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2.
Medicine (Baltimore) ; 99(1): e18503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895784

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In clinical practice, we have observed that some HLH patients who have features of systemic autoinflammatory diseases (SAIDs) exhibit unique clinical manifestations and outcomes different from other HLH patients.We analyzed data from 25 HLH patients who were considered to have SAIDs; data were collected from patients of our center between January 1, 2015 and September 1, 2018.The median age of the patients was 1.75 years. In the early phase, all patients had a fever and 92% of patients had a rash; 96% of patients had high white blood cell count (WBC), C-reaction protein, and erythrocyte sedimentation rate. With progression, the above laboratory results decreased gradually. During the HLH period, we compared SAIDs-related HLH and Epstein-Barr virus (EBV)-related HLH and found that rash was more common (92%, P < .001) and splenomegaly was less common (64%, P = .023) in SAIDs-related HLH. Further, WBC, ferritin, and Interleukin-6 levels in SAIDs-related HLH patients were higher than those in EBV-related HLH patients. In contrast, hemoglobin, triglyceride, sCD25, Interleukin-10, and interferon-γ levels in SAIDs-related HLH patients were lower compared with those in EBV-related HLH patients. SAIDs-related HLH patients received a modified HLH-2004 protocol at our center. Most patients had a good prognosis.We provide a summary of the unique clinical and laboratory features, treatment protocols, and outcomes of SAIDs patients with HLH at onset. The findings indicate that these patients had a better response to corticosteroids and cyclosporin compared with EBV-related HLH patients.


Assuntos
Doenças Autoimunes/patologia , Infecções por Vírus Epstein-Barr/patologia , Exantema/etiologia , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica/patologia , Corticosteroides/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Sedimentação Sanguínea , Proteína C-Reativa , Ciclosporina/uso terapêutico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Exantema/patologia , Exantema/virologia , Feminino , Humanos , Lactente , Contagem de Leucócitos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Esplenomegalia/imunologia , Esplenomegalia/virologia , Resultado do Tratamento
3.
Cancer Sci ; 111(1): 72-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31691433

RESUMO

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


Assuntos
Calpaína/genética , Sistema de Sinalização das MAP Quinases/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Metástase Neoplásica/genética , Fator de Transcrição AP-1/genética , Proteínas da Matriz Viral/genética , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/patogenicidade , Humanos , NF-kappa B/genética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Metástase Neoplásica/patologia , Fosforilação/genética , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Regulação para Cima/genética
4.
Cancer Sci ; 111(1): 279-287, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743514

RESUMO

Epstein-Barr virus (EBV) is a well-established tumor virus that has been implicated in a wide range of immunodeficiency-associated lymphoproliferative disorders (LPDs). Although rituximab, a CD20 mAb, has proven effective against EBV-associated LPDs, prolonged use of this drug could lead to resistance due to the selective expansion of CD20- cells. We have previously shown that cyclin-dependent kinase (CDK) inhibitors are able to specifically suppress the expression of viral late genes, particularly those encoding structural proteins; however, the therapeutic effect of CDK inhibitors against EBV-associated LPDs is not clear. In this study, we examined whether CDK inhibitors confer a therapeutic effect against LPDs in vivo. Treatment with alsterpaullone, an inhibitor of the CDK2 complex, resulted in a survival benefit and suppressed tumor invasion in a mouse model of LPDs. Inhibition of CDK efficiently induced G1 cell cycle arrest and apoptosis in EBV-positive B cells. These results suggest that alsterpaullone suppresses cell cycle progression, resulting in the antitumor effect observed in vivo.


Assuntos
Antineoplásicos/farmacologia , Benzazepinas/farmacologia , Herpesvirus Humano 4/patogenicidade , Indóis/farmacologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/virologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Fase G1/efeitos dos fármacos , Células HEK293 , Humanos , Transtornos Linfoproliferativos/genética , Camundongos , Camundongos Endogâmicos NOD
5.
Ann Hematol ; 99(2): 343-349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879790

RESUMO

Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Pirazóis/administração & dosagem , Dermatopatias , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Resistência a Medicamentos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/mortalidade , Esteroides/administração & dosagem , Taxa de Sobrevida
6.
Int J Cancer ; 146(1): 181-191, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31090066

RESUMO

Mechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in the host DNA. Here we show, after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC mutations preferentially occurring in the genomic loci of the most active transcripts. This EBV infection and APOBEC3 mutation-signature axis were confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.


Assuntos
Citidina Desaminase/genética , DNA de Neoplasias/genética , Herpesvirus Humano 4/patogenicidade , Neoplasias Gástricas/virologia , Carcinogênese , Genes Virais , Herpesvirus Humano 4/genética , Humanos , Mutação , Neoplasias Gástricas/patologia
7.
Int J Cancer ; 146(1): 272-280, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162842

RESUMO

Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8-9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.


Assuntos
DNA Viral/sangue , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Gástricas/virologia , Carga Viral , Idoso , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Quintessence Int ; 51(1): 18-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31781689

RESUMO

OBJECTIVE: This study aimed to investigate the Epstein-Barr virus (EBV) prevalence and viral load in subgingival sites of human immunodeficiency virus type 1 (HIV-1) positive (HIV+) individuals, correlating subgingival EBV load to the clinical periodontal condition, HIV systemic load, EBV systemic load, and use of antiretroviral therapy (ART). METHOD AND MATERIALS: Ninety individuals were recruited and divided into three categories: those without periodontal disease (G1), with gingivitis (G2), and with periodontitis (G3). Subgingival biofilm and blood samples were analyzed by quantitative polymerase chain reactions (qPCR). A questionnaire was administered to collect general information about patients, and data regarding HIV and use of ART were accessed from their medical records. RESULTS: EBV was detected in 85.6% of the samples. Comparing subgingival and systemic load of EBV in G1, G2, and G3, there was a statistical difference only in G3 (3.93 log10 copies/mL and 5.47 log10 copies/mL, respectively; P = .014), where EBV load was higher in periodontal pockets than in the blood. All groups had high EBV loads in subgingival sites (> 2,000 copies/mL). A positive linear correlation between systemic HIV load and EBV subgingival load was found in G1 and G2 (r = 0.647; P < .001), but not in G3. Only G1 individuals using ART had lower subgingival EBV loads than those not using it (5.03 log10 copies/mL, and 7.14 log10 copies/mL, respectively; P = .0348). CONCLUSIONS: Subgingival sites, especially the periodontal pockets, are suggested to act as a reservoir of EBV in HIV+ individuals. Therefore, the identification of latent EBV infections in this easily accessible site might help to improve quality of life in patients with HIV by maintaining oral/periodontal health. In addition it might encourage new approaches in investigating EBV-associated disorders in HIV+ patients.


Assuntos
Infecções por HIV , Herpesvirus Humano 4 , Brasil , Estudos Transversais , DNA Viral , HIV , Humanos , Reação em Cadeia da Polimerase , Qualidade de Vida
9.
Rinsho Ketsueki ; 60(11): 1573-1576, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31839637

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in the elderly was revised from the category EBV-positive DLBCL not otherwise specified in WHO 2017. The prognosis of this lymphoma is very poor. We report a case of an 82-year-old woman diagnosed with gastric EBV-positive DLBCL (WHO 2008). Gastroduodenoscopy revealed multiple ulcers and fold thickening. She was followed-up without any treatment because of her old age. Repeat endoscopy one year and eight months later revealed a single ulcer with no lymphoma cells found in a biopsy specimen. Two years later, the lesion had spontaneously disappeared.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Idoso de 80 Anos ou mais , Feminino , Herpesvirus Humano 4 , Humanos , Prognóstico , Remissão Espontânea
10.
Autops. Case Rep ; 9(4): e2019117, Oct.-Dec. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1024240

RESUMO

Sporadic Burkitt lymphoma (SBL) is a variant of Burkitt lymphoma that occurs worldwide, affecting mainly children and young adults. Association with Epstein-Barr virus (EBV) can be identified in approximately 20-30% of cases. Herein we described a case of a 63-year-old male presenting intraoral bilateral mandibular swelling, subjacent to fixed dental prosthesis, with one month of duration. Incisional biopsies were performed, and after two days, the patient was hospitalized due to malaise and breathing difficulty, and died after a week when an abdominal tumor was detected. The mandibular biopsies revealed a diffuse proliferation of medium-sized monomorphic atypical lymphoid cells exhibiting numerous mitoses and areas of "starry-sky" pattern. The tumor showed immunohistochemical positivity for CD20, CD10, Bcl-6, and Ki-67 (≈ 100%); it was negative for CD3, Bcl-2, Vs38c, and MUM-1. Positivity for EBV was found by in situ hybridization. The final diagnosis was intraoral SBL positive for EBV. Clinical, morphological and molecular criteria are necessary for the correct diagnosis of aggressive B-cell neoplasms positive for EBV in elderly patients.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Linfoma de Burkitt/patologia , Herpesvirus Humano 4 , Linfoma não Hodgkin/patologia
11.
BMC Infect Dis ; 19(1): 1007, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779585

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11-14 year olds throughout adolescence (68.6% in 15-18 year olds) and stabilising by early adulthood (93.0% in those aged 22-24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13-4.78]). Smoking was less strongly associated with EBV seropositivity. CONCLUSIONS: By the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/imunologia , Adolescente , Criança , Estudos Transversais , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Inglaterra/epidemiologia , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
12.
Virchows Arch ; 475(6): 757-762, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673776

RESUMO

Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low- and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/patogenicidade , Neoplasias Gástricas/virologia , Estômago/virologia , Idoso , Carcinoma/patologia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Feminino , Mucosa Gástrica/patologia , Mucosa Gástrica/virologia , Humanos , Hibridização In Situ/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/patologia , Neoplasias Gástricas/patologia
13.
Transplant Proc ; 51(9): 3159-3162, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711585

RESUMO

BACKGROUND: Allogenic hematopoietic stem cell transplantation may be the best currently available method to treat relapsed hemophagocytic lymphohistiocytosis (HLH) related to Epstein-Barr virus. The high rate of transplantation-related complications was initially the main obstacle preventing the wider adoption of this protocol; however, the previously more common complications, such as infection and graft failure, have fallen to very low levels with the development of new drugs and methods. Some other complications, such as veno-occlusive disease and transplantation associated thrombotic microangiopathy, are rare after allogenic hematopoietic stem cell transplantation, but the morbidity and mortality associated with them are very high. CASE PRESENTATION: A patient with relapsed HLH related to Epstein-Barr virus showed the sequential severe complications of veno-occlusive disease, transplantation-associated thrombotic microangiopathy, and acute graft-vs-host disease after haploidentical transplantation. This patient was successfully treated by stopping administration of calcineurin inhibitors and instead treating with defibrotide, rituximab, CD25 monoclonal antibody, atorvastatin calcium tablets, methylprednisolone, budesonide, continuous plasma exchange, and bedside ultrafiltration. At the last follow-up, the patient had been living disease free for 2 years without any other complications. CONCLUSION: Epstein-Barr virus related-HLH patients have severe clinical features and currently poor prognosis. Allogenic hematopoietic stem cell transplantation may be the best way to treat this disease; however, the management of related complications is vital in the improvement of long-term survival.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Linfo-Histiocitose Hemofagocítica/cirurgia , Microangiopatias Trombóticas/etiologia , Criança , Infecções por Vírus Epstein-Barr/complicações , Feminino , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva/terapia , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/virologia , Recidiva , Microangiopatias Trombóticas/terapia
14.
Enzymes ; 46: 81-96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727278

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the most common head and neck tumors in Southern China. At present, the interaction of genetic susceptibility, Epstein-Barr virus (EBV) infection and environmental factors has been considered to be the main cause of NPC. However, the detailed molecular mechanisms of tumorigenesis and tumor metastasis have not been fully understood. The effective therapeutic drugs targeting NPC are still being developed and discovered. NPC cell lines and normal nasopharyngeal epithelial cell lines were frequently used by researchers, but not represent the complex situation in vivo. Establishing an ideal animal model of NPC is one of the keys to solving the above problems. Here, we introduce the development of in vitro and in vivo models of NPC.


Assuntos
Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Herpesvirus Humano 4 , Humanos
17.
Isr Med Assoc J ; 21(7): 444-448, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507118

RESUMO

BACKGROUND: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed. OBJECTIVES: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential. METHODS: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases. RESULTS: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10). CONCLUSIONS: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.


Assuntos
Autoantígenos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Proteoma , Complemento C4/imunologia , Reações Cruzadas/imunologia , Bases de Dados Factuais , Herpesvirus Humano 4/imunologia , Humanos , Interleucina-10/imunologia
19.
PLoS Pathog ; 15(9): e1008030, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518366

RESUMO

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with multiple human malignancies. EBV drives B-cell proliferation, which contributes to the pathogenesis of multiple lymphomas. Yet, knowledge of how EBV subverts host biosynthetic pathways to transform resting lymphocytes into activated lymphoblasts remains incomplete. Using a temporal proteomic dataset of EBV primary human B-cell infection, we identified that cholesterol and fatty acid biosynthetic pathways were amongst the most highly EBV induced. Epstein-Barr nuclear antigen 2 (EBNA2), sterol response element binding protein (SREBP) and MYC each had important roles in cholesterol and fatty acid pathway induction. Unexpectedly, HMG-CoA reductase inhibitor chemical epistasis experiments revealed that mevalonate pathway production of geranylgeranyl pyrophosphate (GGPP), rather than cholesterol, was necessary for EBV-driven B-cell outgrowth, perhaps because EBV upregulated the low-density lipoprotein receptor in newly infected cells for cholesterol uptake. Chemical and CRISPR genetic analyses highlighted downstream GGPP roles in EBV-infected cell small G protein Rab activation. Rab13 was highly EBV-induced in an EBNA3-dependent manner and served as a chaperone critical for latent membrane protein (LMP) 1 and 2A trafficking and target gene activation in newly infected and in lymphoblastoid B-cells. Collectively, these studies identify highlight multiple potential therapeutic targets for prevention of EBV-transformed B-cell growth and survival.


Assuntos
Linfócitos B/virologia , Ácidos Graxos/biossíntese , Herpesvirus Humano 4/patogenicidade , Ácido Mevalônico/metabolismo , Alquil e Aril Transferases/metabolismo , Linfócitos B/patologia , Proliferação de Células , Sobrevivência Celular , Colesterol/biossíntese , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Redes e Vias Metabólicas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteínas Virais/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
20.
Kardiologiia ; 59(8S): 56-62, 2019 Sep 16.
Artigo em Russo | MEDLINE | ID: mdl-31526362

RESUMO

AIM: The assessment of infectious status in patients with acutely decompensated chronic heart faiure (ADCHF) without evident signs of acute inflammatory stress and its impact on the 1 year prognosis. MATERIAL AND METHODS: Totally, 65 patients with ADCHF of ischemic origin investigated, age 67,3±2,3 y.o. All patients were taken markers of phagocytosis and inflammatory stress as well as antibodies to Streptococcus, Cytomegalovirus (CMV), Epstein-Barr virus (VEB), Candida albicans, Toxoplasma gondii, Aspergillus, Mycoplasma hominis and pneumonia and also level of lipopolysaccharids (LPS) of gram-negative bacteriae. RESULTS: More often LPS of gram-negative bacteriae were revealed in patients with ADCHF and further in decreasing order - antibodies to CMV, VEB, Streptococcus, Candida, Aspergillus and LPS. All patients have been infected by at least 2 pathogens, more than 90 % of them had 3 ones or more. Mortality in first 12 months observation correlated with quantity of patient`s pathogenic patterns (r=0,52, p=0,004). Dependency of one-year mortality from degree of viral-bacterial mixt contamination was almost linear. CMV was a monopathogen with strongest correlation with mortality (r=0,39, p=0,001). In patients with more significant infection bigger rate of re-hospitalizations about new ADCHF correlated with number of pathogens was observed (r=0,61, p=0,001). CONCLUSION: Chronic latent infection with a significant number of pathogens is characteristic of patients with low-ejection ADCHF of ischemic genesis with a significant number of pathogens: more than 90 % of patients had three or more. The most common exogenous pathogens in the study sample of patients with chronic obstructive heart failure were CMV, EBV, and hemolytic streptococcus, of the potentially endogenous ones, gram-negative intestinal bacteria. The number of infectious agents in patients with chronic obstructive heart failure has a direct correlation with deaths and re-admission to hospital with total heart failure within 1 year after discharge from the hospital.


Assuntos
Infecções por Citomegalovirus , Insuficiência Cardíaca , Doença Aguda , Idoso , Doença Crônica , Citomegalovirus , Herpesvirus Humano 4 , Humanos , Prognóstico
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