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1.
J Glob Health ; 10(1): 010405, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32257153

RESUMO

Background: Epstein Barr Virus (EBV) infects 90%-95% of all adults globally and causes ~ 1% of all cancers. Differing proportions of Burkitt's lymphoma (BL), gastric carcinoma (GC), Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC) are associated with EBV. We sought to systematically review the global epidemiological evidence for risk factors that (in addition to EBV) contribute to the development of the EBV-associated forms of these cancers, assess the quality of the evidence, and compare and contrast the cancers. Methods: MEDLINE, Embase and Web of Science were searched for studies of risk factors for EBV-associated BL, GC, HL and NPC without language or temporal restrictions. Studies were excluded if there was no cancer-free comparator group or where analyses of risk factors were inadequately documented. After screening and reference list searching, data were extracted into standardised spreadsheets and quality assessed. Due to heterogeneity, a narrative synthesis was undertaken. Results: 9916 hits were retrieved. 271 papers were retained: two BL, 24 HL, one GC and 244 NPC. The majority of studies were from China, North America and Western Europe. Risk factors were categorised as dietary, environmental/non-dietary, human genetic, and infection and clinical. Anti-EBV antibody load was associated with EBV-associated GC and BL. Although the evidence could be inconsistent, HLA-A alleles, smoking, infectious mononucleosis and potentially other infections were risk factors for EBV-associated HL. Rancid dairy products; anti-EBV antibody and EBV DNA load; history of chronic ear, nose and/or throat conditions; herbal medicine use; family history; and human genetics were risk factors for NPC. Fresh fruit and vegetable and tea consumption may be protective against NPC. Conclusions: Many epidemiological studies of risk factors in addition to EBV for the EBV-associated forms of BL, GC, HL and NPC have been undertaken, but there is a dearth of evidence for GC and BL. Available evidence is of variable quality. The aetiology of EBV-associated cancers likely results from a complex intersection of genetic, clinical, environmental and dietary factors, which is difficult to assess with observational studies. Large, carefully designed, studies need to be strategically undertaken to harmonise and clarify the evidence. Registration: PROSPERO CRD42017059806.


Assuntos
Carcinoma/virologia , Herpesvirus Humano 4/patogenicidade , Neoplasias/virologia , Linfoma de Burkitt/virologia , Doença de Hodgkin/virologia , Humanos , Neoplasias Nasofaríngeas/virologia , Fatores de Risco , Neoplasias Gástricas/virologia
2.
J Laryngol Otol ; 134(4): 338-343, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32172705

RESUMO

OBJECTIVES: The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach. METHODS: A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ('PRISMA') checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts. RESULTS AND CONCLUSION: The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65-2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27-3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Carcinoma Nasofaríngeo/enzimologia , Neoplasias Nasofaríngeas/patologia , Tratamento Farmacológico/métodos , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/terapia , Prognóstico , Radioterapia/métodos , Análise de Sobrevida , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(10): e19360, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150078

RESUMO

BACKGROUND: A systemic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy, toxicity and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Research searching was performed in Web of Science, PubMed, The Cochrane Library, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database for Chinese Technical Periodicals and Wanfang Database. RCTs including patients diagnosed with locoregionally advanced NPC without metastasis and randomly treated with IC plus CCRT and CCRT alone were included. Survival and outcome data were extracted and meta-analysis was performed using the Revman 5.3.0 software. RESULTS: Ten RCTs (2280 patients) were selected and used for pooled meta-analysis. In comparison with CCRT, IC plus CCRT treatment significantly improved the overall survival (OS; HR = 0.70, 95%CI 0.56-0.87, P = .002), progression-free survival (PFS; HR = 0.75, 95%CI 0.65-0.87, P < .0001), distant metastasis failure-free survival (DMFS; HR = 0.71, 95%CI 0.58-0.85, P = .0003) and loco-regional failure-free survival (LFES; HR = 0.72, 95%CI 0.59-0.88, P = .002) of patients with locoregionally advanced NPC. Patients treated with IC and CCRT had higher incidence of grade 3-4 leucopenia and thrombocytopenia than patients treated with CCRT alone (P < .0001). No significant difference in other grade 3-4 adverse events and radiation toxicity was observed between the two groups. IC combined with CCRT improved the survival of patients with locoregionally advanced NPC. CONCLUSIONS: Combined IC and CCRT therapy was an efficacy treatment regimen for locoregionally advanced NPC.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia de Indução/normas , Neoplasias Nasofaríngeas/tratamento farmacológico , Terapia Combinada , Humanos , Quimioterapia de Indução/métodos , Quimioterapia de Indução/tendências , Neoplasias Nasofaríngeas/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
4.
Crit Rev Oncol Hematol ; 148: 102892, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32120328

RESUMO

BACKGROUND: Incidence and mortality rates of childhood cancer represent a global public health issue, however, the worldwide prevalence of head and neck cancer in pediatric patients (HNCPP) is still unknown. Therefore, this study aimed to describe the frequency and distribution of HNCPP worldwide. METHODS: A specific search strategy was performed using MEDLINE, Scopus, and EMBASE to include studies based on hospital records, national cancer registries, and pathology files. Studies quality was assessed using the risk of bias checklist of the Joanna Briggs Institute Critical Appraisal. RESULTS: Nineteen publications (15,970 cases) were included. Global frequency ranged from 0.25 % to 15 %. Male patients older than 10 years of age were most affected by lymphomas, followed by carcinomas and sarcomas. Non-Hodgkin lymphoma, Hodgkin lymphoma, rhabdomyosarcoma, thyroid carcinoma, and nasopharyngeal carcinoma were the main histopathological subtypes. Neck/lymph nodes were anatomical hotspots. CONCLUSIONS: This HNCPP global overview may guide secondary prevention strategies and future etiological studies.


Assuntos
Saúde Global , Neoplasias de Cabeça e Pescoço/epidemiologia , Pediatria , Adolescente , Distribuição por Idade , Criança , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Incidência , Linfoma/epidemiologia , Linfoma/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Masculino , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/patologia , Sarcoma/epidemiologia , Sarcoma/patologia , Distribuição por Sexo , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia
5.
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
6.
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
7.
Medicine (Baltimore) ; 99(10): e19517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150113

RESUMO

INTRODUCTION: Radiotherapy is a valid treatment option for nasopharyngeal carcinoma. However, complications can occur following irradiation of the closest anatomical structures, including brainstem radionecrosis (BRN). The rehabilitation is poorly described in patients with BRN, despite its usefulness in improving functional independence in patients with brain tumors. We aimed at testing the usefulness of intensive, robot-assisted neurorehabilitation program to improve functional independence in a 57-year-old male with BRN. PATIENT CONCERNS: A 57-year-old male diagnosed with a nasopharyngeal carcinoma, received a radiation total dose of 72 Gy. Owing to the appearance of a severe symptomatology characterized by dysphagia, hearing loss, and left sided hemiparesis, the patient was hospitalized to be provided with intensive pharmacological and neurorehabilitation treatment. DIAGNOSIS: Follow-up brain magnetic resonance imaging disclosed no residual cancer, but some brainstem lesions compatible with BRN areas were appreciable. INTERVENTION: The patient underwent a 2-month conventional, respiratory, and speech therapy. Given that the patient only mildly improved, he was provided with intensive robot-aided upper limb and gait training and virtual reality-based cognitive rehabilitation for other 2 months. OUTCOMES: The patient reported a significant improvement in functional independence, spasticity, cognitive impairment degree, and balance. CONCLUSION: Our case suggests the usefulness of neurorobotic intensive rehabilitation in BRN to reduce functional disability. Future studies should investigate whether an earlier, even multidisciplinary rehabilitative treatment could lead to better functional outcome in patients with BRN.


Assuntos
Tronco Encefálico/lesões , Terapia por Exercício , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/reabilitação , Robótica , Tronco Encefálico/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paresia/reabilitação , Lesões por Radiação/diagnóstico por imagem
8.
Cancer Radiother ; 24(2): 93-98, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057645

RESUMO

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use. METHODS: Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results. RESULTS: Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011). CONCLUSION: Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.


Assuntos
Antibacterianos/uso terapêutico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe/efeitos da radiação , Lesões por Radiação/microbiologia , Adulto , Idoso , Candida albicans/efeitos dos fármacos , Ciprofloxacino/uso terapêutico , Feminino , Gentamicinas/uso terapêutico , Humanos , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Necrose/diagnóstico por imagem , Necrose/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Resultado do Tratamento
9.
Br J Radiol ; 93(1109): 20190767, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32026724

RESUMO

OBJECTIVE: Due to the influence of gravity, inertia and friction, there will be deviation between the position of multileaf collimator (MLC) in the delivered field and the initial intensity modulated radiotherapy (IMRT) plan. This study explores the effects of the fragmentation level of subfield sequences on this deviation and seeks ways to improve the accuracy of field delivery in IMRT for nasopharyngeal carcinoma (NPC). METHODS: 30 patients with NPC were selected, and two groups (groups A and B) of IMRT plans were made in Pinnacle planning system. Different planning parameters were used for optimization so that the subfield sequence fragmentation level of Group B was significantly lower than that of Group A. With the MapCheck2, verification plan was implemented in two ways: 0o gantry angle and the actual treatment angle, then the differences between the two verification results of each group plan were analyzed. RESULTS: The γ-passing rate verified at the actual treatment angle was lower than that of 0o gantry angle for each group plan, whereas the Group B plan shows small reduction. Mean change value (Δ) was decreased from 1.01% (Group A) to 0.40% (Group B) with 3%/3 mm criteria and 2.88% (Group A) to 1.52% (Group B) with 2%/2 mm criteria, respectively. The smaller the difference (Δ), the actual output dose of the field is more consistent with the original plan. There was no significant correlation between this change and the angle of the field. CONCLUSION: Appropriately reducing the fragmentation level of subfield sequence can reduce the effect of field angle on MLC position and improve the delivery accuracy of IMRT plan. ADVANCES IN KNOWLEDGE: The fragmentation level of the subfield sequence may have an impact on the accuracy of the delivery of the plan. This study demonstrates this assumption by comparing the differences between 0° and actual angle verification. Mean change value (Δ) was decreased from Group A to Group B. The smaller the difference (Δ), the actual output dose of the field is more consistent with the original plan. The result of this study may help us to understand that appropriately increasing the subfield area and reducing the fragmentation level of the subfield sequence can reduce the difference between the two verification results, which can further improve the accuracy of the plan delivery in IMRT and tumor treatment.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/normas , Desenho de Equipamento , Humanos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco , Planejamento de Assistência ao Paciente , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/instrumentação , Radioterapia de Intensidade Modulada/métodos , Sensibilidade e Especificidade
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
Cancer Radiother ; 24(1): 38-43, 2020 Feb.
Artigo em Francês | MEDLINE | ID: mdl-31992518

RESUMO

PURPOSE: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts. PATIENTS AND METHODS: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary). RESULTS: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid. CONCLUSION: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco , Radioterapia de Intensidade Modulada , Carcinoma/diagnóstico por imagem , Carcinoma/radioterapia , Humanos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Hipófise/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Glândula Submandibular/efeitos da radiação , Glândula Tireoide/efeitos da radiação , Tomografia Computadorizada por Raios X
17.
Int J Cancer ; 146(8): 2305-2314, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31950498

RESUMO

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Quimiorradioterapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia
18.
PLoS Pathog ; 16(1): e1008223, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905218

RESUMO

Epstein-Barr virus (EBV) infection is closely linked to several human malignancies including endemic Burkitt's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinomas (NPC). Latent membrane protein 2 (LMP-2) of EBV plays a pivotal role in pathogenesis of EBV-related tumors and thus, is a potential target for diagnosis and targeted therapy of EBV LMP-2+ malignant cancers. Affibody molecules are developing as imaging probes and tumor-targeted delivery of small molecules. In this study, four EBV LMP-2-binding affibodies (ZEBV LMP-212, ZEBV LMP-2132, ZEBV LMP-2137, and ZEBV LMP-2142) were identified by screening a phage-displayed LMP-2 peptide library for molecular imaging and targeted therapy in EBV xenograft mice model. ZEBV LMP-2 affibody has high binding affinity for EBV LMP-2 and accumulates in mouse tumor derived from EBV LMP-2+ xenografts for 24 h after intravenous (IV) injection. Subsequent fusion of Pseudomonas exotoxin PE38KDEL to the ZEBV LMP-2 142 affibody led to production of Z142X affitoxin. This fused Z142X affitoxin exhibits high cytotoxicity specific for EBV+ cells in vitro and significant antitumor effect in mice bearing EBV+ tumor xenografts by IV injection. The data provide the proof of principle that EBV LMP-2-speicifc affibody molecules are useful for molecular imaging diagnosis and have potentials for targeted therapy of LMP-2-expressing EBV malignancies.


Assuntos
Herpesvirus Humano 4 , Imunotoxinas/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Proteínas da Matriz Viral/metabolismo , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Imunotoxinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Imagem Molecular , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/virologia , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/terapia , Biblioteca de Peptídeos , Ligação Proteica , Proteínas da Matriz Viral/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
19.
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
20.
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
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