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Tumor infiltrating neutrophils

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https://www.readbyqxmd.com/read/28611085/ccr6-cc-chemokine-receptor-6-is-essential-for-the-migration-of-detrimental-natural-interleukin-17-producing-%C3%AE-%C3%AE-t-cells-in-stroke
#1
Priyadharshini Arunachalam, Peter Ludewig, Patrick Melich, Thiruma Valavan Arumugam, Christian Gerloff, Immo Prinz, Tim Magnus, Mathias Gelderblom
BACKGROUND AND PURPOSE: Immune-mediated tissue damage after stroke evolves within the first days, and lymphocytes contribute to the secondary injury. Our goal was to identify T-cell subpopulations, which trigger the immune response. METHODS: In a model of experimental stroke, we analyzed the immune phenotype of interleukin-17 (IL-17)-producing γδ T cells and explored the therapeutic potential of neutralizing anti-IL-17 antibodies in combination with mild therapeutic hypothermia...
June 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28587842/sustained-sensitizing-effects-of-tumor-necrosis-factor-alpha-on-sensory-nerves-in-lung-and-airways
#2
REVIEW
Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee
Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 h later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and cytokines in the lung and airways...
June 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28575876/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#3
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539837/ezh2-acts-as-a-tumor-suppressor-in-kras-driven-lung-adenocarcinoma
#4
Yanxiao Wang, Ning Hou, Xuan Cheng, Jishuai Zhang, Xiaohong Tan, Chong Zhang, Yuling Tang, Yan Teng, Xiao Yang
Previous studies have suggested that enhancer zeste homolog 2 (Ezh2), a histone methyltransferase subunit of polycomb repressive complex 2 (PRC2), acts as an oncogene in lung adenocarcinoma (ADC) development. However, we found that in human lung ADC samples, deletion and mutations of EZH2 were also frequently present, with 14% of patients harboring loss-of-function EZH2 alterations. To explore the effect of Ezh2 loss on lung tumor formation, lung epithelial Ezh2 gene was deleted in Kras-driven lung ADC mouse model...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28535510/heat-shock-protein-a12b-protects-vascular-endothelial-cells-against-sepsis-induced-acute-lung-injury-in-mice
#5
Yi Chen, Lei Wang, Qiuxiang Kang, Xu Zhang, Guifang Yu, Xiaojian Wan, Jiafeng Wang, Keming Zhu
BACKGROUND: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. METHODS: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534140/protective-effects-of-neural-crest-derived-stem-cell-conditioned-media-against-ischemia-reperfusion-induced-lung-injury-in-rats
#6
Chung-Kan Peng, Shu-Yu Wu, Shih-En Tang, Min-Hui Li, Shih-Shiuan Lin, Shi-Jye Chu, Kun-Lun Huang
Current treatments for ischemia-reperfusion (IR)-induced acute lung injury are limited. Mesenchymal stem cell-conditioned medium (CM) has been reported to attenuate lung injury. Neural crest stem cells (NCSCs), a type of multipotent stem cells, are more easily obtained than mesenchymal stem cells. We hypothesize that NCSC-CM has anti-inflammatory properties that could protect against IR-induced lung injury in rats. In this study, NCSC-CM was derived from rat NCSCs. Typical acute lung injury was induced by 30-min ischemia followed by 90-min reperfusion in adult male Sprague-Dawley rats...
May 23, 2017: Inflammation
https://www.readbyqxmd.com/read/28522566/nedd8-modification-of-cullin-5-regulates-lipopolysaccharide-induced-acute-lung-injury
#7
Ziyan Zhu, Lei Sun, Rui Hao, Hongchao Jiang, Feng Qian, Richard D Ye
Lung infections are major causes of acute lung injury (ALI), with limited effective treatment available. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential adaptor regulating Toll-like receptors (TLRs). We recently identified Cullin-5 (Cul-5) as a prominent component in the regulation of TRAF6 polyubiquitination, but its physiological significance in acute lung injury has not been explored. In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-protumorigenic-actions-via-neutrophil-elastase
#8
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here, it is reported that granulocytic myeloid-derived suppressor cells (MDSC) are the predominant tumor-infiltrating cells in prostate cancer xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#9
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507798/tumor-infiltrating-neutrophils-predict-benefit-from-adjuvant-chemotherapy-in-patients-with-muscle-invasive-bladder-cancer
#10
Lin Zhou, Le Xu, Lingli Chen, Qiang Fu, Zheng Liu, Yuan Chang, Zongming Lin, Jiejie Xu
Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in tumorigenesis. The objective of this study is to assess the prognostic effect of TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the study. TINs were evaluated by immunohistochemical staining of CD66b or the CIBERSORT method. Patients with high TINs had a significantly poorer overall survival (p = 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505114/osteopontin-deficiency-suppresses-intestinal-tumor-development-in-apc-deficient-min-mice
#11
Rikako Ishigamori, Masami Komiya, Shinji Takasu, Michihiro Mutoh, Toshio Imai, Mami Takahashi
Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and is suggested to enhance cancer progression. In this study, the effect of deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was investigated. At 16 weeks of age, the number of small intestinal polyps in Min/OPN(+/-) and Min/OPN(-/-) mice was lower than that of Min/OPN(+/+) mice. Colorectal tumor incidences and multiplicities in Min/OPN(+/-) and Min/OPN(-/-) mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0...
May 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28504320/photosensitization-priming-of-tumor-microenvironments-improves-delivery-of-nanotherapeutics-via-neutrophil-infiltration
#12
Dafeng Chu, Xinyue Dong, Qi Zhao, Jingkai Gu, Zhenjia Wang
Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition...
May 15, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28487990/inhibition-of-btk-protects-lungs-from-trauma-hemorrhagic-shock-induced-injury-in-rats
#13
Xinwei Liu, Jingdong Zhang, Wenfeng Han, Yu Wang, Yunen Liu, Yubiao Zhang, Dapeng Zhou, Liangbi Xiang
The present study aimed to investigate the role of Bruton's tyrosine kinase (BTK) in the pathogenesis of lung injury induced by trauma‑hemorrhagic shock (THS), and to examine the pulmonary protective effects of BTK inhibition. Male Sprague‑Dawley rats were divided into four groups (n=12/group): i) A Sham group, which received surgery without induced trauma; ii) a THS‑induced injury group; iii) a THS‑induced injury group that also received treatment with the BTK inhibitor LFM‑A13 prior to trauma induction; and iv) a Sham group that was pretreated with LFM‑A13 prior to surgery but did not receive induced trauma...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487374/dioxin-induced-increase-in-leukotriene-b4-biosynthesis-through-the-aryl-hydrocarbon-receptor-and-its-relevance-to-hepatotoxicity-owing-to-neutrophil-infiltration
#14
Tomoki Takeda, Yukiko Komiya, Takayuki Koga, Takumi Ishida, Yuji Ishii, Yasushi Kikuta, Michio Nakaya, Hitoshi Kurose, Takehiko Yokomizo, Takao Shimizu, Hiroshi Uchi, Masutaka Furue, Hideyuki Yamada
Dioxin and related chemicals alter the expression of a number of genes by activating the aryl hydrocarbon receptors (AHRs) to produce a variety of disorders including hepatotoxicity. However, it remains largely unknown how these changes in gene expression are linked to toxicity. To address this issue, we initially examined the effect of 2,3,7,8-tetrachrolodibenzo-p-dioxin (TCDD), a most toxic dioxin, on the hepatic and serum metabolome in male pubertal rats. The results obtained showed that TCDD causes many changes in the level of fatty acids, bile acids, amino acids and their metabolites...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28482378/high-expression-of-tumor-necrosis-factor-receptor-associated-factor-2-promotes-tumor-metastasis-and-is-associated-with-unfavorable-prognosis-in-gastric-cancer
#15
Junjie Zhao, Haojie Li, Lingqiang Min, Xu Han, Ping Shu, Yupeng Yang, Qiangjun Gan, Xuefei Wang, Hongshan Wang, Yuanyuan Ruan, Jing Qin, Yihong Sun, Xinyu Qin
BACKGROUND: Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a key effector in the activation of nuclear factor kappa B (NF-κB). Nevertheless, the role of TRAF2 in gastric tumorigenesis remains little defined. METHODS: Immunohistochemistry (IHC) was used to find the relationship between TRAF2 expression and clinicopathological characteristics of gastric cancer (GC) patients, and nomogram was applied to predict the overall survival of patients. Besides, we performed transwell assays to detect the function of TRAF2 in promoting metastasis, and explored the correlations between TRAF2, NF-κB, and interleukin-8 (IL-8) in vitro...
May 8, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28480221/liver-x-receptor-agonist-to901317-attenuates-paraquat-induced-acute-lung-injury-through-inhibition-of-nf-%C3%AE%C2%BAb-and-jnk-p38-mapk-signal-pathways
#16
Xiao Hu, Haitao Shen, Yu Wang, Min Zhao
Paraquat (PQ) is a widely used herbicide with extremely high poisoning mortality mostly from acute lung injury (ALI) or progressive pulmonary fibrosis. Toxicity mechanisms remain unclear, but a redox cycling process that generates reactive oxygen species (ROS) is involved, as are inflammation and cell apoptosis. We established an ALI mouse model by intraperitoneal injection of PQ (28 mg/kg) and then investigated the effects of a potent liver X receptor (LXR) agonist, TO901317 (5 or 20 mg/kg), injected intraperitoneally 30 min after PQ administration...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28468657/hsya-alleviates-secondary-neuronal-death-through-attenuating-oxidative-stress-inflammatory-response-and-neural-apoptosis-in-sd-rat-spinal-cord-compression-injury
#17
Jun-Peng Pei, Li-Hong Fan, Kai Nan, Jia Li, Xiao-Qian Dang, Kun-Zheng Wang
BACKGROUND: Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved. METHODS: Sprague-Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group)...
May 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28465358/mutant-idh1-regulates-the-tumor-associated-immune-system-in-gliomas
#18
Nduka M Amankulor, Youngmi Kim, Sonali Arora, Julia Kargl, Frank Szulzewsky, Mark Hanke, Daciana H Margineantu, Aparna Rao, Hamid Bolouri, Jeff Delrow, David Hockenbery, A McGarry Houghton, Eric C Holland
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28462384/trif-differentially-regulates-hepatic-steatosis-and-inflammation-fibrosis-in-mice
#19
Ling Yang, Kouichi Miura, Bi Zhang, Hiroshi Matsushita, Yoon Mee Yang, Shuang Liang, Jingyi Song, Yoon Seok Roh, Ekihiro Seki
BACKGROUND & AIMS: Toll-like receptor 4 (TLR4) signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF). TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH) and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. METHODS: A choline-deficient amino acid defined (CDAA) diet was used for the mouse NASH model...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28453950/histological-assessment-of-the-carotid-sheath-in-patients-with-oral-squamous-cell-carcinoma
#20
Manjari Palliyalil, Venkatesh Anehosur, Abhijit Joshi, Swetha Acharya
PURPOSE: During surgical management of the neck using various types of neck dissection, the carotid sheath is removed, in particular, the part adjacent to the jugular lymph node chain, with the intention of preventing recurrence from the lymphatics present within it. The role of the carotid sheath as a potential origin for nodal recurrence has not been proved thus far. Working in a tissue plane between the carotid sheath and the neurovascular structures of the neck can lead to a greater chance of damage to these structures...
April 4, 2017: Journal of Oral and Maxillofacial Surgery
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