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Toll like receptors and cancer

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https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#1
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911090/antitumor-activity-of-portulaca-oleracea-l-polysaccharide-on-hela-cells-through-inducing-tlr4-nf-%C3%AE%C2%BAb-signaling
#2
Rui Zhao, Tao Zhang, Baoling Ma, Xing Li
Abstarct We have previously shown that Portulaca oleracea L. polysaccharide (POL-P3b) possesses the ability to inhibit cervical cancer cell growth in vitro and in vivo. In this study, we explored how toll-like receptor 4 (TLR4) signaling correlated with the antitumor mechanism of POL-P3b. Western blotting was utilized to detect the expression of TLR4 and the downstream signaling pathway. The level of inflammatory mediator was quantified using enzyme-linked immunosorbent assay (ELISA) kits. The effects of POL-P3b on the proliferation and apoptosis in HeLa cells were determined by WST-8 assay and Hoechst 33342/propidium iodide (PI) assay...
December 2, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#3
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
#4
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/27900049/toll-like-receptors-and-cutaneous-melanoma
#5
Ilaria Coati, Serena Miotto, Irene Zanetti, Mauro Alaibac
Innate immune cells recognize highly conserved pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Previous studies have demonstrated that PRRs also recognize endogenous molecules, termed damage-associated molecular patterns (DAMPs) that are derived from damaged cells. PRRs include Toll-like receptors (TLRs), scavenger receptors, C-type lectin receptors and nucleotide oligomerization domain-like receptors. To date, 10 TLRs have been identified in humans and each receptor responds to a different ligand...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#6
Yuanyuan Chen, Yang Xu, Jicong Du, Jiaming Guo, Xiao Lei, Jianguo Cui, Cong Liu, Ying Cheng, Bailong Li, Fu Gao, Jintao Ju, Jianming Cai, Yanyong Yang
BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27890776/epigallocatechin-3-gallate-alleviates-paraquat-induced-acute-lung-injury-and-inhibits-upregulation-of-toll-like-receptors
#7
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/27889995/the-roles-of-the-unique-prolyl-isomerase-pin1-in-cancer-related-viral-and-bacterial-infections
#8
J Wang, X-H Liao, M Zheng, D Yang, X Z Zhou, H Liu, K P Lu
Infection is the process of pathogen invasion, as well as the host reaction to the foreign agents. Proline-directed phosphorylation is a major regulatory mechanism that regulates the function of fundamental proteins involved in infection and infection-induced cancer. Recently, the identification of the phosphorylation-dependent prolyl isomerase Pin1 has uncovered a unique regulatory signaling mechanism controlling protein conformation and function after phosphorylation. Pin1 is the only proline isomerase that specifically recognizes certain Pro-directed Ser/Thr phosphorylation motifs...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27888633/toll-like-receptor-9-expression-is-associated-with-breast-cancer-sensitivity-to-the-growth-inhibitory-effects-of-bisphosphonates-in-vitro-and-in-vivo
#9
Jouko Sandholm, Jaakko Lehtimäki, Tamiko Ishizu, Sadanandan E Velu, Jeremy Clark, Pirkko Härkönen, Arja Jukkola-Vuorinen, Aleksi Schrey, Kevin W Harris, Johanna M Tuomela, Katri S Selander
Bisphosphonates are standard treatments for bone metastases. When given in the adjuvant setting, they reduce breast cancer mortality and recurrence in bone but only among post-menopausal patients. Optimal drug use would require biomarker-based patient selection. Such biomarkers are not yet in clinical use. Based on the similarities in inflammatory responses to bisphosphonates and Toll-like receptor (TLR) agonists, we hypothesized that TLR9 expression may affect bisphosphonate responses in cells. We compared bisphosphonate effects in breast cancer cell lines with low or high TLR9 expression...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869178/importance-of-the-c-terminal-histidine-residues-of-helicobacter-pylori-groes-for-toll-like-receptor-4-binding-and-interleukin-8-cytokine-production
#10
Haur Lee, Yu-Lin Su, Bo-Shih Huang, Feng-Tse Hsieh, Ya-Hui Chang, Shiou-Ru Tzeng, Chun-Hua Hsu, Po-Tsang Huang, Kuo-Long Lou, Yeng-Tseng Wang, Lu-Ping Chow
Helicobacter pylori infection is associated with the development of gastric and duodenal ulcers as well as gastric cancer. GroES of H. pylori (HpGroES) was previously identified as a gastric cancer-associated virulence factor. Our group showed that HpGroES induces interleukin-8 (IL-8) cytokine release via a Toll-like receptor 4 (TLR4)-dependent mechanism and domain B of the protein is crucial for interactions with TLR4. In the present study, we investigated the importance of the histidine residues in domain B...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27863400/differentiated-regulation-of-immune-response-related-genes-between-luad-and-lusc-subtypes-of-lung-cancers
#11
Mengzhu Chen, Xiuying Liu, Jie Du, Xiu-Jie Wang, Lixin Xia
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27862857/casticin-induced-apoptotic-cell-death-and-altered-associated-gene-expression-in-human-colon-cancer-colo-205-cells
#12
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/27859308/resatorvid-based-pharmacological-antagonism-of-cutaneous-tlr4-blocks-uv-induced-nf-%C3%AE%C2%BAb-and-ap-1-signaling-in-keratinocytes-and-mouse-skin
#13
Jaroslav Janda, Nichole Burkett, Karen Blohm-Mangone, Vivian Huang, Clara Curiel-Lewandrowski, David S Alberts, Emanuel F Petricoin, Valerie S Calvert, Janine Einspahr, Zigang Dong, Ann M Bode, Georg T Wondrak, Sally E Dickinson
Cutaneous exposure to solar ultraviolet (UV) radiation is a major causative factor in skin carcinogenesis, and improved molecular strategies for efficacious chemoprevention of non-melanoma skin cancer (NMSC) are urgently needed. Toll-like receptor 4 (TLR4) signaling has been shown to drive skin inflammation, photoimmunosuppression and chemical carcinogenesis. Here we have examined the feasibility of genetic and pharmacological antagonism targeting cutaneous TLR4 for the suppression of UV-induced NF-κB and AP-1 signaling in keratinocytes and mouse skin...
November 10, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27848120/characterization-of-genes-and-pathways-that-respond-to-heat-stress-in-holstein-calves-through-transcriptome-analysis
#14
Krishnamoorthy Srikanth, Anam Kwon, Eunjin Lee, Hoyoung Chung
This study aimed to investigate the genes and pathways that respond to heat stress in Holstein bull calves exposed to severe ranges of temperature and humidity. A total of ten animals from 4 to 6 months of age were subjected to heat stress at 37 °C and 90 % humidity for 12 h. Skin and rectal temperatures were measured before and after heat stress; while no correlation was found between them before heat stress, a moderate correlation was detected after heat stress, confirming rectal temperature to be a better barometer for monitoring heat stress...
November 16, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27846717/-endoplasmic-reticulum-chaperones-at-the-tumor-cell-surface-and-in-the-extracellular-space
#15
V Brychtová, B Vojtěšek
BACKGROUND: Endoplasmic reticulum chaperones are stress induced proteins capable of translocation into cytosol, cell membrane or extracellular space. The chaperones are transported from the endoplasmic reticulum particularly under endoplasmic reticulum stress conditions, while their constitutive extracellular expression was found in many cancers. Cell surface or extracellular endoplasmic reticulum chaperones take up distinct functions compared to their endoplasmic reticulum resident variants because they act like multifunctional receptors and thus affect cell signaling and proliferation...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27845762/recent-progress-in-the-molecular-recognition-and-therapeutic-importance-of-interleukin-1-receptor-associated-kinase-4
#16
REVIEW
Mahesh Chandra Patra, Sangdun Choi
Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the cell, which detect pathogen associated molecular patterns and initiate signal transduction, culminating in the transcription of pro-inflammatory cytokines and antiviral interferon. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in TLR (except for TLR3) and interleukin-1 receptor signaling pathways. The loss of kinase function of IRAK4 is associated with increased susceptibility to various pathogens, while its over-activation causes autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and cancer...
November 13, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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/27837433/tlr4-mediated-galectin-1-production-triggers-epithelial-mesenchymal-transition-in-colon-cancer-cells-through-adam10-and-adam17-associated-lactate-production
#18
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...
November 12, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#19
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27805282/toll-like-receptor-3-stimulation-triggers-metabolic-reprogramming-in-pharyngeal-cancer-cell-line-through-myc-mapk-and-hif
#20
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
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