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https://www.readbyqxmd.com/read/29915328/presymptomatic-change-in-micrornas-modulates-tau-pathology
#1
Salil Sharma, Ines Khadimallah, Adam Williamson Corya, Yousuf Omar Ali, Xi Rao, Yunlong Liu, Hui-Chen Lu
MicroRNAs (miRs) are 18~23 nucleotides long non-coding RNAs that regulate gene expression. To explore whether miR alterations in tauopathy contribute to pathological conditions, we first determined which hippocampal miRs are altered at the presymptomatic and symptomatic stages of tauopathy using rTg4510 mice (Tau mice), a well-characterized tauopathy model. miR-RNA pairing analysis using QIAGEN Ingenuity Pathway Analysis (IPA) revealed 401 genes that can be regulated by 71 miRs altered in Tau hippocampi at the presymptomatic stage...
June 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29913557/effective-control-of-neuropathic-pain-by-transient-expression-of-hepatocyte-growth-factor-in-a-mouse-chronic-constriction-injury-model
#2
Boram Nho, Junghun Lee, Junsub Lee, Kyeong Ryang Ko, Sung Joong Lee, Sunyoung Kim
Hepatocyte growth factor (HGF) is a multifunctional protein that contains angiogenic and neurotrophic properties. In the current study, we investigated the analgesic effects of HGF by using a plasmid DNA that was designed to express 2 isoforms of human HGF-pCK-HGF-X7 (or VM202)-in a chronic constriction injury (CCI) -induced mouse neuropathic pain model. Intramuscular injection of pCK-HGF-X7 into proximal thigh muscle induced the expression of HGF in the muscle, sciatic nerve, and dorsal root ganglia (DRG)...
April 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29911608/increased-c-fiber-response-induced-by-experimental-disc-herniation-is-associated-with-upregulation-of-fractalkine-and-its-receptor-in-nucleus-pulposus-and-dorsal-root-ganglion
#3
D P Jacobsen, A Moen, F Haugen, J Gjerstad
Aims Lumbar radicular pain following intervertebral disc herniation may be caused by a local inflammatory response induced by nucleus pulposus (NP) cells. Here in an animal model mimicking the clinical situation following disc herniation we investigated the effect of NP on the spinal nociceptive signaling and local gene expression. Methods In anaesthetized Lewis rats, extracellular single unit recordings of spinal nociceptive activity and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3-L5)...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29875321/compensation-between-csf1r-macrophages-and-foxp3-treg-cells-drives-resistance-to-tumor-immunotherapy
#4
David Gyori, Ee Lyn Lim, Francis M Grant, Dominik Spensberger, Rahul Roychoudhuri, Stephen J Shuttleworth, Klaus Okkenhaug, Len R Stephens, Phillip T Hawkins
Redundancy and compensation provide robustness to biological systems but may contribute to therapy resistance. Both tumor-associated macrophages (TAMs) and Foxp3+ regulatory T (Treg) cells promote tumor progression by limiting antitumor immunity. Here we show that genetic ablation of CSF1 in colorectal cancer cells reduces the influx of immunosuppressive CSF1R+ TAMs within tumors. This reduction in CSF1-dependent TAMs resulted in increased CD8+ T cell attack on tumors, but its effect on tumor growth was limited by a compensatory increase in Foxp3+ Treg cells...
June 7, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769604/macrophage-cytokines-enhance-cell-proliferation-of-normal-prostate-epithelial-cells-through-activation-of-erk-and-akt
#5
Tu Dang, Geou-Yarh Liou
Macrophage infiltrations (inflammation) are associated with prostate disorders such as prostatitis, prostatic hyperplasia and prostate cancer. All prostate disorders have elevated cell proliferation, and are initiated from normal prostate epithelial cells. To date, the mechanism of how macrophages regulate normal prostate epithelial cell proliferation remains largely unknown. Using a 3D co-culture system, we here show that Raw 264.7 macrophages increased cell proliferation of normal prostate epithelial PZ-HPV-7 cells...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769439/csf1r-dependent-myeloid-cells-are-required-for-nk%C3%A2-mediated-control-of-metastasis
#6
Michal Beffinger, Paulino Tallón de Lara, Sònia Tugues, Marijne Vermeer, Yannick Montagnolo, Isabel Ohs, Virginia Cecconi, Giulia Lucchiari, Aron Gagliardi, Nikola Misljencevic, James Sutton, Roman Spörri, Burkhard Becher, Anurag Gupta, Maries van den Broek
Myeloid leukocytes are essentially involved in both tumor progression and control. We show that neo-adjuvant treatment of mice with an inhibitor of CSF1 receptor (CSF1R), a drug that is used to deplete tumor-associated macrophages, unexpectedly promoted metastasis. CSF1R blockade indirectly diminished the number of NK cells due to a paucity of myeloid cells that provide the survival factor IL-15 to NK cells. Reduction of the number of NK cells resulted in increased seeding of metastatic tumor cells to the lungs but did not impact on progression of established metastases...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29761385/growing-murine-bone-marrow-derived-macrophages
#7
Anaïs Assouvie, Lisa P Daley-Bauer, Germain Rousselet
Bone marrow-derived macrophages (BMDM) are primary macrophages obtained by in vitro differentiation of bone marrow cells in the presence of macrophage colony-stimulating factor (M-CSF or CSF1). They are easy to obtain in high yields, can be stored by freezing, and can be obtained from genetically modified mice strains. They are therefore widely used as prototypical macrophages for in vitro studies. In this chapter, we present the method for obtaining BMDMs and freezing them.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29704232/prognostic-and-microrna-profile-analysis-for-cd44-positive-expression-pediatric-posterior-fossa-ependymoma
#8
C Shu, Q Wang, X Yan, J Wang
BACKGROUND: Ependymoma is the third most common pediatric brain tumor and occurs most frequently in the posterior fossa. However, the lack of immortalized cell lines, xenografts, or animal models has significantly hindered the study of pediatric posterior fossa ependymoma (P-PF-EPN) pathogenesis. This prompted us to use clinical big data to study this rare disease. METHODS: Application of the robust rank aggregation method revealed CD44 as a reliable biomarker in P-PF-EPN...
April 27, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29689740/pilot-feasibility-study-to-detect-mesenchymal-stem-cell-biomarkers-of-bronchopulmonary-dysplasia-in-the-tracheal-aspirate-fluid-of-preterm-infants
#9
R G LaGrandeur, M Singhal, F Bany-Mohammed, C Uy, R Koeppel, F Zaldivar, F Haddad, A Nalbandian, P Donovan, D M Cooper, M Aslam
OBJECTIVE: This study aimed to detect novel mesenchymal stem cell peptides/biomarkers of bronchopulmonary dysplasia (BPD) in the tracheal aspirate fluid (TAF) of preterm infants. STUDY DESIGN: Participants included infants less than 32 weeks' gestational age or birth weight under 1500 grams who required endotracheal intubation and mechanical ventilation within first 24 hours of life. TAF sample collection was performed at the time of the first clinically indicated routine suctioning...
2018: Journal of Neonatal-perinatal Medicine
https://www.readbyqxmd.com/read/29668829/complete-response-to-csf1r-inhibitor-in-a-translocation-variant-of-teno-synovial-giant-cell-tumor-without-genomic-alteration-of-the-csf1-gene
#10
M Brahmi, L Alberti, F Tirode, M Karanian, L Eberst, D Pissaloux, P Cassier, J Y Blay
No abstract text is available yet for this article.
April 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29666241/muscularis-macrophage-development-in-the-absence-of-an-enteric-nervous-system
#11
Marina Avetisyan, Julia E Rood, Silvia Huerta Lopez, Rajarshi Sengupta, Elizabeth Wright-Jin, Joseph D Dougherty, Edward M Behrens, Robert O Heuckeroth
The nervous system of the bowel regulates the inflammatory phenotype of tissue resident muscularis macrophages (MM), and in adult mice, enteric neurons are the main local source of colony stimulating factor 1 (CSF1), a protein required for MM survival. Surprisingly, we find that during development MM colonize the bowel before enteric neurons. This calls into question the requirement for neuron-derived CSF1 for MM colonization of the bowel. To determine if intestinal innervation is required for MM development, we analyzed MM of neonatal Ret -/- ( Ret KO) mice that have no enteric nervous system in small bowel or colon...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29643229/t-cell-induced-csf1-promotes-melanoma-resistance-to-pd1-blockade
#12
Natalie J Neubert, Martina Schmittnaegel, Natacha Bordry, Sina Nassiri, Noémie Wald, Christophe Martignier, Laure Tillé, Krisztian Homicsko, William Damsky, Hélène Maby-El Hajjami, Irina Klaman, Esther Danenberg, Kalliopi Ioannidou, Lana Kandalaft, George Coukos, Sabine Hoves, Carola H Ries, Silvia A Fuertes Marraco, Periklis G Foukas, Michele De Palma, Daniel E Speiser
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8+ T cells...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29593242/the-role-of-csf1r-dependent-macrophages-in-control-of-the-intestinal-stem-cell-niche
#13
Anuj Sehgal, David S Donaldson, Clare Pridans, Kristin A Sauter, David A Hume, Neil A Mabbott
Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in the maintenance of the intestinal stem cell niche and differentiation of Paneth cells, but evidence of expression of CSF1R within the crypt is equivocal. Here we show that CSF1R-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted to macrophages which are intimately associated with the crypt epithelium, and is undetectable in Paneth cells...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29571946/nilotinib-in-locally-advanced-pigmented-villonodular-synovitis-a-multicentre-open-label-single-arm-phase-2-trial
#14
Hans Gelderblom, Claire Cropet, Christine Chevreau, Richard Boyle, Martin Tattersall, Silvia Stacchiotti, Antoine Italiano, Sophie Piperno-Neumann, Axel Le Cesne, Virginia Ferraresi, Nicolas Penel, Florence Duffaud, Philippe Cassier, Maud Toulmonde, Paolo Casali, Sophie Taieb, Séverine Guillemaut, Séverine Metzger, David Pérol, Jean-Yves Blay
BACKGROUND: Pigmented villonodular synovitis (alternatively known as diffuse-type giant cell tumour) is a rare, locally aggressive tumour driven by a specific translocation resulting in the overexpression of colony-stimulating factor 1 (CSF1). CSF1 receptor (CSF1R) inhibitors (ie, tyrosine kinase inhibitors and antibodies) induce a response in patients with pigmented villonodular synovitis. We investigated the safety and efficacy of a CSF1R tyrosine kinase inhibitor, nilotinib, in patients with locally advanced non-resectable pigmented villonodular synovitis...
May 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29501441/change-in-populations-of-macrophages-promotes-development-of-delayed-gastric-emptying-in-mice
#15
Gianluca Cipriani, Simon J Gibbons, Katie E Miller, Daniel S Yang, Matthew L Terhaar, Seth T Eisenman, Tamas Ördög, David R Linden, Gabriela B Gajdos, Joseph H Szurszewski, Gianrico Farrugia
BACKGROUND & AIMS: Muscularis propria macrophages lie close to cells that regulate gastrointestinal motor function, including interstitial cells of Cajal (ICC) and myenteric neurons. In animal models of diabetic gastroparesis, development of delayed gastric emptying has been associated with loss of macrophages that express cytoprotective markers and reduced networks of ICC. Mice with long-term diabetes and normal gastric emptying have macrophages that express anti-inflammatory markers and have normal gastric ICC...
March 6, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29499713/efficient-targeted-tumor-imaging-and-secreted-endostatin-gene-delivery-by-anti-cd105-immunoliposomes
#16
Huiqin Zhuo, Baoshi Zheng, Jianming Liu, Yong Huang, Huiling Wang, Duo Zheng, Naiquan Mao, Jinyu Meng, Sufang Zhou, Liping Zhong, Yongxiang Zhao
BACKGROUND: Anti-CD105 mAb-conjugated immunoliposomes, loaded with secreted mouse endostatin gene, were developed for targeted tumor imaging and antiangiogenic gene therapy. METHODS: The liposomes were investigated for size, zeta-potential, lipid content, antibody binding ability, and pcDNA loading capacity. The ability of immunoliposomes to target tumor-derived endothelial cells and perform gene transfer in vitro was measured and their basic biocompatibility was evaluated...
March 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29496785/csf1r-inhibition-prevents-radiation-pulmonary-fibrosis-by-depletion-of-interstitial-macrophages
#17
Lydia Meziani, Michele Mondini, Benoît Petit, Alexandre Boissonnas, Vincent Thomas de Montpreville, Olaf Mercier, Marie-Catherine Vozenin, Eric Deutsch
Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate...
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29440290/a-spatio-temporal-model-of-macrophage-mediated-drug-resistance-in-glioma-immunotherapy
#18
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...
April 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
#19
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 F4/80hi MHCIIhi macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hi MHCIIlow 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, F4/80hi MHCIIlow 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
#20
Guangfu Li, Dai Liu, Eric T Kimchi, Jussuf T Kaifi, Xiaoqiang Qi, Yariswamy Manjunath, Xinjian Liu, Tye Deering, Diego M Avella, Todd Fox, Don C Rockey, Todd D Schell, Mark Kester, 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...
March 2018: Gastroenterology
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