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cancer and inflammasome

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https://www.readbyqxmd.com/read/28811967/il-18-receptor-marks-functional-cd8-t-cells-in-non-small-cell-lung-cancer
#1
Eleonora Timperi, Chiara Focaccetti, Daniela Gallerano, Mariangela Panetta, Sheila Spada, Enzo Gallo, Paolo Visca, Federico Venuta, Daniele Diso, Arsela Prelaj, Flavia Longo, Francesco Facciolo, Paola Nisticò, Vincenzo Barnaba
IL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen- or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28796840/yes-research-matters
#2
Mari L Shinohara
My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#3
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755170/identification-and-validation-of-uterine-stimulant-methylergometrine-as-a-potential-inhibitor-of-caspase-1-activation
#4
Guillermo García-Laínez, Mónica Sancho, Vanessa García-Bayarri, Mar Orzáez
Inflammasomes are intracellular multiprotein complexes of the innate immune system. Upon an inflammatory insult, such as infection or intracellular damage, a nucleotide-binding oligomerization domain-like receptor (NLR) sensor protein and the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) are assembled to activate protease procaspase-1. This protease processes pro-IL-1β and pro-IL-18 cytokines, which are released to induce the inflammatory response...
July 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28740569/dna-oncogenic-virus-induced-oxidative-stress-genomic-damage-and-aberrant-epigenetic-alterations
#5
REVIEW
Mankgopo Magdeline Kgatle, Catherine Wendy Spearman, Asgar Ali Kalla, Henry Norman Hairwadzi
Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28739604/s1pr1-on-tumor-associated-macrophages-promotes-lymphangiogenesis-and-metastasis-via-nlrp3-il-1%C3%AE
#6
Benjamin Weichand, Rüdiger Popp, Sarah Dziumbla, Javier Mora, Elisabeth Strack, Eiman Elwakeel, Ann-Christin Frank, Klaus Scholich, Sandra Pierre, Shahzad N Syed, Catherine Olesch, Julia Ringleb, Bilge Ören, Claudia Döring, Rajkumar Savai, Michaela Jung, Andreas von Knethen, Bodo Levkau, Ingrid Fleming, Andreas Weigert, Bernhard Brüne
Metastasis is the primary cause of cancer death. The inflammatory tumor microenvironment contributes to metastasis, for instance, by recruiting blood and lymph vessels. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1) alone in CD11b(hi) CD206(+) TAMs infiltrating mouse breast tumors prevents pulmonary metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also observed in the nonrelated methylcholanthrene-induced fibrosarcoma model...
July 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28733143/mechanisms-of-nlrp1-mediated-autoinflammatory-disease-in-humans-and-mice
#7
REVIEW
Chien-Hsiung Yu, Jonas Moecking, Matthias Geyer, Seth L Masters
NLRP1 was the first NOD-like receptor described to form an inflammasome, recruiting ASC to activate caspase-1, which processes interleukin-1β and interleukin-18 to their active form. A wealth of new genetic information has now redefined our understanding of this innate immune sensor. Specifically, rare loss-of-function variants in the N-terminal pyrin domain indicate that this part of NLRP1 is autoinhibitory and normally acts to prevent a familial autoinflammatory skin disease associated with cancer. In the absence of a ligand to trigger human NLRP1, these mutations have now confirmed the requirement of NLRP1 autolytic cleavage within the FIIND domain, which had previously been implicated in NLRP1 activation...
July 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#8
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#9
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722711/limiting-inflammation-the-negative-regulation-of-nf-%C3%AE%C2%BAb-and-the-nlrp3-inflammasome
#10
REVIEW
Inna S Afonina, Zhenyu Zhong, Michael Karin, Rudi Beyaert
A properly mounted immune response is indispensable for recognizing and eliminating danger arising from foreign invaders and tissue trauma. However, the 'inflammatory fire' kindled by the host response must be tightly controlled to prevent it from spreading and causing irreparable damage. Accordingly, acute inflammation is self-limiting and is normally attenuated after elimination of noxious stimuli, restoration of homeostasis and initiation of tissue repair. However, unresolved inflammation may lead to the development of chronic autoimmune and degenerative diseases and cancer...
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28714351/activation-of-nlrp3-inflammasome-in-peripheral-nerve-contributes-to-paclitaxel-induced-neuropathic-pain
#11
Min Jia, Caihua Wu, Fang Gao, Hongchun Xiang, Ning Sun, Ping Peng, Jingjing Li, Xiaocui Yuan, Hongping Li, Xianfang Meng, Bo Tian, Jing Shi, Man Li
Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1β. Growing evidences have supported that peripheral interleukin-1β is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28701727/free-immunoglobulin-light-chain-flc-promotes-murine-colitis-and-colitis-associated-colon-carcinogenesis-by-activating-the-inflammasome
#12
Junfan Ma, Dongyang Jiang, Xiaoting Gong, Wenwei Shao, Zhu Zhu, Weiyan Xu, Xiaoyan Qiu
Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associated colon carcinogenesis (CAC). In this study, we found a significant increase in FLC in murine models of DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls. Peptide F991, a functional blocker of FLC, significantly attenuated colitis progression, which included abrogating the development of diarrhea and tumor burden, elevating survival rate, greatly reducing the infiltration of inflammatory cells (such as ROS(+) active neutrophils), especially reducing tumorigenesis in CAC...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698859/inflammasome-as-a-therapeutic-target-for-cancer-prevention-and-treatment
#13
REVIEW
Huyen Trang Ha Thi, Suntaek Hong
Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28690082/regulation-and-functions-of-inflammasome-mediated-cytokines-in-helicobacter-pylori-infection
#14
REVIEW
Le Son Tran, Michelle Chonwerawong, Richard L Ferrero
Persistent stomach infection with Helicobacter pylori causes chronic mucosal inflammation (gastritis), which is widely recognized as an essential precursor to gastric cancer. The IL-1 interleukin family cytokines IL-1β and IL-18 have emerged as central mediators of mucosal inflammation. Here, we review the regulation and function of these cytokines in H. pylori-induced inflammation and carcinogenesis.
July 6, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28663562/expression-analysis-of-inflammasome-sensors-and-implication-of-nlrp12-inflammasome-in-prostate-cancer
#15
Dev Karan, Ossama Tawfik, Seema Dubey
Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines. The selected expression of NLRP3 and NLRP12 inflammasomes was validated, and the clinical association was evaluated in human prostate archival tumor tissues...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637493/the-role-of-nlrp3-inflammasome-in-5-fluorouracil-resistance-of-oral-squamous-cell-carcinoma
#16
Xiaodong Feng, Qingqiong Luo, Han Zhang, Han Wang, Wantao Chen, Guangxun Meng, Fuxiang Chen
BACKGROUND: 5-Fluorouracil (5-FU) is a widely used drug for the therapy of cancer. However, the chemoresistance of tumor cells to 5-FU usually limits its clinical effectiveness. In this study, we explored the role of NLRP3 inflammasome in 5-FU resistance of oral squamous cell carcinoma (OSCC). METHODS: The mRNA and protein expression levels of NLRP3, Caspase1 and IL-1β in resected OSCC specimens or cell lines were measured respectively by quantitative real time-PCR (qRT-PCR) and western blot...
June 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#17
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#18
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
June 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28588495/a-brief-history-of-il-1-and-il-1-ra-in-rheumatology
#19
Jean-Michel Dayer, Francesca Oliviero, Leonardo Punzi
The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28586167/card9-dependent-il-1%C3%AE-regulates-il-22-production-from-group-3-innate-lymphoid-cells-and-promotes-colitis-associated-cancer
#20
Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R Greten, Jürgen Ruland
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model...
June 6, 2017: European Journal of Immunology
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