Editorial: “Encontrando a Biologia Vegetal” Maria Fabíola Gomes da Silva de Barros; Benoît Francis Patrice Loeuille; Marccus Vinícius da Silva Alves
Revista Brasileira de Meio Ambiente,
09/2018, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
O Programa de Pós-Graduação em Biologia Vegetal (PPGBV) é parte do Departamento de Botânica, da Universidade Federal de Pernambuco (UFPE). Tem conceito seis pela Coordenação de Aperfeiçoamento de ...Nível Superior (CAPES) e concentra-se em duas grandes áreas de pesquisa: Sistemática & Evolução e Ecologia & Conservação. O principal interesse do programa é contribuir com a formação de mestres e doutores, tornando-os aptos a desenvolver atividades relacionadas ao ensino, pesquisa e extensão. Há três anos, os alunos do PPGBV vêm planejando e executando o Encontro da Biologia Vegetal (EBV). Cada ano, o EBV elegeu um tema como central. Em sua terceira edição, em 2018, teve como tema “Caatinga: alinhando biodiversidade à sustentabilidade”. O EBV conta com a participação ativa dos alunos, pós-doutorandos e professores do PPGBV, desde a organização do evento (e.g. construir uma rede de patrocinadores, contatar pesquisadores de outras instituições de ensino e elaborar uma programação) a ministrante de palestras e minicursos. A programação do EBV é majoritariamente voltada para a apresentação das pesquisas desenvolvidas pelos docentes e pós-graduandos do PPGBV, além de temas transversais pertinentes a comunidade científica e que merecem espaço para debate e discussão. Isso tem permitido que graduandos (i.e. público alvo do EBV) conheçam as diferentes faces e desafios da biologia vegetal, entrem em contato com as pesquisas em andamento e seus principais resultados, aproximando-os do ambiente acadêmico e científico, o que permite refletir como a pesquisa local se insere no cenário científico nacional e mundial. Além, de apresentar o PPGBV aos participantes, divulgando-o como um centro de excelência e uma fonte de formação e capacitação de recursos humanos. Ao longo de três edições, o EBV já atingiu cerca de 500 estudantes (de graduação e pós-graduação), tanto do estado de Pernambuco como outros (e.g. Alagoas, Paraíba, Rio Grande do Norte, Ceará e Amazonas). É notório que as edições do EBV têm se tornado mais participativas e atraentes, o que reflete o desejo de consolidação como um evento científico importante na área de Biodiversidade no Nordeste do Brasil, atingindo cada vez mais alunos. Em nome do EBV, agradecemos a confiança dos participantes em submeter suas pesquisas, aos avaliadores das mesmas pela minuciosa e imparcial análise e a Revista Brasileira de Meio Ambiente (RVBMA), por reconhecer o EBV como atuante na produção de conhecimento científico de alta qualidade e formação de pesquisadores no Brasil. Até a próxima edição do EBV.
Background
More than 90% of the adult population globally is chronically infected by the Epstein–Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and ...advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers.
Method
We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein.
Conclusion
We estimated that EBV-related cases from these six cancers accounted for 239,700–357,900 new cases and 137,900–208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.
Elderly patients with Epstein‐Barr virus (EBV) infection are at increased risk for developing B‐cell lymphoproliferative disorder (B‐LPD) due to immunosenescence. Here, we describe a case of a ...75‐year‐old man who developed an EBV‐positive (EBV+) mucocutaneous ulcer (EBVMCU) in the gingiva with spontaneous regression. Eighteen months after regression, he had a cervical lymph node enlargement that was diagnosed as EBV+ nodal polymorphous B‐LPD, Ann Arbor stage IA. Clinicians decided to observe his clinical course without any treatment. Fourteen months later, the patient developed EBV‐positive diffuse large B‐cell lymphoma (DLBCL), Ann Arbor stage IIA, and received six courses of age‐adjusted dose chemotherapy and achieved a complete remission. No evidence of a clonal relationship was found among these three lesions by standard polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain. However, they all had expression of PD‐L1 in the EBV+ large B‐cells and Hodgkin Reed‐Sternberg‐like cells. This is the first case report of a PD‐L1‐positive (PD‐L1+) EBVMCU and the development of multiple EBV‐driven B‐LPDs in the setting of immunosenescence within a 32‐month period.
EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a significant contributor to ...the burden of autoimmune diseases. Thus, EBV represents a significant public health burden. Upon infection, EBV remains dormant in host cells for long periods of time. However, the presence or episodic reactivation of the virus increases the risk of transforming healthy cells to malignant cells that routinely escape host immune surveillance or of producing pathogenic autoantibodies. Cancers caused by EBV display distinct molecular behaviors compared to those of the same tissue type that are not caused by EBV, presenting opportunities for targeted treatments. Despite some encouraging results from exploration of vaccines, antiviral agents and immune- and cell-based treatments, the efficacy and safety of most therapeutics remain unclear. Here, we provide an up-to-date review focusing on underlying immune and environmental mechanisms, current therapeutics and vaccines, animal models and emerging technologies to study EBV-associated diseases that may help provide insights for the development of novel effective treatments.
•A large patient cohort was tested with qPCR for EBV-DNA in plasma and whole blood.•Primary infection, T-cell and Hodgkin lymphomas were predominant EBV diseases.•WHO qPCR for EBV-DNA had a low ...positive predictive value for proven EBV disease.•The analysis had an excellent negative predictive value for proven EBV disease.•The risk of diagnostic latency was high for patients with EBV-positive lymphoma.
Quantitative polymerase chain reaction (qPCR) for Epstein–Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging.
We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort.
Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas.
EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3–19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2–90.7%) and 87.8% (95% CI; 85.6–90%), yielding a PPV of 32.2% (95% CI; 24.9–39.5%) and NPV of 98.6% (95% CI; 97.7–99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6–73.1%) and 18.1% (95% CI; 7.5–28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4–4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas.
WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis.
Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosal lining. A high incidence was recorded in EBV-endemic areas (EA) ...such as East and Southeast Asia 1 while in Europe, a non-endemic area (NEA), is low (1/105/year); however, the estimated survival rate is much lower than that recorded in Asian EA (5-year age-standardized relative survival = 54–57% vs. 74%) 2. Risk factors of NPC include genetic, ethnic and environmental factors 3. Differences in incidence and survival rates between EA and NEA NPCs could involve several factors, including EBV-related factors, genetic susceptibility of the population to EBV infections, and environmental factors such as diet and pollution 4-7. Nevertheless, all proposed models of NPC pathogenesis are based on data derived from EA in Asia. Furthermore, clinical, pathogenic, and microenvironmental characteristics may play additional roles. EBV-related NPC in EA has already been characterized using genomic and transcriptomic data analysis 8-9. However, gene expression analysis data 10 of NEA NPC is limited. Comparing gene expression data from EA and NEA diseases allows the recognition of similarities and differences in incidence and outcome among diseases arising in different geographical areas. We investigated the transcriptomic patterns of genes involved in EA NPC to interpret these differences and verifying them to an Italian cohort with available tumor tissue and clinical data. The immune and biological/functional characterization of EA and NEA NPC could improve the identification of new therapeutic strategies. Currently, the treatment for localized NPC includes radiotherapy, which is often combined with platinum-based chemotherapy, especially for locally advanced cancer. Neoadjuvant chemotherapy with cisplatin and gemcitabine was administered in the case of high-risk disease 11 -12. Immunotherapy with checkpoint inhibitors has shown clinical efficacy in recurrent/metastatic advanced NPC and is currently under evaluation to define its mechanism of action 13. Our study aimed to dissect the gene expression (GE) and microenvironment of NPC, leading to the identification of the molecular subtypes of EA and NEA NPC. We also aimed to elucidate the biological and functional differences within EA NPC and between EA NPC and NEA NPC to eventually provide new insights into novel treatment strategies.
Six GE datasets of NPC-EA transcriptomic repositories, including tumor and normal samples (GSE12452, GSE34573, GSE132112, GSE53819, GSE68799, GSE102349) and one validation dataset including both EA and NEA (https://doi.org/10.5281/zenodo.5347891) were retrieved. Four GE signatures associated to EBV related NPC prognosis (PMID: 24297049, 35262435, 32596151, 33096113), genes/pathways and gene sets (PMID: 35846746, 35394843, 35105963) were applied on EA and NEA NPC cohorts (Liu_NPC, Wood EBV EBNA1 Targets Down, Sengupta NPC_with LMP1 UP, REACTOME DNA Repair; Hallmarks). A bioinformatic meta-analysis approach was used to integrate the six EA datasets, and the classifier method was applied to the validation dataset in order to identify the subtype with worst prognosis. Moreover, RNA sequencing was performed on 50 Italian NEA NPC samples (study number: INT188/19; GSE208281). Biological and functional profiling of EA and NEA were performed using xCell, Gene set enrichment analyses, and treatment prediction methods (radiosensitivity index PMID: 16103067, pRRophetic R package, Immunophenoscore PMID: 28052254).
Through the meta-analysis of EA-NPC datasets, four clusters (Cl) were identified. Prognostic analyses revealed that Cl3 had the worst prognosis (P=0.0476), confirmed by three of the four prognostic signatures and in the validation dataset (P=0.0368). The biological and functional characterization of these clusters disclosed the relative GE subtypes: Cl1, Immune-active; Cl2, Defense-response; Cl3, Proliferation;Cl4, Perineural-interaction/EBV-exhaustion. According to the treatment prediction methods, the sensitivity of each cluster was radiotherapy and immunotherapy for immune-active, radiochemotherapy and immunotherapy for defense-response, chemotherapy for proliferation, and cisplatin treatment for perineural-interaction/EBV-exhaustion. Only three clusters, excluding perineural-interaction/EBV-exhaustion, were expressed in our NEA cohort. Immune/biological characterization and treatment prediction analyses of NEA partially replicated the EA results.
Our study provides a relevant biological overview of EBV-related NPC in both EA and NEA. The immune microenvironment plays a critical role in NPC owing to the viral etiology of this malignancy. The presence of a perineural-interaction/EBV-exhaustion cluster in EA suggests an inactive EBV infection according to the viral related “hit and run theory”. Evaluation of miRNAs is ongoing along with miRNA/gene expression integration. Well characterized EA- and NEA-NPC retrospective and prospective cohorts are needed to validate the obtained results and can help designing future clinical studies.
Nasopharyngeal carcinomas (NPC) are non-endemic in most parts of India except in the northeastern region. We aimed to evaluate the use of estimation of plasma EBV (Epstein Bar Virus) DNA copy numbers ...on epidemiology and its impact on survival in NPC at a tertiary cancer center in India.
In this ambispective study, we included treatment naïve biopsy-proven NPC treated at our institute between December 2013 and March 2023. Estimation of plasma EBV DNA was done at baseline, and at first follow-up, 3 months post-treatment completion. Plasma EBV analysis was done using the EBNA probe (n= 240) till September 2019 and the BAMH1 (n= 76) probe thereafter. The endpoints estimated were baseline EBV positivity rates, response rates based on EBV positivity/EBV copy numbers, and correlation of EBV positivity/EBV copy numbers with clinicoradiologic stage, FDG-PETCT parameters, and survival endpoints: Loco-regional Control (LRC), Distant Control (DC), Event Free Survival (EFS) and Overall Survival (OS). The study was approved by the Institutional Ethics Committee.
Three hundred and sixteen patients were accrued in the study. The median age of patients was 43 (IQR: 28-54) years, and the majority were males (n=222, 70.3%). Sixty-two (19.6%) patients were from Endemic (Northeast India) regions out of which only 24 (36.1%) were plasma EBV positive. The most common histology was non-keratinizing or undifferentiated (WHO Types IIA & B) {n=248, (78.5%)}. T1/T2 and T3/T4 were equally distributed among the entire cohort (n=158, 50%) and N2/N3 (n=234, 74.1%) was the most common nodal classification. Metastatic disease (M1) was present in 25 (7.9%) patients. Most of the patients had stage III (n=105, 33.2%) or stage IV (n=169, 53.5%) disease. One hundred and seventeen (37%) patients were EBV-positive at baseline {n=82, (34.1%) with EBNA and n=35, (46.1%) with BAM H1}. Tissue diagnosis by IHC was available for 91 out of these patients. Out of these, there was a discordance in EBV status between EBV status by DNA copy number and tissue diagnosis in 36 (39.6%). The median copy numbers in those with detectable EBV (EBV positive) with EBNA was 712 copies/ml (IQR:332-1989), and BAM H1 was 425 copies/ml (IQR:162-1210). A high baseline EBV DNA copy number with BAMH1 (but not EBNA) was associated with a higher T stage (p=0.02). At the first follow-up, 283 (89.5%) patients had a complete response, and 33 (10.5%) patients had residual disease. Higher baseline EBV DNA copy numbers with BAMH1 (but not EBNA) correlated with an inferior complete response rate at the first follow-up (p=0.05).
The median follow-up was 63.2 (IQR:33.5–87.4) months. At the last follow-up, 90 patients had failed, 27 (30%) locoregional (LR), 45 (50%) distant, and 18 (20%) combined locoregional and distant relapses. The 5-year LRC, DC, EFS, and OS for the entire cohort were 83.2% (95%CI:78.4-88), 77.5% (95% CI:72.3-82.7), 68.2% (95%CI: 62.6-73.8), 74.5 (95% CI:68.9-80.1).
There was no significant difference in LRC, DC, EFS, and OS rates based on the overall EBV positivity vs negativity at baseline. None of the survival outcomes correlated with EBV positivity or EBV DNA copy number using the EBNA probe.
The median follow-up of patients with BAMH1 probe analysis was 21 (IQR:13.1-33.5) months. There was no difference in survival outcomes based on EBV positivity vs negativity with the BAMH1 probe. However, in the patients with detectable EBV DNA with BAMH1, a higher DNA copy number/ml was associated with an inferior EFS (p=0.05). A cut-off value of 335 copies/ml (BAMH1) was most sensitive for predicting an inferior EFS.
EBV positivity remained low in this nonendemic NPC population with both EBNA and BAMH1 probes, even amongst patients from the northeast. Hence, EBV DNA estimation cannot be routinely used as a screening, predictive, or prognostic marker uniformly for NPC patients in India. However, in those patients who have measurable EBV DNA copies, we found that the BAMH1 probe assay at baseline has a better predictive and prognostic value than the EBNA probe. The BAM H1 DNA copy number values may be incorporated as a baseline evaluation tool into routine clinical practice for further validation as a treatment decision aid in NPC in nonendemic regions. However, we would also like to further strengthen this estimation in a larger number of patients.
Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative ...disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders.
Background. University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune ...correlates of disease severity. Methods. EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. Results. Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (< .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8⁺ T-cells but not in numbers of CD4⁺ T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8⁺ lymphocytosis (P = .0003). Conclusions. Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8⁺ lymphocytosis correlated with disease severity.
Epstein-Barr virus-associated lymphomas decoded Bednarska, Karolina; Chowdhury, Rakin; Tobin, Joshua W D ...
British journal of haematology,
02/2024, Letnik:
204, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Epstein-Barr virus (EBV)-associated lymphomas cover a range of histological B- and T-cell non-Hodgkin and Hodgkin lymphoma subtypes. The role of EBV on B-cell malignant pathogenesis and its impact on ...the tumour microenvironment are intriguing but incompletely understood. Both the International Consensus Classification (ICC) and 5th Edition of the World Health Organization (WHO-HAEM5) proposals give prominence to the distinct clinical, prognostic, genetic and tumour microenvironmental features of EBV in lymphoproliferative disorders. There have been major advances in our biological understanding, in how to harness features of EBV and its host immune response for targeted therapy, and in using EBV as a method to monitor disease response. In this article, we showcase the latest developments and how they may be integrated to stimulate new and innovative approaches for further lines of investigation and therapy.
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