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1.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502134

RESUMO

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.


Assuntos
COVID-19/imunologia , Moléculas de Adesão Celular/genética , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Lectinas Tipo C/genética , Receptores de Superfície Celular/genética , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , COVID-19/patologia , COVID-19/virologia , Moléculas de Adesão Celular/metabolismo , Conjuntos de Dados como Assunto , Células Dendríticas/metabolismo , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Lectinas Tipo C/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Análise da Randomização Mendeliana , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/virologia , RNA-Seq , Receptores de Superfície Celular/metabolismo , Índice de Gravidade de Doença , Análise de Célula Única
2.
Cell ; 184(18): 4713-4733.e22, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34352228

RESUMO

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ "hillock"-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Imunidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Adulto , Idoso , Efeito Espectador , COVID-19/genética , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/patologia , Nasofaringe/virologia , RNA Viral/análise , RNA Viral/genética , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Transcrição Genética , Carga Viral
3.
EBioMedicine ; 70: 103525, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392148

RESUMO

BACKGROUND: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets. METHODS: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model. FINDINGS: The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs. INTERPRETATION: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. FUNDING: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.


Assuntos
COVID-19/genética , Nasofaringe/virologia , Proteoma/genética , Transcriptoma/genética , Adulto , Animais , Biomarcadores/metabolismo , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Chlorocebus aethiops , Estudos de Coortes , Feminino , Células HEK293 , Humanos , Inflamação/genética , Inflamação/virologia , Interleucina-6/genética , Masculino , Mesocricetus , Pessoa de Meia-Idade , Nasofaringe/patologia , Pandemias , Prognóstico , RNA Mensageiro/genética , SARS-CoV-2/patogenicidade , Regulação para Cima/genética , Células Vero , Replicação Viral/genética
4.
Clin Anat ; 34(6): 969-975, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216513

RESUMO

Nasopharyngeal swabs are performed to collect material for diagnosing diseases affecting the respiratory system, such as Covid-19. Yet, no systematic anatomical study defines concrete prerequisites for successfully targeting the nasopharyngeal mucosa. We therefore aim at simulating nasopharyngeal swabs in human body donors to characterize parameters allowing and supporting to enter the nasopharynx with a swab, while avoiding endangering the cribriform plate. With the aid of metal probes and commercial swabs a total of 314 nasopharyngeal swabs in anatomical head/neck specimens stemming from 157 body donors were simulated. Important anatomical parameters were photo-documented and measured. We provide information on angles and distances between prominent anatomical landmarks and particularly important positions the probe occupies during its advancement through the nares to the upper and lower parts of the nasopharynx and cribriform plate. Based on these data we suggest a simple and safe three-step procedure for conducting nasopharyngeal swabs. In addition, we define easily recognizable signals for its correct performance. Evaluations prove that this procedure in all specimens without deformations of the nasal cavity allows the swab to enter the nasopharynx, whereas a widespread used alternative only succeeds in less than 50%. Our data will be the key for the successful collection of nasopharyngeal material for detecting and characterizing pathogens, such as SARS-CoV-2, which have a high affinity to pharyngeal mucosa. They demonstrate that the danger for damaging the cribriform plate or olfactory mucosa with swabs is unlikely, but potentially higher when performing nasal swabs.


Assuntos
Teste para COVID-19 , COVID-19/diagnóstico , Nasofaringe/patologia , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Manejo de Espécimes/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
5.
Nat Commun ; 12(1): 4193, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234122

RESUMO

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Evasão Tumoral/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Viral da Expressão Gênica/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Camundongos , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/cirurgia , Nasofaringe/virologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Deleção de Sequência , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Evasão Tumoral/efeitos dos fármacos , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Laryngoscope ; 131(8): 1798-1804, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33616259

RESUMO

OBJECTIVES/HYPOTHESIS: The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN: The effectiveness evaluation of diagnostic methods. METHODS: Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS: The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P < .001). No severe complications occurred after FNAB. CONCLUSIONS: FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1798-1804, 2021.


Assuntos
Biópsia por Agulha Fina/métodos , Endoscopia/métodos , Biópsia Guiada por Imagem/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Nasofaringe/patologia , Nasofaringe/cirurgia , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
8.
J Immunother Cancer ; 9(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33574054

RESUMO

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.


Assuntos
COVID-19/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pneumonia/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/virologia , Diagnóstico Diferencial , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/patologia , Lesão Pulmonar/virologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/virologia , Masculino , Nasofaringe/metabolismo , Nasofaringe/patologia , Metástase Neoplásica , Pandemias , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Pneumonia/virologia , SARS-CoV-2/patogenicidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
10.
Cancer Lett ; 499: 301-313, 2021 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-33160003

RESUMO

Circular RNAs (circRNAs) act as competing endogenous RNAs, which are involved in the regulation of many types of cancers. They primarily function by sponging microRNAs (miRNAs) and influencing the expression of miRNA by target messenger RNA. However, the role of circRNAs in the progression of nasopharyngeal carcinoma (NPC) remains largely unclear. In this study, differentially expressed miRNAs associated with NPC were screened using microarray analyses, from which miR-107 was identified. Increased miR-107 expression was associated with poor prognosis in NPC, and miR-107 promoted the proliferation and migration of NPC cells. TGFBR2 was identified as the direct target of miR-107, which could reverse its effect on NPC cells. Furthermore, the expression of circTGFBR2 was downregulated in NPC tissue samples, while circTGFBR2 overexpression correlated with favorable prognosis in NPC. Functionally, circTGFBR2 overexpression inhibited the proliferation and migration of NPC cells both in vitro and in vivo. Further analysis showed that circTGFBR2 sponged miR-107, leading to the upregulation of TGFBR2 expression and suppression of NPC progression. Therefore, circTGFBR2 may serve as a novel tumor suppressive factor and potential target for new therapies in NPC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Circular/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/cirurgia , Nasofaringe/patologia , Nasofaringe/cirurgia , Prognóstico , RNA Circular/genética , RNA Interferente Pequeno/metabolismo , Mucosa Respiratória/patologia , Mucosa Respiratória/cirurgia , Transdução de Sinais , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Laryngoscope ; 131(7): 1455-1457, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33174222

RESUMO

Juvenile nasopharyngeal angiofibroma (JNA) is a locally aggressive tumor that predominantly affects adolescent males. Surgical resection is generally considered the standard treatment for both primary and recurrent tumors, regardless of staging. The natural history of these tumors, particularly when untreated or in the setting of residual tumor, is not well characterized. In this article, we report a case of true spontaneous JNA involution. Although the involution of residual tumor after surgical resection has previously been reported, to our knowledge, this is the first documented case of spontaneous JNA involution following a period of tumor growth post-treatment. Laryngoscope, 131:1455-1457, 2021.


Assuntos
Angiofibroma/cirurgia , Endoscopia , Neoplasias Nasofaríngeas/cirurgia , Nasofaringe/patologia , Adolescente , Angiofibroma/diagnóstico , Angiofibroma/patologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Nasofaringe/diagnóstico por imagem , Nasofaringe/cirurgia , Neoplasia Residual , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Laryngoscope ; 131(7): 1509-1515, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33355921

RESUMO

OBJECTIVES/HYPOTHESIS: Somatostatin receptors (SSTRs) are highly expressed in neuroendocrine tumors and is exploited for its imaging and treatment. SSTRs expression is also demonstrated in diverse benign and malignant tumor cell types and proliferating peri-tumoral vessels. Similarly, Juvenile Nasopharyngeal Angiofibroma (JNA) expresses different SSTRs and may be utilized for its imaging and treatment using DOTA, 1-Nal3-octreotide (DOTANOC)-PET/CT scan. STUDY DESIGN: Prospective cohort. METHODS: Nineteen clinico-radiologically diagnosed primary JNA patients underwent a 68 Ga-DOTANOC PET-CT scan. Using a dedicated PET/CT scanner, a low-dose head and neck spot CT scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi(74-111 MBq) of DOTANOC. The primary objective was to assess the intensity and pattern of DOTANOC uptake in these patients. RESULTS: DOTANOC expression was noted in all cases (n = 19) of primary JNA (100%). The mean (SD) DOTANOC SUVmax ratio of tumor and background was 6.9+/-1.4(range, 3.8-9.5). Intra-cranial extension in all 13/19 patients was prominently visualized due to the absence of DOTANOC uptake in the brain. Compared to the background all stages of JNA showed significant DOTANOC uptake (P < .0001). No difference in uptake between advanced-stage tumors and early tumors was noted (P = .47). A statistically non-significant negative trend was noted for decreasing uptake with increasing age (Spearman correlation coefficient, r = -0.19). CONCLUSIONS: This first study of 68 Ga-DOTANOC-PET/CT scan in JNA demonstrates consistent and reliable uptake activity in all patients irrespective of age and stage. This opens up possibilities to physiological diagnostic imaging with a promise of greater specificity and sensitivity and may have applications in ambivalent diagnostic situations such as the detection of recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1509-1515, 2021.


Assuntos
Angiofibroma/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Compostos Organometálicos/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Adolescente , Angiofibroma/patologia , Angiofibroma/terapia , Antineoplásicos Hormonais/administração & dosagem , Quimioterapia Adjuvante/métodos , Criança , Feminino , Flutamida/administração & dosagem , Humanos , Masculino , Imagem Molecular/métodos , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Nasofaringe/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Compostos Organometálicos/farmacocinética , Projetos Piloto , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Receptores de Somatostatina/metabolismo , Reprodutibilidade dos Testes , Adulto Jovem
13.
PLoS One ; 15(12): e0243942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33306743

RESUMO

Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. In a retrospective analysis of clinical samples collected from a prospectively-enrolled cohort of 358 children we sought associations between physician-attended illness visits and bacterial colonization in the first five years of life. A subset of children was identified by unsupervised clustering analysis as infection and allergy prone (IAP). Several respiratory infection- and allergy-mediated illnesses co-occurred at higher rates in IAP children, while the rates of other illnesses were not significantly different between the groups. Analyses of nasopharyngeal (NP) pathobionts and microbiota commensals showed that early age of first colonization with pathobionts Streptococcus pneumonia, non-typeable Haemophilus influenzae, and Moraxella catarrhalis was associated with IAP children, and particularly Moraxella abundance was negatively associated with NP microbiome diversity. We conclude that mucosal pathobiont exposures in early life can influence susceptibility to respiratory illnesses in children.


Assuntos
Portador Sadio/epidemiologia , Doenças Nasofaríngeas/epidemiologia , Pneumonia Pneumocócica/epidemiologia , Infecções Respiratórias/epidemiologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Feminino , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/patogenicidade , Humanos , Lactente , Masculino , Microbiota , Moraxella catarrhalis/isolamento & purificação , Moraxella catarrhalis/patogenicidade , Doenças Nasofaríngeas/microbiologia , Nasofaringe/microbiologia , Nasofaringe/patologia , Pneumonia Pneumocócica/microbiologia , Infecções Respiratórias/microbiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade
14.
J Cancer Res Ther ; 16(Supplement): S43-S47, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33380650

RESUMO

Purpose: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. Patients and Methods: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. Results: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). Conclusion: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Adolescente , Adulto , Idoso , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Biópsia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Nasofaringe/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Adulto Jovem
15.
Theranostics ; 10(26): 11921-11937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204320

RESUMO

Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of EBV-related tumors. This study aimed to explore the inner relationship and regulatory mechanism among oxidative stress, EBV reactivation, and radioresistance and to identify new molecular subtyping models and treatment strategies to improve the therapeutic effects of radiotherapy. Methods: ROS, NADP+/NADPH, and GSSG/GSH were detected to evaluate the oxidative stress of cells. 8-OHdG is a reliable oxidative stress marker to evaluate the oxidative stress in patients. Its concentration in serum was detected using an ELISA method and in biopsies was detected using IHC. qPCR array was performed to evaluate the expression of essential oxidative stress genes. qPCR, Western blot, and IHC were used to measure the level of EBV reactivation in vitro and in vivo. A Rta-IgG ELISA kit and EBV DNA detection kit were used to analyze the reactivation of EBV in serum from NPC patients. NPC tumor tissue microarrays was used to investigate the prognostic role of oxidative stress and EBV reactivation. Radiation resistance was evaluated by a colony formation assay. Xenografts were treated with NAC, radiation, or a combination of NAC and radiation. EBV DNA load of tumor tissue was evaluated using an EBV DNA detection kit. Oxidative stress, EBV reactivation, and the apoptosis rate in tumor tissues were detected by using 8-OHdG, EAD, and TUNEL assays, respectively. Results: We found that EBV can induce high oxidative stress, which promotes its reactivation and thus leads to radioresistance. Basically, EBV caused NPC cells to undergo a process of 'Redox Resetting' to acquire a new redox status with higher levels of ROS accumulation and stronger antioxidant systems by increasing the expression of the ROS-producing enzyme, NOX2, and the cellular master antioxidant regulator, Nrf2. Also, EBV encoded driving protein LMP1 promotes EBV reactivation through production of ROS. Furthermore, high oxidative stress and EBV reactivation were positively associated with poor overall survival of patients following radiation therapy and were significant related to NPC patients' recurrence and clinical stage. By decreasing oxidative stress using an FDA approved antioxidant drug, NAC, sensitivity of tumors to radiation was increased. Additionally, 8-OHdG and EBV DNA could be dual prognostic markers for NPC patients. Conclusions: Oxidative stress mediates EBV reactivation and leads to radioresistance. Targeting oxidative stress can provide therapeutic benefits to cancer patients with radiation resistance. Clinically, we, for the first time, generated a molecular subtyping model for NPC relying on 8-OHdG and EBV DNA level. These dual markers could identify patients who are at a high risk of poor outcomes but who might benefit from the sequential therapy of reactive oxygen blockade followed by radiation therapy, which provides novel perspectives for the precise treatment of NPC.


Assuntos
Quimiorradioterapia/métodos , Infecções por Vírus Epstein-Barr/terapia , Sequestradores de Radicais Livres/administração & dosagem , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Acetilcisteína/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia , Linhagem Celular Tumoral , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Humanos , Infecção Latente/sangue , Infecção Latente/patologia , Infecção Latente/terapia , Infecção Latente/virologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Nasofaringe/patologia , Nasofaringe/virologia , Estresse Oxidativo/efeitos dos fármacos , Seleção de Pacientes , Prognóstico , Intervalo Livre de Progressão , Tolerância a Radiação/efeitos dos fármacos , Espécies Reativas de Oxigênio , Carga Viral , Proteínas da Matriz Viral/metabolismo , Ativação Viral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
16.
AJNR Am J Neuroradiol ; 41(12): 2339-2344, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33122214

RESUMO

BACKGROUND AND PURPOSE: T1ρ imaging is a new quantitative MR imaging pulse sequence with the potential to discriminate between malignant and benign tissue. In this study, we evaluated the capability of T1ρ imaging to characterize tissue by applying T1ρ imaging to malignant and benign tissue in the nasopharynx and to normal tissue in the head and neck. MATERIALS AND METHODS: Participants with undifferentiated nasopharyngeal carcinoma and benign hyperplasia of the nasopharynx prospectively underwent T1ρ imaging. T1ρ measurements obtained from the histogram analysis for nasopharyngeal carcinoma in 43 participants were compared with those for benign hyperplasia and for normal tissue (brain, muscle, and parotid glands) in 41 participants using the Mann-Whitney U test. The area under the curve of significant T1ρ measurements was calculated and compared using receiver operating characteristic analysis and the Delong test, respectively. A P < . 05 indicated statistical significance. RESULTS: There were significant differences in T1ρ measurements between nasopharyngeal carcinoma and benign hyperplasia and between nasopharyngeal carcinoma and normal tissue (all, P < . 05). Compared with benign hyperplasia, nasopharyngeal carcinoma showed a lower T1ρ mean (62.14 versus 65.45 × ms), SD (12.60 versus 17.73 × ms), and skewness (0.61 versus 0.76) (all P < .05), but no difference in kurtosis (P = . 18). The T1ρ SD showed the highest area under the curve of 0.95 compared with the T1ρ mean (area under the curve = 0.72) and T1ρ skewness (area under the curve = 0.72) for discriminating nasopharyngeal carcinoma and benign hyperplasia (all, P < .05). CONCLUSIONS: Quantitative T1ρ imaging has the potential to discriminate malignant from benign and normal tissue in the head and neck.


Assuntos
Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cabeça/diagnóstico por imagem , Humanos , Hiperplasia/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Curva ROC , Estatísticas não Paramétricas
17.
Clin Immunol ; 220: 108576, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32866645

RESUMO

Upper respiratory tract is the primary site of SARS-CoV-2 replication. Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-ß1 and RANTES at mRNA level. Forty five SARS-CoV-2 infected patients were enrolled, whose were divided in two groups: asymptomatic and symptomatic. Twenty healthy persons, SARS-CoV-2 negative were included as controls. Higher IFN-γ expression was detected in SARS-CoV-2 infected patients in comparison with controls (p = 0.0393). IFN-γ expression was increased in symptomatic patients (p = 0.0405). TGF-ß1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p < 0.0001; p = 0.0011, respectively). A significant correlation between IFN-γ and TGF-ß1 was observed in SARS-CoV-2 asymptomatic patients (r = +0.61, p = 0.0014). The findings suggest that imbalance between IFN-γ and TGF-ß1 expression could be an impact in clinical expression of SARS-CoV-2 infection.


Assuntos
Betacoronavirus/patogenicidade , Quimiocina CCL5/genética , Infecções por Coronavirus/imunologia , Interferon gama/genética , Pneumonia Viral/imunologia , RNA Mensageiro/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Doenças Assintomáticas , Betacoronavirus/imunologia , COVID-19 , Estudos de Casos e Controles , Quimiocina CCL5/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferon gama/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Mensageiro/imunologia , SARS-CoV-2 , Índice de Gravidade de Doença , Fator de Crescimento Transformador beta1/imunologia
18.
Artigo em Chinês | MEDLINE | ID: mdl-32911888

RESUMO

Objective: To explore and analyze the clinical characteristics, diagnosis and treatment of infant hairy polyp. Methods: A retrospective analysis was made on 13 cases of hairy polyp confirmed by pathology, who were admitted to the Children's Hospital of Hebei Province from January 2010 to September 2019, including 4 males and 9 females, with a male-female ratio of 1∶2.25. The age ranged from 3 hours to 1 year, and the median age was 1 month. Twelve of the 13 children were found to have difficulty breathing or feeding. All the children received coblation resection under general anesthesia. The root pedicle of the mass was found in the lateral nasopharyngeal wall in 8 cases, in the junction of palatine and palatopharyngeal arch of tonsil and the tongue and esophageal entrance in 1 case, respectively. Nasal septum was found in 2 cases, including 1 case located between two incisors. The wound at the root pedicle was ablated and the bleeding was stopped completely. Results: Postoperative follow-up lasted from 3 months to 2 years, and there was no recurrence in 12 cases. Fibrolaryngoscope showed a mass of the right eustachian tube and pharyngeal mouth in 1 case 2 years after the surgery, which was considered recurrence of hairy polyps and lost after that. Conclusion: Hairy polyps in infants is a rare clinical disease, and its main symptom is upper respiratory tract obstruction. Early diagnosis and radical surgery are the key to the treatment of the disease.


Assuntos
Pólipos , Tuba Auditiva/patologia , Feminino , Humanos , Lactente , Masculino , Nasofaringe/patologia , Faringe/patologia , Pólipos/diagnóstico , Pólipos/patologia , Pólipos/cirurgia , Estudos Retrospectivos
20.
Am J Trop Med Hyg ; 103(4): 1493-1495, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748768

RESUMO

Mucosal leishmaniasis (ML) affects predominantly the nose and occurs usually weeks or months after the cure of the primary cutaneous lesion. The pathology of ML is characterized by an exaggerated inflammatory reaction with infiltration of lymphocytes, macrophages, and plasma cells. There is also a paucity of parasites and a strong delayed-type hypersensitivity reaction. Herein, we report a case of a young man who had a large ulcer in his left leg and complained of dysphagia. In nasofibrolaryngoscopy, there were nodular lesions in the oropharynx and rhinopharynx. The skin lesion biopsy showed a chronic inflammation with amastigotes inside macrophages, and DNA of Leishmania braziliensis confirmed the diagnosis of ML in tissue biopsied from the pharynx. The leishmaniasis skin test was negative. Cytokine evaluation showed lack of production of interferon (IFN)-γ, interleukin (IL)-1ß, and IL-17 with enhancement of these cytokine levels after cure.


Assuntos
Leishmania braziliensis/isolamento & purificação , Leishmaniose Mucocutânea , Antiprotozoários/uso terapêutico , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Mucocutânea/patologia , Macrófagos/parasitologia , Masculino , Antimoniato de Meglumina/uso terapêutico , Pessoa de Meia-Idade , Nasofaringe/parasitologia , Nasofaringe/patologia , Orofaringe/parasitologia , Orofaringe/patologia , Pele/parasitologia , Pele/patologia
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