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1.
Cancer Treat Rev ; 85: 101995, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113080

RESUMO

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Biópsia por Agulha , Quimiorradioterapia/métodos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
2.
Zhonghua Zhong Liu Za Zhi ; 42(2): 133-138, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135648

RESUMO

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Docetaxel/administração & dosagem , Cronoterapia Farmacológica , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
3.
Artigo em Chinês | MEDLINE | ID: mdl-32086923

RESUMO

Objective:The aim of this study is to investigate the effect of fibreoptic endoscopic of sallowing (FEES) in the assessment of pharyngeal dysphagia in post-irradiated patients with nasopharyngeal carcinoma. Method:Fifty-three NPC patients with post-irradiated underwent FEES and video fluoroscopy(VF).The results were analyzed using the Bolus Residue Scale and Rosenbek's penetration aspiration scale. Result:The agreement in the detection of penetration and aspiration between FEES and VF of liquid(κ=0.56, 95%CI 0.38-0.73) and porridge(κ=0.64, 95%CI 0.43-0.81) was "fair". The detection rates of penetration on FEES with liquid and porridge were 60% and 51%, the detection rates of aspiration on VF with liquid and porridge were 70% and 53%. There were no statistical differences. The agreement in the detection of pharyngeal residue between FEES and VF of liquid (κ=0.38, 95%CI0.12-0.62) and porridge (κ=0.66, 95%CI 0.44-0.86) was "fair". The detection rates of pharyngeal residue on FEES and VF with porridge were 43% and 45%, the difference was not statistically significant. The detection rates of pharyngeal residue on FEES and VF with liquid were 44% and 24%, and the difference was statistically significant. Conclusion:FEES is an effective and valuable tool for evaluating pharyngeal dysphagia in post-irradiated patients with nasopharyngeal carcinoma.


Assuntos
Transtornos de Deglutição/diagnóstico por imagem , Endoscópios , Carcinoma Nasofaríngeo/complicações , Neoplasias Nasofaríngeas/complicações , Deglutição , Transtornos de Deglutição/etiologia , Tecnologia de Fibra Óptica , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia
4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(1): 136-141, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32096387

RESUMO

The segmentation of organs at risk is an important part of radiotherapy. The current method of manual segmentation depends on the knowledge and experience of physicians, which is very time-consuming and difficult to ensure the accuracy, consistency and repeatability. Therefore, a deep convolutional neural network (DCNN) is proposed for the automatic and accurate segmentation of head and neck organs at risk. The data of 496 patients with nasopharyngeal carcinoma were reviewed. Among them, 376 cases were randomly selected for training set, 60 cases for validation set and 60 cases for test set. Using the three-dimensional (3D) U-NET DCNN, combined with two loss functions of Dice Loss and Generalized Dice Loss, the automatic segmentation neural network model for the head and neck organs at risk was trained. The evaluation parameters are Dice similarity coefficient and Jaccard distance. The average Dice Similarity coefficient of the 19 organs at risk was 0.91, and the Jaccard distance was 0.15. The results demonstrate that 3D U-NET DCNN combined with Dice Loss function can be better applied to automatic segmentation of head and neck organs at risk.


Assuntos
Processamento de Imagem Assistida por Computador , Carcinoma Nasofaríngeo/patologia , Órgãos em Risco , Cabeça , Humanos , Pescoço , Tomografia Computadorizada por Raios X
5.
Anticancer Res ; 40(2): 677-688, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014908

RESUMO

BACKGROUND/AIM: The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA -1154 G/A (rs1570360), -2578 A/C (rs699947), -1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS -671 A/G (rs1800682) was performed by using Sanger sequencing. RESULTS: The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA -2578, VEGFA -1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA -2578 CC as compared to AC (HR=0.24, p=0.060). CONCLUSION: The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group.


Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Adulto Jovem
6.
Artigo em Chinês | MEDLINE | ID: mdl-32086902

RESUMO

Objective:To investigate the effect of Notch1 gene on radiosensitivity of nasopharyngeal carcinoma cells and its molecular mechanism. Method:A Notch1-knockout CNE-2 cell line was constructed using CRISPR/Cas9 system, and the expression of Notch1 gene was detected by RT-PCR and Western blot. After treatment with different doses of radiation, the survival fraction (SF) of each group was calculated, and used the GraphPad Prism 6.0 software and the Linear quadratic model were used to calculate the fitted dose survival curve and the sensitivity enhancement ratio(SER). Taking 6 Gy as radiation dose, the experiment was divided into four groups: Notch1(+) group, Notch1(-) group, IR+Notch1(+) group and IR+Notch1(-) group. CCK-8 assay was used to detect cell proliferation in each group. Annexin V-FITC/PI double staining assay was used to detect the changes of apoptosis in each group. The expression of H2AX, CyclinD1, Bax, Bcl-2 and GAPDH proteins were detected by Western blot. Result:The CNE-2 cell line with Notch1 gene knockout was successfully constructed. The clonogenic assay showed knockout of Notch1 enhanced the radiosensitivity of NPC cells. The CCK-8 assay showed that cell proliferation and cell viability were significantly reduced in the IR+Notch1(-) group compared with the IR+Notch1(+) group(P<0.05). Annexin V-FITC/PI double staining assay showed that the IR+Notch1(-) group had the highest apoptosis rate compared with the other groups (P<0.05). Western blotting demonstrated that the expression of γH2AX was significantly increased after irradiation of Notch1 nasopharyngeal carcinoma cells, the expression of Cyclin-D1 was increased, and the ratio of Bax:Bcl-2 was higher. Conclusion:Knockout of Notch1 signaling molecule can effectively improve the radiosensitivity of NPC cells cultured in vitro, which may be a potential target for radiosensitization of NPC.


Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Tolerância a Radiação , Receptor Notch1/genética , Apoptose , Linhagem Celular Tumoral/efeitos da radiação , Proliferação de Células , Técnicas de Inativação de Genes , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia
7.
Medicine (Baltimore) ; 99(2): e18545, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914029

RESUMO

This study aimed to determine the impact of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of nasopharyngeal carcinoma (NPC) before and after intensity modulated radiotherapy (IMRT).Pre/post-treatment and changes in inflammatory biomarker levels of 207 patients who were diagnosed with NPC and received IMRT between January 2012 and December 2014 were analyzed, and the cellular biomarker analyses were from patient blood. ROC (receiver operating characteristic) analysis was used to decide the optimal cutoff values of NLR and changes in NLR (ΔNLR) and PLR (ΔPLR). The Kaplan-Meier and logarithmic rank methods were used to compare overall survival times between groups. Univariate analysis was used to investigate the effects of age, gender, histology, Karnofsky performance score (KPS), TNM stage, clinical stage, course of disease and lymphocyte, neutrophil and platelet counts as well as alkaline phosphatase (ALP) levels on the prognosis of NPC. The independent predictors of OS were determined by Cox multivariate regression analysis.The optimal cut-off values of NLR, PLR, ΔNLR and ΔPLR were 2.49, 155.82, 1.80, and 100.00, respectively. These were used to classify patients into high (NLR > 2.49) and low NLR groups (NLR < 2.49); high (PLR>155.82) and low (PLR < 155.82) PLR groups; high (ΔNLR>1.80) and low ΔNLR groups (ΔNLR < 1.80); high (ΔPLR > 100.00) and low ΔPLR groups (ΔPLR < 100.00). TNM stage, clinical stage and ALP levels were highly correlated with high NLR and PLR. Cox multivariate regression analysis suggested that the ΔNLR (HR = 2.89, 95% CI: 1.33∼2.78) was independent of the characteristics for NPC.As a novel inflammatory index, ΔNLR appears to have some predictive power for the prognosis of patients with NPC.


Assuntos
Linfócitos/efeitos da radiação , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neutrófilos/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Contagem de Células Sanguíneas , Plaquetas/patologia , Plaquetas/efeitos da radiação , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias/métodos , Neutrófilos/patologia , Valor Preditivo dos Testes , Prognóstico , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
8.
Cancer Sci ; 111(3): 857-868, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930596

RESUMO

Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell-to-cell communication. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan-2 (SDC2) and synaptotagmin-like-4 (SYTL4) through nuclear factor (NF)-κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF-κB signaling to promote EV secretion, and further enhance cancer progression of NPC.


Assuntos
Vesículas Extracelulares/metabolismo , Herpesvirus Humano 4/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Sindecana-2/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia
9.
Oncology ; 98(3): 154-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995803

RESUMO

INTRODUCTION: Nasopharyngeal cancer (NPC) is a common malignancy in Southeast Asia with a high mortality rate. Previous studies have shown that the patient survival rate is <80% worldwide. At the Dharmais Cancer Hospital, NPC is the first of the top 10 diseases with the highest rate of stage III cancer progression. OBJECTIVE: This study aims to determine the 5-year survival rate of patients with NPC based on tumor response and their prognostic factors after receiving neoadjuvant chemotherapy, followed by chemoradiation. METHODS: The records of 261 patients between January 2009 and December 2013 were retrospectively analyzed. All patients with NPC who received neoadjuvant chemotherapy, followed by chemoradiation, at the Dharmais Cancer Hospital from 2009 to 2013 were identified. Patients with metastasis were excluded. The primary endpoint of this study was overall survival, which was defined as the time from the date of treatment to the date of death. The survival curve was analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used for the multivariate analysis of prognostic factors. RESULTS: The tumor response rates for patients with complete response (CR), partial response (PR), and progressive disease (PD) were 33.7, 45.2, and 21.2%, respectively. The 5-year overall survival rate was 38.6%. The 5-year survival rates based on tumor response among CR, PR, and PD patients were 71.0, 30.4, and 10.6%, respectively. The significant independent prognostic factors were tumor response, educational background, job, alcohol consumption, clinical stage, and prompt treatment. CONCLUSION: The survival probability of patients with NPC receiving neoadjuvant chemotherapy, followed by chemoradiation, was higher in the CR group than in the PR and PD groups. This confirms that early detection can improve the patient's survival. Long-term follow-up is required to determine the factors influencing tumor response in NPC.


Assuntos
Quimiorradioterapia Adjuvante , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Terapia Neoadjuvante , Adulto , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Progressão da Doença , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
10.
Medicine (Baltimore) ; 99(4): e18974, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977914

RESUMO

We aimed to develop a nomogram based on a population-based cohort to estimate the individualized overall survival (OS) for patients with nasopharyngeal carcinoma (NPC) and compare its predictive value with that of the traditional staging system.Data for 3693 patients with NPC were extracted from the Surveillance, Epidemiology, and End Results dataset and randomly divided into two sets: training (n = 2585) and validation (n = 1108). On the basis of multivariate Cox regression analysis, a nomogram was constructed to predict the 3-, 5-, and 10-year survival probability for a patient. The performance of the nomogram was quantified with respect to discrimination, calibration, and clinical utility.In the training set, age, sex, race, marital status, histological type, T stage, N stage, M stage, radiotherapy, and chemotherapy were selected to develop a nomogram for predicting the OS probability based on the multivariate Cox regression model. The nomogram was generally more discriminative compared with the American Joint Committee on Cancer 7th staging system. Calibration plots exhibited an excellent consistency between the observed probability and the nomogram's prediction. Categorical net classification improvement and integrated discrimination improvement suggested that the predictive accuracy of the nomogram exceeded that of the classic staging system. With respect to decision curve analyses, the nomogram exhibited preferable net benefit gains than the staging system across a wide range of threshold probabilities.This proposed nomogram exhibits an excellent performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and thus can be used as a convenient and reliable tool for prognosis prediction in patients with NPC.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Melhoria de Qualidade , Programa de SEER/estatística & dados numéricos , Adulto Jovem
11.
Ann Otol Rhinol Laryngol ; 129(3): 287-293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31701754

RESUMO

AIM: Endoscopic endonasal nasopharyngectomy (EEN) for recurrent nasopharyngeal carcinoma (rNPC) is being increasingly used due to the added high magnification, reduced morbidities associated with open procedures and good survival outcomes. Most studies looked at usage of EEN in patients with lower recurrent staging (rT1 and rT2) although more and more surgeons are studying the outcome of EEN in advanced rNPC (rT3 and rT4). The aims of this study were to report the long-term 5-year survival outcome of EEN performed in patients with advanced rNPC, and to determine any prognostic factors for patients' survival. METHODS: All patients who underwent EEN for advanced rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah. We reported the 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. RESULTS: Twelve patients with rNPC (2 rT3 and 10 rT4) were followed-up over a mean duration of 44.8 months (range, 40-440 weeks). The 5-year OS was 50.0% (mean 44.75 months), DFS was 25.0% (mean 35.25 months) and the DSS was 58.3% (mean 43.33 months). No severe operative complications were encountered and no independent prognostic factors for survival outcome were identified. CONCLUSION: This is the first report in English that exclusively described the long-term 5-year survival data in patients with both rT3 and rT4 recurrent NPC after EEN. The data suggest that EEN is a feasible treatment to improve survival with minimal morbidities in patients with rT3 and rT4 recurrent NPC. However, more studies with larger patient size is recommended.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/cirurgia , Cirurgia Endoscópica por Orifício Natural , Recidiva Local de Neoplasia/cirurgia , Faringectomia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Reoperação , Terapia de Salvação
12.
J Cancer Res Clin Oncol ; 146(2): 429-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677113

RESUMO

PURPOSE: To compare the clinical results and functional outcomes between two-dimensional conventional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) with skull-base invasion. METHODS: A total of 1258 patients were subclassified into two groups: mild skull-base invasion group (792; 63%) and severe skull-base invasion group (466; 37%). Patients were pair matched (1:1 ratio) using six clinical factors into 2DRT or IMRT groups. The Kaplan-Meier method and Cox regression model were performed to assess overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Toxicities were evaluated. RESULTS: IMRT significantly improved four-year OS compared with 2DRT (65.6% vs. 81.8%, P = 0.000), DFS (57.3% vs. 73.3%, P = 0.000) and LRRFS (76.5% vs. 87.5%, P = 0.003) in NPC with severe skull-base invasion, but similar results were observed in patients with mild skull-base invasion (P > 0.05). In patients with severe invasion, radiation therapy techniques were found to be an independent prognostic factor for OS (HR = 0.457, P = 0.000), DFS (HR = 0.547, P = 0.000) and LRRFS (HR = 0.503, P = 0.004). IMRT was associated with better OS. In subgroups analysis, IMRT group also had a better survival in OS, DFS (P < 0.05 for all rates) for patients received concurrent chemotherapy and sequential chemotherapy compared to 2DRT in the severe invasion group. The IMRT group displayed lower incidence of mucositis, xerostomia, trismus (< 1 cm) and temporal lobe necrosis than the 2DRT group. CONCLUSIONS: IMRT significantly improved patient survival compared with 2DRT in NPC patients with severe skull-base invasion, but a similar survival rate was noted in mild invasion patients. Chemotherapy can improve survival in NPC patients with severe invasion. Among the two therapies, IMRT significantly decreased therapy-related toxicity.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Quimiorradioterapia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Base do Crânio/patologia , Adulto Jovem
13.
Cancer Sci ; 111(1): 72-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31691433

RESUMO

Capn4, also known as CapnS1, is a member of the calpain family, which plays a crucial role in maintaining the activity and function of calpain. We previously reported that Capn4 also plays an essential role in the migration of nasopharyngeal carcinoma (NPC) cells through regulation of (MMP-2) by nuclear factor-kappa B activation. Epstein-Barr virus latent membrane protein 1 (LMP1) is closely related to the malignant functions of NPC; however, the relationship between LMP1 and Capn4 in NPC remain unclear. Immunohistochemical studies showed that the level of LMP1 and Capn4 expression was high in both primary and metastatic NPC tissues, with a significantly positive correlation. We further found that LMP1 was able to upregulate the Capn4 promoter in a dose-dependent way through the C-terminal activation region (CTAR)1 and CTAR2 domains to activate AP-1. Moreover, we also found that LMP1 activated AP-1 through ERK/JNK phosphorylation. These findings indicate that Capn4 coordination with LMP1 promotes actin rearrangement and, ultimately, cellular migration. These results show that Capn4 coordination with LMP1 enhances NPC migration by increasing actin rearrangement involving ERK/JNK/AP-1 signaling. Therapeutically, additional and more specific LMP1 and Capn4 targeted inhibitors could be exploited to treat NPC.


Assuntos
Calpaína/genética , Sistema de Sinalização das MAP Quinases/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Metástase Neoplásica/genética , Fator de Transcrição AP-1/genética , Proteínas da Matriz Viral/genética , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/patogenicidade , Humanos , NF-kappa B/genética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Metástase Neoplásica/patologia , Fosforilação/genética , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Regulação para Cima/genética
14.
Gene ; 727: 144243, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31743768

RESUMO

BACKGROUND: Circulating microRNAs have become reliable sources of non-invasive biomarkers for cancer diagnosis. miRNA expression analysis in blood circulation for the identification of novel signatures might assist the early detection of nasopharyngeal carcinoma (NPC) patients. METHODS: In the screening stage, the Exiqon miRNA qPCR panel was applied for the selection of candidate miRNAs. Serum samples taken from 208 NPC patients and 238 healthy donors (as normal controls (NCs)) were assigned to into the following three stages (training (30 NPC VS. 30 NCs), testing (138 NPC VS. 166 NCs) and external validation stage (40 NPC VS. 42 NCs)) for further confirmation of differently expressed miRNAs using qRT-PCR. The identified miRNA signatures were further explored in tissue specimens (48 NPC VS. 32 NCs) and serum-derived exosomes samples (32 NPC VS. 32 NCs). RESULTS: Five miRNAs in serum including let-7b-5p, miR-140-3p, miR-192-5p, miR-223-3p and miR-24-3p were found to be significantly up-regulated in NPC patients compared to NCs. The five identified miRNAs were further combined into one panel and the areas under the receiver operating characteristic curve (AUCs) for three independent stages were 0.910 (training), 0.916 (testing) and 0.968 (external validation), respectively. miR-192-5p and miR-24-3p were consistently up-regulated in NPC tissues while let-7b-5p and miR-140-3p were conversely down-regulated. In serum-derived exosomes samples, no expression difference was observed between NPC patients and NCs. CONCLUSION: A five-miRNA signature was identified in serum to be potential biomarkers for NPC detection.


Assuntos
Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/genética , Exossomos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Neoplasias Nasofaríngeas/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Transcriptoma/genética
15.
Cancer Sci ; 111(2): 592-600, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31834989

RESUMO

The detection of Epstein-Barr virus (EBV) DNA load in nasopharyngeal (NP) brushing samples for diagnosis of nasopharyngeal carcinoma (NPC) has attracted great attention. Further improvements that eliminate the need for clinical settings will greatly extend its application. A total of 250 participants were recruited to obtain NP brushing samples. Brush sampling both with and without the guide of endoscopy was conducted in 38 NPC patients. EBV DNA load, EBV RNA transcript and EBV DNA C promoter methylation status were, respectively, evaluated. Typical latency II transcripts were observed in brushing samples from NPC patients but not controls. Unlike in tissues, multiple lytic gene transcripts were observed not only in NPC patients but also in controls. Apart from EBV RNA transcript, samples from NPC patients also showed higher levels of EBV DNA load and C promoter methylation degree than their controls. Qualitative analysis further showed that EBV DNA C promoter was methylated in all NPC patients but in only 18.4% of the control group. Combined analysis of EBV DNA methylated degree and EBV DNA load increased the sensitivity to 100% in the detection of NPC. Using qualitative methylated type as the criteria, up to 89.5% of samples collected via blind brushing showed consistent results with samples collected via endoscopy-guided brushing from NPC patients. Detection of the methylation status of EBV DNA C promoter in NP brushing samples shows great potential in diagnosing NPC and may provide an appealing alternative for the non-invasive detection and screening of NPC without the need for clinical settings.


Assuntos
Metilação de DNA , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Feminino , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/fisiologia , Humanos , Masculino , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Regiões Promotoras Genéticas , Sensibilidade e Especificidade , Proteínas Virais/genética , Latência Viral
16.
Eur Radiol ; 30(1): 537-546, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31372781

RESUMO

OBJECTIVES: To establish and validate a radiomics nomogram for prediction of induction chemotherapy (IC) response and survival in nasopharyngeal carcinoma (NPC) patients. METHODS: One hundred twenty-three NPC patients (100 in training and 23 in validation cohort) with multi-MR images were enrolled. A radiomics nomogram was established by integrating the clinical data and radiomics signature generated by support vector machine. RESULTS: The radiomics signature consisting of 19 selected features from the joint T1-weighted (T1-WI), T2-weighted (T2-WI), and contrast-enhanced T1-weighted MRI images (T1-C) showed good prognostic performance in terms of evaluating IC response in two cohorts. The radiomics nomogram established by integrating the radiomics signature with clinical data outperformed clinical nomogram alone (C-index in validation cohort, 0.863 vs 0.549; p < 0.01). Decision curve analysis demonstrated the clinical utility of the radiomics nomogram. Survival analysis showed that IC responders had significant better PFS (progression-free survival) than non-responders (3-year PFS 84.81% vs 39.75%, p < 0.001). Low-risk groups defined by radiomics signature had significant better PFS than high-risk groups (3-year PFS 76.24% vs 48.04%, p < 0.05). CONCLUSIONS: Multiparametric MRI-based radiomics could be helpful for personalized risk stratification and treatment in NPC patients receiving IC. KEY POINTS: • MRI Radiomics can predict IC response and survival in non-endemic NPC. • Radiomics signature in combination with clinical data showed excellent predictive performance. • Radiomics signature could separate patients into two groups with different prognosis.


Assuntos
Quimioterapia de Indução/métodos , Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Nomogramas , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Máquina de Vetores de Suporte , Análise de Sobrevida , Resultado do Tratamento
17.
Int J Radiat Oncol Biol Phys ; 106(1): 134-145, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568813

RESUMO

PURPOSE: To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW). METHODS AND MATERIALS: This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status. RESULTS: Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW. CONCLUSIONS: The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.


Assuntos
Sobreviventes de Câncer , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Retorno ao Trabalho , Adulto , Ansiedade/psicologia , Canadá , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Estudos Transversais , Depressão/psicologia , Intervalo Livre de Doença , Emprego/estatística & dados numéricos , Feminino , Humanos , Renda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/psicologia , Neoplasias Nasofaríngeas/psicologia , Ocupações , Desempenho Físico Funcional , Qualidade de Vida , Retorno ao Trabalho/psicologia , Retorno ao Trabalho/estatística & dados numéricos , Tolerância ao Trabalho Programado
19.
Eur Radiol ; 30(1): 110-118, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31372786

RESUMO

OBJECTIVES: To explore the utility of dynamic contrast-enhanced MRI (DCE-MRI) and readout-segmented diffusion-weighted imaging (RESOLVE-DWI) in the differentiation of nasopharyngeal carcinoma (NPC) and nasopharyngeal lymphoma (NPL). METHODS: Sixty-two patients with NPC and 39 patients with NPL who underwent DCE-MRI and RESOLVE-DWI examinations were evaluated. The time signal-intensity curve (TIC) types, time to peak (TTP), enhancement peak (EP), maximum contrast enhancement ratio (MCER), washout ratio (WR), apparent diffusion coefficient (ADC), and relative ADC (rADC) values were calculated. Statistical analysis between the two groups was performed to determine the statistical significance of each parameter. Receiver operating characteristic (ROC) curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing NPC from NPL. RESULTS: The most common TIC curve was type III in patients with NPC (n = 26), while the majority of the curves were types I (n = 14) and II (n = 19) in patients with NPL. TTP, EP, MCER, ADC, and rADC were statistically significantly different between NPCs and NPLs (p < 0.05). Among these factors, ADC revealed the most reliable diagnostic performance, followed by rADC, TTP, MCER, and EP. Moreover, the diagnostic efficiency of the combined DCE-MRI parameters was higher than that of TTP, MCER, and EP each alone. In addition, the combination of all DCE-MRI and DWI parameters together demonstrated the highest diagnostic efficiency (area under the curve = 0.961). However, none of the parameters was significantly different between keratinising NPC and non-keratinising NPC or between NK/T lymphoma and diffuse large B cell lymphoma (all p > 0.05). CONCLUSION: DCE-MRI and RESOLVE-DWI are effective in differentiating NPC from NPL. KEY POINTS: • RESOLVE offers high image quality in the head and neck regions. • Dynamic contrast-enhanced MRI and RESOLVE-DWI help clinicians to make the differential diagnosis between NPC and NPL. • The combination of all the DCE-MRI and DWI parameters together demonstrated the highest diagnostic efficiency compared with each parameter alone.


Assuntos
Linfoma/diagnóstico , Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1166-1172, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801705

RESUMO

OBJECTIVE: To investigate the effect of down-regulation of miR-205-5p on 3-bromopyruvate-induced apoptosis in human nasopharyngeal carcinoma CNE2Z cells. METHODS: Nasopharyngeal carcinoma CNE2Z cells were transfected with miR- 205-5p-mimic or miR-205-5p-inhibitor, treated with 80 µmol/L 3-bromopyruvate alone, or exposed to both of the treatments. The proliferation of the treated cells was examined with MTT assay, and early apoptosis of the cells was detected using a mitochondrial membrane potential detection kit (JC-1). DAPI fluorescence staining was used to detect morphological changes of the cell nuclei and late cell apoptosis; Annexin V-FITC/PI double staining was employed to detect the cell apoptosis rate. Western blotting was used to detect the expressions of Bcl-2, Bax, Mcl-1 and Bak proteins. RESULTS: Exposure to 3-bromopyruvate significantly inhibited the proliferation of CNE2Z cells, and increasing the drug concentration and extending the treatment time produced stronger inhibitory effects. Treatment with 80 µmol/L 3-bromopyruvate for 24, 48 and 72 h resulted in inhibition rates of (45.7±1.21)%, (64.4±2.02)% and (78.3±1.55)% in non-transfected CNE2Z cells, respectively; the inhibition rates were (27.7±1.04)%, (34.8±2.10)% and (44.3±1.57)% in the cells transfected with miR-205-5p-mimic, and were (80.5 ± 0.94)%, (87.9 ± 0.50)% and (93.8 ± 1.16)% in cells transfected with miR-205-5p-inhibitor, respectively. The results of mitochondrial membrane potential detection showed that the relative proportion of red and green fluorescence decreased significantly in miR-205-5p-inhibitor-transfected cells with 3-bromopyruvate treatment. Combined treatment of the cells with 3-bromopyruvate and miR-205-5p-inhibitor transfection obviously increased nuclear fragmentation and nuclear pyknosis and significantly increased cell apoptotic rate as compared with the two treatments alone (P < 0.01), causing also decreased expressions of Bcl-2 and Mcl-1 proteins and increased expressions of Bax and Bak proteins. CONCLUSIONS: Inhibition of miR-205-5p enhances the proapototic effect of 3-bromopyruvate in CNE2Z cells possibly in relation to the down-regulation of Mcl-1 and Bcl-2 and the up-regulation of Bak and Bax proteins.


Assuntos
Apoptose , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Piruvatos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
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