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https://www.readbyqxmd.com/read/29212030/loss-of-caveolin-1-in-metastasis-associated-macrophages-drives-lung-metastatic-growth-through-increased-angiogenesis
#1
Ward Celus, Giusy Di Conza, Ana Isabel Oliveira, Manuel Ehling, Bruno M Costa, Mathias Wenes, Massimiliano Mazzone
Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-suppressive functions. However, the role of Cav1 in bone-marrow-derived cells is unknown. Here, we describe Cav1 as an anti-metastatic regulator in mouse models of lung and breast cancer pulmonary metastasis...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29152381/selective-deletion-of-the-soluble-colony-stimulating-factor-1-isoform-in-vivo-prevents-estrogen-deficiency-bone-loss-in-mice
#2
Gang-Qing Yao, Nancy Troiano, Christine A Simpson, Karl L Insogna
Neutralizing CSF1 in vivo completely prevents ovariectomy (OVX)-induced bone loss in mice. There are two isoforms of CSF1, soluble (sCSF1), and membrane-bound (mCSF1), but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout (K/O) and wild type (Wt) female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected (sCSF1 K/O)...
2017: Bone Research
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#3
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136508/cancer-associated-fibroblasts-neutralize-the-anti-tumor-effect-of-csf1-receptor-blockade-by-inducing-pmn-mdsc-infiltration-of-tumors
#4
Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W Speicher, Ashani T Weeraratna, Timothy Chao, Robert H Vonderheide, Lucia R Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A Sepulveda, Linda A Snyder, Dmitry I Gabrilovich
Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29080683/interaction-between-astrocytic-colony-stimulating-factor-and-its-receptor-on-microglia-mediates-central-sensitization-and-behavioral-hypersensitivity-in-chronic-post-ischemic-pain-model
#5
Yuying Tang, Lian Liu, Dan Xu, Wensheng Zhang, Yi Zhang, Jieshu Zhou, Wei Huang
Accumulation of microglia occurs in the dorsal horn in the rodent model of chronic post ischemic pain (CPIP), while the mechanism how microglia affects the development of persistent pain largely remains unknown. Here, using a rodent model of CPIP induced by ischemia-reperfusion (IR) injury in the hindpaw, we observed that microglial accumulation occurred in the ipsilateral dorsal horn after ischemia 3h, and in ipsilateral and contralateral dorsal horn in the rats with ischemia 6h. The accumulated microglia released BDNF, increased neuronal excitability in dorsal horn, and produced pain behaviors in the modeled rodents...
October 30, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29038312/dynamic-stroma-reorganization-drives-blood-vessel-dysmorphia-during-glioma-growth
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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