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https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#1
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330011/mutations-in-pi3k110%C3%AE-cause-impaired-nk-cell-function-partially-rescued-by-rapamycin-treatment
#2
Raquel Ruiz-García, Alexander Vargas-Hernandez, Ivan K Chinn, Laura S Angelo, Tram N Cao, Zeynep Coban-Akdemir, Shalini N Jhangiani, Qingchang Meng, Lisa R Forbes, Donna M Muzny, Luis M Allende, Mohammed S Ehlayel, Richard A Gibbs, James R Lupski, Gulbu Uzel, Jordan S Orange, Emily M Mace
BACKGROUND: Heterozygous gain-of-function mutations in PI3K110 lead to lymphadenopathy, lymphoid hyperplasia, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, and sinopulmonary infections. OBJECTIVE: The known role of NK cell function in the control of EBV and CMV prompted us to investigate the functional and phenotypic effect of PI3K110δ mutations on NK cell subsets and cytotoxic function. METHODS: Patient mutations were identified by whole exome or targeted sequencing...
January 9, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29329079/the-interactome-of-ebv-lmp1-evaluated-by-proximity-based-bioid-approach
#3
Mark A Rider, Mujeeb R Cheerathodi, Stephanie N Hurwitz, Dingani Nkosi, Lauren A Howell, Deanna C Tremblay, Xia Liu, Fanxiu Zhu, David G Meckes
Epstein-Barr virus LMP1 is an oncoprotein required for immortalizing B lymphocytes and also plays important roles in transforming non-lymphoid tissue. The discovery of LMP1 protein interactions will likely generate targets to treat EBV-associated cancers. Here, we define the broader LMP1 interactome using the recently developed BioID method. Combined with mass spectrometry, we identified over 1000 proteins across seven independent experiments with direct or indirect relationships to LMP1. Pathway analysis suggests that a significant number of the proteins identified are involved in signal transduction and protein or vesicle trafficking...
January 9, 2018: Virology
https://www.readbyqxmd.com/read/29328411/dna-methylation-enzyme-inhibitor-rg108-suppresses-the-radioresistance-of-esophageal-cancer
#4
Yao Ou, Quan Zhang, Yiting Tang, Zhonghua Lu, Xujing Lu, Xifa Zhou, Changmin Liu
Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca‑109 and TE‑1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca‑109 cells were inoculated into nude mice to establish tumors...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29325854/considerations-in-the-diagnosis-of-oral-hairy-leukoplakia-an-institutional-experience
#5
Andres Flores-Hidalgo, Si On Lim, Alice E Curran, Ricardo J Padilla, Valerie Murrah
OBJECTIVE: We report here the 10-year experience with oral hairy leukoplakia (OHL) at the Division of Oral and Maxillofacial Pathology at the University of North Carolina at Chapel Hill, NC, USA. STUDY DESIGN: All the associated hematoxylin and eosin and Epstein-Barr virus encoding region in situ hybridization slides of OHL cases between January 1, 2008, and February 1, 2017, were retrieved and reviewed. Collected demographic characteristics, clinical presentation, medical and social histories were reviewed and reported...
November 15, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29325308/-opportunistic-infection-in-systemic-lupus-erythematosus-patients-the-disease-spectrum-and-the-characteristics-of-peripheral-lymphocyte-subsets
#6
L Qin, Z F Qiu, J Xie, T R Geng, J L Zhao, L Wan, T S Li
Objective: To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections (OIs) . The lymphocyte subsets in healthy donors were used as normal control group. Results: A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs...
January 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29324572/epstein-barr-virus-ebv-induced-b-cell-lymphoproliferative-disorder-mimicking-the-recurrence-of-ebv-associated-hemophagocytic-lymphohistiocytosis
#7
Yuki Yatsushiro, Takuro Nishikawa, Aki Saito, Yozo Nakazawa, Ken-Ichi Imadome, Shunsuke Nakagawa, Yuichi Kodama, Yasuhiro Okamoto, Hirokazu Kanegane, Yoshifumi Kawano
We describe the case of a 23-month-old male infant with Epstein-Barr virus (EBV)-associated lymphoproliferative disorder, which mimicked the recurrence of EBV-associated hemophagocytic lymphohistiocytosis. Chemotherapy with dexamethasone, etoposide, and cyclosporine resolved fever, hepatosplenomegaly, and pancytopenia. However, on day 81 of illness, the patient developed similar symptoms. Plasma EBV-DNA levels markedly increased again, but no T-cell clonality was observed. B cells were identified to be infected with EBV...
January 10, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29317752/epstein-barr-virus-encoded-rnas-ebers-complement-the-loss-of-herpesvirus-telomerase-rna-vtr-in-virus-induced-tumor-formation
#8
Ahmed Kheimar, Benedikt B Kaufer
Marek's disease virus (MDV) is an alphaherpesvirus that causes fatal lymphomas in chickens and is used as a natural virus-host model for herpesvirus-induced tumorigenesis. MDV encodes a telomerase RNA subunit (vTR) that is crucial for efficient MDV-induced lymphoma formation; however, the mechanism is not completely understood. Similarly, Epstein Barr-virus (EBV) encodes two RNAs (EBER-1 and EBER-2) that are highly expressed in EBV-induced tumor cells, however their role in tumorigenesis remains unclear. Intriguingly, vTR and EBER-1 have interaction partners in common that are highly conserved in humans and chickens...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316828/hodgkin-s-lymphoma-and-its-association-with-ebv-and-hiv-infection
#9
Ravnit Grewal, Alexandra Irimie, Nasheen Naidoo, Nooroudien Mohamed, Bobe Petrushev, Manogari Chetty, Ciprian Tomuleasa, Emmanuel-Akinola Abayomi
Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis...
January 9, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29316040/herpesviruses-viral-loads-and-levels-of-proinflammatory-cytokines-in-apical-periodontitis
#10
Aleksandar Jakovljevic, Aleksandra Knezevic, Nadja Nikolić, Ivan Soldatović, Tanja Jovanovic, Jelena Milasin, Miroslav Andric
OBJECTIVES: This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β, and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines . MATERIALS AND METHODS: 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29315650/levels-of-oxidative-stress-biomarkers-and-bone-resorption-regulators-in-apical-periodontitis-lesions-infected-by-epstein-barr-virus
#11
A Jakovljevic, M Andric, N Nikolic, V Coric, S Krezovic, J Carkic, A Knezevic, K Beljic-Ivanovic, M Plješa-Ercegovac, M Miletić, I Soldatovic, T Radosavljevic, T Jovanovic, T Simic, V Ivanovic, J Milasin
AIM: To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers (8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)) and bone resorption regulators (receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)) compared to EBV negative periapical lesions and healthy pulp tissues. METHODOLOGY: The experimental group consisted of 30 EBV positive and 30 EBV negative periapical lesions collected in conjunction with apicoectomy...
January 9, 2018: International Endodontic Journal
https://www.readbyqxmd.com/read/29315015/tumor-specific-t-cells-engineered-to-overcome-tumor-immune-evasion-induce-clinical-responses-in-patients-with-relapsed-hodgkin-lymphoma
#12
Catherine M Bollard, Tamara Tripic, Conrad Russell Cruz, Gianpietro Dotti, Stephen Gottschalk, Vicky Torrano, Olga Dakhova, George Carrum, Carlos A Ramos, Hao Liu, Meng-Fen Wu, Andrea N Marcogliese, Cecilia Barese, Youli Zu, Daniel Y Lee, Owen O'Connor, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney
Purpose Transforming growth factor-β (TGF-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) on the safety, survival, and activity of infused tumor-directed T cells. Materials and Methods In a dose escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received two to 12 doses of between 2 × 107 and 1...
January 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29313728/the-potential-of-currently-unavailable-herpes-virus-vaccines
#13
Július Rajcáni, Ferenc Bánáti, Kálmán Szenthe, Susan Szathmary
Despite overwhelming experimental work, there are no licensed vaccines against the most frequent Alphaherpesviruses, namely herpes simplex virus 1 and 2 (HSV1 and 2) nor against the Epstein-Barr virus (EBV), a member of the subfamily Gammaherpesvirus. Areas covered: Since the DNAs of both HSVs reside in the regional sensory ganglia in a latent state (i.e. as circularized episomal molecules), a corresponding vaccine might be useful for immunotherapy rather than prevention of primary infection. Here we describe the design of a purified subunit vaccine (a mix of at least 3 glycoproteins) as well as the preparation and efficacy of a recombinant fusion protein consisting of the gD ectodomain from our domestic attenuated HSV1 strain HSZP...
January 9, 2018: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29311309/signaling-by-the-epstein-barr-virus-lmp1-protein-induces-potent-cytotoxic-cd4-and-cd8-t-cell-responses
#14
Il-Kyu Choi, Zhe Wang, Qiang Ke, Min Hong, Yu Qian, Xiujuan Zhao, Yuting Liu, Hye-Jung Kim, Jerome Ritz, Harvey Cantor, Klaus Rajewsky, Kai W Wucherpfennig, Baochun Zhang
The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29303964/new-interactors-of-the-truncated-ebna-lp-protein-identified-by-mass-spectrometry-in-p3hr1-burkitt-s-lymphoma-cells
#15
Sonia Chelouah, Emilie Cochet, Sophie Couvé, Sandy Balkaran, Aude Robert, Evelyne May, Vasily Ogryzko, Joëlle Wiels
The Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) acts as a co-activator of EBNA-2, a transcriptional activator essential for Epstein-Barr virus (EBV)-induced B-cell transformation. Burkitt's lymphoma (BL) cells harboring a mutant EBV strain that lacks both the EBNA-2 gene and 3' exons of EBNA-LP express Y1Y2-truncated isoforms of EBNA-LP (tEBNA-LP) and better resist apoptosis than if infected with the wild-type virus. In such BL cells, tEBNA-LP interacts with the protein phosphatase 2A (PP2A) catalytic subunit (PP2A C), and this interaction likely plays a role in resistance to apoptosis...
January 5, 2018: Cancers
https://www.readbyqxmd.com/read/29302900/epstein-barr-virus-positive-large-cell-neuroendocrine-carcinoma-of-the-nasopharynx-report-of-a-case-with-complete-clinical-and-radiological-response-after-combined-chemoradiotherapy
#16
Jason K Wasserman, Sylvia Papp, Andrew J Hope, Bayardo Perez-Ordóñez
Neuroendocrine carcinomas of the head and neck are rare and are classified as well differentiated, moderately differentiated, and poorly differentiated carcinomas with the latter category being subdivided into small cell and large cell neuroendocrine carcinoma (LCNEC). While most carcinomas in the nasopharynx are associated with Epstein-Barr virus (EBV), there has been only one previous report demonstrating a link between EBV and LCNEC of the nasopharynx. In this report we describe a second case of EBV-positive LCNEC arising in the nasopharynx with bilateral cervical metastases...
January 4, 2018: Head and Neck Pathology
https://www.readbyqxmd.com/read/29301829/identification-of-a-novel-ebv-based-antibody-risk-stratification-signature-for-early-detection-of-nasopharyngeal-carcinoma-in-taiwan
#17
Anna E Coghill, Ruth M Pfeiffer, Carla Proietti, Wan-Lun Hsu, Yin-Chu Chien, Lea Lekieffre, Lutz Krause, Andy Teng, Jozelyn Pablo, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Zhiwei Liu, Chien-Jen Chen, Jaap M Middeldorp, Jason P Mulvenna, Jeffrey Bethony, Allan Hildesheim, Denise L Doolan
BACKGROUND: Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, ~90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. METHODS: We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29301129/amegakaryocytic-thrombocytopenia-and-subsequent-aplastic-anemia-associated-with-apparent-epstein-barr-virus-infection
#18
Ilana Levy, Ruth Laor, Nizar Jiries, Jacob Bejar, Aaron Polliack, Tamar Tadmor
Acquired amegakaryocytic thrombocytopenia (AAT), a rare entity characterized by severe thrombocytopenia and the absence of megakaryocytes in the bone marrow, may mimic or precede the diagnosis of aplastic anemia (AA). Here, we describe a patient who presented with apparent Epstein-Barr virus (EBV)-associated immune thrombocytopenia resistant to several lines of therapies, which was in fact a form of AAT with some features of AA. He eventually responded to therapy with eltrombopag, cyclosporine A (CSA), and antithymocyte globulin (ATG) and recovered completely...
January 5, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29300240/childhood-nasopharyngeal-carcinoma-state-of-the-art-and-questions-for-the-future
#19
Marie-Emilie Dourthe, Stéphanie Bolle, Stéphane Temam, Anais Jouin, Line Claude, Yves Reguerre, Anne-Sophie Defachelles, Daniel Orbach, Brice Fresneau
In children, nasopharyngeal carcinoma (NPC) is a very rare tumor, mostly Epstein-Barr Virus related and quite always diagnosed at a locally advanced stage. With current protocols associating induction cisplatin-based chemotherapy and concomitant chemoradiotherapy, prognosis is excellent with overall survival higher than 85%. However, long-term toxicities are frequent. Improvement in radiation therapy modalities like intensity-modulated radiation therapy and new strategies with radiation dose adaptation to chemotherapy response have been introduced to reduce acute and long-term toxicities...
January 3, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29297965/the-impact-of-alternative-donor-types-on-viral-infections-in-pediatric-hematopoietic-stem-cell-transplantation
#20
D Atay, A Akcay, F Erbey, G Ozturk
Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy-one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele-matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele-matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31)...
January 3, 2018: Pediatric Transplantation
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