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EBV, Cancer

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
L C Hewitt, I Z Inam, Y Saito, T Yoshikawa, A Quaas, A Hoelscher, E Bollschweiler, G E Fazzi, V Melotte, R E Langley, M Nankivell, D Cunningham, W Allum, G G Hutchins, H I Grabsch
BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status...
March 15, 2018: European Journal of Cancer
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
March 1, 2018: Cancer Treatment Reviews
Hiroyuki Abe, Ruri Saito, Takashi Ichimura, Akiko Iwasaki, Sho Yamazawa, Aya Shinozaki-Ushiku, Teppei Morikawa, Tetsuo Ushiku, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0...
March 13, 2018: Virchows Archiv: An International Journal of Pathology
Marina A Pereira, Marcus F K P Ramos, Sheila F Faraj, Andre R Dias, Osmar K Yagi, Bruno Zilberstein, Ivan Cecconello, Venancio A F Alves, Evandro S de Mello, Ulysses Ribeiro
BACKGROUND AND OBJECTIVES: Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray...
March 13, 2018: Journal of Surgical Oncology
Alessia Gallo, Monica Miele, Ester Badami, Pier Giulio Conaldi
Patients following solid organ transplantation show a higher risk of developing cancer compared to the general population. Elevated risk is likely due to the interplay of a combination of factors, such as chronic inflammation, coexisting medical conditions, immunosuppressive regimen and persistent infection with oncogenic viruses. In addition, the tumor microenvironment plays a pivotal role in cancer progression, by driving recruitment and in situ differentiation of anti-inflammatory cells of the adaptive and innate immune system such as regulatory T cells, Th17, Dendritic Cells, Myeloid Derived Suppressor Cells, Type 2 Macrophages...
February 16, 2018: Cellular Immunology
Chawalit Lertbutsayanukul, Danita Kannarunimit, Buntipa Netsawang, Sarin Kitpanit, Chakkapong Chakkabat, Pokrath Hansasuta, Anussara Prayongrat
Objective: Plasma Epstein-Barr virus (EBV) DNA concentration at the time of diagnosis (pre-EBV) can be used to stratify risk for nasopharyngeal cancer (NPC) patients. However, pre-EBV cut-off values vary among studies. Methods: This was a post hoc analysis of 208 NPC patients from a phase II/III study comparing sequential (SEQ) vs. simultaneous integrated boost (SIB) intensity modulated radiation therapy. The objective was to identify the optimal pre-EBV cut-off value to predict overall survival (OS), progression free survival (PFS) and distant metastatic free survival (DMFS) rates...
March 7, 2018: Japanese Journal of Clinical Oncology
Kimberly Boyd, Joshua M Harrison, Michael J Kavanaugh
The heterophile antibody (Monospot), initial test of choice for Epstein-Barr virus (EBV)-associated infectious mononucleosis, is both sensitive (70-92%) and specific (96-100%). False positives have been demonstrated in cases of viral hepatitis, human immunodeficiency virus, leukemia, lymphoma, pancreatic cancer, systemic lupus erythematosus, and rubella. We present a case of a 46-yr-old male who developed fever, chills, headaches, myalgia, fatigue, and photophobia 1 d after returning from the Philippines. He demonstrated a mild transaminitis and significant thrombocytopenia (12,000 cells/μL)...
March 1, 2018: Military Medicine
Renu Verma, Prakash C Sharma
Gastric cancer (GC) is one of the leading causes of cancer related mortality in the world. Being asymptomatic in nature till advanced stage, diagnosis of gastric cancer becomes difficult in early stages of the disease. The onset and progression of gastric cancer has been attributed to multiple factors including genetic alterations, epigenetic modifications, Helicobacter pylori and Epstein-Barr Virus (EBV) infection, and dietary habits. Next Generation Sequencing (NGS) based approaches viz . Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), RNA-Seq, and targeted sequencing have expanded the knowledge base of molecular pathogenesis of gastric cancer...
2018: American Journal of Cancer Research
Zhiwei Liu, Anna E Coghill, Ruth M Pfeiffer, Carla Proietti, Wan-Lun Hsu, Yin-Chu Chien, Lea Lekieffre, Lutz Krause, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Jason Mulvenna, Jaap M Middeldorp, Jeff Bethony, Chien-Jen Chen, Denise L Doolan, Allan Hildesheim
Background: Little is known about variation in antibody response targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk. Methods: We utilized a microarray to measure IgG and IgA antibody responses against 199 EBV protein sequences from five EBV strains in 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the association between environmental and genetic risk factors and variation in antibody responses...
March 2, 2018: Journal of Infectious Diseases
Bhushan Dharmadhikari, Emily Nickles, Zulkarnain Harfuddin, Nur Diana Binte Ishak, Qun Zeng, Antonio Bertoletti, Herbert Schwarz
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs...
March 5, 2018: Cancer Immunology, Immunotherapy: CII
Nannan Zhang, Jingyu Deng
Gastric cancer is one of the most important diseases that endangers people's health. Beside gastric adenocarcinoma, gastric carcinoma also includes the following types: adenosquamous carcinoma, squamous carcinoma, gastric neuroendocrine tumor, gastric hepatoid adenocarcinoma, AFP-producing gastric cancer, EBV-associated gastric cancer, lymphoepithelioma-like carcinoma, undifferentiated-type gastric cancer, gastric carcinosarcoma and so on. The adenosquamous carcinoma, squamous carcinoma of stomach, gastric hepatoid adenocarcinoma, AFP-producing gastric cancer and gastric carcinosarcoma mainly occurred in old men, while the linitisplastica gastric cancer was common in young women...
February 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Haibo Qiu, Zhiwei Zhou
The National Comprehensive Cancer Network (NCCN) issued the clinical practice guidelines for gastric cancer 2017 edition version 5, which has been fully updated for the treatment of gastric cancer, including systematic treatment, surgery and radiotherapy. This article review and summarize the updated NCCN clinical practice guidelines for gastric cancer in 2017 and try to interpret it. (1)Biomarkers: mismatch repair defect (dMMR) or high microsatellite instability (MSI-H), programmed death ligand 1 (PD-L1) and tumor Epstein Barr virus (EBV) status should be considered for patients with gastric cancer...
February 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Tingdong Li, Xiaoyi Guo, Mingfang Ji, Fugui Li, Han Wang, Weimin Cheng, Honglin Chen, Munhon Ng, Shengxiang Ge, Yong Yuan, Ningshao Xia
Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein-Barr virus (EBV), is one of the most prevalent cancers in southeast China. Most NPC patients are diagnosed at late stage due to inconspicuous symptoms at the early stage, and the prognosis of these patients is poor. The early diagnosis rate of NPC could be significantly increased by serological screening, but the positive predictive value (PPV) is relatively low. A simple two-step serological screening scheme was established to improve the PPV of the screening strategy and was validated by a prospective cohort...
February 25, 2018: Cancer Medicine
Patrice Vallin, Olivier Désy, Stéphanie Béland, François Bouchard-Boivin, Isabelle Houde, S A De Serres
BACKGROUND: The successful development of immunosuppressive agents has paradoxically led to an era in which adverse effects of immunosuppression, such as infections and cancer, are now a major concern in solid organ recipients. Nevertheless, the main focus of immune monitoring research remains the identification of rejection. There is currently no clinical tool to assess the net state of immunosuppression or to identify patients at increased risk of infectious complications. METHODS: We report a prospective, longitudinal study in which we conducted detailed phenotyping of over 300 peripheral blood mononuclear cell samples from 45 kidney recipients during the first 24 months posttransplant...
February 20, 2018: Transplantation
Yih-Lin Chung, Mei-Ling Wu
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated lymphoepithelioma. The aim of the present study was to characterize the homogeneity and distinctness of the T-cell repertoires within and between primary and metastatic NPCs. We used ultra-deep sequencing of the hypervariably rearranged antigen-binding CDR3 regions of T-cell receptor beta (TCRbeta ) to comprehensively profile the T-cell repertoires in NPC patients receiving definitive chemoradiotherapy with long-term follow-up. We observed not only various spatially heterogeneous patient-specific TCRbeta clone compositions that changed with time but also several commonly enriched TCRbeta subclones that were constantly shared between primary NPCs in the head and neck regions, locally recurrent tumors after treatment, and later-developed distant metastatic tumors in the liver, lung and bone...
February 22, 2018: International Journal of Cancer. Journal International du Cancer
Mahiuddin Ahmed, Andres Lopez-Albaitero, Dmitry Pankov, Brian H Santich, Hong Liu, Su Yan, Jingyi Xiang, Pei Wang, Aisha N Hasan, Annamalai Selvakumar, Richard J O'Reilly, Cheng Liu, Nai-Kong V Cheung
EBV infection is associated with a number of malignancies of clinical unmet need, including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and posttransplant lymphoproliferative disease (PTLD), all of which express the EBV protein latent membrane protein 2A (LMP2A), an antigen that is difficult to target by conventional antibody approaches. To overcome this, we utilized phage display technology and a structure-guided selection strategy to generate human T cell receptor-like (TCR-like) monoclonal antibodies with exquisite specificity for the LMP2A-derived nonamer peptide, C426LGGLLTMV434 (CLG), as presented on HLA-A*02:01...
February 22, 2018: JCI Insight
Chong Wang, Hufeng Zhou, Yong Xue, Jun Liang, Yohei Narita, Catherine Gerdt, Amy Y Zheng, Runsheng Jiang, Stephen Trudeau, Chih-Wen Peng, Benjamin Gewurz, Bo Zhao
Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B cell immortalization. EBNALP is thought to function primarily by co-activaing EBNA2-mediated transcription. Chromatin immune precipitation followed by deep-sequencing (ChIP-seq) studies highlight that EBNALP frequently co-occupies DNA sites with host cell transcription factors (TFs), in particular EP300, implicating a broader role in transcription regulation...
February 21, 2018: Journal of Virology
Chao Xie, Xia Xu, Bian Wu, Kun-Yu Yang, Jing Huang
RATIONALE: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of lung squamous cell carcinoma. In situ hybridization test for Epstein-Bar virus-encoded RNA (EBER) is generally used for distinguishing it from other lung cancers. Although plasma EBV DNA quantification has been widely used as a tumor biomarker in nasopharyngeal carcinoma (NPC), only a limiting number of studies have suggested that plasma EBV DNA quantification may be used as a tumor marker in pulmonary LELC patients...
February 2018: Medicine (Baltimore)
Ling Wang, Mary E A Howell, Brooke McPeak, Katrina Riggs, Carissa Kohne, Jether Uel Yohanon, Daniel E Foxler, Tyson V Sharp, Jonathan P Moorman, Zhi Q Yao, Shunbin Ning
LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor, being deregulated in many cancers to include hematological malignancies; however, very little is known about the underlying mechanisms of its deregulation and its roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of malignancies of lymphocytic and epithelial origin. Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies...
January 19, 2018: Oncotarget
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