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https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#1
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28053098/the-viral-bcl-2-homologs-of-kaposi-s-sarcoma-associated-herpesvirus-and-rhesus-rhadinovirus-share-an-essential-role-for-viral-replication
#2
Antonio Gallo, Melanie Lampe, Thomas Günther, Wolfram Brune
: KS-Bcl-2 is a Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral Bcl-2 homolog (vBcl-2), which has apoptosis and autophagy inhibiting activity when expressed in transfected cells. However, little is known about its function during viral infection. As KS-Bcl-2 is expressed during the lytic replication cycle, we used constitutively lytic and inducible-lytic KSHV mutants to investigate the role of KS-Bcl-2 during the lytic cycle. We show that KSHV cannot complete the lytic replication cycle and produce infectious progeny in the absence of KS-Bcl-2, indicating that the protein is essential for KSHV replication...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28046107/rna-sequencing-reveals-that-kaposi-sarcoma-associated-herpesvirus-infection-mimics-hypoxia-gene-expression-signature
#3
Coralie Viollet, David A Davis, Shewit S Tekeste, Martin Reczko, Joseph M Ziegelbauer, Francesco Pezzella, Jiannis Ragoussis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28040691/ultraviolet-radiation-and-kaposi-sarcoma-incidence-in-a-nationwide-us-cohort-of-hiv-infected-men
#4
Elizabeth K Cahoon, Eric A Engels, D Michal Freedman, Mary Norval, Ruth M Pfeiffer
BACKGROUND: Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression...
May 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28035362/mir-628-3p-regulates-osteoblast-differentiation-by-targeting-runx2-possible-role-in-atrophic-non-union
#5
Hua Chen, Xinran Ji, Fei She, Yuan Gao, Peifu Tang
Atrophic non-union is a serious complication of fractures. The underlying biological mechanisms involved in its pathogenesis are not yet completely understood. MicroRNAs (miRNAs or miRs) are a type of endogenous small non-coding RNA, which participate in various physiological and pathophysiological processes. In this study, differentially expressed miRNAs were screened in patients with atrophic non-union. In total, 4 miRNAs (miR‑149*, miR‑221, miR‑628-3p and miR‑654-5p) were upregulated and 7 miRNAs (let-7b*, miR‑220b, miR‑513a-3p, miR‑551a, miR‑576-5p, miR‑1236 and kshv-miR‑K12-6-5p) were downregulated at the fracture sites in patients with atrophic non-union...
December 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28004818/3-d-microwell-array-system-for-culturing-virus-infected-tumor-cells
#6
Rami El Assal, Umut A Gurkan, Pu Chen, Franceline Juillard, Alessandro Tocchio, Thiruppathiraja Chinnasamy, Chantal Beauchemin, Sebnem Unluisler, Serli Canikyan, Alyssa Holman, Srikar Srivatsa, Kenneth M Kaye, Utkan Demirci
Cancer cells have been increasingly grown in pharmaceutical research to understand tumorigenesis and develop new therapeutic drugs. Currently, cells are typically grown using two-dimensional (2-D) cell culture approaches, where the native tumor microenvironment is difficult to recapitulate. Thus, one of the main obstacles in oncology is the lack of proper infection models that recount main features present in tumors. In recent years, microtechnology-based platforms have been employed to generate three-dimensional (3-D) models that better mimic the native microenvironment in cell culture...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27966015/oral-shedding-of-human-herpesviruses-in-patients-undergoing-radiotherapy-chemotherapy-treatment-for-head-and-neck-squamous-cell-carcinoma
#7
Michelle Palmieri, Victor Adriano de Oliveira Martins, Laura Masami Sumita, Tania Regina Tozetto-Mendoza, Bruna Baraldi Romano, Clarisse Martins Machado, Claudio Sergio Pannuti, Thaís Bianca Brandão, Ana Carolina Prado Ribeiro, Luciana Corrêa, Paulo Henrique Braz-Silva
OBJECTIVE: Opportunistic infections may affect the oral mucosa of patients undergoing radio/chemotherapy through exacerbation of oral mucositis. The aim of this study is to evaluate the oral shedding of all eight human herpesviruses and its possible association with oral mucositis. MATERIALS AND METHODS: In this prospective cohort study, we analyzed oral rinse samples, collected weekly, from 20 patients during radiotherapy treatment. Serologic status to HSV1 and HSV2, EBV, CMV, and VZV in three different periods was performed by ELISA assay...
December 14, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27939840/niclosamide-inhibits-lytic-replication-of-epstein-barr-virus-by-disrupting-mtor-activation
#8
Lu Huang, Mengtian Yang, Yan Yuan, Xiaojuan Li, Ersheng Kuang
Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27936107/structural-analysis-of-thymidylate-synthase-from-kaposi-s-sarcoma-associated-herpesvirus-with-the-anticancer-drug-raltitrexed
#9
Yong Mi Choi, Hyun Ku Yeo, Young Woo Park, Jae Young Lee
Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1...
2016: PloS One
https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#10
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27932611/kaposi-s-sarcoma-associated-herpesvirus-infection-of-neurons-in-hiv-positive-patients
#11
For Yue Tso, Ashley Sawyer, Eun Hee Kwon, Victor Mudenda, Dianne Langford, You Zhou, John West, Charles Wood
BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), one of the leading cancers in HIV patients in Zambia. KSHV was detected in the human central nervous system (CNS) by PCR, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV positive individuals with KSHV, we sought to determine whether the CNS can be infected by KSHV in HIV positive Zambian individuals...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27928018/expression-of-the-antisense-to-latency-transcript-long-noncoding-rna-in-kaposi-s-sarcoma-associated-herpesvirus
#12
Jason M Schifano, Kathleen Corcoran, Hemant Kelkar, Dirk P Dittmer
: The regulation of latency is central to herpesvirus biology. Recent transcriptome-wide surveys have uncovered evidence for promiscuous transcription across the entirety of the Kaposi sarcoma-associated herpesvirus genome and postulated the existence of multiple viral long noncoding RNAs (lncRNAs). NextGen sequencing studies are highly dependent on the specific experimental approach and particular algorithms of analysis, and therefore benefit from independent confirmation of the results...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27926458/changes-in-relative-and-absolute-concentrations-of-plasma-phospholipid-fatty-acids-observed-in-a-randomized-trial-of-omega-3-fatty-acids-supplementation-in-uganda
#13
Xiaoling Song, Pho Diep, Jeannette M Schenk, Corey Casper, Jackson Orem, Zeina Makhoul, Johanna W Lampe, Marian L Neuhouser
Expressing circulating phospholipid fatty acids (PLFAs) in relative concentrations has some limitations: the total of all fatty acids are summed to 100%; therefore, the values of individual fatty acid are not independent. In this study we examined if both relative and absolute metrics could effectively measure changes in circulating PLFA concentrations in an intervention trial. 66 HIV and HHV8 infected patients in Uganda were randomized to take 3g/d of either long-chain omega-3 fatty acids (1856mg EPA and 1232mg DHA) or high-oleic safflower oil in a 12-week double-blind trial...
November 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27912080/the-itch-ubiquitin-ligase-is-required-for-kshv-rta-induced-vflip-degradation
#14
Jennifer C Chmura, Kevin Herold, Ayana Ruffin, Trudymae Atuobi, Yetunde Fabiyi, Ashley E Mitchell, Young Bong Choi, Elana S Ehrlich
Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27898752/-tocilizumab-treatment-of-hhv8-positive-hiv-negative-multricentric-plasma-cell-type-castleman-s-disease
#15
Györgyi Mûzes, Judit Csomor, Ferenc Sipos
This is a case presentation of a HHV8-positive multicentric Castleman's disease (MCD) of plasma cell type. The patient failed to respond to combined immunosuppressive therapy and monoclonal anti-CD20 therapy. Interestingly, administration of anti-IL-6R antibody stabilized the disease and resulted in clearance of HHV8 from the involved lymph nodes.
November 29, 2016: Magyar Onkologia
https://www.readbyqxmd.com/read/27893813/azidothymidine-sensitizes-primary-effusion-lymphoma-cells-to-kaposi-sarcoma-associated-herpesvirus-specific-cd4-t-cell-control-and-inhibits-virf3-function
#16
Samantha J Williamson, Samantha M Nicol, Michael Stürzl, Shereen Sabbah, Andrew D Hislop
Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27893764/virus-mediated-alterations-in-mirna-factors-and-degradation-of-viral-mirnas-by-mcpip1
#17
Christine Happel, Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation...
November 2016: PLoS Biology
https://www.readbyqxmd.com/read/27890943/recapitulation-of-acquired-immuno-deficiency-syndrome-associated-kaposi-s-sarcoma
#18
REVIEW
Balaji Govindan
Acquired immuno deficiency syndrome (AIDS) associated Kaposi's sarcoma (KS) is one of the clinical forms of KS. KS is caused by human herpes viruses 8 or KS associated herpes virus (KSHV). In India, till now, only 16 cases of AIDS associated KS was reported. Of all the clinical forms of KS, AIDS associated KS is distinct in many ways viz.; cutaneous manifestations commonly affects face and trunk rather than lower limbs, more mucosal lesions, rapidly progressive, and early systemic involvement. When human immunodeficiency virus (HIV) is co-infected with KSHV, in addition to the other pathogenic factors for the development of KS, HIV Tat protein promotes the proliferation of cytokine-activated endothelial cells and stimulates KS...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27888664/ebv-associated-but-hhv8-unrelated-double-hit-effusion-based-lymphoma
#19
Bo-Jung Chen, David Yen-Ting Chen, Chun-Chi Kuo, Shih-Sung Chuang
Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion...
November 26, 2016: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/27872774/pulmonary-kaposi-sarcoma-an-uncommon-cause-of-respiratory-failure-in-the-era-of-highly-active-antiretroviral-therapy-case-report-and-review-of-the-literature
#20
Stanley M Nwabudike, Stefan Hemmings, Yonette Paul, Yordanis Habtegebriel, Octavius Polk, Alem Mehari
Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges...
2016: Case Reports in Infectious Diseases
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