 treatment was assessed by qRT-PCR, and the relationship of LMP1, NLRC5 and BTN2A1/BTN3A1 was examined by transfection, reporter assay, Western blot, and inhibition experiments. Results: Zol- or PTA-expanded the Vδ2 subset of γδ T cells that exerted killing against certain NPC cells. (L2)P4 reactivates latent EBV, which increased BTN2A1 and BTN3A1 expression and conferred higher susceptibility towards Vδ2 T cells cytotoxicity in vitro, as well as enhanced tumor regression in vivo by adoptive transfer of Vδ2 T cells. Mechanistically, (L2)P4 induced EBV LMP1, leading to IFN-γ/p-JNK and NLRC5 activation, and subsequently stimulated the expression of BTN2A1 and BTN3A1. Conclusions: This study demonstrated the effectiveness of using the EBV-targeting probe (L2)P4 and adoptive γδ T cells as a promising combinatorial immunotherapy against NPC. The identification of the LMP1-IFN-γ/p-JNK-NLRC5-BTN2A1/BTN3A1 axis may lead to new insight and therapeutic targets against NPC and other EBV+ tumors.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Camundongos , Animais , Humanos , Carcinoma Nasofaríngeo/terapia , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Carcinoma/terapia , Carcinoma/patologia , Neoplasias Nasofaríngeas/metabolismo , Butirofilinas , Peptídeos e Proteínas de Sinalização Intracelular , Antígenos CD
14.
Sci Adv ; 9(1): eadd0960, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608137

RESUMO

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m6A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.


Assuntos
Proteínas de Ligação a DNA , Neoplasias Nasofaríngeas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
BMC Med ; 21(1): 18, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647058

RESUMO

BACKGROUND: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated efficacy in nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse events. This study aimed to explore the clinical pattern of thyroid dysfunction and its relationship with survival marker in nonmetastatic NPC after immunotherapy. METHODS: From January 1, 2019, to December 31, 2021, 165 pairs of nonmetastatic NPC patients (165 with and 165 without anti-PD-1 immunotherapy) matched by the propensity score matching method were included in this study. Thyroid function was assessed retrospectively before the first treatment and during each immunotherapy cycle. RESULTS: The spectrum of thyroid dysfunction was different between the immunotherapy and control groups (P < 0.001). Compared with the control group, patients in the immunotherapy group developed more hypothyroidism (14.545% vs. 7.273%), less hyperthyroidism (10.909% vs. 23.636%), and a distinct pattern, biphasic thyroid dysfunction (3.030% vs. 0%). Immunotherapy also accelerates the onset of hypothyroidism, which was earlier with a median onset time difference of 32 days (P < 0.001). Patients who acquired thyroid dysfunction during immunotherapy had better complete biological response to treatment (OR, 10.980; P = 0.042). CONCLUSIONS: For nonmetastatic NPC, thyroid dysfunction was associated with better response to treatment in immunotherapy but not in routine treatment. Thyroid function could be used as a predictor for survival and should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy for nonmetastatic NPC.


Assuntos
Hipotireoidismo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Estudos Retrospectivos , Hipotireoidismo/induzido quimicamente , Neoplasias Nasofaríngeas/tratamento farmacológico
20.
BMC Cancer ; 23(1): 7, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597072

RESUMO

OBJECTIVE: We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies. METHODS: This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan-Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models. RESULTS: The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease. CONCLUSIONS: The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Prognóstico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias
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