scholarly journals A 3D spheroid-specific role of Wnt/β-catenin and Eph-Ephrin in nasopharyngeal carcinoma cells

2021 ◽  
Author(s):  
Canhui Yi ◽  
Sook Ling Lai ◽  
Chi Man Tsang ◽  
Margarita Artemenko ◽  
Maggie Kei Shuen Tang ◽  
...  
Keyword(s):  
Drug Targets ◽  
Cost Effective ◽  
Transcriptional Level ◽  
Barr Virus ◽  
Tumor Phenotype ◽  
Epstein Barr ◽  
Migration Capacity ◽  
Approved Drugs ◽  
Effective Models ◽  
3D Spheroids

One of the greatest unmet needs hindering the successful treatment of nasopharyngeal carcinomas (NPC) is the lack of representative, physiological, and cost-effective models. Although Epstein-Barr virus (EBV) infection is consistently present in NPC, most studies have focused on EBV-negative NPC. For the first time, 3D spheroids model of EBV-positive and -negative NPC cells were established and analyzed as compared to classical 2D culture in various aspects of tumor phenotype and drugs response. Compared to 2D monolayer, 3D spheroids showed a significant increase in their migration capacity, stemness characteristics, hypoxia and drug resistance. Coculture with endothelial cells that mimic the essential interactions in the tumor microenvironment effectively enhanced spheroid dissemination. Furthermore, RNA-sequencing showed significant changes at the transcriptional level compared to 2D monolayer. Particularly, we identified known (VEGF, AKT, mTOR) and novel (Wnt/β-catenin, Eph-Ephrin) cell signaling involved in NPC spheroids. Their targeting using FDA-approved drugs are effective in monoculture and coculture. These findings provide the first evidence on the establishment of an EVB-positive and -negative NPC 3D spheroids in resembling advanced/metastatic features, and the potential in identifying new drug targets.

Cost-Effectiveness of Nasopharyngeal Carcinoma Screening with Epstein-Barr Virus Polymerase Chain Reaction or Serology in High-Incidence Populations Worldwide

2020 ◽  
Author(s):  
Jacob A Miller ◽  
Quynh-Thu Le ◽  
Benjamin A Pinsky ◽  
Hannah Wang
Keyword(s):  
Cost Effectiveness ◽  
Epstein Barr Virus ◽  
Cost Effective ◽  
Chain Reaction ◽  
Men And Women ◽  
Barr Virus ◽  
Screening Strategies ◽  
High Incidence ◽  
Polymerase Chain ◽  
Epstein Barr

Abstract Background The incidence of endemic Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) varies considerably worldwide. In high-incidence regions, screening trials have been conducted. We estimated the mortality reduction and cost-effectiveness of EBV-based NPC screening in populations worldwide. Methods We identified 380 populations in 132 countries with incident NPC and developed a decision-analytic model to compare ten unique onetime screening strategies to no screening for men and women at age 50 years. Screening performance and the stage distribution of undiagnosed NPC were derived from a systematic review of prospective screening trials. Results Screening was cost-effective in up to 14.5% of populations, depending on the screening strategy. These populations were limited to East Asia, Southeast Asia, North Africa, or were Asian, Pacific Islander, or Inuit populations in North America. A combination of serology and nasopharyngeal polymerase chain reaction (PCR) was most cost-effective, but other combinations of serologic and/or plasma PCR screening were also cost-effective. The estimated reduction in NPC mortality was similar across screening strategies. For a hypothetical cohort of patients in China, 10-year survival improved from 71.0% (95%CI = 68.8%–73.0%) without screening to a median of 86.3% (range = 83.5%–88.2%) with screening. This corresponded to a median 10-year reduction in NPC mortality of 52.9% (range= 43.1%–59.3%). Screening interval impacted absolute mortality reduction and cost-effectiveness. Conclusions We observed decreased NPC mortality with EBV-based screening. Screening was cost-effective in many high-incidence populations and could be extended to men and women as early as age 40 years in select regions. These findings may be useful when choosing among local public health initiatives.

scholarly journals EBNA2 Interferes with the Germinal Center Phenotype by Downregulating BCL6 and TCL1 in Non-Hodgkin's Lymphoma Cells

2006 ◽  
Vol 81 (5) ◽  
pp. 2274-2282 ◽  
Author(s):  
Francesco Boccellato ◽  
Eleni Anastasiadou ◽  
Paola Rosato ◽  
Bettina Kempkes ◽  
Luigi Frati ◽  
...  
Keyword(s):  
Germinal Center ◽  
B Cell Lymphoma ◽  
Cell System ◽  
Negative Regulation ◽  
Immunoglobulin M ◽  
Transcriptional Level ◽  
Barr Virus ◽  
Hla Dr ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV)-negative diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma-derived cell lines infected in vitro with a recombinant EBV expressed type II/III latency. High expression of EBNA2 inversely correlated with expression of germinal center (GC)-associated genes, BCL6 and TCL1. The decreased expression of BCL6 appeared to be dose dependent, with almost complete abrogation in highly EBNA2-expressing clones. The role of EBNA2 in negative regulation of these genes was confirmed by transfection and in a hormone-inducible EBNA2 cell system. LMP1 transfection reduced expression of TCL1, but not of BCL6, in DLBCLs. The GC-associated gene repression was at the transcriptional level and CBF1 independent. A decrease in HLA-DR, surface immunoglobulin M, and class II transactivator expression and an increase in CCL3, a BCL6 repression target, was observed in EBNA2-expressing clones. Since BCL6 is indispensable for GC formation and somatic hypermutations (SHM), we suggest that the previously reported lack of SHM seen in EBNA2-expressing GC cells from infectious mononucleosis tonsils could be due to negative regulation of BCL6 by EBNA2. These findings suggest that EBNA2 interferes with the GC phenotype.

Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective

2015 ◽  
Vol 33 (29) ◽  
pp. 3356-3364 ◽  
Author(s):  
Anne W.M. Lee ◽  
Brigette B.Y. Ma ◽  
Wai Tong Ng ◽  
Anthony T.C. Chan
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Drug Targets ◽  
Southern China ◽  
Future Perspective ◽  
Cancer Site ◽  
Barr Virus ◽  
Distant Failure ◽  
Novel Biomarkers ◽  
Epstein Barr ◽  
Patient Prognosis

Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research.

scholarly journals In Cellulo Protein-mRNA Interaction Assay to Determine the Action of G-Quadruplex-Binding Molecules

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3124 ◽  
Author(s):  
Rodrigo Prado Martins ◽  
Sarah Findakly ◽  
Chrysoula Daskalogianni ◽  
Marie-Paule Teulade-Fichou ◽  
Marc Blondel ◽  
...  
Keyword(s):  
Rna Structure ◽  
Messenger Rna ◽  
Drug Targets ◽  
Specific Protein ◽  
Proximity Ligation Assay ◽  
Barr Virus ◽  
G Quadruplex ◽  
Screening Assays ◽  
Epstein Barr

Protein-RNA interactions (PRIs) control pivotal steps in RNA biogenesis, regulate multiple physiological and pathological cellular networks, and are emerging as important drug targets. However, targeting of specific protein-RNA interactions for therapeutic developments is still poorly advanced. Studies and manipulation of these interactions are technically challenging and in vitro drug screening assays are often hampered due to the complexity of RNA structures. The binding of nucleolin (NCL) to a G-quadruplex (G4) structure in the messenger RNA (mRNA) of the Epstein-Barr virus (EBV)-encoded EBNA1 has emerged as an interesting therapeutic target to interfere with immune evasion of EBV-associated cancers. Using the NCL-EBNA1 mRNA interaction as a model, we describe a quantitative proximity ligation assay (PLA)-based in cellulo approach to determine the structure activity relationship of small chemical G4 ligands. Our results show how different G4 ligands have different effects on NCL binding to G4 of the EBNA1 mRNA and highlight the importance of in-cellulo screening assays for targeting RNA structure-dependent interactions.

Drug Targets in Herpes Simplex and Epstein Barr Virus Infections

2009 ◽  
Vol 9 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Genevieve Billaud ◽  
Danielle Thouvenot ◽  
Florence Morfin
Keyword(s):  
Herpes Simplex ◽  
Drug Targets ◽  
Epstein Barr Virus ◽  
Virus Infections ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals A New Method with General Diagnostic Utility for the Calculation of Immunoglobulin G Avidity

1999 ◽  
Vol 6 (5) ◽  
pp. 725-728 ◽  
Author(s):  
Maria H. Korhonen ◽  
John Brunstein ◽  
Heikki Haario ◽  
Alexei Katnikov ◽  
Roberto Rescaldani ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Logistic Model ◽  
Epstein Barr Virus ◽  
Parvovirus B19 ◽  
Reference Method ◽  
Cost Effective ◽  
Barr Virus ◽  
Titration Curves ◽  
Igg Avidity ◽  
Epstein Barr

ABSTRACT The reference method for immunoglobulin G (IgG) avidity determination includes reagent-consuming serum titration. Aiming at better IgG avidity diagnostics, we applied a logistic model for the reproduction of antibody titration curves. This method was tested with well-characterized serum panels for cytomegalovirus, Epstein-Barr virus, rubella virus, parvovirus B19, and Toxoplasma gondii. This approach for IgG avidity calculation is generally applicable and attains the diagnostic performance of the reference method while being less laborious and twice as cost-effective.

scholarly journals Activation of the Epstein-Barr Virus Transcription Factor BZLF1 by 12-O-Tetradecanoylphorbol-13-Acetate-Induced Phosphorylation

1998 ◽  
Vol 72 (10) ◽  
pp. 8105-8114 ◽  
Author(s):  
Matthias Baumann ◽  
Harald Mischak ◽  
Sascha Dammeier ◽  
Walter Kolch ◽  
Olivier Gires ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Affinity ◽  
Epstein Barr Virus ◽  
Phorbol Esters ◽  
Transcriptional Level ◽  
Serine Residue ◽  
Barr Virus ◽  
Dna Binding Affinity ◽  
Epstein Barr

ABSTRACT BZLF1 is a member of the extended AP-1 family of transcription factors which binds to specific BZLF1 sequence motifs within early Epstein-Barr virus (EBV) promoters and to closely related AP-1 motifs. BZLF1’s activity is regulated at the transcriptional level as well as through protein interactions and posttranslational modifications. Phorbol esters or immunoglobulin cross-linking both reactivate EBV from latently infected B cells via transactivation of BZLF1. We report here that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is capable of inducing BZLF1’s activity even further. The induction occurs at the posttranscriptional level and depends on a single serine residue located in the DNA binding domain of BZLF1. This serine residue (S186) is phosphorylated by protein kinase C in vitro and in vivo after stimulation with TPA. Phosphorylation of S186 per se interferes with the DNA binding affinity of BZLF1 in vitro but is mandatory for TPA-induced increase in DNA binding of BZLF1, as shown in gel retardation assays and reconstruction experiments with cellular extracts. In transcriptional reporter assays, S186 is essential for the activation of BZLF1 by TPA. Presumably, a yet-to-be-identified cellular factor restores the DNA binding affinity and enhances the transcriptional activity of S186-phosphorylated BZLF1, which is required to induce the lytic phase of EBV’s life cycle.

Cost-effectiveness of Screening for Nasopharyngeal Carcinoma among Asian American Men in the United States

2019 ◽  
Vol 161 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Jeremy P. Harris ◽  
Anirudh Saraswathula ◽  
Brian Kaplun ◽  
Yushen Qian ◽  
K. C. Allen Chan ◽  
...  
Keyword(s):  
United States ◽  
Cost Effectiveness ◽  
Asian American ◽  
Epstein Barr Virus ◽  
Cost Effective ◽  
The United States ◽  
Barr Virus ◽  
Life Years ◽  
Asian American Men ◽  
Epstein Barr

Objective Most patients with nasopharyngeal carcinoma (NPC) in the United States are diagnosed with stage III-IV disease. Screening for NPC in endemic areas results in earlier detection and improved outcomes. We examined the cost-effectiveness of screening for NPC with plasma Epstein-Barr virus DNA among Asian American men in the United States. Study Design We used a Markov cohort model to estimate discounted life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios for screening as compared with usual care without screening. Setting The base case analysis considered onetime screening for 50-year-old Asian American men. Subjects and Methods Confirmatory testing was magnetic resonance imaging and nasopharyngoscopy. Cancer-specific outcomes, health utility values, and costs were determined from cancer registries and the published literature. Results For Asian American men, usual care without screening resulted in the detection of NPC at stages I, II, III-IVB, and IVC among 6%, 29%, 54%, and 11% of those with cancer, respectively, whereas screening resulted in earlier detection with a stage distribution of 43%, 24%, 32%, and 1%. This corresponded to an additional 0.00055 QALYs gained at a cost of $63 per person: an incremental cost of $113,341 per QALY gained. In probabilistic sensitivity analysis, screening Asian American men was cost-effective at $100,000 per QALY gained in 35% of samples. Conclusion Although screening for NPC with plasma Epstein-Barr virus DNA for 50-year-old Asian American men may result in earlier detection, in this study it was unlikely to be cost-effective. Screening may be reasonable for certain subpopulations at higher risk for NPC, but clinical studies are necessary before implementation.

scholarly journals Current Approaches for the Management of Multiple Sclerosis – A Review

2021 ◽  
pp. 222-228
Author(s):  
Lakhwinder Singh ◽  
Sabina Yasmin ◽  
Rajiv Sharma
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Viral Infections ◽  
Nigella Sativa ◽  
Herbal Medicines ◽  
Cost Effective ◽  
Barr Virus ◽  
Neuroinflammatory Disease ◽  
Epstein Barr ◽  
Disease Modifying Agents

Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease which interfere with the central nervous system and damage the myelin sheath and axons. It is mediated by auto-reactive lymphocytes that cross the blood brain barrier cause inflammation, demyelination and axonal loss disturb the communications between the neurons. The exact cause of the MS is not known but it is reported that it may be due to the genetic, environmental factors, viral infections (Epstein Barr virus). There are various approaches for the management of Multiple sclerosis like disease modifying agents are mainly used. Some of the monoclonal antibodies (Ocrelizumab) are approved recently for the management of MS. Due to various unwanted side effects with conventional medicines people are eager to use cost effective medicines with no or less side effects; therefore herbal medicines are best choice for them, they works by different pharmacological actions like reduce oxidative stress, anti-inflammatory, antioxidant effects and others. Mainly used herbal plants like Ginkgobiloba, Salvia officinalis, Nigella sativa.

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