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Toll like receptor 3 and cancer

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https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#1
Hee Dong Han, Yeongseon Byeon, Jong-Hwa Jang, Hat Nim Jeon, Ga Hee Kim, Min Gi Kim, Chan-Gi Pack, Tae Heung Kang, In Duk Jung, Yong Taik Lim, Young Joo Lee, Jeong-Won Lee, Byung Cheol Shin, Hyung Jun Ahn, Anil K Sood, Yeong-Min Park
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909407/the-tlr4-active-morphine-metabolite-morphine-3-glucuronide-does-not-elicit-macrophage-classical-activation-in-vitro
#2
Samira Khabbazi, Nan Xie, Wenjun Pu, Yannick Goumon, Marie-Odile Parat
Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27890776/epigallocatechin-3-gallate-alleviates-paraquat-induced-acute-lung-injury-and-inhibits-upregulation-of-toll-like-receptors
#3
Haitao Shen, Na Wu, Zhenning Liu, Hongyu Zhao, Min Zhao
AIMS: To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on paraquat (PQ)-induced acute lung injury in mice, and to explore the action mechanisms. MAIN METHODS: Following administration of PQ, the mice received a low, a medium or a high dose of EGCG daily for three days. Histopathology of the lungs were examined by H&E staining. The levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay...
November 24, 2016: Life Sciences
https://www.readbyqxmd.com/read/27862857/casticin-induced-apoptotic-cell-death-and-altered-associated-gene-expression-in-human-colon-cancer-colo-205-cells
#4
Hung-Sheng Shang, Jia-You Liu, Hsu-Feng Lu, Han-Sun Chiang, Chia-Hain Lin, Ann Chen, Yuh-Feng Lin, Jing-Gung Chung
Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca(2+) productions, level of mitochondria membrane potential (ΔΨm ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death...
November 14, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27843314/toll-like-receptor-3-induced-immune-response-by-poly-d-l-lactide-co-glycolide-nanoparticles-for-dendritic-cell-based-cancer-immunotherapy
#5
Hee Dong Han, Yeongseon Byeon, Tae Heung Kang, In Duk Jung, Jeong-Won Lee, Byung Cheol Shin, Young Joo Lee, Anil K Sood, Yeong-Min Park
Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(d,l-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27805282/toll-like-receptor-3-stimulation-triggers-metabolic-reprogramming-in-pharyngeal-cancer-cell-line-through-myc-mapk-and-hif
#6
Tanja Matijevic Glavan, Ana Cipak Gasparovic, Benjamin Vérillaud, Pierre Busson, Jasminka Pavelic
Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27729782/characterization-of-tlr-induced-inflammatory-responses-in-copd-and-control-lung-tissue-explants
#7
Anna Pomerenke, Simon R Lea, Sarah Herrick, Mark A Lindsay, Dave Singh
PURPOSE: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD). They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers. METHODS: We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27619885/tumoricidal-efficacy-coincides-with-cd11c-up-regulation-in-antigen-specific-cd8-t-cells-during-vaccine-immunotherapy
#8
Yohei Takeda, Masahiro Azuma, Misako Matsumoto, Tsukasa Seya
BACKGROUND: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27510663/a-tissue-microarray-study-of-toll-like-receptor-4-decoy-receptor-3-and-external-signal-regulated-kinase-1-2-expressions-in-astrocytoma
#9
Chih-Kung Lin, Chun-Chieh Ting, Wen-Chiuan Tsai, Yuan-Wu Chen, Dueng-Yuan Hueng
INTRODUCTION: Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. MATERIAL AND METHODS: The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen...
July 2016: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/27505671/tumor-exosomal-rnas-promote-lung-pre-metastatic-niche-formation-by-activating-alveolar-epithelial-tlr3-to-recruit-neutrophils
#10
Yanfang Liu, Yan Gu, Yanmei Han, Qian Zhang, Zhengping Jiang, Xiang Zhang, Bo Huang, Xiaoqing Xu, Jianming Zheng, Xuetao Cao
The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models...
August 8, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27503954/conformational-dynamics-of-cancer-associated-myd88-tir-domain-mutant-l252p-l265p-allosterically-tilts-the-landscape-toward-homo-dimerization
#11
Chendi Zhan, Ruxi Qi, Guanghong Wei, Emine Guven-Maiorov, Ruth Nussinov, Buyong Ma
MyD88 is an essential adaptor protein, which mediates the signaling of the toll-like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation has been identified in diffuse large B-cell lymphoma. The identification of this mutation has been a major advance in the diagnosis of patients with aldenstrom macroglobulinemia and related lymphoid neoplasms. Here we used computational methods to characterize the conformational effects of the mutation. Our molecular dynamics simulations revealed that the mutation allosterically quenched the global conformational dynamics of the toll/IL-1R (TIR) domain, and readjusted its salt bridges and dynamic community network...
September 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27467941/nucleic-acid-sensing-toll-like-receptors-3-7-and-8-in-esophageal-epithelium-barrett-s-esophagus-dysplasia-and-adenocarcinoma
#12
Olli Helminen, Heikki Huhta, Petri P Lehenkari, Juha Saarnio, Tuomo J Karttunen, Joonas H Kauppila
Toll-like receptors (TLRs) are immunological receptors recognizing various microbial and endogenous ligands, such as DNA, RNA, and other microbial and host components thus activating immunological responses. The expression of TLRs in esophageal adenocarcinoma is not well known. The aim of this study was to evaluate expression patterns of those TLRs that sense nucleic acids in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinoma. TLRs 3, 7 and 8 were stained immunohistochemically and evaluated in a cohort of patients with esophageal adenocarcinoma or dysplasia...
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27434289/functional-snp-in-stem-of-mir-146a-affects-her2-status-and-breast-cancer-survival
#13
Mahboobeh Meshkat, Hamzeh Mesrian Tanha, Marjan Mojtabavi Naeini, Kamran Ghaedi, Mohammad H Sanati, Marzieh Meshkat, Fatemeh Bagheri
In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR...
July 8, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27384877/tlr-signaling-inhibitor-phenylmethimazole-in-combination-with-tamoxifen-inhibits-human-breast-cancer-cell-viability-and-migration
#14
Anthony L Schwartz, Eric Dickerson, Nilesh Dagia, Ramiro Malgor, Kelly D McCall
Heightened co-expression and dysregulated signaling associated with Toll-like receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and hematological malignancies. Our previous findings in pancreatic cancer and melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor, phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3 phosphorylation, minimal cancer cell migration and reduced cancer cell growth in vitro and in vivo. In this study, we extended our earlier observations by performing studies in human breast cancer cells...
July 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27363264/-combination-of-tlr7-agonist-t7-ethacrynic-acid-conjugate-with-ror1-has-a-stronger-anti-breast-cancer-effect
#15
Na Zhang, Guangyi Jin, Zhenchao Jin, Bing Liu, Boya Peng, Ningning Gao, Yunlong Hu, Li Tang
Objective To investigate the synergistic anti-breast cancer effect of Toll-like receptor 7 agonist T7-ethacrynic acid conjugate (T7-EA) in combination with receptor-tyrosine-kinase-like orphan receptor 1 (ROR1). Methods ROR1 cytotoxic T lymphocyte (CTL) epitope was predicted using Syfpeithi online software. Mouse spleen lymphocytes and bone marrow dendritic cells (DCs) were separately stimulated with 4 μmol/L T7-EA and 4 μmol/L ROR1 alone or in combination. ELISA assay was used to measure the levels of interferon-γ (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α)...
July 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27354629/dewaxed-brown-rice-contains-a-significant-amount-of-lipopolysaccharide-pointing-to-macrophage-activation-via-tlrs
#16
Hiroyuki Inagawa, Toshiyuki Saika, Takashi Nisizawa, Chie Kohchi, Maya Uenobe, Gen-Ichiro Soma
BACKGROUND/AIM: Oral ingestion of lipopolysaccharide (LPS) has been shown to be effective in diseases' prevention. Brown rice contains large amounts of LPS not actively consumed because of bad taste. Recently, a new type of brown rice with its wax layer removed has been produced. In this report, we measured the LPS content of this dewaxed rice and evaluated the function of innate immune activation on macrophages. MATERIALS AND METHODS: Dewaxed brown rice and polished rice were prepared using the Saika-style rice polishing process...
July 2016: Anticancer Research
https://www.readbyqxmd.com/read/27354597/enhanced-tlr4-expression-on-colon-cancer-cells-after-chemotherapy-promotes-cell-survival-and-epithelial-mesenchymal-transition-through-phosphorylation-of-gsk3%C3%AE
#17
Yoon Hee Chung, Daejin Kim
BACKGROUND: Phosphorylation of glycogen synthase kinase 3β (GSK3β) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3β with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3β activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post-chemotherapy cancer cells. MATERIALS AND METHODS: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting...
July 2016: Anticancer Research
https://www.readbyqxmd.com/read/27352928/opposite-effects-of-coinjection-and-distant-injection-of-mesenchymal-stem-cells-on-breast-tumor-cell-growth
#18
Huilin Zheng, Weibin Zou, Jiaying Shen, Liang Xu, Shu Wang, Yang-Xin Fu, Weimin Fan
UNLABELLED: : Mesenchymal stem cells (MSCs) usually promote tumor growth and metastasis. By using a breast tumor 4T1 cell-based animal model, this study determined that coinjection and distant injection of allogeneic bone marrow-derived MSCs with tumor cells could exert different effects on tumor growth. Whereas the coinjection of MSCs with 4T1 cells promoted tumor growth, surprisingly, the injection of MSCs at a site distant from the 4T1 cell inoculation site suppressed tumor growth...
September 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27344437/triterpenes-in-cancer-significance-and-their-influence
#19
REVIEW
Balraj Singh Gill, Sanjeev Kumar, Navgeet
Natural products are enriched with numerous compounds with a broad spectrum of therapeutics indication suggesting the role of functional moieties as a core pharmacophore. This review highlights the role of triterpene in targeting signaling pathways in cancer. Advancement in cellular, biochemical, experimental, and computational approaches provides new insights into various pathways in cancer. In signaling network, triterpenes primarily target membrane receptors which control and modulates expression level of the biological responses...
September 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27336891/application-potential-of-toll-like-receptors-in-cancer-immunotherapy-systematic-review
#20
Ming Shi, Xi Chen, Kangruo Ye, Yuanfei Yao, Yu Li
Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application...
June 2016: Medicine (Baltimore)
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