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1.
Cell Death Dis ; 15(7): 466, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956029

RESUMO

Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.


Assuntos
Fatores de Transcrição ARNTL , Proteínas Adaptadoras de Transdução de Sinal , Angiomotinas , Movimento Celular , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividade Neoplásica , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Animais , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/metabolismo , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Sinalização YAP/metabolismo , Movimento Celular/genética , Camundongos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Masculino , Metástase Neoplásica , Feminino , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética
3.
Eur Radiol ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38514481

RESUMO

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

4.
BMJ ; 380: e072133, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36746459

RESUMO

OBJECTIVES: To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma. DESIGN: Open-label, non-inferiority, multicentre, randomised, phase 3 trial. SETTING: Three Chinese hospitals between 20 November 2017 and 3 December 2018. PARTICIPANTS: Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement. INTERVENTIONS: Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy. MAIN OUTCOME MEASURES: Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than -8%. RESULTS: 568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3% v 95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of -0.2% ((one sided 97.5% confidence interval -3.6 to ∞), Pnon-inferiority<0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5% v 35.1%, P=0.01) and late dysphagia (24.0% v 34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference -5.6 (95% confidence interval -9.1 to -2.0), P=0.002), role functioning (-5.5 (-7.4 to -3.6), P<0.001), social functioning (-6.2 (-8.9 to -3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference). CONCLUSION: Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT03346109.


Assuntos
Transtornos de Deglutição , Neoplasias Nasofaríngeas , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfonodos/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/radioterapia
5.
Clin Respir J ; 16(8): 562-571, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35871756

RESUMO

INTRODUCTION: Community-acquired pneumonia (CAP) is the major cause of infection-related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia. OBJECTIVES: The aim of this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes. METHODS: In this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30-day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed. RESULTS: Of the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30-day mortality both in non-diabetic and diabetic patients. Furthermore, Kaplan-Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30-day mortality in patients with CAP (P < 0.001). CONCLUSION: Admission blood glucose is correlated with 30-day hospital mortality, ICU admission, and IMV of CAP in elderly patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L was a significant risk factor for 30-day hospital mortality.


Assuntos
Infecções Comunitárias Adquiridas , Diabetes Mellitus , Pneumonia , Idoso , Glicemia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pneumonia/complicações , Prognóstico , Estudos Retrospectivos
6.
J Chin Polit Sci ; : 1-25, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35602544

RESUMO

This paper explores cycles in innovative outcomes corresponding with the timing of political turnover. Using data on local government officials and firm level innovation activities in China, firm innovation is found to be negatively associated with a turnover of local political leaders. We examine several potential explanations and find evidence supporting the premise that political turnover reduces firms' incentives to innovate until the uncertainty is resolved. This paper also indicates that local political turnover significantly inhibits firms' research and development investment, government subsidies, and expansion decisions, leading to less innovative outcomes. Moreover, reductions in innovation are greater in cities with higher levels of government expenditure or intellectual property rights trials, or in smaller firms or non-state-owned enterprises during the rotation of local government leaders.

7.
Front Immunol ; 13: 818411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140722

RESUMO

Background: Inhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC). Methods: The expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model. Results: PD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all P < 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all P < 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; P < 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023). Conclusions: The expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Antígenos B7/metabolismo , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
8.
FASEB J ; 35(10): e21885, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34478585

RESUMO

In a recently published phase III clinical trial, gemcitabine (GEM) plus cisplatin (DDP) induction chemotherapy significantly improved recurrence-free survival and overall survival and became the standard of care among patients with locoregionally advanced NPC. However, the molecular mechanisms of GEM synergized with DPP in NPC cells remain elucidated. These findings prompt us to explore the effect of the combination between GEM and DDP in NPC cell lines through proliferative phenotype, immunofluorescence, flow cytometry, and western blotting assays. In vitro studies reveal that GEM or DPP treated alone induces cell cycle arrest, promotes cell apoptosis, forces DNA damage response, and GEM synergism with DDP significantly increases the above effects in NPC cells. In vivo studies indicate that GEM or DPP treated alone significantly inhibits the tumor growth and prolongs the survival time of mice injected with SUNE1 cells compared to the control group. Moreover, the mice treated with GEM combined with DDP have smaller tumors and survive longer than those in GEM or DPP treated alone group. In addition, P-gp may be the key molecule that regulates the synergistic effect of gemcitabine and cisplatin. GEM synergizes with DPP to inhibit NPC cell proliferation and tumor growth by inducing cell cycle arrest, cell apoptosis, and DNA damage response, which reveals the mechanisms of combined GEM and DDP induction chemotherapy in improving locoregionally advanced NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proliferação de Células/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cisplatino/agonistas , Cisplatino/farmacologia , Desoxicitidina/agonistas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
9.
Exp Biol Med (Maywood) ; 246(24): 2618-2629, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34424090

RESUMO

Non-keratinizing nasopharyngeal carcinoma, the major subtype of nasopharyngeal carcinoma, is characterized by low differentiation and a close relation to Epstein-Barr virus infection, which indicates a link between Epstein-Barr virus oncogenesis and loss of differentiation, and raises our interest in investigating the involvement of Epstein-Barr virus in nasopharyngeal carcinoma dedifferentiation. Our previous study showed abundant expression of an Epstein-Barr virus-encoded microRNA, BART10-3p, in nasopharyngeal carcinoma tissues, but the association between BART10-3p and nasopharyngeal carcinoma differentiation remains unknown. Here, we examined the expression and prognostic value of BART10-3p, and undertook bioinformatics analysis and functional assays to investigate the influence of BART10-3p on nasopharyngeal carcinoma differentiation and proliferation and the underpinning mechanism. Microarray analysis identified BART10-3p as the most significantly upregulated Epstein-Barr virus-encoded microRNA in nasopharyngeal carcinoma tissues and the upregulation was confirmed in two public datasets. The expression of BART10-3p was an independent unfavorable prognosticator in nasopharyngeal carcinoma and its integration with the clinical stage showed improved prognosis predictive performance. Bioinformatics analysis suggested a potential role of BART10-3p in tumor differentiation and progression. Functional assays demonstrated that BART10-3p could promote nasopharyngeal carcinoma cell dedifferentiation, epithelial-mesenchymal transition, and proliferation in vitro, and tumorigenicity in vivo. Mechanistically, BART10-3p directly targeted the 3'UTR of ALK7 and suppressed its expression. Reconstitution of ALK7 rescued BART10-3p-induced malignant phenotypes. Overall, our study demonstrates that BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7, suggesting a promising therapeutic opportunity to reverse the malignant phenotypes of nasopharyngeal carcinoma.


Assuntos
Receptores de Ativinas Tipo I/metabolismo , Infecções por Vírus Epstein-Barr/virologia , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , RNA Viral/metabolismo , Desdiferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/virologia , Células Tumorais Cultivadas
10.
J Chin Polit Sci ; 26(4): 651-674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33903790

RESUMO

This paper provides empirical evidence on the incentive role of personnel control in China in the twenty-first century. Employing the city-level turnover data of political leaders in China between 2000 and 2018 and utilizing the fixed effects ordered logit model, we find that the likelihood of promotion of local leaders rises with their economic performance. This relationship holds more firmly in the municipal party secretary. The probability is also found to decrease with the economic performance of their immediate predecessors and neighboring cities. This finding is robust to various robustness tests. We interpret the finding as evidence that the relative economic performance (peer effects) also contributes to the local political turnover, in particular within a province. Moreover, after the Third Plenary Session of the 18th CPC Central Committee, a material change in the personnel arrangement within the party arises and this promotion mechanism shows a dynamic change. Our study sheds some light on the growing literature emphasizing the relationship between political turnover and economic performance.

11.
J Chin Polit Sci ; 26(1): 189-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33424220

RESUMO

Utilizing national migration data regarding the outbreak of the novel coronavirus (2019-nCoV), this paper employs a difference-in-differences approach to empirically analyze the relationship between human mobility and the transmission of infectious diseases in China. We show that national human mobility restrictions ascribed to the first-level public health emergency response policy effectively reduce both intercity and intracity migration intensities, thus leading to a declining scale of human mobility, which improves the effectiveness in controlling the epidemic. Human mobility restrictions have greater influences on cities with better economic development, denser populations, or larger passenger volumes. Moreover, mobility restriction measures are found to be better implemented in regions with increased public awareness, or with provincial leaders who have healthcare crisis management experience, local administrative experience, or the opportunity to serve a consecutive term.

12.
Radiother Oncol ; 157: 114-121, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33516790

RESUMO

BACKGROUND AND PURPOSE: To explore the prognostic value of different radiologic extranodal extension (rENE) grades and their potential improvement for the 8th edition N category in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From 2009 to 2013, a cohort of 1887 patients with NPC was retrospectively enrolled and randomized to the training (n = 955) and validation (n = 932) groups. rENE was categorized as follows: grade 0, nodes without rENE; grade 1, nodes with rENE infiltrating the surrounding fat only; grade 2, matted nodes; grade 3, nodes with rENE infiltrating adjacent structures. RESULTS: The percentage of patients with MRI-positive cervical nodes was 66.5% (1254/1887), of whom grade 0, 1, 2 and 3 rENE cases accounted for 33.2% (416/1254), 14.9% (187/1254), 36.5% (458/1254) and 15.4% (193/1254), respectively. The kappa coefficients for the inter-rater and intra-rater assessments were 0.63, 0.51, 0.65 and 0.93, and 0.76, 0.69, 0.72 and 1.0 in grade 0, 1, 2 and 3 rENE, respectively. Grade 3 rENE rather than grades 0-2 rENE was an independent unfavorable predictor of overall survival and disease-free survival (P < 0.001). Recursive partitioning analysis was applied to refine the N category: eN0 (N0), eN1 (N1 without grade 3), eN2 (N2 without grade 3), and eN3 (N1/N2 with grade 3, N3). Compared to the current system, the proposed N category performed better in hazard consistency, hazard discrimination, sample size balance and outcome prediction. CONCLUSION: Grade 3 rENE was an independent unfavorable indicator of NPC. Upstaging patients in N1-2 with grade 3 rENE to N3 led to a superior prognostic performance.


Assuntos
Extensão Extranodal , Neoplasias Nasofaríngeas , Humanos , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
13.
Radiother Oncol ; 155: 56-64, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33039423

RESUMO

BACKGROUND AND PURPOSE: In the intensity-modulated radiotherapy (IMRT) era, the role of concurrent chemoradiotherapy (CCRT) after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is undetermined, while concerns exist about CCRT-associated excessive toxicity. We aimed to combine tumor response and risk assessment to guide decisions about concurrent chemotherapy. MATERIALS AND METHODS: From April 2009 to December 2015, 744 LANPC patients treated with CCRT/IMRT after IC were included. Matching techniques were performed for treatment effect evaluation. Tumor response to IC was used for patient stratification. A nomogram was built based on multivariable Cox regression analysis to predict overall survival (OS). RESULTS: After IC, 508 patients (68.3%) had favorable tumor response (complete or partial response), among whom IC + CCRT achieved significantly superior 5-year disease-free survival and OS than IC + IMRT (82.2% vs. 72.5%, P = 0.025; 89.2% vs. 79.9%, P = 0.025). However, no significant difference was found in patients with unfavorable response (both P > 0.05). For favorable responders, a nomogram was built integrating age, smoking, T category, N category, pretreatment Epstein-Barr virus DNA and treatment modality. The concordance index was 0.713 and calibration was good. The nomogram determined three risk groups with distinct OS. High-risk patients benefited from CCRT after IC regarding disease-free survival, OS and distant metastasis-free survival, whereas low- and intermediate-risk patients did not. CONCLUSIONS: For LANPC patients with unfavorable response to IC, subsequent CCRT seems inadequate, rendering intensification necessary. For favorable responders with low risk, IC + IMRT represents a reasonable de-intensification approach, although confirmation by prospective data is needed.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Quimiorradioterapia/efeitos adversos , Herpesvirus Humano 4 , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos
14.
Cells ; 9(3)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120844

RESUMO

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.


Assuntos
Cortactina/metabolismo , Metilação de DNA/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Proteólise , Ubiquitina Tiolesterase/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Regiões Promotoras Genéticas , Ligação Proteica , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
15.
Ther Adv Med Oncol ; 11: 1758835919877729, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598143

RESUMO

BACKGROUND: Few studies have evaluated the prognostic value of the integrated model consisting of gross tumor volume of lymph nodes (GTVnd) and pretreatment plasma Epstein-Barr virus DNA (pre-EBV DNA) in nasopharyngeal carcinoma (NPC) patients. METHODS: A well-established big-data intelligence platform with 10,126 NPC patients was used for a retrospective review. A total of 1500 cases with cervical nodal metastases but without distant metastases were randomly assigned to a training (n = 503) or test condition (n = 997) for analyses. The cut-off point for the GTVnd derived from the receiver operating characteristic (ROC) curve was combined with the published cut-off point for pre-EBV DNA to develop an integrated model by which patients were classified into four groups. RESULTS: Both GTVnd and pre-EBV DNA were independent prognostic factors. Regardless of whether patients received induction chemotherapy (IC), the 5-year distant metastasis-free survival (DMFS) (69.5%) and overall survival (OS) (68.4%) were significantly worse in those with both a GTVnd >20 ml and pre-EBV DNA >2000 copies/ml (all p-values < 0.001). In patients with IC, all others had better 5-year DMFS and OS; in patients without IC, those with either a GTVnd >20 ml or pre-EBV DNA >2000 copies/ml had the medium 5-year DMFS and OS, while patients with neither of them had the best. CONCLUSIONS: The integrated GTVnd and pre-EBV DNA model not only predicted DMFS and OS in NPC patients effectively, but was an indicator of timely adjustment of therapeutic strategies for NPC patients, especially those completing IC.

16.
Oral Oncol ; 91: 7-12, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926066

RESUMO

OBJECTIVES: Epstein-Barr virus (EBV)-positive cervical lymph node (CLN) metastasis of unknown primary origin is classified as nasopharyngeal carcinoma (NPC) T0 by the American Joint Committee on Cancer staging manual (8th edition). We aimed to investigate the possible primary sites and patterns of EBV-positive CLN metastases and to provide implications for the management of NPC T0 classification. MATERIALS AND METHODS: We retrospectively reviewed 269 patients with newly diagnosed EBV-positive CLN metastatic disease who underwent EBV detection via EBV-encoded RNA in situ hybridization. Fifteen patients with unknown primary tumors underwent follow-up after initial treatment. RESULTS: In patients with EBV-positive CLNs, the most common primary sites after the nasopharynx (51.7%) were the salivary gland (24.5%), lung (7.8%), oropharynx (3.3%), nasal cavity/maxillary (3.3%), oral cavity (2.2%), orbit (1.1%), and liver (0.4%). No primary site was found in 15 patients (5.6%). For salivary gland malignancies, level II and I were the most frequently involved regions. Tumors arising from the lung or liver metastasized to the lower neck (level IV, V, and VI) rather than the upper neck. After initial treatment, 2/15 patients with EBV-positive CLNs of unknown primary exhibited primary NPC and oropharyngeal tumor, respectively. Further, even without prophylactic irradiation to the nasopharynx, only one of 13 unknown primary patients developed NPC. CONCLUSIONS: The origins of EBV-positive CLNs may not be restricted to the nasopharynx alone, and are likely to involve the head and neck or non-head and neck regions. NPC T0 classification should be cautiously assigned to such tumors.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Neoplasias de Cabeça e Pescoço/virologia , Linfonodos/patologia , Pescoço/patologia , Neoplasias Primárias Desconhecidas/virologia , Adolescente , Adulto , Idoso , Criança , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/classificação , Carcinoma Nasofaríngeo/terapia , Neoplasias Primárias Desconhecidas/patologia , Estudos Retrospectivos , Adulto Jovem
17.
Light Sci Appl ; 8: 16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30701074

RESUMO

The unrestricted control of circularly polarized (CP) terahertz (THz) waves is important in science and applications, but conventional THz devices suffer from issues of bulky size and low efficiency. Although Pancharatnam-Berry (PB) metasurfaces have shown strong capabilities to control CP waves, transmission-mode PB devices realized in the THz regime are less efficient, limiting their applications in practice. Here, based on Jones matrix analysis, we design a tri-layer structure (thickness of ~λ/5) and experimentally demonstrate that the structure can serve as a highly efficient transmissive meta-atom (relative efficiency of ~90%) to build PB metadevices for manipulating CP THz waves. Two ultrathin THz metadevices are fabricated and experimentally characterized with a z-scan THz imaging system. The first device can realize a photonic spin Hall effect with an experimentally demonstrated relative efficiency of ~90%, whereas the second device can generate a high-quality background-free CP Bessel beam with measured longitudinal and transverse field patterns that exhibit the nondiffracting characteristics of a Bessel beam. All the experimental results are in excellent agreement with full-wave simulations. Our results pave the way to freely manipulate CP THz beams, laying a solid basis for future applications such as biomolecular control and THz signal transportation.

18.
Sci Rep ; 7(1): 1354, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28465543

RESUMO

Efficiently exciting surface plasmon polaritons (SPP) is highly desired in many photonic applications, but most approaches (such as prism and grating couplers) cannot control flexibly their SPP excitation directions. While Pancharatnam-Berry (PB) metasurfaces were recently proposed to achieve direction-controllable SPP excitations, such scheme suffers from low-efficiency issue due to both direct reflections at the coupler surface and the mode mismatch between the coupler and the guiding-out plasmonic structure. In this article, we solve these issues via imposing two criterions to guide design both the metasurface and the plasmonic metal, based on which a direction-controllable SPP excitation with very high efficiency can be realized. As a proof of concept, we designed/fabricated a realistic device working in the microwave regime, and performed both near-field and far-field measurements to demonstrate that it can achieve an spoof SPP conversion efficiency ~78%, much higher than previous devices. Full-wave simulations are in good agreement with experiments, showing that the efficiency can be further pushed to 92% with optimized designs. Our findings can stimulate spoof SPP-related applications, particularly can help enhance the spin-dependent light-matter interactions in low frequency regime.

19.
Sci Rep ; 6: 38255, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27901088

RESUMO

Controlling the phase distributions on metasurfaces leads to fascinating effects such as anomalous light refraction/reflection, flat-lens focusing, and optics-vortex generation. However, metasurfaces realized so far largely reply on passive resonant meta-atoms, whose intrinsic dispersions limit such passive meta-devices' performances at frequencies other than the target one. Here, based on tunable meta-atoms with varactor diodes involved, we establish a scheme to resolve these issues for microwave metasurfaces, in which the dispersive response of each meta-atom is precisely controlled by an external voltage imparted on the diode. We experimentally demonstrate two effects utilizing our scheme. First, we show that a tunable gradient metasurface exhibits single-mode high-efficiency operation within a wide frequency band, while its passive counterpart only works at a single frequency but exhibits deteriorated performances at other frequencies. Second, we demonstrate that the functionality of our metasurface can be dynamically switched from a specular reflector to a surface-wave convertor. Our approach paves the road to achieve dispersion-corrected and switchable manipulations of electromagnetic waves.

20.
IEEE Trans Biomed Eng ; 63(4): 694-706, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26292335

RESUMO

A wireless power transfer system based on the weakly inductive coupling makes it possible to provide the endoscope microrobot (EMR) with infinite power. To facilitate the patients' inspection with the EMR system, the diameter of the transmitting coil is enlarged to 69 cm. Due to the large transmitting range, a high quality factor of the Litz-wire transmitting coil is a necessity to ensure the intensity of magnetic field generated efficiently. Thus, this paper builds an analytical model of the transmitting coil, and then, optimizes the parameters of the coil by enlarging the quality factor. The lumped model of the transmitting coil includes three parameters: ac resistance, self-inductance, and stray capacitance. Based on the exact two-dimension solution, the accurate analytical expression of ac resistance is derived. Several transmitting coils of different specifications are utilized to verify this analytical expression, being in good agreements with the measured results except the coils with a large number of strands. Then, the quality factor of transmitting coils can be well predicted with the available analytical expressions of self- inductance and stray capacitance. Owing to the exact estimation of quality factor, the appropriate coil turns of the transmitting coil is set to 18-40 within the restrictions of transmitting circuit and human tissue issues. To supply enough energy for the next generation of the EMR equipped with a Ø9.5×10.1 mm receiving coil, the coil turns of the transmitting coil is optimally set to 28, which can transfer a maximum power of 750 mW with the remarkable delivering efficiency of 3.55%.


Assuntos
Endoscopia/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Desenho de Equipamento , Humanos , Campos Magnéticos
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