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Toll like receptor 3 and cancer

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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#2
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#3
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#4
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205610/cr-laao-an-l-amino-acid-oxidase-from-calloselasma-rhodostoma-venom-as-a-potential-tool-for-developing-novel-immunotherapeutic-strategies-against-cancer
#5
Tássia R Costa, Danilo L Menaldo, Karina F Zoccal, Sandra M Burin, Alexandre F Aissa, Fabíola A de Castro, Lúcia H Faccioli, Lusânia M Greggi Antunes, Suely V Sampaio
L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses in vivo, with recruitment of neutrophils and release of IL-6, IL-1β, LTB4 and PGE2. In vitro, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191612/high-toll-like-receptor-tlr-9-expression-is-associated-with-better-prognosis-in-surgically-treated-pancreatic-cancer-patients
#6
Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio, Tuomo J Karttunen
Pancreatic cancer remains one of the deadliest malignancies in the world. Inflammatory response and tumor environment are thought to play a major role in its pathogenesis. Knowledge on TLR expression and impact on patient survival in pancreatic cancer is limited. The study's aim was to clarify the role of different TLRs in pancreatic cancer. TLR2, TLR4, and TLR9 expression was investigated in 65 surgically resected pancreatic ductal adenocarcinoma specimens by immunohistochemistry. The association between TLR expression, clinical parameters, and local inflammatory response to the tumor was assessed using chi-square test...
February 12, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#7
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28114604/topical-imiquimod-plus-nab-paclitaxel-for-breast-cancer-cutaneous-metastases-a-phase-2-clinical-trial
#8
Lupe G Salazar, Hailing Lu, Jessica L Reichow, Jennifer S Childs, Andrew L Coveler, Doreen M Higgins, James Waisman, Kimberly H Allison, Yushe Dang, Mary L Disis
Importance: Salvage chemotherapy for recurrent chest wall lesions in breast cancer results in response rates of 20% to 30%. Preclinical studies showed significant disease regression could be induced in murine chest wall mammary cancers with a topical toll-like receptor (TLR)-7 agonist, imiquimod. Objective: To evaluate the safety and objective response rate (ORR) of imiquimod in combination with systemic albumin bound paclitaxel in treatment-refractory breast cancer of the chest wall...
January 19, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28110063/curcumin-ameliorates-liver-damage-and-progression-of-nash-in-nash-hcc-mouse-model-possibly-by-modulating-hmgb1-nf-%C3%AE%C2%BAb-translocation
#9
Rejina Afrin, Somasundaram Arumugam, Azizur Rahman, Mir Imam Ibne Wahed, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding...
January 18, 2017: International Immunopharmacology
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
#10
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/28043874/intrahepatic-innate-immune-response-pathways-are-downregulated-in-untreated-chronic-hepatitis-b-patients
#11
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 & 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. We aimed to comprehensively analyse the expression of intrahepatic host genes as well as serum and liver HBV markers in a large cohort of untreated CHB patients. METHODS: One-hundred and five 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/27993530/genetic-variants-of-tlr4-and-tlr9-are-risk-factors-for-chronic-helicobacter-pylori-infection-in-south-indian-tamils
#12
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/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#13
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
#14
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
#15
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...
February 1, 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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