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https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#1
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714025/effect-of-ccl2-sirna-on-proliferation-and-apoptosis-in-the-u251-human-glioma-cell-line
#2
Bin Lu, Yue Zhou, Zhongzhou Su, Ai Yan, Peng Ding
Glioma is one of the most common types of tumor of the central nervous system. Increased expression of C‑C motif chemokine 2 (CCL2) has previously been observed in various types of cancer. The effect of CCL2 small interfering (si)RNA on the proliferation, angiogenesis and apoptosis of the glioma cell line U251 was investigated in the present study. Data on CCL2 expression in glioma and normal tissues were obtained from The Cancer Genome Atlas. A total of 30 patients with glioma were enrolled in the present study...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28705496/the-effect-of-cxcr2-inhibition-on-seizure-activity-in-the-pilocarpine-epilepsy-mouse-model
#3
Tao Xu, Xinyuan Yu, Teng Wang, Ying Liu, Xi Liu, Shu Ou, Yangmei Chen
C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized chemokine receptors and is a potential target for treating brain pathologies involving inflammatory processes, including epilepsy. However, the role of CXCR2 in epilepsy has not been investigated, and whether CXCR2 modulates seizure activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed to determine the potential role of CXCR2 in intractable TLE patients and in pilocarpine-induced epileptic mice. Here, through Western blotting and semi-quantitative immunohistochemistry, we detected that CXCR2 protein expression was up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of pilocarpine mice model...
July 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28703802/an-autocrine-inflammatory-forward-feedback-loop-after-chemotherapy-withdrawal-facilitates-the-repopulation-of-drug-resistant-breast-cancer-cells
#4
Deyong Jia, Li Li, Sulaiman Andrew, David Allan, Xuguang Li, Jonathan Lee, Guang Ji, Zemin Yao, Suresh Gadde, Danial Figeys, Lisheng Wang
Stromal cells, infiltrating immune cells, paracrine factors and extracellular matrix have been extensively studied in cancers. However, autocrine factors produced by tumor cells and communications between autocrine factors and intracellular signaling pathways in the development of drug resistance, cancer stem-like cells (CSCs) and tumorigenesis have not been well investigated, and the precise mechanism and tangible approaches remain elusive. Here we reveal a new mechanism by which cytokines produced by breast cancer cells after chemotherapy withdrawal activate both Wnt/β-catenin and NF-κB pathways, which in turn further promote breast cancer cells to produce and secrete cytokines, forming an autocrine inflammatory forward-feedback loop to facilitate the enrichment of drug-resistant breast cancer cells and/or CSCs...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28675123/adam9-expression-promotes-an-aggressive-lung-adenocarcinoma-phenotype
#5
Céline Mongaret Kossmann, Maxime Annereau, Audrey Thomas-Schoemann, Carole Nicco-Overney, Christiane Chéreau, Frédéric Batteux, Jérôme Alexandre, François Lemare
A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive-invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic processes in vivo and in angiogenesis. We first found that high ADAM9 expression was correlated with poor lung adenocarcinoma patient prognosis on Prognoscan data base...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28668699/cxcr2-1208-ct-genotype-may-predict-earlier-clinical-stage-at-diagnosis-in-patients-with-prostate-cancer
#6
Juliana M Franz, Pâmela Portela, Patricia H Salim, Milton Berger, Luiz Fernando Jobim, Rafael Roesler, Mariana Jobim, Gilberto Schwartsmann
Interleukin-8 (IL-8) is an angiogenic CXC chemokine that plays an important role in both the development and progression of several human malignancies including prostate cancer (PC). A single nucleotide polymorphism (SNP) at -251 upstream of the transcriptional start site of the IL-8 gene has been shown to influence its production. The effects of IL-8 are mediated by two highly related chemokine receptors, CXCR1 and CXCR2. The present study investigated the influence of the IL-8 and CXCR2 gene variation on susceptibility and clinicopathological characteristics of PC in a group of Brazilian subjects...
June 29, 2017: Cytokine
https://www.readbyqxmd.com/read/28663317/a-sputum-gene-expression-signature-predicts-oral-corticosteroid-response%C3%A2-in%C3%A2-asthma
#7
Bronwyn S Berthon, Peter G Gibson, Lisa G Wood, Lesley K MacDonald-Wicks, Katherine J Baines
Biomarkers that predict responses to oral corticosteroids (OCS) facilitate patient selection for asthma treatment. We hypothesised that asthma patients would respond differently to OCS therapy, with biomarkers and inflammometry predicting response.Adults with stable asthma underwent a randomised controlled cross-over trial of 50 mg prednisolone daily for 10 days (n=55). A six-gene expression biomarker signature (CLC, CPA3, DNASE1L3, IL1B, ALPL and CXCR2) in induced sputum, and eosinophils in blood and sputum were assessed and predictors of response were investigated (changes in forced expiratory volume in 1 s (ΔFEV1), six-item Asthma Control Questionnaire score (ΔACQ6) or exhaled nitric oxide fraction (ΔFeNO))...
June 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#8
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28642884/cxcl8b-and-cxcr2-regulate-neutrophil-migration-through-bloodstream-in-zebrafish
#9
Constanza Zuñiga-Traslaviña, Karina Bravo, Ariel E Reyes, Carmen G Feijóo
Neutrophils play an essential role during an inflammatory response, which is dependent on their rapid recruitment from the bone marrow to the vasculature. However, there is no information about the molecular signals that regulate neutrophil entry to circulation during an inflammatory process in humans. This is mainly due to the lack of a suitable model of study that contains similar set of molecules and that allows in vivo analyses. In this study, we used the zebrafish to assess the role of Cxcl8a, Cxcl8b, and Cxcr2 in neutrophil migration to blood circulation after injury...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28611093/danirixin-a-reversible-and-selective-antagonist-of-the-cxc-chemokine-receptor-2
#10
Jakob Busch-Petersen, Donald C Carpenter, Miriam Burman, James Foley, Gerald E Hunsberger, David J Kilian, Michael Salmon, Ruth J Mayer, John G Yonchuk, Ruth Tal-Singer
CXC chemokine receptor 2 (CXCR2) is a key receptor in the chemotaxis of neutrophils to sites of inflammation. The studies reported here describe the pharmacological characterization of danirixin, a CXCR2 antagonist in the diaryl urea chemical class. Danirixin has high affinity for CXCR2, with a negative log of the 50% inhibitory concentration (pIC50) of 7.9 for binding to Chinese hamster ovary cell (CHO)-expressed human CXCR2, and 78-fold selectivity over binding to CHO-expressed CXCR1. Danirixin is a competitive antagonist against CXCL8 in Ca2+ mobilization assays, with a Kb of 6...
June 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28596972/targets-of-neutrophil-influx-and-weaponry-therapeutic-opportunities-for-chronic-obstructive-airway-disease
#11
REVIEW
Carina Kärrman Mårdh, James Root, Mohib Uddin, Kristina Stenvall, Anna Malmgren, Kostas Karabelas, Matthew Thomas
Neutrophils are important effector cells of antimicrobial immunity in an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), there is excessive infiltration and activation of neutrophils, subsequent production of reactive oxygen species, and release of serine proteases, matrix metalloproteinases, and myeloperoxidase-resulting in collateral damage as the cells infiltrate into the tissue...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28587921/cxcl1-cxcr2-signaling-in-pathological-pain-role-in-peripheral-and-central-sensitization
#12
REVIEW
Rangel L Silva, Alexandre H Lopes, Rafaela M Guimarães, Thiago M Cunha
Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is associated with plasticity of nociceptive pathway in which pain is prolonged even after healing of the injured tissue. Generally combinations of analgesic drugs are not sufficient to achieve selective palliation from chronic pain, besides causing a greater number of side effects. In order to identify novel alternatives for more effective treatments, it is necessary to clarify the underlying mechanisms of pathological pain...
September 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28575019/clinicopathologic-significance-of-the-cxcl1-cxcr2-axis-in-the-tumor-microenvironment-of-gastric-carcinoma
#13
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
PURPOSE: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. METHODS: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28544630/synthesis-admet-properties-and-biological-evaluation-of-benzothiazole-compounds-targeting-chemokine-receptor%C3%A2-2-cxcr2
#14
Wesam E Mehanna, Tiangong Lu, Bikash Debnath, Deena S Lasheen, Rabah A T Serya, Khaled A Abouzid, Nouri Neamati
Herein we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric chemokine receptor 2 (CXCR2) inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2, with IC50 values less than 10 μm and selectivity over CXCR4. Our ADMET simulations suggest favorable drug-like properties for the active compounds. Importantly, we developed a predictive model that can distinguish active from inactive compounds; this will serve as a valuable tool to guide the design of optimized compounds to be evaluated in preclinical models...
May 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#15
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28538177/chemokine-signaling-and-the-regulation-of-bidirectional-leukocyte-migration-in-interstitial-tissues
#16
Davalyn Powell, Sebastien Tauzin, Laurel E Hind, Qing Deng, David J Beebe, Anna Huttenlocher
Motile cells navigate through complex tissue environments that include both attractive and repulsive cues. In response to tissue wounding, neutrophils, primary cells of the innate immune response, exhibit bidirectional migration that is orchestrated by chemokines and their receptors. Although progress has been made in identifying signals that mediate the recruitment phase, the mechanisms that regulate neutrophil reverse migration remain largely unknown. Here, we visualize bidirectional neutrophil migration to sterile wounds in zebrafish larvae and identify specific roles for the chemokine receptors Cxcr1 and Cxcr2 in neutrophil recruitment to sterile injury and infection...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28533661/macrophage-inflammatory-protein-2-as-mediator-of-inflammation-in-acute-liver-injury
#17
REVIEW
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#18
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28514506/human-adipose-derived-mesenchymal-stem-cell-secreted-cxcl1-and-cxcl8-facilitate-breast-tumor-growth-by-promoting-angiogenesis
#19
Yuan Wang, Junli Liu, Qingyuan Jiang, Jie Deng, Fen Xu, Xiaolei Chen, Fuyi Cheng, Yujing Zhang, Yunqi Yao, Zhemin Xia, Xia Xu, Xiaolan Su, Meijuan Huang, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Robert Chunhua Zhao, Yuquan Wei, Hongxin Deng
Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In this study, we demonstrated that human ADSCs (hADSCs) could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs...
May 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/28484461/blockade-of-neutrophil-s-chemokine-receptors-cxcr1-2-abrogate-liver-damage-in-acute-on-chronic-liver-failure
#20
Arshi Khanam, Nirupma Trehanpati, Peggy Riese, Archana Rastogi, Carlos Alberto Guzman, Shiv Kumar Sarin
BACKGROUND: Neutrophils serve as critical players in the pathogenesis of liver diseases. Chemokine receptors CXCR1 and CXCR2 are required for neutrophil chemotaxis to the site of inflammation/injury and are crucial in hepatic inflammatory response. However, key mechanism of neutrophil-mediated liver injury in acute-on-chronic liver failure (ACLF) remains highly elusive; which could be targeted for the development of new therapeutic interventions. METHODS: To demonstrate the role of CXCR1/CXCR2-expressing neutrophils in hepatic injury, we investigated CXCR1/CXCR2 receptor expression in 17 hepatitis B virus-related ACLF patients in comparison to 42 chronic hepatitis B and 18 healthy controls...
2017: Frontiers in Immunology
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