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Toll like receptors and colon cancer

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https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#1
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/28418857/multi-factorial-modulation-of-colorectal-carcinoma-cells-motility-partial-coordination-by-the-tetraspanin-co-029-tspan8
#2
Yingying Zhu, Naouel Ailane, Monica Sala-Valdés, Farhad Haghighi-Rad, Martine Billard, Viet Nguyen, Raphael Saffroy, Antoinette Lemoine, Eric Rubinstein, Claude Boucheix, Céline Greco
Colorectal carcinoma cells Isreco1 display an ability to migrate controlled by a complex set of signals issued from the membrane. By comparing cells infected by mycoplasmas and mycoplasmas free cells, we have established that basal 2D migration is dependent on a double signal mediated by the collagen receptors integrins alpha1/2 and the Toll-Like receptor TLR2. The signal issued from mycoplasmas can be replaced by a TLR2 ligand and the functional effect is neutralized by silencing of MyD88. Following previous observation that downregulation of E-cadherin/p120 catenin increases cell motility, we now report that EGFR or CD44 inhibition have a similar effect on cell motility that is restricted to tetraspanin Co-029/tspan8 transduced IsrecoI cells (Is1-Co029)...
April 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418004/host-determinants-of-expression-of-the-helicobacter-pylori-baba-adhesin
#3
Mary E Kable, Lori M Hansen, Cathy M Styer, Samuel L Deck, Olena Rakhimova, Anna Shevtsova, Kathryn A Eaton, Miriam E Martin, Pär Gideonsson, Thomas Borén, Jay V Solnick
Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2-/- mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4-/- mice that are defective in toll like receptor signaling...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28346430/il-17c-mediates-the-recruitment-of-tumor-associated-neutrophils-and-lung-tumor-growth
#4
C Jungnickel, L H Schmidt, L Bittigkoffer, L Wolf, A Wolf, F Ritzmann, A Kamyschnikow, C Herr, M D Menger, T Spieker, R Wiewrodt, R Bals, C Beisswenger
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and is the major pathogen triggering exacerbations. The epithelial cytokine interleukin-17C (IL-17C) promotes the recruitment of neutrophils into inflamed tissues. The purpose of this study was to investigate the function of IL-17C in the pulmonary tumor microenvironment...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28344880/protective-function-of-interleukin-27-in-colitis-associated-cancer-via-suppression-of-inflammatory-cytokines-in-intestinal-epithelial-cells
#5
Bijun Cui, Shen Lu, Lihua Lai, Yiwei Xie, Jia He, Yue Xue, Peng Xiao, Ting Pan, Luoquan Chen, Yang Liu, Xuetao Cao, Qingqing Wang
Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28296893/hnrnp-i-regulates-neonatal-immune-adaptation-and-prevents-colitis-and-colorectal-cancer
#6
Zhigang Jin, Feng Liang, Jing Yang, Wenyan Mei
The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses. During the neonatal stage, the intestinal epithelium is under immune repression, allowing the transition for newborns from a relatively sterile intra-uterine environment to one that is rich in foreign antigens. The mechanism underlying such immune repression remains largely unclear, but involves downregulation of IRAK1 (interleukin-1 receptor-associated kinase), an essential component of toll-like receptor-mediated NF-κB signaling...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28279655/nontypeable-haemophilus-influenzae-promoted-proliferation-of-kras-induced-early-adenomatous-lesions-is-completely-dependent-on-toll-like-receptor-signaling
#7
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease is a risk factor for lung cancer. COPD is characterized by chronic airway inflammation and lung infections. The airways of patients with COPD are frequently colonized with bacteria [eg, nontypeable Haemophilus influenzae (NTHi)] that cause pulmonary inflammation and exacerbations. Pulmonary adenocarcinomas are frequently associated with an activating mutation in the KRAS gene. We determined the function of Toll-like receptor (TLR) signaling on the progression of KRas-induced early adenomatous lesions in the lung...
March 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28228598/beware-are-bacteria-raising-your-oxidative-stress
#8
Purna Kashyap
Peptostreptococcus anaerobius, enriched in patients with colon cancer, induces cellular proliferation and dysplasia by toll-like receptor (TLR) 2- and TLR4-dependent increase in oxidative stress and cholesterol biosynthesis.
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#9
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28179508/two-step-enhanced-cancer-immunotherapy-with-engineered-salmonella-typhimurium-secreting-heterologous-flagellin
#10
Jin Hai Zheng, Vu H Nguyen, Sheng-Nan Jiang, Seung-Hwan Park, Wenzhi Tan, Seol Hee Hong, Myung Geun Shin, Ik-Joo Chung, Yeongjin Hong, Hee-Seung Bom, Hyon E Choy, Shee Eun Lee, Joon Haeng Rhee, Jung-Joon Min
We report a method of cancer immunotherapy using an attenuated Salmonella typhimurium strain engineered to secrete Vibrio vulnificus flagellin B (FlaB) in tumor tissues. Engineered FlaB-secreting bacteria effectively suppressed tumor growth and metastasis in mouse models and prolonged survival. By using Toll-like receptor 5 (TLR5)-negative colon cancer cell lines, we provided evidence that the FlaB-mediated tumor suppression upon bacterial colonization is associated with TLR5-mediated host reactions in the tumor microenvironment...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28126350/peptostreptococcus-anaerobius-induces-intracellular-cholesterol-biosynthesis-in-colon-cells-to-induce-proliferation-and-causes-dysplasia-in-mice
#11
Ho Tsoi, Eagle S H Chu, Xiang Zhang, Jianqiu Sheng, Daniel Nakatsu, Siew C Ng, Anthony W H Chan, Francis K L Chan, Joseph J Y Sung, Jun Yu
BACKGROUND & AIMS: Stool samples from patients with colorectal cancer (CRC) have a higher abundance of Peptostreptococcus anaerobius than stool from individuals without CRC, based on metagenome sequencing. We investigated whether P anaerobius contributes to colon tumor formation in mice and its possible mechanisms of carcinogenesis. METHODS: We performed quantitative polymerase chain reaction analyses to measure P anaerobius in 112 stool samples and 255 colon biopsies from patients with CRC or advanced adenoma and from healthy individuals (controls) undergoing colonoscopy examination at hospitals in Hong Kong and Beijing...
January 23, 2017: Gastroenterology
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
#12
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/27993530/genetic-variants-of-tlr4-and-tlr9-are-risk-factors-for-chronic-helicobacter-pylori-infection-in-south-indian-tamils
#13
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...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27862857/casticin-induced-apoptotic-cell-death-and-altered-associated-gene-expression-in-human-colon-cancer-colo-205-cells
#14
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/27837433/tlr4-mediated-galectin-1-production-triggers-epithelial-mesenchymal-transition-in-colon-cancer-cells-through-adam10-and-adam17-associated-lactate-production
#15
Ga Bin Park, Daejin Kim
Toll-like receptor 4 (TLR4) activation is a key contributor to the carcinogenesis of colon cancer. Overexpression of galectin-1 (Gal-1) also correlates with increased invasive activity of colorectal cancer. Lactate production is a critical predictive factor of risk of metastasis, but the functional relationship between intracellular lactate and Gal-1 expression in TLR4-activated colon cancer remains unknown. In this study, we investigated the underlying mechanism and role of Gal-1 in metastasis and invasion of colorectal cancer (CRC) cells after TLR4 stimulation...
January 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27733853/the-role-of-toll-like-receptors-in-hematopoietic-malignancies
#16
REVIEW
Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
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/27328732/eritoran-suppresses-colon-cancer-by-altering-a-functional-balance-in-toll-like-receptors-that-bind-lipopolysaccharide
#18
Wei-Ting Kuo, Tsung-Chun Lee, Linda Chia-Hui Yu
Colorectal carcinogenesis is affected by overexpression of the lipopolysaccharide (LPS) receptors CD14 and TLR4, which antagonize each other by affecting epithelial cell proliferation and apoptosis. Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor. In the present study, we explored the potential therapeutic uses and mechanisms of action of eritoran in reducing colon cancer progression. Eritoran administration via intracolonic, intragastric, or intravenous routes significantly reduced tumor burden in a chemically induced mouse model of colorectal carcinoma...
August 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27308544/janus-faced-bacterial-regulation-of-epithelial-cell-death-and-survival-association-with-colon-carcinogenesis
#19
Wei-Ting Kuo, Tsung-Chun Lee, Linda Chia-Hui Yu
Gut microbiota and lipopolysaccharide (LPS) signaling have been associated with colon cancer development. Our recent findings demonstrated that LPS receptor subunits expressed on colonocytes have antagonistic roles in cell death and tumorigenesis: epithelial toll-like receptor 4 (TLR4) confers resistance to the apoptosis induced by its co-receptor CD14 and contributes to epithelial transition to cancer.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27279714/quercetin-suppresses-the-migration-and-invasion-in-human-colon-cancer-caco-2-cells-through-regulating-toll-like-receptor-4-nuclear-factor-kappa-b-pathway
#20
Mingyang Han, Yucheng Song, Xuedong Zhang
OBJECTIVE: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism...
May 2016: Pharmacognosy Magazine
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