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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#1
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#2
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28076322/aeroallergen-der-p-2-promotes-motility-of-human-non-small-cell-lung-cancer-cells-via-toll-like-receptor-mediated-up-regulation-of-urokinase-type-plasminogen-activator-and-integrin-focal-adhesion-kinase-signaling
#3
Chun-Hsiang Lin, Hui-Han Lin, Cheng-Yi Kuo, Shao-Hsuan Kao
House dust mite (HDM) allergens are one of the major causes leading to respiratory hypersensitiveness and airway remodeling. Here we hypothesized that a major HDM allergen Der p 2 could increase cell motility and invasiveness of non-small cell lung cancer (NSCLC) cells. Our results showed that low dose (1 and 3 μg/mL) recombinant Der p 2 protein (DP2) enhanced the migration and invasiveness of human NSCLC cell A549, H1299 and CL1-5, but nonsignificantly altered their growth. Further investigation revealed that integrin αV level was increased and its downstream signaling including focal adhesion kinase (FAK) and paxillin were activated in A549 cells exposed to DP2...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075473/spirulina-lipopolysaccharides-inhibit-tumor-growth-in-a-toll-like-receptor-4-dependent-manner-by-altering-the-cytokine-milieu-from-interleukin-17-interleukin-23-to-interferon-%C3%AE
#4
Hiromi Okuyama, Akira Tominaga, Satoshi Fukuoka, Takahiro Taguchi, Yutaka Kusumoto, Shiro Ono
Th17 cells and the cytokine they produce, interleukin (IL)-17, play an important role in tumor progression in humans and in mice. IL-6 and IL-23 are critical cytokines for the differentiation and propagation of Th17 cells, respectively. Bacterial lipopolysaccharides (LPS) are known to stimulate immune cells to produce such inflammatory cytokines. Contrary to Escherichia coli (E. coli) LPS, LPS from Spirulina has low toxicity and barely induces in vivo production of IL-6 and IL-23 in mice. We examined the antitumor effects of Spirulina LPS compared to E...
January 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28069554/encapsulation-of-two-different-tlr-ligands-into-liposomes-confer-protective-immunity-and-prevent-tumor-development
#5
Banu Bayyurt, Gizem Tincer, Kubra Almacioglu, Esin Alpdundar, Mayda Gursel, Ihsan Gursel
Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading...
January 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28060562/pathogen-recognition-and-toll-like-receptor-targeted-therapeutics-in-innate-immune-cells
#6
Sarang Tartey, Osamu Takeuchi
The innate immune system deploys a variety of pattern-recognition receptors (PRRs) which include Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors to detect the invasion of pathogens and initiate protective responses. The intercellular and intracellular orchestration of signals from different PRRs, their endogenous or microbial ligands and accessory molecules determine the stimulatory or inhibitory responses. Progressing over the last two decades, considerable research on the molecular mechanisms underlying host-pathogen interactions has led to a paradigm shift of our understanding of TLR signaling in the innate immune system...
January 6, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28057523/surface-engineering-tumor-cells-with-adjuvant-loaded-particles-for-use-as-cancer-vaccines
#7
Kawther K Ahmed, Sean M Geary, Aliasger K Salem
Cell surface engineering is an expanding field and whilst extensive research has been performed decorating cell surfaces with biomolecules, the engineering of cell surfaces with particles has been a largely unexploited area. This study reports on the assembly of cell-particle hybrids where irradiated tumor cells were surface engineered with adjuvant-loaded, biodegradable, biocompatible, polymeric particles, with the aim of generating a construct capable of functioning as a therapeutic cancer vaccine. Successfully assembled cell-particle hybrids presented here comprised either melanoma cells or prostate cancer cells stably adorned with Toll-like receptor-9 ligand-loaded particles using streptavidin-biotin cross-linking...
January 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28057304/drosophila-as-a-model-for-human-diseases-focus-on-innate-immunity-in-barrier-epithelia
#8
P Bergman, S Seyedoleslami Esfahani, Y Engström
Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28052019/tlr-activated-plasmacytoid-dendritic-cells-inhibit-breast-cancer-cell-growth-in-vitro-and-in-vivo
#9
Jing Wu, Shuang Li, Yang Yang, Shan Zhu, Mingyou Zhang, Yuan Qiao, Yong-Jun Liu, Jingtao Chen
Plasmacytoid dendritic cells (pDCs) are a unique subset of naturally occurring dendritic cells, which triggers the production of large amounts of type I interferons (IFNs) after viral infections through Toll-like receptor (TLR) 7 and TLR9. Recent studies have demonstrated that the activation of pDCs kills melanoma cells. However, the role of activated pDCs in breast cancer remains to be determined. In the present study, we generated mouse models of breast cancer and demonstrated that activated pDCs can directly kill breast tumor cells through TRAIL and Granzyme B...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28043874/intrahepatic-innate-immune-response-pathways-are-down-regulated-in-untreated-chronic-hepatitis-b
#10
Fanny Lebossé, Barbara Testoni, Judith Fresquet, Floriana Facchetti, Enrico Galmozzi, Maëlenn Fournier, Valérie Hervieu, Pascale Berthillon, Françoise Berby, Isabelle Bordes, David Durantel, Massimo Levrero, Pietro Lampertico, Fabien Zoulim
BACKGROUND AND AIMS: Hepatitis B virus (HBV) persistence and the pathobiology of chronic HBV (CHB) infections result from the interplay between viral replication and host immune responses. Intrahepatic host genes expression and a comprehensive analysis of serum and liver HBV markers were performed in a large cohort of untreated CHB patients. PATIENTS AND METHODS: 105 CHB patients untreated at the time of liver biopsy (34 HBeAg(+) and 71 HBeAg(-)) were analysed for the intrahepatic expression profile of 67 genes belonging to multiple innate immunity pathways...
December 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28036266/combining-vasculature-disrupting-agent-and-toll-like-receptor-7-8-agonist-for-cancer-therapy
#11
Anushree Seth, Hyunseung Lee, Mi Young Cho, Cheongsoo Park, Sovannarith Korm, Joo-Yong Lee, Inpyo Choi, Yong Taik Lim, Kwan Soo Hong
This study evaluates the effect of combination of two different treatment regimens for solid tumor therapy: vasculature targeting agent and immune-stimulation. Poly lactide-co-glycolide (PLGA) nanoparticles were synthesized for intracellular delivery of toll-like receptor (TLR) 7/8 agonist-gardiquimod. Spherical and mono-disperse gardiquimod encapsulated PLGA nanoparticles (Gardi-PLGA), approximately 194 nm in size were formulated. Gardi-PLGA induced immune-stimulation, and vasculature disrupting agent (VDA)-5,6-Dimethylxanthenone-4-acetic acid (DMXAA) was used in combination to assessing the influence on bone marrow derived dendritic cells (BMDCs) and B16-F10 melanoma cells...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032932/androgen-induced-lncrna-potef-as1-regulates-apoptosis-related-pathway-to-facilitate-cell-survival-in-prostate-cancer-cells
#12
Aya Misawa, Ken-Ichi Takayama, Tetsuya Fujimura, Yukio Homma, Yutaka Suzuki, Satoshi Inoue
Although long noncoding RNAs (lncRNA) have been associated with a variety of cancers, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified an androgen-dependent lncRNA, prostate, ovary, testis expressed protein family member-F antisense transcript-1 (POTEF-AS1), whose expression was regulated by AR in two androgen-dependent cells by using directional RNA-seq analysis. POTEF-AS1 promoted cell growth, repressed genes related to the toll-like receptor (TLR) signaling and apoptosis pathways and inhibited apoptosis in docetaxel-treated LNCaP cells...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28013346/the-expression-of-foxp3-and-tlr4-in-cervical-cancer-association-with-immune-escape-and-clinical-pathology
#13
Huijie Zhang, Shulan Zhang
PURPOSE: To explore the expression of forkhead/winged helix transcription factor p3(Foxp3) and toll-like receptor 4(TLR4) in cervical cancer and evaluate their clinical significance. METHODS: Foxp3 and TLR4 protein expression was detected in 105 cervical tissue specimens including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Their relationship with clinicopathologic parameters was also determined...
December 24, 2016: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28012316/the-effect-of-trimethylamine-n-oxide-on-helicobacter-pylori-induced-changes-of-immunoinflammatory-genes-expression-in-gastric-epithelial-cells
#14
Daoyan Wu, Mei Cao, Jingshan Peng, Ningzhe Li, Sijun Yi, Liju Song, Xuege Wang, Mao Zhang, Jian Zhao
Colonization of Helicobacter pylori (H. pylori) induces immune and inflammatory response in gastric mucosa. Trimethylamine N-oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28011980/potential-safety-concerns-of-tlr4-antagonism-with-irinotecan-a-preclinical-observational-report
#15
Janet K Coller, Joanne M Bowen, Imogen A Ball, Hannah R Wardill, Ysabella Z A van Sebille, Romany L Stansborough, Zenab Lightwala, Anthony Wignall, Joseph Shirren, Kate Secombe, Rachel J Gibson
PURPOSE: Irinotecan-induced gut toxicity is mediated in part by Toll-Like receptor 4 (TLR4) signalling. The primary purpose of this preclinical study was to determine whether blocking TLR4 signalling by administering (-)-naloxone, a TLR4 antagonist, would improve irinotecan-induced gut toxicity. Our secondary aim was to determine the impact of (-)-naloxone on tumour growth. METHODS: Female Dark Agouti (DA) tumour-bearing rats were randomly assigned to four treatments (n = 6 in each); control, (-)-naloxone (100 mg/kg oral gavage at -2, 24, 48, and 72 h), irinotecan (175 mg/kg intraperitoneal at 0 h), and (-)-naloxone and irinotecan...
December 23, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28009429/association-between-toll-like-receptor-and-tumor-necrosis-factor-immunological-pathways-in-uterine-cervical-neoplasms
#16
Lucas G G de Matos, Eduardo B Cândido, Paula V T Vidigal, Polyanna H C Bordoni, Rivia M Lamaita, Márcia M Carneiro, Agnaldo L da Silva-Filho
INTRODUCTION: The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions...
November 15, 2016: Tumori
https://www.readbyqxmd.com/read/28009353/pellino-1-promotes-lung-carcinogenesis-via-the-stabilization-of-slug-and-snail-through-k63-mediated-polyubiquitination
#17
Yoon Kyung Jeon, Chung Kwon Kim, Kyung Rim Hwang, Hye-Young Park, Jaemoon Koh, Doo Hyun Chung, Chang-Woo Lee, Geun-Hyoung Ha
Pellino-1 is an E3 ubiquitin ligase acting as a critical mediator for a variety of immune receptor signaling pathways, including Toll-like receptors, interleukin-1 receptor and T-cell receptors. We recently showed that the Pellino-1-transgenic (Tg) mice developed multiple tumors with different subtypes in hematolymphoid and solid organs. However, the molecular mechanism underlying the oncogenic role of Pellino-1 in solid tumors remains unknown. Pellino-1-Tg mice developed adenocarcinoma in the lungs, and Pellino-1 expression was higher in human lung adenocarcinoma cell lines compared with non-neoplastic bronchial epithelial cell lines...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27999742/reprogramming-of-tlr7-signaling-enhances-antitumor-nk-and-cytotoxic-t-cell-responses
#18
Christian Hotz, Marina Treinies, Ines Mottas, Laurin C Rötzer, Anne Oberson, Lorenzo Spagnuolo, Maurizio Perdicchio, Thibaud Spinetti, Tina Herbst, Carole Bourquin
Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly(I:C) that mimics virally induced immune activation...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27993530/genetic-variants-of-tlr4-and-tlr9-are-risk-factors-for-chronic-helicobacter-pylori-infection-in-south-indian-tamils
#19
Rekha Loganathan, Mehnaz Nazeer, Vaishnavi Goda, Panneer Devaraju, Mohammed Ali, Premkumar Karunakaran, Megala Jayaraman
Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection...
December 16, 2016: Human Immunology
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#20
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
December 11, 2016: Oncotarget
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