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https://www.readbyqxmd.com/read/29440290/a-spatio-temporal-model-of-macrophage-mediated-drug-resistance-in-glioma-immunotherapy
#1
Yongjiang Zheng, Jiguang Bao, Qiyi Zhao, Tianshou Zhou, Xiaoqiang Sun
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29422500/the-tumour-microenvironment-creates-a-niche-for-the-self-renewal-of-tumour-promoting-macrophages-in-colon-adenoma
#2
Irene Soncin, Jianpeng Sheng, Qi Chen, Shihui Foo, Kaibo Duan, Josephine Lum, Michael Poidinger, Francesca Zolezzi, Klaus Karjalainen, Christiane Ruedl
Circulating CCR2+ monocytes are crucial for maintaining the adult tissue-resident F4/80hiMHCIIhi macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hiMHCIIlow macrophages, which are the most abundant F4/80hi cells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80hi cells. In colon adenomas of ApcMin/+ mice, F4/80hiMHCIIlow macrophages are not only preserved, but become the dominant subpopulation among tumour-resident macrophages during tumour progression...
February 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29408569/nanoliposome-c6-ceramide-increases-the-anti-tumor-immune-response-and-slows-growth-of-liver-tumors-in-mice
#3
Guangfu Li, Dai Liu, Eric T Kimchi, Jussuf T Kaifi, Xiaoqiang Qi, Yariswamy Manjunath, Xinjian Liu, Tye Deering, Todd Fox, Don C Rockey, Todd D Schell, Mark Kester, Diego M Avella, Kevin F Staveley-O'Carroll
BACKGROUND & AIMS: Ceramide, a sphingolipid metabolite, affects T-cell signaling, induces apoptosis of cancer cells, and slows tumor growth in mice. However, it has not been used as a chemotherapeutic agent because of its cell impermeability and precipitation in aqueous solution. We developed a nanoliposome-loaded C6-ceremide (LipC6) to overcome this limitation and investigated its effects in mice with liver tumors. METHODS: Immune competent C57BL/6 mice received intraperitoneal injections of carbon tetrachloride and intra-splenic injections of oncogenic hepatocytes...
January 30, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29363541/vitamin-a-coupled-liposomes-containing-sirna-against-hsp47-ameliorate-skin-fibrosis-in-chronic-graft-versus-host-disease
#4
Tomohiro Yamakawa, Hiroyuki Ohigashi, Daigo Hashimoto, Eiko Hayase, Shuichiro Takahashi, Miyono Miyazaki, Kenjiro Minomi, Masahiro Onozawa, Yoshiro Niitsu, Takanori Teshima
Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiple-organ fibrosis, profoundly affects quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amount of collagen deposit and accumulation of F4/80+ macrophages as well as myofibroblasts expressing HSP47 and retinol binding protein 1 in the skin after allogeneic SCT...
January 23, 2018: Blood
https://www.readbyqxmd.com/read/29351395/macrophage-colony-stimulating-factor-increases-hepatic-macrophage-content-liver-growth-and-lipid-accumulation-in-neonatal-rats
#5
Clare Pridans, Kristin A Sauter, Katharine M Irvine, Gemma M Davis, Lucas Lefevre, Anna Raper, Rocio Rojo, Ajit J Nirmal, Philippa Beard, Michael Cheeseman, David A Hume
Signaling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages. Mutations in CSF1, or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of CSF1-Fc as a therapy for low birth weight (LBW) at term, using a model based upon maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth, and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated the lipid droplet accumulation seen in the dexamethasone LBW model...
December 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29350446/differential-gene-expression-in-trigeminal-ganglia-of-male-and-female-rats-following-chronic-constriction-of-the-infraorbital-nerve
#6
O A Korczeniewska, S Husain, J Khan, E Eliav, P Soteropoulos, R Benoliel
BACKGROUND: The mechanisms underlying sex-based differences in pain and analgesia are poorly understood. In this study, we investigated gene expression changes in trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve chronic constriction injury (IoN-CCI). METHODS: Somatosensory assessments were performed prior to IoN-CCI and at selected time points postsurgery. Selected gene expression changes were examined with real-time quantitative polymerase chain reaction (RT-PCR) in ipsilateral TG at 21 days postsurgery...
January 19, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29338314/inflammatory-cytokines-in-the-papillary-tips-and-urine-of-nephrolithiasis-patients
#7
Andrew Yang Sun, Bryan Hinck, Benjamin R Cohen, Karen Keslar, Robert L Fairchild, Manoj Monga
INTRODUCTION: Intrarenal inflammation has been implicated in the pathogenesis of nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8, and CCL-2 in stone patients. However, no studies have assessed for inflammation in the renal papillae. We sought to characterize novel papillary tip and urinary biomarkers in stone patients. METHODS: 92 patients with nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary tip biopsies, kidney urine, and bladder urine were collected, as well as voided urine from 8 healthy volunteers...
January 16, 2018: Journal of Endourology
https://www.readbyqxmd.com/read/29319809/increased-microglial-csf1r-expression-in-the-siv-macaque-model-of-hiv-cns-disease
#8
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/29314558/neutrophil-derived-csf1-induces-macrophage-polarization-and-promotes-transplantation-tolerance
#9
Mounia S Braza, Patricia Conde, Mercedes Garcia, Isabel Cortegano, Manisha Brahmachary, Venu Pothula, Francois Fay, Peter Boros, Sherry A Werner, Florent Ginhoux, Willem J M Mulder, Jordi Ochando
The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance...
January 4, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29311623/basal-p53-expression-is-indispensable-for-mesenchymal-stem-cell-integrity
#10
Siddaraju V Boregowda, Veena Krishnappa, Jacqueline Strivelli, Christopher L Haga, Cori N Booker, Donald G Phinney
Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels...
January 8, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29306096/embryotoxic-cytokines-potential-roles-in-embryo-loss-and-fetal-programming
#11
REVIEW
Sarah A Robertson, Peck-Yin Chin, Joseph G Femia, Hannah M Brown
Cytokines in the reproductive tract environment at conception mediate a dialogue between the embryo and maternal tissues to profoundly influence embryo development and implantation success. Through effects on gene expression and the cell stress response, cytokines elicit an epigenetic impact with consequences for placental development and fetal growth, which in turn affect metabolic phenotype and long-term health of offspring. There is substantial evidence demonstrating that pro-survival cytokines, such as GM-CSF, CSF1, LIF, HB-EGF and IGFII, support embryos to develop optimally...
December 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29304539/expression-and-cellular-localization-of-cxcr4-and-cxcl12-in-human-carotid-atherosclerotic-plaques
#12
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/29212030/loss-of-caveolin-1-in-metastasis-associated-macrophages-drives-lung-metastatic-growth-through-increased-angiogenesis
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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