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https://www.readbyqxmd.com/read/29141219/preventive-inhibition-of-liver-tumorigenesis-by-systemic-activation-of-innate-immune-functions
#1
Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M Varki, Shuang-Jian Qiu, Bing Ren, Wenxian Fu, Gen-Sheng Feng
Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140572/dissecting-human-ilc-heterogeneity-more-than-just-three-subsets
#2
REVIEW
Yannick Simoni, Evan W Newell
Innate lymphoid cells (ILCs) have been divided into three distinct groups based on functional capacities, cytokine profiles and transcription factor expression. Studies done mostly in mice have demonstrated the importance of ILCs in chronic inflammation, infection, allergy and cancer. In this review, we discuss the heterogeneity of human ILC and focus primarily on the taxonomy of human ILC cell subsets and their phenotypic and functional diversity. We summarize recent findings about the diversity of ILCs between and within the major subsets (NK, ILC1, ieILC1, ILC2, ILC3, LTi, ILCP), as well as the abundance of each in human tissues...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29138377/-safety-evaluation-of-paclitaxel-injection-nk-in-tri-weekly-administration-of-paclitaxel-plus-carboplatin-tc-therapy-for-gynecological-cancers
#3
Takashi Ikeda, Iori Kisu, Yasunori Sakamoto
Paclitaxel is a key drug used for the treatment of gynecological cancers, breast cancer, and gastric cancer. While there is a great deal of safety information on the weekly administration of generic paclitaxel NK(paclitaxel injection NK)and proprietary paclitaxel(Taxol®injection), little is known about their safety when administered tri-weekly, partly due to a small sample size. Therefore, to gain more information and to validate the safety of using generic paclitaxel NK in a tri-weekly regimen, we investigated the incidences of adverse events in response to it in a larger number of patients...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29138302/disruption-of-the-opal-stop-codon-attenuates-chikungunya-virus-induced-arthritis-and-pathology
#4
Jennifer E Jones, Kristin M Long, Alan C Whitmore, Wes Sanders, Lance R Thurlow, Julia A Brown, Clayton R Morrison, Heather Vincent, Kayla M Peck, Christian Browning, Nathaniel Moorman, Jean K Lim, Mark T Heise
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#5
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34(+) hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#6
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#7
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137237/cryoablation-combined-with-allogenic-natural-killer-cell-immunotherapy-improves-the-curative-effect-in-patients-with-advanced-hepatocellular-cancer
#8
Mao Lin, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu, Kecheng Xu
In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137183/lactobacillus-plantarum-enhanced-il-22-production-in-natural-killer-nk-cells-that-protect-the-integrity-of-intestinal-epithelial-cell-barrier-damaged-by-enterotoxigenic-escherichia-coli
#9
Yueqin Qiu, Zongyong Jiang, Shenglan Hu, Li Wang, Xianyong Ma, Xuefen Yang
Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136142/the-forkhead-transcription-factor-foxo3-negatively-regulates-natural-killer-cell-function-and-viral-clearance-in-myocarditis
#10
Madlen Loebel, Luise Holzhauser, Jelka A Hartwig, Praphulla C Shukla, Konstantinos Savvatis, Alexander Jenke, Martina Gast, Felicitas Escher, Sonya C Becker, Sandra Bauer, Andrea Stroux, Antje Beling, Meike Kespohl, Sandra Pinkert, Henry Fechner, Uwe Kuehl, Dirk Lassner, Wolfgang Poller, Heinz-Peter Schultheiss, Tanja Zeller, Stefan Blankenberg, Anna-Pia Papageorgiou, Stephane Heymans, Ulf Landmesser, Carmen Scheibenbogen, Carsten Skurk
Aims: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. Methods and results: Effects of Foxo3 on viral load and immune responses were investigated in a model of coxsackie virus B3 myocarditis in wild-type (WT) and Foxo3 deficient mice. Reduced immune cell infiltration, viral titres, and pro-inflammatory cytokines in cardiac tissue were observed in Foxo3-/- mice 7 days post-infection (p...
November 9, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29134614/acute-exercise-during-hemodialysis-prevents-the-decrease-in-natural-killer-cells-in-patients-with-chronic-kidney-disease-a-pilot-study
#11
Maria Isabel Fuhro, Gilson P Dorneles, Francini P Andrade, Pedro R T Romão, Alessandra Peres, Mariane B Monteiro
PURPOSE: To evaluate the acute response of natural killer (NK) cell subsets of chronic kidney disease patients submitted to intradialytic exercise in a randomized crossover study. METHODS: Nine patients were submitted to a single bout of 20-min intradialytic exercise and a control hemodialysis (HD) session with an interval of 7 days between them. Peripheral blood sample was collected at baseline, during HD and immediately after HD in each trial to evaluate the peripheral frequency of NK cells and their subsets (CD3-CD56(bright) and CD3-CD56(dim)), systemic cortisol concentrations, C-reactive protein (CRP), creatine kinase activity (CK), and urea and creatinine levels...
November 13, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29133294/proinflammatory-t-cell-status-associated-with-early-life-adversity
#12
Martha M C Elwenspoek, Xenia Hengesch, Fleur A D Leenen, Anna Schritz, Krystel Sias, Violetta K Schaan, Sophie B Mériaux, Stephanie Schmitz, Fanny Bonnemberger, Hartmut Schächinger, Claus Vögele, Jonathan D Turner, Claude P Muller
Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73)...
November 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29133133/boosting-natural-killer-cell-based-immunotherapy-with-anticancer-drugs-a-perspective
#13
REVIEW
Loredana Cifaldi, Franco Locatelli, Emiliano Marasco, Lorenzo Moretta, Vito Pistoia
Natural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29133053/synthesis-and-biological-evaluation-of-new-berberine-derivatives-as-cancer-immunotherapy-agents-through-targeting-ido1
#14
Yan-Xiang Wang, Wei-Qiang Pang, Qing-Xuan Zeng, Zhe-Song Deng, Tian-Yun Fan, Jian-Dong Jiang, Hong-Bin Deng, Dan-Qing Song
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29132010/inhibition-of-sonic-hedgehog-signaling-blocks-cell-migration-and-growth-but-induces-apoptosis-via-suppression-of-foxq1-in-natural-killer-t-cell-lymphoma
#15
Pingyi Liu, Lingling Chen
The present study explored the effects of Forkhead box Q1 (FOXQ1) on cell proliferation, cell cycle and apoptosis via the Sonic hedgehog (Shh) pathway in Natural killer/T-cell lymphoma (NKTCL). Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect FOXQ1 expression in 117 NKTCL patients and 120 healthy controls. Additionally, FOXQ1 expression in NKTCL cell lines (HANK-1, NK-92, SNK-6, SNT-8 and YT) was determined by western blotting and qRT-PCR. SNK-6 cells were transfected with FOXQ1-shRNA or Shh pathway inhibitor Cyclopamine/recombinant protein Shh...
November 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29131866/association-between-mental-health-status-and-bone-mineral-density-analysis-of-the-2008-2010-korea-national-health-and-nutrition-examination-survey
#16
Changtae Hahn, Ji Hoon Oh, Soo-Hyun Joo, Jo-Eun Jeong, Jeong-Ho Chae, Chang-Uk Lee, Tae-Suk Kim
The current study aimed to investigate the association between mental health status and bone mineral density (BMD) using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2010. We enrolled 15,876 South Korean participants (4,010 postmenopausal females, 4,836 premenopausal females, and 7,016 males, all aged 20 years or older). BMD was measured using dual-energy radiography absorptiometry at the femoral neck (NK), lumbar spine (LSP), and total femur (TFM). Mental health status data were obtained from a self-report questionnaire that assessed psychological stress, depressed mood, and suicidal ideation...
2017: PloS One
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#17
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29128673/bi-allelic-irf8-mutation-a-complex-immunodeficiency-syndrome-with-dendritic-cell-deficiency-monocytopenia-and-immune-dysregulation
#18
Venetia Bigley, Sheetal Maisuria, Urszula Cytlak, Laura Jardine, Matthew A Care, Kile Green, Merry Gunawan, Paul Milne, Rachel Dickinson, Sarah Wiscombe, David Parry, Rainer Doffinger, Arian Laurence, Claudia Fonseca Lic, Oda Stoevesandt, Andrew Gennery, Andrew Cant, Reuben Tooze, A John Simpson, Sophie Hambleton, Sinisa Savic, Gina Doody, Matthew Collin
BACKGROUND: Homozygous K108E mutation of interferon regulatory factor 8 (IRF8) is reported to cause dendritic cell and monocyte deficiency. However, more widespread immune dysfunction is predicted from the multiple roles ascribed to IRF8 in immune cell development and function. OBJECTIVE: We sought to describe the effect on hematopoiesis and immunity of compound heterozygous R83C/ R291Q mutation of IRF8, present in a patient with recurrent viral infection, granulo-proliferation and intracerebral calcification...
November 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29128662/activation-of-innate-immunity-in-primary-human-cells-using-a-plant-virus-derived-nanoparticle-tlr7-8-agonist
#19
Damien Carignan, Sabine Herblot, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Michel Duval, Pierre Savard, Denis Leclerc
Rod-shaped virus-like nanoparticles (VLNP) made of papaya mosaic virus (PapMV) coat proteins (CP) self-assembled around a single stranded RNA (ssRNA) were showed to be a TLR7 agonist. Their utilization as an immune modulator in cancer immunotherapy was showed promising. To establish a clinical relevance in human for PapMV VLNP, we showed that stimulation of human peripheral blood mononuclear cells (PBMC) with VLNP induces the secretion of interferon alpha (IFNα) and other pro-inflammatory cytokines and chemokines...
November 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29128554/immunomodulatory-effects-of-tyrosine-kinase-inhibitors-tkis-in-vitro-and-in-vivo-study
#20
Elena Marinelli Busilacchi, Andrea Costantini, Nadia Viola, Benedetta Costantini, Jacopo Olivieri, Luca Butini, Giorgia Mancini, Ilaria Scortechini, Martina Chiarucci, Monica Poiani, Antonella Poloni, Pietro Leoni, Attilio Olivieri
Pathogenesis of chronic Graft Versus Host Disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes, as well as B cells. Standard treatment is lacking for steroid dependent/refractory cases; potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent anti-fibrotic effect. However, TKI seems to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function...
November 8, 2017: Biology of Blood and Marrow Transplantation
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