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https://www.readbyqxmd.com/read/29777109/tak1-mediates-microenvironment-triggered-autocrine-signals-and-promotes-triple-negative-breast-cancer-lung-metastasis
#1
Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777034/membrane-fluctuations-and-acidosis-regulate-cooperative-binding-of-marker-of-self-cd47-with-macrophage-checkpoint-receptor-sirp%C3%AE
#2
Jan Steinkühler, Bartosz Różycki, Cory Alvey, Reinhard Lipowsky, Thomas R Weikl, Rumiana Dimova, Dennis E Discher
Cell-cell interactions that result from membrane proteins binding weakly in trans can cause accumulations in cis that suggest cooperativity and thereby an acute sensitivity to environmental factors. The ubiquitous "marker of self" protein CD47 binds weakly to SIRPα on a macrophage, which leads to accumulation of SIRPα at a phagocytic synapse and ultimately to inhibition of engulfment of 'self' cells - including cancer cells. We reconstituted this macrophage checkpoint with CD47-GFP displayed on giant vesicles generated from plasma membranes and then imaged vesicles adhering to SIRPα immobilized on a surface...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29776955/high-fat-diet-induced-inflammation-accelerates-prostate-cancer-growth-via-il6-signaling
#3
Takuji Hayashi, Kazutoshi Fujita, Satoshi Nojima, Yujiro Hayashi, Kosuke Nakano, Yu Ishizuya, Cong Wang, Yoshiyuki Yamamoto, Toshiro Kinouchi, Kyosuke Matsuzaki, Kentaro Jingushi, Taigo Kato, Atsunari Kawashima, Akira Nagahara, Takeshi Ujike, Motohide Uemura, Maria Del Carmen Rodriguez Pena, Jennifer B Gordetsky, Eiichi Morii, Kazutake Tsujikawa, George J Netto, Norio Nonomura
OBJECTIVE: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. MATERIALS AND METHODS: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+; Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29773403/synthesis-of-chitin-glucan-aldehyde-quercetin-conjugate-and-evaluation-of-anticancer-and-antioxidant-activities
#4
Anu Singh, P K Dutta, Hridyesh Kumar, Amit Kumar Kureel, Ambak Kumar Rai
In the present study, we have synthesized chitin-glucan-aldehyde-quercetin (chi-glu-ald-que) conjugate via condensation reaction. Synthesis of chitin-glucan-aldehyde (chi-glu-ald) complex was facilitated by the oxidation of chitin-glucan (chi-glu) complex. Formation of conjugate was confirmed by Proton nuclear magnetic resonance spectroscopy (1 H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Morphological studies showed that after grafting of quercetin, several changes on surface were depicted and a more crystalline nature was observed...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#5
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772561/thyroid-cancer-phenotypes-in-relation-to-inflammation-and-autoimmunity
#6
Loredana Pagano, Chiara Mele, Maria Teresa Sama, Marco Zavattaro, Marina Caputo, Lucrezia De Marchi, Samuele Paggi, Flavia Prodam, Gianluca Aimaretti, Paolo Marzullo
Thyroid cancer represents the most frequent endocrine neoplasm and is epidemiologically linked to a growing incidence worldwide, which is only in part explained by the increased detection of small cancers in a preclinical stage. Understanding the molecular pathogenesis of well-differentiated thyroid cancers and poorly-differentiated thyroid cancers has prompted interest into the identification of crucial signaling pathways and molecular derangements related to genetic and epigenetic alterations. Increasing attention has been recently focused on inflammation and immunity as major culprit mechanisms involved in thyroid tumourigenesis, through the detection of activated immune cells, pro-inflammatory cytokines, as well as signal integrations between inflammatory and proliferative pathways within the thyroid tumour micro-environment...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29771951/antitumor-antioxidant-and-anti-inflammatory-activities-of-kaempferol-and-its-corresponding-glycosides-and-the-enzymatic-preparation-of-kaempferol
#7
Jingqiu Wang, Xianying Fang, Lin Ge, Fuliang Cao, Linguo Zhao, Zhenzhong Wang, Wei Xiao
Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells...
2018: PloS One
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#8
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771377/alternative-splicing-analysis-in-human-monocytes-and-macrophages-reveals-mbnl1-as-major-regulator
#9
Hongfei Liu, Paolo A Lorenzini, Fan Zhang, Shaohai Xu, Mei Su M Wong, Jie Zheng, Xavier Roca
We report the detailed transcriptomic profiles of human innate myeloid cells using RNA sequencing. Monocytes migrate from blood into infected or wounded tissue to differentiate into macrophages, and control inflammation via phagocytosis or cytokine secretion. We differentiated culture primary monocytes with either GM- or M-CSF to obtain pro- or anti-inflammatory macrophages, and respectively activated them with either LPS/IFNγ or anti-inflammatory cytokines. We also treated the THP-1 monocytic cell line with PMA and similar cytokines to mimic differentiation and activation...
May 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#10
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29770354/3d-co-culture-system-of-tumor-associated-macrophages-and-ovarian-cancer-cells
#11
Lingli Long, Mingzhu Yin, Wang Min
Ovarian cancer is fairly unique in that ovarian carcinoma cells can detach and spread directly through peritoneal cavity. It has been unclear, however, how detached cancer cells survive in the peritoneum and form spheroid structure. We have recently reported that there is a strong correlation between Tumor-associated macrophages (TAMs)-associated spheroid and clinical pathology of ovarian cancer, and that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in orthotopic mouse models...
April 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29769604/macrophage-cytokines-enhance-cell-proliferation-of-normal-prostate-epithelial-cells-through-activation-of-erk-and-akt
#12
Tu Dang, Geou-Yarh Liou
Macrophage infiltrations (inflammation) are associated with prostate disorders such as prostatitis, prostatic hyperplasia and prostate cancer. All prostate disorders have elevated cell proliferation, and are initiated from normal prostate epithelial cells. To date, the mechanism of how macrophages regulate normal prostate epithelial cell proliferation remains largely unknown. Using a 3D co-culture system, we here show that Raw 264.7 macrophages increased cell proliferation of normal prostate epithelial PZ-HPV-7 cells...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768197/induction-of-nitric-oxide-metabolism-in-enterocytes-alleviates-colitis-and-inflammation-associated-colon-cancer
#13
Noa Stettner, Chava Rosen, Biana Bernshtein, Shiri Gur-Cohen, Julia Frug, Alon Silberman, Alona Sarver, Narin N Carmel-Neiderman, Raya Eilam, Inbal Biton, Meirav Pevsner-Fischer, Niv Zmora, Alexander Brandis, Keren Bahar Halpern, Ram Mazkereth, Diego di Bernardo, Nicola Brunetti-Pierri, Muralidhar H Premkumar, Gillian Dank, Sandesh C S Nagamani, Steffen Jung, Alon Harmelin, Ayelet Erez
Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767307/virus-vector-mediated-genetic-modification-of-brain-tumor-stromal-cells-after-intravenous-delivery
#14
Adrienn Volak, Stanley G LeRoy, Jeya Shree Natasan, David J Park, Pike See Cheah, Andreas Maus, Zachary Fitzpatrick, Eloise Hudry, Kelsey Pinkham, Sheetal Gandhi, Bradley T Hyman, Dakai Mu, Dwijit GuhaSarkar, Anat O Stemmer-Rachamimov, Miguel Sena-Esteves, Christian E Badr, Casey A Maguire
The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively...
May 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29765169/m1-m2-macrophage-polarization-in-human-obese-adipose-tissue
#15
Jaroslava Chylikova, Jana Dvorackova, Zdenek Tauber, Vojtech Kamarad
Obesity and insulin resistance are closely associated with chronic inflammation in adipose tissue, where macrophages play an important role. Adipose tissue macrophages can be divided into two main phenotypes: the classical M1 macrophages and alternatively activated macrophages M2. M1 macrophages produce pro-inflammatory cytokines (TNF-α, interleukin IL-6 and MCP-1) and thus contribute to the development of insulin resistance. On the other hand, M2 macrophages, anti-inflammatory, are involved in the maintenance of tissue homeostasis and are typical in the adipose tissue of slender individuals...
May 16, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29764866/lrrc15-is-a-novel-mesenchymal-protein-and-stromal-target-for-antibody-drug-conjugates
#16
James W Purcell, Sonia G Tanlimco, Jonathan A Hickson, Melvin Fox, Mien Sho, Lisa Durkin, Tamar Uziel, Rick Powers, Kelly D Foster-Duke, Thomas McGonigal, Subashri Kumar, Josue Samayoa, Dong Zhang, Joann P Palma, Sasmita Mishra, Diane Hollenbaugh, Kurt Gish, Susan E Morgan-Lappe, Eric D Hsi, Debra T Chao
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764855/magnetic-resonance-imaging-of-tumor-associated-macrophages-clinical-translation
#17
Maryam Aghighi, Ashok Joseph Theruvath, Anuj Pareek, Laura Pisani, Raphael Alford, Anne Monika Muehe, Tarsheen K Sethi, Samantha J Holdsworth, Florette K Hazard, Dita Gratzinger, Sandra Luna-Fineman, Ranjana H Advani, Sheri L Spunt, Heike E Daldrup-Link
PURPOSE: Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. EXPERIMENTAL DESIGN: In a first-in-patient , IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764444/molecular-and-clinical-characterization-of-ptpn2-expression-from-rna-seq-data-of-996-brain-gliomas
#18
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29761921/trans-cinnamic-aldehyde-inhibit-aggregatibacter-actinomycetemcomitans-induced-inflammation-thp-1-derived-macrophages-via-autophagy-activation
#19
Jin Chung, Sumi Kim, Hyun Ah Lee, Mi Hee Park, Seyeon Kim, Yu Ri Song, HeeSam Na
OBJECTIVES: Inflammation is an essential response against bacterial infection as a host defense mechanism, which can lead to tissue damage. Aggregatibacter actinomycetemcomitans (Aa) is major pathogen for aggressive periodontitis characterized by rapid destruction of periodontal tissue surrounding teeth. Trans-cinnamic aldehyde is a key bioactive compound of the cinnamon extracts, which has anti-inflammatory, antioxidant, antipyretic, antimicrobial, and anti-cancer properties. The objective of the present study was to investigate the anti-inflammatory effect of trans-cinnamic aldehyde against Aa infection in human THP-1 derived macrophages and on Aa-induced periodontitis in mice...
May 15, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29761396/macrophage-bactericidal-assays
#20
Mourad Aribi
The search for the bactericidal activity of macrophage (Mϕ) is crucial not only during infection, but also to explore its functional activities in normal and pathological conditions, such as autoimmune and inflammatory disorders, allergic inflammation, and cancer. There are several methods exploring the phagocytic and bactericidal activities of Mϕ. This chapter focuses specifically on the technique called antibiotic protection assay and on the methods for the determination of Mϕ production of nitric oxide and hydrogen peroxide as antimicrobial agents and biomarkers of respiratory burst...
2018: Methods in Molecular Biology
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