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1.
Int J Med Sci ; 17(16): 2561-2569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029098

RESUMO

Background: During the outbreak period of COVID-19 pneumonia, cancer patients have been neglected and in greater danger. Furthermore, the differential diagnosis between COVID-19 pneumonia and radiation pneumonitis in cancer patients remains a challenge. This study determined their clinical presentations and radiological features in order to early diagnose and separate COVID-19 pneumonia from radiation pneumonitis patients promptly. Methods and Findings: From January 21, 2020 to February 18, 2020, 112 patients diagnosed with suspected COVID-19 were selected consecutively. A retrospective analysis including all patients' presenting was performed. Four patients from 112 suspected individals were selected, including 2 males and 2 females with a median age of 54 years (range 39-64 years). After repeated pharyngeal swab nucleic acid tests, 1 case was confirmed and 3 cases were excluded from COVID-19 pneumonia. Despite the comparable morphologic characteristics of lung CT imaging, the location, extent, and distribution of lung lesions between COVID-19 pneumonia and radiation pneumonitis differed significantly. Conclusions: Lung CT imaging combined with clinical and laboratory findings can facilitate early diagnosis and appropriate management of COVID-19 pneumonia with a history of malignancy and radiation therapy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Diagnóstico Diferencial , Neoplasias/radioterapia , Pneumonia Viral/diagnóstico por imagem , Pneumonite por Radiação/diagnóstico por imagem , Adulto , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias/virologia , Pandemias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
2.
Medicine (Baltimore) ; 99(39): e22283, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991429

RESUMO

For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), induction chemotherapy (IC) regimens based on TPF (docetaxel, cisplatin, and 5-fluorouracil), TP (docetaxel and cisplatin), and GP (gemcitabine and cisplatin) have shown excellent survival outcomes as the first-line therapy; however, no trials comparing the efficacy and safety of TPF, TP, and GP have been reported. We report 2 phase II trials comparing the treatment outcomes and side effects of 3 different IC regimens followed by concurrent chemoradiotherapy in locoregionally advanced patients with NPC.A total of 206 locoregionally advanced patients with NPC treated with a combination treatment from January 2012 to January 2014 were enrolled in the 2 studies. The patients received TPF-, TP-, and GP-based IC regimens every 3 weeks, followed by intensity-modulated radiotherapy and concurrent therapy with cisplatin every 3 weeks.After a median follow-up duration of 47 months (10-60 months), the 3-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival rates were 96.4%, 100%, 87.7%, 86%, and 94.7% in the TPF arm; 91.7%, 95.9%, 91.9%, 85.2%, and 92% in the TP arm; 98.6%, 100%, 89.0%, 87.6%, and 89.2% in the GP arm. The survival differences among the 3 arms were not statistically significant (P > .05). The multivariate analysis demonstrated that the IC regimen was not an independent prognostic factor for any survival outcomes. The patients in the TP arm experienced significantly lower grade 3/4 toxicities than the patients in the other 2 arms.TP-based IC regimen has similar efficacy compared with TPF- and GP-based IC regimens; however, TP-based IC regimen has a lower toxicity profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estudos Prospectivos , Radioterapia de Intensidade Modulada , Adulto Jovem
3.
Medicine (Baltimore) ; 99(30): e21325, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791728

RESUMO

The present study aimed to retrospectively analyze the survival outcomes and prognostic factors for patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).Clinical data was collected from 691 patients with NPC receiving IMRT from January 2009 to August 2015. A survival analysis was performed and prognostic factors were analyzed using the Kaplan-Meier method, the Cox proportional hazards regression model, and the log-rank test.The median follow-up time was 62.8 months. Sixty-three patients experienced relapse, 44 cases (70%) of which occurred within 3 years. Six cases (9.5%) remained in remission for over 5 years. Seventy-two patients developed metastasis, 63 cases (87.5%) of which occurred within 3 years and only 1 case occurred after 5 years (1.3%). Five-year disease special survival (DSS), progression free survival, locoregional recurrence free survival, and distant metastasis free survival were 86.5%, 82.5%, 90.7%, and 89.4%, respectively in patients with NPC. Patients with stage III NPC with and without induction chemotherapy had 5-year DSS rates of 95.8% and 89.3%, respectively (P = .00). Patients with stage IVa NPC with and without induction chemotherapy had 5-year DSS rates of 73.1% and 68.9%, respectively (P = .04). The 5-year DSS rates of patients with stage III with or without concurrent chemotherapy were 92.8% and 85.5%, respectively (P = .04). The 5-year DSS rates of patients with stage IV with or without concurrent chemotherapy were 72.7% and 53.0% (P = .02).IMRT improves the survival rate of patients with NPC. Recurrence and metastasis mainly occur within 2 to 3 years after radiotherapy. Induction and concurrent chemotherapy improve the 5-year DSS of patients with locally advanced NPC.


Assuntos
Quimiorradioterapia/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Quimiorradioterapia/métodos , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(29): e20443, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702809

RESUMO

BACKGROUND: Although common, the use of concurrent chemoradiotherapy with adjuvant chemotherapy for stage II nasopharyngeal carcinoma (NPC) is controversial due to its undefined clinical benefits. We, therefore, conducted a retrospective cohort study to investigate whether adjuvant chemotherapy confers survival gains to stage II NPC patients. METHODS: In this study, we examined whether combining adjuvant chemotherapy (AC) and/or concurrent chemotherapy with radiotherapy (CCRT) improved survival in patients with stage II NPC. Three hundred thirty-five stage II NPC patients were retrospectively analyzed between June 2003 and June 2016 and received CCRT; some patient groups also received AC every 3 weeks for 2 to 3 cycles. RESULTS: The median follow-up duration was 72 months for all patients (range, 26-151 months) and the estimated 5-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 95.1%, 97.8%, 93.5%, and 94.3%. At the last follow-up, there were no statistically significant differences among the CCRT and CCRT+AC groups in 5-year LRRFS (95.2% vs 94.9%, P = .599), DMFS (98.5% vs 92.4%, P = .152), PFS (93.8% vs 90.2%, P = .599), or OS (95.5% vs 93.9%, P = .682) rates. CONCLUSION: The analyses revealed that a combined regimen was not an independent prognostic factor for any survival outcome. However, patients who received CCRT plus AC experienced more acute adverse events than those who received CCRT alone. Thus, the addition of AC to CCRT did not improve survival outcomes, but was associated with higher incidences of acute treatment-associated toxicities than CCRT alone in patients with stage II NPC.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(29): e20760, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702820

RESUMO

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.


Assuntos
Braquiterapia/métodos , Carcinoma/radioterapia , Planejamento da Radioterapia Assistida por Computador/instrumentação , Algoritmos , Braquiterapia/tendências , Fracionamento da Dose de Radiação , Feminino , Humanos , Radioisótopos de Irídio/metabolismo , Masculino , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Doses de Radiação , Dosagem Radioterapêutica/normas , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia
6.
PLoS One ; 15(7): e0236841, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730364

RESUMO

PURPOSE: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters have shown prognostic value in nasopharyngeal carcinomas (NPC), mostly in monocenter studies. The aim of this study was to assess the prognostic impact of standard and novel PET parameters in a multicenter cohort of patients. METHODS: The established PET parameters metabolic tumor volume (MTV), total lesion glycolysis (TLG) and maximal standardized uptake value (SUVmax) as well as the novel parameter tumor asphericity (ASP) were evaluated in a retrospective multicenter cohort of 114 NPC patients with FDG-PET staging, treated with (chemo)radiation at 8 international institutions. Uni- and multivariable Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), event-free survival (EFS), distant metastases-free survival (FFDM), and locoregional control (LRC) was performed for clinical and PET parameters. RESULTS: When analyzing metric PET parameters, ASP showed a significant association with EFS (p = 0.035) and a trend for OS (p = 0.058). MTV was significantly associated with EFS (p = 0.026), OS (p = 0.008) and LRC (p = 0.012) and TLG with LRC (p = 0.019). TLG and MTV showed a very high correlation (Spearman's rho = 0.95), therefore TLG was subesequently not further analysed. Optimal cutoff values for defining high and low risk groups were determined by maximization of the p-value in univariate Cox regression considering all possible cutoff values. Generation of stable cutoff values was feasible for MTV (p<0.001), ASP (p = 0.023) and combination of both (MTV+ASP = occurrence of one or both risk factors, p<0.001) for OS and for MTV regarding the endpoints OS (p<0.001) and LRC (p<0.001). In multivariable Cox (age >55 years + one binarized PET parameter), MTV >11.1ml (hazard ratio (HR): 3.57, p<0.001) and ASP > 14.4% (HR: 3.2, p = 0.031) remained prognostic for OS. MTV additionally remained prognostic for LRC (HR: 4.86 p<0.001) and EFS (HR: 2.51 p = 0.004). Bootstrapping analyses showed that a combination of high MTV and ASP improved prognostic value for OS compared to each single variable significantly (p = 0.005 and p = 0.04, respectively). When using the cohort from China (n = 57 patients) for establishment of prognostic parameters and all other patients for validation (n = 57 patients), MTV could be successfully validated as prognostic parameter regarding OS, EFS and LRC (all p-values <0.05 for both cohorts). CONCLUSIONS: In this analysis, PET parameters were associated with outcome of NPC patients. MTV showed a robust association with OS, EFS and LRC. Our data suggest that combination of MTV and ASP may potentially further improve the risk stratification of NPC patients.


Assuntos
Quimiorradioterapia/mortalidade , Glicólise , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Tomografia por Emissão de Pósitrons/métodos , Feminino , Fluordesoxiglucose F18/metabolismo , Seguimentos , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
7.
Artigo em Inglês | MEDLINE | ID: mdl-32646021

RESUMO

Deciding between palliative and overly aggressive therapies for advanced cancer patients who present to the emergency department (ED) with acute issues requires a prediction of their short-term survival. Various scoring systems have previously been studied in hospices or intensive care units, though they are unsuitable for use in the ED. We aim to examine the use of a shock index (SI) in predicting the 60-day survival of advanced cancer patients presenting to the ED. Identified high-risk patients and their families can then be counseled accordingly. Three hundred and five advanced cancer patients who presented to the EDs of three tertiary hospitals were recruited, and their data retrospectively analyzed. Relevant data regarding medical history and clinical presentation were extracted, and respective shock indices calculated. Multivariate logistic regression analyses were performed. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the SI. Nonsurvivors within 60 days had significantly lower body temperatures and blood pressure, as well as higher pulse rates, respiratory rates, and SI. Each 0.1 SI increment had an odds ratio of 1.39 with respect to 60-day mortality. The area under the ROC curve was 0.7511. At the optimal cut-off point of 0.94, the SI had 81.38% sensitivity and 73.11% accuracy. This makes the SI an ideal evaluation tool for rapidly predicting the 60-day mortality risk of advanced cancer patients presenting to the ED. Identified patients can be counseled accordingly, and they can be assisted in making informed decisions on the appropriate treatment goals reflective of their prognoses.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Mortalidade Hospitalar , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Choque/mortalidade , Humanos , Masculino , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Choque/fisiopatologia , Fatores de Tempo
9.
Anticancer Res ; 40(6): 3255-3264, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487620

RESUMO

BACKGROUND/AIM: Rta, a transactivator of Epstein-Barr virus, is associated with progression of nasopharyngel carcinoma (NPC); however, its mechanism of contribution to the pathogenesis of NPC remains unclear. Interleukin-6 (IL-6), a tumor promoter, is detected in NPC. This in vitro study examined whether and how Rta promotes NPC progression by up-regulating IL-6. MATERIALS AND METHODS: Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, ELISA, immunoblotting assays, reporter gene assays, and transwell migration assays were performed. RESULTS: In NPC cells, Rta up-regulated IL-6 expression at the mRNA and protein levels, and the Rta's C-terminus was essential for promoter activation and expression of IL-6. The induction of IL-6 by Rta also required activation of extracellular signal-regulated kinase 1/2 and activator protein-1. Furthermore, IL-6 secreted from Rta-expressing NPC cells promoted migration of Rta-negative NPC cells by activating IL-6 receptor/Janus kinase/signal transducer and activator of transcription 3 pathway. CONCLUSION: Rta contributes to progression of NPC cells through induction of IL-6 in vitro.


Assuntos
Proteínas Imediatamente Precoces/metabolismo , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Neoplasias/metabolismo , Receptores de Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Transativadores/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Humanos , Proteínas Imediatamente Precoces/genética , Interleucina-6/biossíntese , Interleucina-6/genética , Sistema de Sinalização das MAP Quinases , Células MCF-7 , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Neoplasias/genética , Neoplasias/patologia , Neoplasias/virologia , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Transativadores/genética , Fator de Transcrição AP-1/metabolismo , Transfecção , Regulação para Cima
10.
Clin Imaging ; 66: 127-132, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32480267

RESUMO

PURPOSE: To probe the utility of diffusion-weighted imaging (DWI) and 3D arterial spin labeling (ASL) in assessing the clinical stage of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This prospective study included sixty-five newly diagnosed NPC patients who underwent DWI and 3D ASL scans on a 3.0-T magnetic resonance imaging (MRI) system. The apparent diffusion coefficient (ADC) and the tumor blood flow (TBF) of NPC were measured. Tumors were classified as low or high T, N and American Joint Committee on Cancer (AJCC) stages. Student's t-test was used to evaluate the differences between tumors with low and high clinical stages. Pearson correlation analyses were performed to determine the correlation between MRI parameters and clinical stages. Receiver operating characteristic (ROC) curves were then used to evaluate diagnostic capability. RESULTS: High T stage (T3/4) NPC showed significantly lower ADCmin (P = 0.000) and higher TBFmax (P = 0.003) and TBFmean (P = 0.008) values than low T stage (T1/2) NPC. High N stage (N2/3) NPC showed significantly lower ADCmin values (P = 0.023) than low N stage (N0/1) NPC. High AJCC stage (III/IV) NPC showed significantly lower ADCmin (P = 0.000) and higher TBFmax (P = 0.005) and TBFmean (P = 0.011) values than low AJCC stage (I/II) NPC. ADCmin values showed moderate negative correlations with T stage (r = -0.512, P = 0.000), N stage (r = -0.281, P = 0.023), and AJCC stage (r = -0.494, P = 0.000). TBFmax values showed moderate positive correlations with T stage (r = 0.369, P = 0.003) and AJCC stage (r = 0.346, P = 0.005). Compared with ADCmin and TBFmax alone, the combination of ADCmin and TBFmax improved the accuracy from 72.3% and 75.4% to 78.5%, respectively, for T staging, as well as from 72.3% and 69.2% to 83.1% for AJCC staging. CONCLUSIONS: ADCmin and TBFmax values in patients with NPC could help evaluate clinical stages. ADCmin and TBFmax values combined could clearly improve the accuracy in the assessment of AJCC stage.


Assuntos
Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Estadiamento de Neoplasias , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Estudos Prospectivos , Curva ROC , Marcadores de Spin
11.
J Cancer Res Ther ; 16(2): 309-319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474518

RESUMO

Objective: Regulatory T cells (Tregs) are critical factors that impair antitumor immunity. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is one of the most pathogenic factors in nasopharyngeal carcinoma (NPC). However, the role of EBV-encoded LMP1 in regulating Treg generation in NPC remains unclear. Materials and Methods: The in vitro stability of activated Tregs (aTregs) influenced by LMP1 was analyzed by flow cytometry. The inhibitory effects of LMP1-HONE1 antigen-induced aTregs on tumor-associated antigen (TAA)-specific T cells were analyzed in vitro and in vivo. Finally, the expression of LMP1, Foxp3, and enhancer of zeste homolog 2 (EZH2) were analyzed in samples from 86 NPC patients by immunohistochemistry and immunofluorescence. Results: LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. EZH2 inhibitor, DZnep, depleted LMP1-HONE1 antigen-induced aTregs in vitro and led to potent TAA-specific T cell antitumor immunity in vivo. In NPC tissues, LMP1 expression level was positively correlated with the number of EZH2+ Tregs, which was positively correlated with clinical stage and overall survival. Conclusions: EZH2 is essential for maintaining the stability and inhibitory functions of aTregs that are induced by EBV-encoded LMP1 in NPC.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Carcinoma Nasofaríngeo/imunologia , Linfócitos T Reguladores/imunologia , Proteínas da Matriz Viral/metabolismo , Animais , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Proteína Potenciadora do Homólogo 2 de Zeste/imunologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Humanos , Imunidade Celular , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Taxa de Sobrevida , Linfócitos T Reguladores/metabolismo , Proteínas da Matriz Viral/imunologia
12.
Ann Otol Rhinol Laryngol ; 129(10): 1011-1019, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32468823

RESUMO

OBJECTIVES: Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein-Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. METHODS: IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. RESULTS: Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size (P < .001). Kaplan-Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression (P = .018). The relationship between these two biomarkers could influence patient survival. CONCLUSION: IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.


Assuntos
Infecções por Vírus Epstein-Barr/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , RNA Viral/metabolismo , Receptor IGF Tipo 1/metabolismo , Proteínas da Matriz Viral/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Nasofaringe/metabolismo , Prognóstico , Mucosa Respiratória/metabolismo , Taxa de Sobrevida , Tunísia , Adulto Jovem
13.
Am J Pathol ; 190(8): 1691-1700, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32360568

RESUMO

The pathologic diagnosis of nasopharyngeal carcinoma (NPC) by different pathologists is often inefficient and inconsistent. We have therefore introduced a deep learning algorithm into this process and compared the performance of the model with that of three pathologists with different levels of experience to demonstrate its clinical value. In this retrospective study, a total of 1970 whole slide images of 731 cases were collected and divided into training, validation, and testing sets. Inception-v3, which is a state-of-the-art convolutional neural network, was trained to classify images into three categories: chronic nasopharyngeal inflammation, lymphoid hyperplasia, and NPC. The mean area under the curve (AUC) of the deep learning model is 0.936 based on the testing set, and its AUCs for the three image categories are 0.905, 0.972, and 0.930, respectively. In the comparison with the three pathologists, the model outperforms the junior and intermediate pathologists, and has only a slightly lower performance than the senior pathologist when considered in terms of accuracy, specificity, sensitivity, AUC, and consistency. To our knowledge, this is the first study about the application of deep learning to NPC pathologic diagnosis. In clinical practice, the deep learning model can potentially assist pathologists by providing a second opinion on their NPC diagnoses.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Bases de Dados Factuais , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Redes Neurais de Computação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Environ Toxicol ; 35(10): 1082-1090, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449842

RESUMO

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharyngeal mucosa. Elderly people above the age of 65 years are more susceptible to NPC. Nasopharyngectomy is the renowned treatment procedure to NPC; however, it is too risky due to its complicated surgical procedure. Other treatment methods also reported with serious side effects such brain injury; hence, the alternative anticancer drug without any side effects was needed. Fucoxanthin is a carotenoid derived from marine algae with the numerous pharmacological functions. This study aims to examine the inhibitory potential in NPC cell proliferation via apoptosis and autophagy. The cytotoxicity of fucoxanthin on C666-1 cells was observed by the MTT assay. The expression of autophagy-linked proteins was assessed with immunoblotting analysis. The expression of autophagy protein LC3 was estimated using immunocytochemical analysis in C666-1 and GFP-LC3 transfected cells. Furthermore, the fucoxanthin-treated C666-1 cells were analyzed with TUNEL assay. The apoptotic level in the fucoxanthin-treated C666-1 cells was evaluated using acridine orange staining. Fucoxanthin significantly increased the expression of autophagy-linked proteins which is clearly depicted in the immunoblotting analysis and immunocytochemical analysis of GFP-tagged LC3 protein. The results of TUNEL assay of fucoxanthin-treated C666-1 in the presence autophagy inhibitors demonstrated the induction of autophagy by fucoxanthin. Acridine orange staining results of C666-1 confirmed fucoxanthin decreases the expression of autophagy-linked proteins during stressed condition thereby causes apoptosis. Our overall results authentically conclude that fucoxanthin induces autophagy and apoptosis in NPC cell line, and it can be ideal agent to treat nasopharyngeal cancer in future with further investigations.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Xantofilas/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Masculino , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo
15.
Clin Nucl Med ; 45(7): e325-e326, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32404701

RESUMO

Prostate-specific membrane antigen (PSMA) is expressed universally in juvenile nasopharyngeal angiofibroma (JNA). As contrast enhancement of postoperative scar is common with contrast-enhanced MRI (CEMRI), diagnosis of residual/recurrent JNA remains perplexing. Prostate-specific membrane antigen PET targets only the neovasculature and may aid in resolving this dilemma. Positive contrast enhancement on CEMRI was noted in a patient after 30 years of initial surgery, simulating recurrence. However, there was no abnormal uptake in PSMA scan, which was confirmed by biopsy as postoperative fibrosis. Ga-PSMA PET/MRI fusion may be an easy and novel technique to aid in differentiating residual/recurrent disease from surgical site reparative tissue.


Assuntos
Angiofibroma/diagnóstico por imagem , Angiofibroma/cirurgia , Imagem por Ressonância Magnética , Glicoproteínas de Membrana , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Idoso , Angiofibroma/patologia , Biópsia , Humanos , Masculino , Imagem Multimodal , Neoplasias Nasofaríngeas/patologia , Período Pós-Operatório
16.
Cancer Sci ; 111(6): 1991-2003, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232887

RESUMO

Alternative polyadenylation (APA), which induces shortening of the 3'-UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA-induced 3'-UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3'-UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3'-UTR could escape from miRNA-mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3'-UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/ß-catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3'-UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B-MYH9-Wnt/ß-catenin axis could represent potential targets for individualized treatment in NPC.


Assuntos
Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Regiões 3' não Traduzidas , Animais , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fibronectinas/genética , Xenoenxertos , Humanos , Camundongos , MicroRNAs , Cadeias Pesadas de Miosina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Via de Sinalização Wnt/fisiologia
17.
Bull Cancer ; 107(5): 565-573, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32245602

RESUMO

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer.


Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Tronco Encefálico/efeitos da radiação , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Pescoço/anatomia & histologia , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Medula Espinal/efeitos da radiação , Carga Tumoral/efeitos da radiação , Perda de Peso
18.
PLoS One ; 15(4): e0230524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271791

RESUMO

BACKGROUND: Aberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC. METHODS: Data of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network. RESULTS: In total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified. CONCLUSIONS: The data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Progressão da Doença , Epigênese Genética/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Marcadores Genéticos/genética , Humanos , Análise em Microsséries/métodos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Transcriptoma
19.
Virchows Arch ; 477(4): 573-579, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32328798

RESUMO

Somatostatin receptor 2a (SSTR2a) is an important diagnostic and scintigraphic marker in several tumors, as well as a potential therapeutic target. However, the expression and clinicopathologic significance of SSTR2a in nasopharyngeal carcinoma (NPC) remain unknown. The expression of SSTR2a was retrospectively analyzed in a large series of NPC tissue samples (106 primary NPC samples, comprising 99 primary non-keratinizing NPC (NK-NPC) and 7 keratinizing NPC (K-NPC) samples, and 41 metastatic NPC samples) by immunohistochemistry, with 24 cases of normal nasopharyngeal mucosa tissues used as a control group. Normal epithelia in nasopharyngeal mucosa were negative for SSTR2a in all 24 cases. The expression of SSTR2a in primary NPC was correlated to the histological subtype. Most cases of primary NK-NPC showed expression of SSTR2a (93.9%, 93/99 cases). The percentage of SSTR2a-positive tumor cells ranged from 10 to 100%, while the intensity ranged from 2+ to 4+. None of the primary K-NPC samples showed SSTR2a expression (0/7, 100%). All cases of NPC showed negative expression of other neuroendocrine markers, including synaptophysin, chromogranin A, and CD56. Of all 41 cases of metastatic NK-NPC lesions, SSTR2a expression is concordant with that of the primary lesions, which shows statistical significance (p < 0.001). Our observations expand the spectrum of recognized SSTR2a-positive tumors and demonstrate for the first time that SSTR2a is frequently expressed in primary and metastatic NK-NPC, highlighting its potential as a scintigraphic and therapeutic target in this disease.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Nasofaríngeo/química , Neoplasias Nasofaríngeas/química , Receptores de Somatostatina/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Cintilografia , Estudos Retrospectivos , Adulto Jovem
20.
Int J Clin Oncol ; 25(7): 1250-1259, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32221802

RESUMO

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.


Assuntos
Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Xerostomia/etiologia
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