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https://www.readbyqxmd.com/read/29038312/dynamic-stroma-reorganization-drives-blood-vessel-dysmorphia-during-glioma-growth
#1
Thomas Mathivet, Claire Bouleti, Matthias Van Woensel, Fabio Stanchi, Tina Verschuere, Li-Kun Phng, Joost Dejaegher, Marly Balcer, Ken Matsumoto, Petya B Georgieva, Jochen Belmans, Raf Sciot, Christian Stockmann, Massimiliano Mazzone, Steven De Vleeschouwer, Holger Gerhardt
Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages...
October 16, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29026368/serum-protein-pattern-associated-with-organ-damage-and-lupus-nephritis-in-systemic-lupus-erythematosus-revealed-by-pea-immunoassay
#2
Anna Petrackova, Andrea Smrzova, Petr Gajdos, Marketa Schubertova, Petra Schneiderova, Pavel Kromer, Vaclav Snasel, Martina Skacelova, Frantisek Mrazek, Josef Zadrazil, Pavel Horak, Eva Kriegova
BACKGROUND: Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index. METHODS: We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23)...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28932635/colony-stimulating-factor-1-induced-aif1-expression-in-tumor-associated-macrophages-enhances-the-progression-of-hepatocellular-carcinoma
#3
Hao Cai, Xiao-Dong Zhu, Jian-Yang Ao, Bo-Gen Ye, Yuan-Yuan Zhang, Zong-Tao Chai, Cheng-Hao Wang, Wen-Kai Shi, Man-Qing Cao, Xiao-Long Li, Hui-Chuan Sun
M2-polarized (alternatively activated) macrophages play an important role in the progression of hepatocellular carcinoma (HCC). Allograft inflammatory factor 1 (AIF1) is overexpressed in M2-polarized macrophages. This study explored the role of AIF1 in tumor-associated macrophages in HCC. Macrophages were stimulated with colony-stimulating factor 1 (CSF1) to characterize the regulatory pathway of AIF1 in macrophages. The chromatin immunoprecipitation and luciferase reporter gene assay were conducted to examine transcription factors associated with AIF1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28859278/the-transcriptome-of-the-endometrium-and-placenta-is-associated-with-pregnancy-development-but-not-lactation-status-in-dairy-cows
#4
Stephen G Moore, Matthew S McCabe, Jacob C Green, Emily M Newsom, Matthew C Lucy
Infertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and nonlactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercaruncular) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28827496/cerebrospinal-fluid-cathelicidin-correlates-with-the-bacterial-load-and-outcomes-in-childhood-bacterial-meningitis
#5
Okko Savonius, Otto Helve, Irmeli Roine, Sture Andersson, Annika Saukkoriipi, Antonio González Mata, Heikki Peltola, Tuula Pelkonen
BACKGROUND: Large cerebrospinal fluid (CSF) bacterial load in bacterial meningitis (BM) relates to poor outcome. However, the antimicrobial peptide cathelicidin seems important to host defense. We studied how cathelicidin concentrations and bacterial load in CSF relate in childhood BM and to what extent they may predict the disease outcome. METHODS: The patient data originated from a large prospective clinical trial in Latin America in 1996-2003 in which the CSF samples were collected on admission (CSF1) and 12-24 hours later (CSF2)...
August 17, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28751473/identification-of-the-macrophage-specific-promoter-signature-in-fantom5-mouse-embryo-developmental-time-course-data
#6
Kim M Summers, David A Hume
The FANTOM5 consortium used cap analysis of gene expression (CAGE) to analyze the time course of gene expression over development from 11 days postcoitum (dpc) to adult in 16 developing organs and the whole body of the mouse. Every tissue in the body contains a large number of resident macrophages that initially infiltrate the embryo from the yolk sac. These cells contribute to organogenesis, and their functions diversify during development as they acquire tissue-specific adaptations. In each of the FANTOM5 time courses, the expression of known macrophage-specific genes, including CSF1 receptor (Csf1r), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (Emr1), and mer receptor tyrosine kinase (Mertk), was readily detectable and increased with time...
October 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28726189/changing-the-properties-of-multipotent-mesenchymal-stromal-cells-by-ifn%C3%AE-administration
#7
N A Petinati, N M Kapranov, A E Bigil'deev, M D Popova, Yu O Davydova, I V Gal'tseva, N I Drize, L A Kuz'mina, E N Parovichnikova, V G Savchenko
We studied changes in the population of human multipotent mesenchymal stromal cells activated by IFNγ. The cells were cultured under standard conditions; IFNγ was added in various concentrations for 4 h or over 2 passages. It was shown that the total cell production significantly decreased after long-term culturing with IFNγ, but 4-h exposure did not affect this parameter. After 4-h culturing, the expression levels of IDO1, CSF1, and IL-6 increased by 300, 7, and 2.4 times, respectively, and this increase persisted 1 and 2 days after removal of IFNγ from the culture medium...
June 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28725426/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#8
REVIEW
Michael A Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H Ries, Dominik Rüttinger
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#9
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
September 2017: Pain
https://www.readbyqxmd.com/read/28716061/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#10
REVIEW
Michael A Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H Ries, Dominik Rüttinger
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28697890/stress-induced-neuronal-colony-stimulating-factor-1-provokes-microglia-mediated-neuronal-remodeling-and-depressive-like-behavior
#11
Eric S Wohleb, Rosemarie Terwilliger, Catharine H Duman, Ronald S Duman
BACKGROUND: Chronic stress exposure causes neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to development of anxiety- and depressive-like behaviors. Concomitantly, microglia in the PFC undergo morphological and functional changes following stress exposure, suggesting that microglia contribute to synaptic deficits underlying behavioral consequences. METHODS: Male and female mice were exposed to chronic unpredictable stress (CUS) to examine the role of neuron-microglia interactions in the medial PFC during development of anxiety- and depressive-like behaviors...
June 12, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28690198/punicalagin-a-ptp1b-inhibitor-induces-m2c-phenotype-polarization-via-up-regulation-of-ho-1-in-murine-macrophages
#12
Xiaolong Xu, Yuhong Guo, Jingxia Zhao, Shasha He, Yan Wang, Yan Lin, Ning Wang, Qingquan Liu
Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC50 value of 1.04μM. Results from NPOI further showed that the Kon and Koff of PUN-PTP1B complex were 3.38e2M(-1)s(-1) and 4.13e-3s(-1), respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation...
July 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28664150/coexpression-and-expression-quantitative-trait-loci-analyses-of-the-angiogenesis-gene-gene-interaction-network-in-prostate-cancer
#13
Hui-Yi Lin, Chia-Ho Cheng, Dung-Tsa Chen, Y Ann Chen, Jong Y Park
BACKGROUND: Prostate cancer (PCa) shows a substantial clinical heterogeneity. The existing risk classification for PCa prognosis based on clinical factors is not sufficient. Although some biomarkers for PCa aggressiveness have been identified, their underlying functional mechanisms are still unclear. We previously reported a gene-gene interaction network associated with PCa aggressiveness based on single nucleotide polymorphism (SNP)-SNP interactions in the angiogenesis pathway. The goal of this study is to investigate potential functional evidence of the involvement of the genes in this gene-gene interaction network...
October 2016: Translational Cancer Research
https://www.readbyqxmd.com/read/28655795/first-in-human-study-of-amg-820-a-monoclonal-anti-colony-stimulating-factor-1-receptor-antibody-in-patients-with-advanced-solid-tumors
#14
Kyriakos P Papadopoulos, Larry Gluck, Lainie P Martin, Anthony J Olszanski, Anthony W Tolcher, Gataree Ngarmchamnanrith, Erik Rasmussen, Benny M Amore, Dirk Nagorsen, John S Hill, Joe Stephenson
Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#15
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28478671/autonomous-cell-migration-to-csf1-sources-via-a-synthetic-protein-based-system
#16
Anam Qudrat, Kevin Truong
Inflammatory lesions, often seen in diseases such as rheumatoid arthritis, atherosclerosis and cancer, feature an acidic (i.e., low pH) microenvironment rampant with cytokines, such as CSF1. For potential therapeutic intervention targeted at these CSF1 sources, we have assembled a system of four proteins inside a cell (i.e., HEK293) that initially had no natural CSF1-seeking ability. This system included a newly engineered CSF1 chimera receptor (named CSF1Rchi), the previously engineered Ca(2+) activated RhoA (i...
May 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28377874/global-mrna-sequencing-of-human-skeletal-muscle-search-for-novel-exercise-regulated-myokines
#17
S Pourteymour, K Eckardt, T Holen, T Langleite, Sindre Lee, J Jensen, K I Birkeland, C A Drevon, M Hjorth
OBJECTIVE: Skeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise. METHODS: Twenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28336462/the-molecular-mechanisms-of-androgen-receptor-in-nephrolithiasis
#18
Ziyu Fang, Yonghan Peng, Ling Li, Min Liu, Zeyu Wang, Shaoxiong Ming, Wenhui Zhang, Xiaofeng Gao
OBJECTIVES: This study aimed to investigate the molecular mechanisms of androgen receptor (AR) in nephrolithiasis. METHODS: Human kidney 2(HK-2) cells were transfected with Lentiviruses expressing AR (DEC-AR), shRNA targeting AR (sh-AR) or the empty vector control using the pLEX lentiviral vector system. The expression levels of AR were measured by qRT-PCR at 72h postinfection, and cells under different treatments were collected for microarray analysis. Differentially expressed genes (DEGs) were identified using Student's t-test...
June 15, 2017: Gene
https://www.readbyqxmd.com/read/28272478/erythro-myeloid-progenitors-can-differentiate-from-endothelial-cells-and-modulate-embryonic-vascular-remodeling
#19
Bahar Kasaai, Vincenza Caolo, Hanna M Peacock, Stephanie Lehoux, Elisa Gomez-Perdiguero, Aernout Luttun, Elizabeth A V Jones
Erythro-myeloid progenitors (EMPs) were recently described to arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages. Questions remain, however, concerning whether EMPs differentiate directly from the endothelium or merely pass through. We provide the first evidence in vivo that EMPs can emerge directly from endothelial cells (ECs) and demonstrate a role for these cells in vascular development. We find that EMPs express most EC markers but late EMPs and EMP-derived cells do not take up acetylated low-density lipoprotein (AcLDL), as ECs do...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263993/analysis-of-the-human-monocyte-derived-macrophage-transcriptome-and-response-to-lipopolysaccharide-provides-new-insights-into-genetic-aetiology-of-inflammatory-bowel-disease
#20
J Kenneth Baillie, Erik Arner, Carsten Daub, Michiel De Hoon, Masayoshi Itoh, Hideya Kawaji, Timo Lassmann, Piero Carninci, Alistair R R Forrest, Yoshihide Hayashizaki, Geoffrey J Faulkner, Christine A Wells, Michael Rehli, Paul Pavli, Kim M Summers, David A Hume
The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria...
March 2017: PLoS Genetics
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