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cancer and inflammasome

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https://www.readbyqxmd.com/read/28212736/tap73-upregulates-il-1%C3%AE-in-cancer-cells-potential-biomarker-in-lung-and-breast-cancer
#1
Polina Vikhreva, Varvara Petrova, Tarik Gokbulut, Ilias Pestlikis, Mara Mancini, Nicola Di Daniele, Richard A Knight, Gerry Melino, Ivano Amelio
p73 is a transcription factor belonging to the p53 tumour suppressor family. p73(-/-) mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28173682/-research-progress-in-inflammasome-and-colorectal-cancer
#2
J Q Feng, M B Feng, F Y Xu
No abstract text is available yet for this article.
February 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28160865/isorhamnetin-and-hyperoside-derived-from-water-dropwort-inhibits-inflammasome-activation
#3
Huijeong Ahn, Geun-Shik Lee
BACKGROUND: Water dropwort (Oenanthe javanica), an umbelliferous plant, has been reported as hypolipidemic, antiplatelet, antitumor, or immune-stimulating agents and it has been suggested to cure cardiovascular disease and cancer. PURPOSE: Present study aimed to evaluate the effect of the extracts of water dropwort (EWD) and its pharmacological molecules, hyperoside and isorhamnetin, on inflammatory response, especially inflammasome activation. STUDY DESIGN/METHODS: The anti-inflammasome properties of EWD, isorhamnetin, and hyperoside were elucidated by human and mouse macrophages...
January 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28155620/nlrp3-inhibitors-as-potential-therapeutic-agents-for-treatment-of-inflammatory-bowel-disease
#4
Agampodi Promoda Perera, Dale Kunde, Rajaraman Eri
BACKGROUND: Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised by chronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis or Crohn's disease and increases the risk of developing colorectal cancer. METHODS: Here, we have reviewed current treatment regimen for IBD utilising anti-inflammatory drugs, immune system suppressors and antibiotics or a combination of these. However, these therapeutics lead to a number of adverse effects, remission or significant non-responsiveness creating an urgent need to develop potent drugs with novel mechanisms of action for IBD...
February 1, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28147282/sr-b1-is-a-silica-receptor-that-mediates-canonical-inflammasome-activation
#5
Misato Tsugita, Nobuyuki Morimoto, Manabu Tashiro, Kengo Kinoshita, Masafumi Nakayama
The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28112987/photoprotective-potential-of-glycolic-acid-by-reducing-nlrc4-and-aim2-inflammasome-complex-proteins-in-uvb-radiation-induced-normal-human-epidermal-keratinocytes-and-mice
#6
Sung-Jen Hung, Sheau-Chung Tang, Pei-Yun Liao, Jheng-Siang Ge, Yu-Ping Hsiao, Jen-Hung Yang
Exposure to UVB radiation induces inflammation and free radical-mediated oxidative stress through reactive oxygen species (ROS) that play a crucial role in the induction of skin cancer. Glycolic acid (GA) is frequently used in cosmetics and dermatology. The aim of the study was to analyze the photoprotective mechanisms through which GA retards UVB-induced ROS accumulation and inflammation in normal human epidermal keratinocytes (NHEKs) and mice skin, respectively. NHEK cell line and C57BL/6J mice were treated with GA (0...
February 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28110208/inflammatory-pathway-genes-associated-with-inter-individual-variability-in-the-trajectories-of-morning-and-evening-fatigue-in-patients-receiving-chemotherapy
#7
Fay Wright, Marilyn Hammer, Steven M Paul, Bradley E Aouizerat, Kord M Kober, Yvette P Conley, Bruce A Cooper, Laura B Dunn, Jon D Levine, Gail DEramo Melkus, Christine Miaskowski
Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue...
January 19, 2017: Cytokine
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#8
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28062361/redox-signaling-in-the-gastrointestinal-tract
#9
REVIEW
Salvador Pérez, Raquel Taléns-Visconti, Sergio Rius-Pérez, Isabela Finamor, Juan Sastre
Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulcer, gastric cancer, ischemic intestinal injury, celiac disease, inflammatory bowel disease and colorectal cancer...
January 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28056049/asc-induces-apoptosis-via-activation-of-caspase-9-by-enhancing-gap-junction-mediated-intercellular-communication
#10
Masato Kitazawa, Shigeaki Hida, Chifumi Fujii, Shun'ichiro Taniguchi, Kensuke Ito, Tomio Matsumura, Nagisa Okada, Takashi Sakaizawa, Akira Kobayashi, Michiko Takeoka, Shin-Ichi Miyagawa
ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28035720/wp1066-suppresses-macrophage-cell-death-induced-by-inflammasome-agonists-independently-of-its-inhibitory-effect-on-stat3
#11
Shino Honda, Daichi Sadatomi, Yasuo Yamamura, Kazutaka Nakashioya, Susumu Tanimura, Kohsuke Takeda
The compound WP1066 was originally synthesized by modifying the structure of AG490, which inhibits the activation of signal transducer and activator of transcription 3 (STAT3) by directly targeting Janus kinases (JAKs). WP1066 exhibits stronger anti-cancer activity than AG490 against malignant glioma and other cancer cells and is regarded as a promising therapeutic agent. By screening a small library of target-known compounds, we identified WP1066 as an inhibitor of macrophage cell death induced by agonists of the NLRP3 inflammasome, an intracellular protein complex required for the processing of the proinflammatory cytokine interleukin (IL)-1β...
December 30, 2016: Cancer Science
https://www.readbyqxmd.com/read/27956668/the-inflammasome-as-a-target-for-pain-therapy
#12
H Zhang, F Li, W-W Li, C Stary, J D Clark, S Xu, X Xiong
The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades...
December 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/27928589/genetic-polymorphisms-of-il-18-rs1946518-and-il-1%C3%AE-rs16944-are-associated-with-prognosis-and-survival-of-acute-myeloid-leukemia
#13
Hong Wang, Mingqiang Hua, Shukang Wang, Jie Yu, Chen Chen, Xueyun Zhao, Chen Zhang, Chaoqin Zhong, Ruiqing Wang, Na He, Ming Hou, Daoxin Ma
BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML...
December 7, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27895640/%C3%AF-3-polyunsaturated-fatty-acids-as-immunomodulators-in-colorectal-cancer-new-potential-role-in-adjuvant-therapies
#14
REVIEW
Stefania Miccadei, Roberta Masella, Anna Maria Mileo, Sandra Gessani
Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27875342/the-multifaceted-roles-of-inflammasome-proteins-in-cancer
#15
Virginie Petrilli
PURPOSE OF REVIEW: Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination. RECENT FINDINGS: Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27842563/novel-extracellular-and-nuclear-caspase-1-and-inflammasomes-propagate-inflammation-and-regulate-gene-expression-a-comprehensive-database-mining-study
#16
Luqiao Wang, Hangfei Fu, Gayani Nanayakkara, Yafeng Li, Ying Shao, Candice Johnson, Jiali Cheng, William Y Yang, Fan Yang, Muriel Lavallee, Yanjie Xu, Xiaoshu Cheng, Hang Xi, Jonathan Yi, Jun Yu, Eric T Choi, Hong Wang, Xiaofeng Yang
BACKGROUND: Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named "inflammasomes" for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. METHODS: We conducted meticulous data analysis methods on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies...
November 14, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27819292/saponin-based-adjuvants-induce-cross-presentation-in-dendritic-cells-by-intracellular-lipid-body-formation
#17
Martijn H den Brok, Christian Büll, Melissa Wassink, Annemarie M de Graaf, Jori A Wagenaars, Marthe Minderman, Mayank Thakur, Sebastian Amigorena, Eric O Rijke, Carla C Schrier, Gosse J Adema
Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation...
November 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27786298/targeting-inflammasome-il-1-pathways-for-cancer-immunotherapy
#18
Beichu Guo, Shunjun Fu, Jinyu Zhang, Bei Liu, Zihai Li
The inflammatory microenvironment has been shown to play important roles in various stages of tumor development including initiation, growth, and metastasis. The inflammasome is a critical innate immune pathway for the production of active IL-1β, a potent inflammatory cytokine. Although inflammasomes are essential for host defense against pathogens and contribute to autoimmune diseases, their role in tumor progression remains controversial. Here, our results demonstrate that the inflammasome and IL-1β pathway promoted tumor growth and metastasis in animal and human breast cancer models...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27768771/silencing-of-asc-in-cutaneous-squamous-cell-carcinoma
#19
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
https://www.readbyqxmd.com/read/27708283/obesity-associated-nlrc4-inflammasome-activation-drives-breast-cancer-progression
#20
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
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