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https://www.readbyqxmd.com/read/28454211/targeting-the-ras-raf-mek-erk-pathway-in-hepatocellular-carcinoma
#1
Sufang Yang, Guohua Liu
Although the biological basis of hepatocellular carcinoma (HCC) remains unclear, effective treatments and improvement of the survival rate remain worthwhile research goals. Abnormal protein signaling pathways contributing to uncontrolled cell proliferation, differentiation, survival and apoptosis are biomarkers of the carcinogenic process. Certain mutated components or overexpression of the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway are increasingly being studied in HCC carcinogenesis...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453414/innate-immune-gene-transcript-level-associated-with-the-infection-of-macrophages-with-ectromelia-virus-in-two-different-mouse-strains
#2
Patryk Dolega, Lidia Szulc-Dąbrowska, Magdalena Bossowska, Matylda Mielcarska, Zuzanna Nowak, Felix N Toka
Poxviruses have evolved numerous mechanisms to avoid the immune response of the infected host, and many of these mechanisms have not been fully described. Here, we studied the transcriptional response of innate immune genes in BALB/c and C57BL/6 peritoneal macrophages following infection with the Moscow strain of ectromelia virus (ECTV-Mos) with the aim of delineating innate immune genes that contribute to the difference between susceptibility and resistance to lethal infection. We show a generalized downregulation of many genes in four categories (toll-like receptor signaling, NOD-like receptor signaling, RIG-I-like receptor signaling, and type I interferon signaling) of antiviral innate immune receptors, downstream signaling pathways, and responsive components...
April 28, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28448848/transmissible-gastroenteritis-virus-infection-induces-nf-%C3%AE%C2%BAb-activation-through-rlr-mediated-signaling
#3
Zhen Ding, Kang An, Lilan Xie, Wei Wu, Ruoxi Zhang, Dang Wang, Ying Fang, Huanchun Chen, Shaobo Xiao, Liurong Fang
Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28448566/il-33-st2-pathway-drives-regulatory-t-cell-dependent-suppression-of-liver-damage-upon-cytomegalovirus-infection
#4
Branka Popovic, Mijo Golemac, Jürgen Podlech, Jelena Zeleznjak, Lidija Bilic-Zulle, Miodrag L Lukic, Luka Cicin-Sain, Matthias J Reddehase, Tim Sparwasser, Astrid Krmpotic, Stipan Jonjic
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection...
April 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28448437/sulfiredoxin-may-promote-cervical-cancer-metastasis-via-wnt-%C3%AE-catenin-signaling-pathway
#5
Kangyun Lan, Yuni Zhao, Yue Fan, Binbin Ma, Shanshan Yang, Qin Liu, Hua Linghu, Hui Wang
The abnormal elevation of sulfiredoxin (Srx/SRXN1)-an antioxidant enzyme whose main function is to protect against oxidative stress-has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28446252/ring-finger-protein-43-associates-with-gastric-cancer-progression-and-attenuates-the-stemness-of-gastric-cancer-stem-like-cells-via-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Yunhe Gao, Aizhen Cai, Hongqing Xi, Jiyang Li, Wei Xu, Yanmei Zhang, Kecheng Zhang, Jianxin Cui, Xiaosong Wu, Bo Wei, Lin Chen
BACKGROUND: Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446055/investigational-drugs-for-nasopharyngeal-carcinoma
#7
Brigette B Y Ma, Edwin P Hui, Anthony T C Chan
Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials. Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#8
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445949/lmp1-slamf1high-cells-are-associated-with-drug-resistance-in-epstein-barr-virus-positive-farage-cells
#9
Heejei Yoon, Young Hyeh Ko
How Epstein-Barr virus (EBV) affects the clinical outcome of EBV-positive diffuse large B-cell lymphoma (DLBCL) remains largely unknown. The viral oncogene LMP1 is at the crux of tumorigenesis and cell survival. Therefore, we examined the association between LMP1high cells drug resistance. We first assessed SLAMF1 as a surrogate marker for LMP1high cells. LMP1 and its target gene CCL22 were highly expressed in SLAMF1high Farage cells. These cells survived longer following treatment with a combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#10
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28444544/methylglyoxal-detoxification-by-a-dj-1-family-protein-provides-dual-abiotic-and-biotic-stress-tolerance-in-transgenic-plants
#11
Prasad Melvin, Kondalarao Bankapalli, Patrick D'Silva, P V Shivaprasad
Methylglyoxal (MG) is a key signaling molecule resulting from glycolysis and other metabolic pathways. During abiotic stress, MG levels accumulate to toxic levels in affected cells. However, MG is routinely detoxified through the action of DJ1/PARK7/Hsp31 proteins that are highly conserved across kingdoms and mutations in such genes are associated with neurodegenerative diseases. Here, we report for the first time that, similar to abiotic stresses, MG levels increase during biotic stresses in plants, likely contributing to enhanced susceptibility to a wide range of stresses...
April 25, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#12
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28443075/grim-19-restricts-hcv-replication-by-attenuating-intracellular-lipid-accumulation
#13
Jung-Hee Kim, Pil S Sung, Eun B Lee, Wonhee Hur, Dong J Park, Eui-Cheol Shin, Marc P Windisch, Seung K Yoon
Gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) targets multiple signaling pathways involved in cell death and growth. However, the role of GRIM-19 in the pathogenesis of hepatitis virus infections remains unexplored. Here, we investigated the restrictive effects of GRIM-19 on the replication of hepatitis C virus (HCV). We found that GRIM-19 protein levels were reduced in HCV-infected Huh7 cells and Huh7 cells harboring HCV replicons. Moreover, ectopically expressed GRIM-19 caused a reduction in both intracellular viral RNA levels and secreted viruses in HCVcc-infected cell cultures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28442605/the-toll-like-receptor-4-antagonist-eritoran-protects-mice-from-lethal-filovirus-challenge
#14
Patrick Younan, Palaniappan Ramanathan, Jessica Graber, Fabian Gusovsky, Alexander Bukreyev
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over in February of 2016, has demonstrated the need for the rapid development of therapeutic intervention strategies. Indirect evidence has suggested that the EBOV infection shares several commonalities associated with the onset of bacterial sepsis, including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4 (TLR4) antagonist, was previously shown to result in protection of mice against lethal influenza virus infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442428/rapamycin-modulation-of-p70-s6-kinase-signaling-inhibits-rift-valley-fever-virus-pathogenesis
#15
Todd M Bell, Virginia Espina, Svetlana Senina, Caitlin Woodson, Ashwini Brahms, Brian Carey, Shih-Chao Lin, Lindsay Lundberg, Chelsea Pinkham, Alan Baer, Claudius Mueller, Elizabeth A Chlipala, Faye Sharman, Cynthia de la Fuente, Lance Liotta, Kylene Kehn-Hall
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA)...
April 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#16
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#17
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28433771/a-versatile-tumor-gene-deletion-system-reveals-a-crucial-role-for-fgfr1-in-breast-cancer-metastasis
#18
Wei Wang, Yanling Meng, Bingning Dong, Jie Dong, Michael M Ittmann, Chad J Creighton, Lu Yang, Hong Zhang, Tao Shen, Jianghua Wang, David R Rowley, Yi Li, Fengju Chen, David D Moore, Feng Yang
RCAS avian viruses have been used to deliver oncogene expression and induce tumors in transgenic mice expressing the virus receptor TVA. Here we report the generation and characterization of a novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. FGF receptor 1 (FGFR1) is a gene that is amplified in human breast cancer, but there have been no definitive studies on its function in mammary tumorigenesis, progression, and metastasis in vivo in spontaneous tumors in mice...
April 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#19
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432378/advances-in-anti-viral-immune-defence-revealing-the-importance-of-the-ifn-jak-stat-pathway
#20
REVIEW
Nicola Raftery, Nigel J Stevenson
Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
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