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https://www.readbyqxmd.com/read/29323162/high-co-expression-of-il-34-and-m-csf-correlates-with-tumor-progression-and-poor-survival-in-lung-cancers
#1
Muhammad Baghdadi, Hiraku Endo, Atsushi Takano, Kozo Ishikawa, Yosuke Kameda, Haruka Wada, Yohei Miyagi, Tomoyuki Yokose, Hiroyuki Ito, Haruhiko Nakayama, Yataro Daigo, Nao Suzuki, Ken-Ichiro Seino
Despite recent advances in diagnosis and treatment of lung cancers, the 5-year survival rate remains unsatisfactory, which necessitates the identification of novel factors that associates with disease progression and malignant degree for improving diagnostic and therapeutic strategies. Recent progress in cancer immunology research has unveiled critical roles for colony stimulating factor 1 receptor (CSF1R) in multiple aspects of the tumor microenvironment. CSF1R is expressed on tumor-associated macrophages (TAMs), and mediates important pro-tumorigenic functions...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319809/increased-microglial-csf1r-expression-in-the-siv-macaque-model-of-hiv-cns-disease
#2
Audrey C Knight, Samuel A Brill, Suzanne E Queen, Patrick M Tarwater, Joseph L Mankowski
Chronic microglial activation and associated neuroinflammation are key factors in neurodegenerative diseases including HIV-associated neurocognitive disorders. Colony stimulating factor 1 receptor (CSF1R)-mediated signaling is constitutive in cells of the myeloid lineage, including microglia, promoting cell survival, proliferation, and differentiation. In amyotrophic lateral sclerosis and Alzheimers disease, CSF1R is upregulated. Inhibiting CSF1R signaling in animal models of these diseases improved disease outcomes...
January 8, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29304539/expression-and-cellular-localization-of-cxcr4-and-cxcl12-in-human-carotid-atherosclerotic-plaques
#3
Sophie Merckelbach, Emiel P C van der Vorst, Michael Kallmayer, Christoph Rischpler, Rainer Burgkart, Yvonne Döring, Gert-Jan de Borst, Markus Schwaiger, Hans-Henning Eckstein, Christian Weber, Jaroslav Pelisek
BACKGROUND AND AIMS:  The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques. METHODS:  Carotid plaques (n = 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29296813/oncogenic-role-and-therapeutic-targeting-of-abl-class-and-jak-stat-activating-kinase-alterations-in-ph-like-all
#4
Kathryn G Roberts, Yung-Li Yang, Debbie Payne-Turner, Wenwei Lin, Jacob K Files, Kirsten Dickerson, Zhaohui Gu, Jack Taunton, Laura J Janke, Taosheng Chen, Mignon L Loh, Stephen P Hunger, Charles G Mullighan
New therapies for Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) patients are urgently needed. The genetic landscape of Ph-like ALL is characterized by a diverse array of kinase-activating alterations (including rearrangements, sequence mutations, and copy number alterations), suggesting that patients with Ph-like ALL are candidates for targeted therapy, similar to BCR-ABL1 ALL. We sought to investigate the functional role and targetability of the spectrum of kinase-activating alterations identified in Ph-like ALL...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29228548/macrophage-depletion-through-colony-stimulating-factor-1-receptor-pathway-blockade-overcomes-adaptive-resistance-to-anti-vegf-therapy
#5
Yasmin A Lyons, Sunila Pradeep, Sherry Y Wu, Monika Haemmerle, Jean M Hansen, Michael J Wagner, Alejandro Villar-Prados, Archana S Nagaraja, Robert L Dood, Rebecca A Previs, Wei Hu, Yang Zhao, Duncan H Mak, Zhilan Xiao, Brenda D Melendez, Gregory A Lizee, Imelda Mercado-Uribe, Keith A Baggerly, Patrick Hwu, Jinsong Liu, Willem W Overwijk, Robert L Coleman, Anil K Sood
Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225599/promoter-specificity-and-efficacy-in-conditional-and-inducible-transgenic-targeting-of-lung-macrophages
#6
Alexandra L McCubbrey, Kristen C Allison, Alisa B Lee-Sherick, Claudia V Jakubzick, William J Janssen
Conditional and inducible Cre-loxP systems are used to target gene deletion to specific cell lineages and tissues through promoter-restricted expression of the bacterial DNA recombinase, Cre. Although Cre-loxP systems are widely used to target gene deletion in lung macrophages, limited data are published on the specificity and efficiency of "macrophage targeting" Cre lines. Using R26-stopfl/fl-TdTomato and tetOn-GFP reporter lines, we assessed the specificity and efficiency of four commercially available Cre driver lines that are often considered "macrophage specific...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29215000/the-evolution-of-the-macrophage-specific-enhancer-fms-intronic-regulatory-element-within-the-csf1r-locus-of-vertebrates
#7
David A Hume, Evi Wollscheid-Lengeling, Rocio Rojo, Clare Pridans
The Csf1r locus encodes the receptor for macrophage colony-stimulating factor, which controls the proliferation, differentiation and survival of macrophages. The 300 bp Fms intronic regulatory element (FIRE), within the second intron of Csf1r, is necessary and sufficient to direct macrophage-specific transcription. We have analysed the conservation and divergence of the FIRE DNA sequence in vertebrates. FIRE is present in the same location in the Csf1r locus in reptile, avian and mammalian genomes. Nearest neighbor analysis based upon this element alone largely recapitulates phylogenies inferred from much larger genomic sequence datasets...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196466/pmn-mdsc-infiltration-blocks-the-antitumor-effects-of-csf1r-inhibition
#8
(no author information available yet)
CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.
December 1, 2017: Cancer Discovery
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
#9
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/29136500/does-csf1r-blockade-turn-into-friendly-fire
#10
Tim F Greten
In this issue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation of tumor-associated macrophages, but also an accumulation of tumor-infiltrating polymorphonuclear mononuclear cells caused by Cxcl-1 released from cancer-associated fibroblasts.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29122458/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-alsp-integrating-the-literature-on-hereditary-diffuse-leukoencephalopathy-with-spheroids-hdls-and-pigmentary-orthochromatic-leukodystrophy-pold
#11
REVIEW
Scott J Adams, Andrew Kirk, Roland N Auer
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder. ALSP was previously recognized as two distinct entities, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). However, recent identification of mutations in the tyrosine kinase domain of the colony stimulating factor 1 receptor (CSF1R) gene, which regulates mononuclear cell lineages including microglia, have provided genetic and mechanistic evidence that POLD and HDLS should be regarded as a single clinicopathologic entity...
November 6, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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
#12
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/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#13
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
October 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29018080/chd7-deficiency-delays-leukemogenesis-in-mice-induced-by-cbfb-myh11
#14
Tao Zhen, Erika Kwon, Ling Zhao, Jingmei Hsu, R Katherine Hyde, Ying Lu, Lemlem Alemu, Nancy A Speck, P Paul Liu
Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia (AML M4Eo), which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-SMMHC (encoded by CBFB-MYH11) and RUNX1 plays a critical role in the pathogenesis of this leukemia. Recently, it was shown that chromodomain-helicase-DNA binding protein 7 (CHD7) interacts with RUNX1 and suppresses RUNX1-induced expansion of hematopoietic stem and progenitor cells...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28975680/yolk-sac-erythromyeloid-progenitors-expressing-gain-of-function-ptpn11-have-functional-features-of-jmml-but-are-not-sufficient-to-cause-disease-in-mice
#15
Stefan P Tarnawsky, Momoko Yoshimoto, Lisa Deng, Rebecca J Chan, Mervin C Yoder
BACKGROUND: Accumulating evidence suggests the origin of juvenile myelomonocytic leukemia (JMML) is closely associated with fetal development. Nevertheless, the contribution of embryonic progenitors to JMML pathogenesis remains unexplored. We hypothesized that expression of JMML-initiating PTPN11 mutations in HSC-independent yolk sac erythromyeloid progenitors (YS EMPs) would result in a mouse model of pediatric myeloproliferative neoplasm (MPN). RESULTS: E9.5 YS EMPs from VavCre+;PTPN11(D61Y) embryos demonstrated growth hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and hyperactive RAS-ERK signaling...
October 4, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28972016/philadelphia-chromosome-like-acute-lymphoblastic-leukemia
#16
REVIEW
Sarah K Tasian, Mignon L Loh, Stephen P Hunger
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1-like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph+) ALL and is suggestive of activated kinase signaling. Although Ph+ ALL is defined by BCR-ABL1 fusion, Ph-like ALL cases contain a variety of genomic alterations that activate kinase and cytokine receptor signaling. These alterations can be grouped into major subclasses that include ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and EPOR that activate JAK/STAT signaling...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/28934252/three-way-interaction-model-to-trace-the-mechanisms-involved-in-alzheimer-s-disease-transgenic-mice
#17
Nasibeh Khayer, Sayed-Amir Marashi, Mehdi Mirzaie, Fatemeh Goshadrou
Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput "omics" datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28932635/colony-stimulating-factor-1-induced-aif1-expression-in-tumor-associated-macrophages-enhances-the-progression-of-hepatocellular-carcinoma
#18
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/28921817/diagnostic-criteria-for-adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-due-to-csf1r-mutation
#19
Takuya Konno, Kunihiro Yoshida, Ikuko Mizuta, Toshiki Mizuno, Toshitaka Kawarai, Masayoshi Tada, Hiroaki Nozaki, Shu-Ichi Ikeda, Osamu Onodera, Zbigniew K Wszolek, Takeshi Ikeuchi
BACKGROUND: To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony stimulating factor 1 receptor (CSF1R) mutation. METHODS: We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide "probable" and "possible" designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions, and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies, and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations...
September 18, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#20
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...
August 22, 2017: Oncotarget
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