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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28886690/transcriptome-profiling-of-antiviral-immune-and-dietary-fatty-acid-dependent-responses-of-atlantic-salmon-macrophage-like-cells
#13
Khalil Eslamloo, Xi Xue, Jennifer R Hall, Nicole C Smith, Albert Caballero-Solares, Christopher C Parrish, Richard G Taylor, Matthew L Rise
BACKGROUND: Due to the limited availability and high cost of fish oil in the face of increasing aquaculture production, there is a need to reduce usage of fish oil in aquafeeds without compromising farm fish health. Therefore, the present study was conducted to determine if different levels of vegetable and fish oils can alter antiviral responses of salmon macrophage-like cells (MLCs). Atlantic salmon (Salmo salar) were fed diets containing 7.4% (FO7) or 5.1% (FO5) fish oil. These diets were designed to be relatively low in EPA + DHA (i...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28886491/interleukin-34-from-pathogenesis-to-clinical-applications
#14
REVIEW
Muhammad Baghdadi, Hiraku Endo, Yoshino Tanaka, Haruka Wada, Ken-Ichiro Seino
Interleukin-34 (IL-34) is a hematopoietic cytokine that was described for the first time in 2008 as a second ligand of CSF1R in addition to M-CSF. IL-34 and M-CSF share no sequence homology, but have similar functions, affecting the biology of myeloid cell lineage. In contrast to M-CSF, IL-34 shows unique signaling and expression patterns. Physiologically, IL-34 expression is restricted to epidermis and CNS, acting as a regulator of Langerhans cells and microglia, respectively. However, IL-34 expression can be induced and regulated by NF-κB under pathological conditions...
September 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28855495/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-a-case-presented-brain-calcification-and-corpus-callosum-atrophy-from-over-10-years-before-the-onset-of-dementia
#15
Miyuki Okamoto, Jun Takeshita, Kazunori Takahashi, Akio Tanaka, Kunihiro Yoshida, Masaru Kuriyama
A 44-year-old man made many mistakes at work over a year. Eleven years prior, he had had medical examination with headache. He presented with symptoms consistent with frontal lobe dysfunction including cognitive decline, and bilateral pyramidal signs. Brain MRI showed cerebral atrophy, localized atrophy of corpus callosum, asymmetrical white matter lesions and multiple cystic lesions. CT images showed bilateral calcifications in the parietal subcortical white matter. Reconstructed sagittal CT images showed bilateral calcifications in the frontal white matter adjacent to the anterior horns of the lateral ventricles, which had a symmetrical "stepping stone appearance" in the frontal pericallosal regions...
September 30, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28827005/cognitive-dysfunction-and-symptoms-of-movement-disorders-in-adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia
#16
Takeshi Ikeuchi, Naomi Mezaki, Takeshi Miura
Adult-onset leukoencephalopathies are clinically and genetically heterogeneous disorders that affect predominantly the cerebral white matter of the central nervous system. Clinical and neuroimaging-based approaches have been developed to improve diagnostic processes for adult-onset leukoencephalopathies. However, the differential diagnosis is often challenging. Recently, knowledge of the genetic basis of leukoencephalopathies has been accumulated rapidly, which provides powerful diagnostic approaches. The article provides an overview of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), focusing on the clinical presentations of cognitive impairment and symptoms of movement disorders...
August 16, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28807982/c-ebp%C3%AE-is-required-for-survival-of-ly6c-monocytes
#17
Akihiro Tamura, Hideyo Hirai, Asumi Yokota, Naoka Kamio, Atsushi Sato, Tsukimi Shoji, Takahiro Kashiwagi, Yusuke Torikoshi, Yasuo Miura, Daniel G Tenen, Taira Maekawa
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis. Further subdivision of monocytes revealed that Cebpb messenger RNA was highly upregulated in Ly6C(-) monocytes in bone marrow. Accordingly, the number of Ly6C(-) monocytes was significantly reduced in Cebpb(-/-) mice. Bone marrow chimera experiments and Mx1-Cre-mediated deletion of Cebpb revealed a cell-intrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/28760770/transcriptional-mechanisms-that-control-expression-of-the-macrophage-colony-stimulating-factor-receptor-locus
#18
REVIEW
Rocio Rojo, Clare Pridans, David Langlais, David A Hume
The proliferation, differentiation, and survival of cells of the macrophage lineage depends upon signals from the macrophage colony-stimulating factor (CSF) receptor (CSF1R). CSF1R is expressed by embryonic macrophages and induced early in adult hematopoiesis, upon commitment of multipotent progenitors to the myeloid lineage. Transcriptional activation of CSF1R requires interaction between members of the E26 transformation-specific family of transcription factors (Ets) (notably PU.1), C/EBP, RUNX, AP-1/ATF, interferon regulatory factor (IRF), STAT, KLF, REL, FUS/TLS (fused in sarcoma/ranslocated in liposarcoma) families, and conserved regulatory elements within the mouse and human CSF1R locus...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28751473/identification-of-the-macrophage-specific-promoter-signature-in-fantom5-mouse-embryo-developmental-time-course-data
#19
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/28745620/identification-of-erythromyeloid-progenitors-and-their-progeny-in-the-mouse-embryo-by-flow-cytometry
#20
Lorea Iturri, Javier Saenz Coronilla, Yvan Lallemand, Elisa Gomez Perdiguero
Macrophages are professional phagocytes from the innate arm of the immune system. In steady-state, sessile macrophages are found in adult tissues where they act as front line sentinels of infection and tissue damage. While other immune cells are continuously renewed from hematopoietic stem and progenitor cells (HSPC) located in the bone marrow, a lineage of macrophages, known as resident macrophages, have been shown to be self-maintained in tissues without input from bone marrow HSPCs. This lineage is exemplified by microglia in the brain, Kupffer cells in the liver and Langerhans cells in the epidermis among others...
July 17, 2017: Journal of Visualized Experiments: JoVE
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