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Toll like receptors and colon cancer

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https://www.readbyqxmd.com/read/29295954/blockade-of-tnfr2-signaling-enhances-the-immunotherapeutic-effect-of-cpg-odn-in-a-mouse-model-of-colon-cancer
#1
Yingjie Nie, Jiang He, Hidekazu Shirota, Anna L Trivett, De Yang, Dennis M Klinman, Joost J Oppenheim, Xin Chen
Through the tumor necrosis factor (TNF) receptor type II (TNFR2), TNF preferentially activates, expands, and promotes the phenotypic stability of CD4+Foxp3+ regulatory T (Treg) cells. Those Treg cells that have a high abundance of TNFR2 have the maximal immunosuppressive capacity. We investigated whether targeting TNFR2 could effectively suppress the activity of Treg cells and consequently enhance the efficacy of cancer immunotherapy. We found that, relative to a suboptimal dose of the immunostimulatory Toll-like receptor 9 ligand CpG oligodeoxynucleotide (ODN), the combination of the suboptimal dose of CpG ODN with the TNFR2-blocking antibody M861 more markedly inhibited the growth of subcutaneously grafted mouse CT26 colon tumor cells...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29239279/radiosensitization-by-cpg-odn7909-in-an-epidermoid-laryngeal-carcinoma-hep-2-cell-line
#2
Shu Wang, Xiaoqun Liu, Tiankui Qiao, Qi Zhang
Objective To evaluate the radiosensitivity effect of CpG oligodeoxyribonucleotide (ODN) 7909 on human epidermoid cancer strain-2 (Hep-2) cells in vitro and discuss the potential for improved radiotherapy treatment in patients with laryngeal squamous cell carcinoma. Methods Toll-like receptor ( TLR) 9 expression was assessed in Hep-2 cells using Western blots and reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to detect Hep-2 cell viability at 24 and 48 h following treatment with different CpG ODN7909 concentrations...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/29209564/leukotriene-b4-receptor-1-mediated-host-response-shapes-gut-microbiota-and-controls-colon-tumor-progression
#3
Venkatakrishna R Jala, Paramahamsa Maturu, Sobha R Bodduluri, Elangovan Krishnan, Steven Mathis, Krishnaprasad Subbarao, Min Wang, Alfred B Jenson, Mary L Proctor, Eric C Rouchka, Rob Knight, Bodduluri Haribabu
Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28943944/andrographolide-suppresses-proliferation-of-human-colon-cancer-sw620-cells-through-the-tlr4-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#4
Rui Zhang, Jian Zhao, Jian Xu, De-Xin Jiao, Jian Wang, Zhi-Qiang Gong, Jian-Hui Jia
Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28766555/the-tlr9-agonist-mgn1703-triggers-a-potent-type-i-interferon-response-in-the-sigmoid-colon
#5
A R Krarup, M Abdel-Mohsen, M H Schleimann, L Vibholm, P A Engen, A Dige, B Wittig, M Schmidt, S J Green, A Naqib, A Keshavarzian, X Deng, R Olesen, A M Petersen, T Benfield, L Østergaard, T A Rasmussen, J Agnholt, J R Nyengaard, A Landay, O S Søgaard, S K Pillai, M Tolstrup, P W Denton
Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28765705/divergent-expression-of-bacterial-wall-sensing-toll-like-receptors-2-and-4-in-colorectal-cancer
#6
Karoliina Paarnio, Sara Väyrynen, Kai Klintrup, Pasi Ohtonen, Markus J Mäkinen, Jyrki Mäkelä, Tuomo J Karttunen
AIM: To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. METHODS: We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28746799/lack-of-interleukin-6-in-the-tumor-microenvironment-augments-type-1-immunity-and-increases-the-efficacy-of-cancer-immunotherapy
#7
Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In the present study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells...
October 2017: Cancer Science
https://www.readbyqxmd.com/read/28700533/cd103-dendritic-cell-function-is-altered-in-the-colons-of-patients-with-ulcerative-colitis
#8
Hiroshi Matsuno, Hisako Kayama, Junichi Nishimura, Yuki Sekido, Hideki Osawa, Soumik Barman, Takayuki Ogino, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Motoi Uchino, Hiroki Ikeuchi, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Tsunekazu Mizushima
BACKGROUND: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). METHODS: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24)...
July 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28627973/profile-of-gene-expression-of-tlr-signaling-pathways-in-colorectal-cancer-tissues
#9
Martyna Bednarczyk, Małgorzata Muc-Wierzgoń, Katarzyna Walkiewicz, Teresa Kokot, Edyta Fatyga, Urszula Mazurek
Toll-like receptors (TLRs) are involved in transduction of molecular signals in immune process such as induction and regulation of immunity, production of cytokines, and recognition of specific molecular patterns on the surface of microorganisms, but also in cancer development-which was partially proven in previous studies. There is a lack of detailed research on differentiating levels of TLR expression in colorectal cancer at different stages of its advancement, so in our study we want to determine whether there is such a difference of TLRs and TLR-connected protein expression...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#10
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...
July 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
#11
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 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418004/host-determinants-of-expression-of-the-helicobacter-pylori-baba-adhesin
#12
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
#13
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...
July 20, 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
#14
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
#15
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
#16
Christopher Jungnickel, Philipp A Schnabel, Rainer Bohle, Rainer Wiewrodt, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic obstructive pulmonary disease (COPD) 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...
May 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28228598/beware-are-bacteria-raising-your-oxidative-stress
#17
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
#18
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
#19
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
#20
Ho Tsoi, Eagle S H Chu, Xiang Zhang, Jianqiu Sheng, Geicho 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...
May 2017: Gastroenterology
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