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Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
Thomas Menter, Alexandar Tzankov
Purpose: Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. Methods: A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. Results: We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28...
2018: Frontiers in Oncology
Marjolein W J Wentink, Yvonne M Mueller, Virgil A S H Dalm, Gertjan J Driessen, P Martin van Hagen, Joris M van Montfrans, Mirjam van der Burg, Peter D Katsikis
Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8+ T cells was suggested to contribute to APDS pathogenesis...
2018: Frontiers in Immunology
Rongrong Wu, Zijun Le, Zhenzhen Wang, Shuying Tian, Yongbo Xue, Yong Chen, Linzhen Hu, Yonghui Zhang
Hyperjaponol H ( 1 ), a new filicinic acid-based meroterpenoid, with a 6/6/10 ring system trans -fused by hetero-Diels-Alder cycloaddition between a germacrane sesquiterpenoid and a filicinic acid moiety, was isolated from aerial parts of Hypericum japonicum . The elucidation of its structure and absolute configuration were accomplished by the analyses of extensive spectroscopic data and the comparison of Cotton effects of electron circular dichroism (ECD) with previously reported ones. The bioactivity assay showed that hyperjaponol H exhibited a moderate inhibitory efficacy on lytic Epstein-Barr virus (EBV) DNA replication in B95-8 cells...
March 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Eveline Hoebe, Coral Wille, Stacy Hagemeier, Shannon Kenney, Astrid Greijer, Jaap Middeldorp
Epstein-Barr Virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is considered a viral oncogene in epithelial cells and has immune-modulating properties. During viral lytic replication BARF1 is expressed as an early gene, regulated by the immediate early EBV protein R. However, in viral latency BARF1 is exclusively expressed in epithelial tumors such as nasopharyngeal (NPC) and gastric carcinoma (GC) but not in lymphomas, indicating that activation of the BARF1 promoter is cell type specific. Undifferentiated NPC is characterized by high expression of ΔNp63 isoforms of the epithelial differentiation marker p63, a member of the p53 family of transcription factors...
March 17, 2018: Cancers
Christine T Styles, Kostas Paschos, Robert E White, Paul J Farrell
The Epstein-Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein-Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in vitro B cell transformation and EBV persistence in vivo. Despite structural and sequence similarities, and evidence of substantial cooperative activity between the EBNA3 proteins, they perform quite different, often opposing functions...
March 17, 2018: Pathogens
Vanessa Couras Regadas, Márcio de Castro E Silva, Lucas Giansante Abud, Luiz Mario Pereira Lopes Labadessa, Rafael Gouvêa Gomes de Oliveira, Cecília Hissae Miyake, Rodolfo Mendes Queiroz
Currently Latin America is undergoing a major epidemic of Zika virus, which is transmitted by Aedes mosquitoes. Concern for Zika virus infection has been increasing as it is suspected of causing brain defects in newborns such as microcephaly and, more recently, potential neurological and autoimmune complications including Guillian-Barré syndrome and acute disseminated encephalomyelitis. We describe a case of virus infection in a 25-year-old woman during the first trimester of her pregnancy, confirmed by laboratory tests only for the detection of viral particles in maternal urine, with imaging studies demonstrating the progression of cranial and encephalic changes in the fetus and later in the newborn, such as head circumference reduction, cerebral calcifications and ventriculomegaly...
January 2018: Revista da Associação Médica Brasileira
Kathy H Y Shair, Akhil Reddy, Vaughn S Cooper
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex...
March 21, 2018: Cancers
Widodo, Nadya Veronica Margarecaesha Anyndita, Nurul Dluha, Muhaimin Rifa'i, Karimatul Himmah, Mulya Dwi Wahyuningsih
Background: Epstein-Barr virus (EBV) can cause cancer in people from around the world. There is no EBV vaccine available for use on a global scale. However, emerging evidence suggests that the epitope on the gp350/220 capsid protein may be developed into an EBV vaccine. Nevertheless, the production of small, single epitope is challenging of stability issues and possible alteration of peptide structure. In this study, a tandem epitope was developed consisting of three single epitopes, aimed to improve stability, antigenicity and preserve epitope structure...
March 2018: Heliyon
Alejandra M Wiedeman, Kyly C Whitfield, Kaitlin M March, Nancy N Chen, Hou Kroeun, Ly Sokhoing, Prak Sophonneary, Roger A Dyer, Zhaoming Xu, David D Kitts, Timothy J Green, Sheila M Innis, Susan I Barr
Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada ( n = 301) and in Cambodia ( n = 67)...
March 20, 2018: Nutrients
Chika Hamaya, Travis Barr, Gary R Strichartz
BACKGROUND AND OBJECTIVES: Local anesthetics (LAs) are often infiltrated subcutaneously for localized perioperative numbing. In addition to blocking nerve conduction, LAs act on pathways used by a variety of pain-inducing and inflammatory mediators. We describe the effects in isolated model sensory neurons of LAs on responses to the algogenic and sensitizing peptide, bradykinin (BK). METHODS: ND/7 sensory neurons were stimulated by different concentrations of BK in the presence or absence of LAs, with transient increases in intracellular calcium (Δ[Ca]in) detected fluorometrically in fields of cells...
March 17, 2018: Regional Anesthesia and Pain Medicine
Hui Chang, Jia-Wang Wei, Kai Chen, Shu Zhang, Fei Han, Li-Xia Lu, Wei-Wei Xiao, Yuan-Hong Gao
Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid)...
2018: Journal of Cancer
Lei Wu, Churong Li, Li Pan
Nasopharyngeal carcinoma (NPC) is a rare malignancy worldwide, but it is endemic in a few areas including Southern China, Southeast Asia, North Africa and the Arctic. The underlying mechanisms behind this remarkable geographic distribution remain unclear. Although Epstein-Barr virus (EBV) infection has been suggested as a necessary cause of undifferentiated NPC, EBV itself is not sufficient to cause this malignancy. Other co-factors, such as environmental risk factors, and/or genetic susceptibility, may interact with EBV to play a role in the carcinogenesis of NPC...
April 2018: Experimental and Therapeutic Medicine
R C Laker, C Garde, D M Camera, W J Smiles, J R Zierath, J A Hawley, R Barrès
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 19, 2018: Scientific Reports
Brigette Ma, Edwin P Hui, Ann King, Sing F Leung, Michael Km Kam, Frankie Mo, Leung Li, Ki Wang, Herbert Loong, Ashley Wong, Charles Ml Chan, K C Allen Chan, S C Cesar Wong, Y M Dennis Lo, Anthony Tc Chan
BACKGROUND: Plasma Epstein-Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response. METHODS: Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy...
March 20, 2018: British Journal of Cancer
Sagar B Kudchodkar, Hyeree Choi, Emma L Reuschel, Rianne Esquivel, Jackie Jin-Ah Kwon, Moonsup Jeong, Joel N Maslow, Charles C Reed, Scott White, J Joseph Kim, Gary P Kobinger, Pablo Tebas, David B Weiner, Kar Muthumani
Vaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective vaccines against infectious pathogens such as influenza, HIV, dengue virus (DENV), chikungunya virus (CHIKV), Ebola virus, and Zika virus (ZIKV) have proven challenging. Zika virus is a mosquito-vectored flavivirus responsible for periodic outbreaks of disease in Africa, Southeast Asia, and the Pacific Islands dating back over 50 years...
March 16, 2018: Microbes and Infection
Yun-Hsuan Lin, Tai-Lin Huang, Chih-Yen Chien, Hui-Chun Chen, Hsuan-Chih Hsu, Eng-Yen Huang, Chong-Jong Wang, Yu-Jie Huang, Yu-Ming Wang, Chun-Chieh Huang, Shang-Yu Chou, Kuan-Cho Liao, Fu-Min Fang
BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed...
March 20, 2018: Radiation Oncology
Weili Wang, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C Knepper, Zhaoqian Liu, Wei Zhang, Howard L Mcleod, Yijing He
Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection. Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy...
February 23, 2018: Oncotarget
Sriraman Priyanka, Gurumoorthy Kaarthikeyan, Jayakumar Doraiswamy Nadathur, Anbarasu Mohanraj, Avinash Kavarthapu
Background: Periodontitis and atherosclerosis represent a chronic inflammatory process. The incidence of periodontitis in cardiac patients with atherosclerosis is a well-established fact. The role of viruses in the etiopathogenesis of both has been proposed. Aim: The aim of the study was to evaluate the prevalence of Torque Teno virus (TTV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in cardiac patients with atherosclerosis and coexisting chronic periodontitis (CP)...
November 2017: Journal of Indian Society of Periodontology
Grant C O'Connell, Madison B Treadway, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n = 3)...
March 17, 2018: Translational Stroke Research
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