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cancer and inflammasome

Michiel C Mommersteeg, Jun Yu, Maikel P Peppelenbosch, Gwenny M Fuhler
Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood...
November 14, 2017: Biochimica et Biophysica Acta
Cornelia Voigt, Peter May, Adrian Gottschlich, Anamarija Markota, Daniel Wenk, Inga Gerlach, Sebastian Voigt, Georgios T Stathopoulos, Kristina A M Arendt, Constanze Heise, Felicitas Rataj, Klaus-Peter Janssen, Melanie Königshoff, Hauke Winter, Isabelle Himsl, Wolfgang E Thasler, Max Schnurr, Simon Rothenfußer, Stefan Endres, Sebastian Kobold
IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4(+) T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells...
November 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
Qinglian Hu, Fenghui Zhao, Fengliang Guo, Chengcheng Wang, Zhengwei Fu
Polymeric nanoparticles gain enormous interests in cancer therapy. Polyethylenimine (PEI) 25 kD is well known for its high transfection efficiency and cytotoxicity. PEI-CyD (PC) was previously synthesized by conjugating low molecular PEI (M w 600) with β-cyclodextrin (β-CyD), which is shown to induce lower cytotoxicity than PEI 25 kD. In the current study, the in vivo immune response of branched PEI 25 kD and PC is investigated. Compared to PC/pDNA, exposure of PEI 25kD/pDNA induces higher level of immune-stimulation evidenced by the increased spleen weight, phagocytic capacity of peritoneal macrophage, and proinflammatory cytokines in serum and liver...
November 13, 2017: Macromolecular Bioscience
Amin Zhang, Jie Yu, Shuxin Yan, Xia Zhao, Chen Chen, Ying Zhou, Xueyun Zhao, Mingqiang Hua, Ruiqing Wang, Chen Zhang, Chaoqin Zhong, Na He, Chunyan Ji, Daoxin Ma
NLRP3 inflammasome has been recently reported as an important risk factor in the development of cancer. But the relationship between polymorphisms of NLRP3 inflammasome related genes and chronic myeloid leukemia (CML) is rarely reported. Therefore, the aim of the present study was to investigate the association of five genetic polymorphisms (NLRP3, IL-1β, IL-18, CARD8 and NF-κB) in 267 CML patients and 344 healthy controls. We found that the AT genotype of CARD8 (rs2043211) was significantly higher compared to TT genotype in high and intermediate risk CML patients...
October 31, 2017: Human Immunology
Cong Xu, Yali Qiao, Daolai Zhang
Objective To analyze the expression profile of the Toll-like receptors (TLRs) in human hepatocellular carcinoma (HCC), and explore its possible mechanism and clinical value in the occurrence and development of HCC. Methods TLRs expression data and HCC clinical information were downloaded from The Cancer Genome Atlas (TCGA). Statistical analysis was performed to analyze the relationship between TLRs expression and clinicopathological factors of HCC, as well as the effect on the prognosis of patients. Results Compared with normal tissues, TLRs expression in cancer tissues was down-regulated except for TLR5, TLR7 and TLR9; the expression level of TLRs was not associated with patients' TNM stages or prognosis...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Spandana Rajendra Kopalli, Tae-Bong Kang, Kwang-Ho Lee, Sushruta Koppula
BACKGROUND: Inflammasomes are recognized as key regulators in innate immunity from the pathogenic to endogenous danger signals. Although controlled activation of inflammasome is highly beneficial, dysregulation of inflammasome activation plays central role in various autoimmune, inflammatory disorders and aid in promoting various forms of cancers in humans such as breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis. NLRP3 inflammasome activation has been emerged as a topic of interest and is under profound investigation for its involvement in multiple forms of cancers...
October 26, 2017: Recent Patents on Anti-cancer Drug Discovery
Francois Ng Kee Kwong, Andrew G Nicholson, Celeste L Harrison, Philip M Hansbro, Ian M Adcock, Kian Fan Chung
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis...
December 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
Luqiao Wang, Gayani Nanayakkara, Qian Yang, Hongmei Tan, Charles Drummer, Yu Sun, Ying Shao, Hangfei Fu, Ramon Cueto, Huimin Shan, Teodoro Bottiglieri, Ya-Feng Li, Candice Johnson, William Y Yang, Fan Yang, Yanjie Xu, Hang Xi, Weiqing Liu, Jun Yu, Eric T Choi, Xiaoshu Cheng, Hong Wang, Xiaofeng Yang
BACKGROUND: Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood. METHODS: To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions...
October 24, 2017: Journal of Hematology & Oncology
S Li, X Liang, L Ma, L Shen, T Li, L Zheng, A Sun, W Shang, C Chen, W Zhao, J Jia
Chronic inflammation is the primary cause of gastric cancer (GC). NLRP3, as an important inflammasome component, has crucial roles in initiating inflammation. However, the potential roles of NLRP3 in GC is unknown. Here, we show that NLRP3 expression is markedly upregulated in GC, which promotes NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in macrophages. In addition, NLRP3 binds to cyclin-D1 (CCND1) promoter and promotes its transcription in gastric epithelial cells. Consequently, NLRP3 enhances epithelial cells proliferation and GC tumorigenesis...
October 23, 2017: Oncogene
Subodh Verma, Lawrence A Leiter, Deepak L Bhatt
Despite overwhelming basic science linking inflammation to the pathobiology of atherothrombosis, the specific clinical evidence indicating cardiovascular benefits from anti-inflammatory pharmacotherapy has been lacking. The CANTOS trial (Ridker et al., 2017a) now provides the first largescale proof of concept that inflammasome targeting can reduce cardiovascular events-and, surprisingly, lung cancer.
November 7, 2017: Cell Metabolism
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 26, 2017: Nature
Mary Gulumian, Charlene Andraos
Multiple applications of nanomaterials have raised concern with regard to their toxicity. With increasing research into nanomaterial safety, mechanisms involved in the toxic effects of nanomaterials have begun to emerge. The importance of nanomaterial-induced lysosomal membrane permeabilization through overloading or direct damage of the lysosomal compartment, resulting in the blockade of autophagosome-lysosome fusion and autophagy dysfunction, as well as inflammasome activation were cited as emerging mechanisms of nanomaterial toxicity...
January 1, 2017: Toxicologic Pathology
Oliver Kepp, Friedemann Loos, Peng Liu, Guido Kroemer
Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells...
November 2017: Immunological Reviews
Giulia Freer, Fabrizio Maggi, Mauro Pistello
The virome is a multifaceted network of viruses inhabiting humans in health and disease. The virome forms a conspicuous portion of the so-called microbiome. Massive amount of data recently emerging demonstrates that the microbiome, once generically referred to as human (or animal) flora, is not a static entity but closely reflects what we eat, how and where we live, what we do, and many other unexpected variables. Composition, location, and amount of the microbiome have a direct impact on innate and adaptive host immune defences...
October 5, 2017: Current Medicinal Chemistry
Huiyuan Zheng, Johan Högberg, Ulla Stenius
Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16HBE lung epithelial cells were exposed silica particles. Reactive oxidative species (ROS), NLRP3 inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were endpoints...
September 15, 2017: Carcinogenesis
Melvin Kantono, Beichu Guo
Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer...
2017: Frontiers in Immunology
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
Giulia Poli, Giovanni Cochetti, Andrea Boni, Maria Giulia Egidi, Stefano Brancorsini, Ettore Mearini
BACKGROUND: Nowadays, the intravesical Bacillus Calmette-Guérin (BCG) instillation is the method of choice for the postsurgical treatment of high-grade nonmuscle-invasive bladder cancer , to reduce both recurrence rate and risk of progression. BCG is hypothesized to correct the immune system disequilibrium occurring during carcinogenesis, through an immunostimulation with detrimental effects for tumoral cells. Inflammation plays a crucial role in tumor progression. The deregulation of inflammasomes upon carcinogenesis underlines its importance both in physiologic and pathologic human conditions...
September 6, 2017: Urologic Oncology
Cong-Fa Huang, Lei Chen, Yi-Cun Li, Lei Wu, Guang-Tao Yu, Wen-Feng Zhang, Zhi-Jun Sun
BACKGROUND: NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. METHODS: In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model...
September 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
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