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https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#1
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28086793/methicillin-resistance-and-virulence-genes-in-invasive-and-nasal-staphylococcus-epidermidis-isolates-from-neonates
#2
Vivian Carolina Salgueiro, Natalia Lopes Pontes Iorio, Marcelle Cristina Ferreira, Raiane Cardoso Chamon, Kátia Regina Netto Dos Santos
BACKGROUND: Staphylococcus epidermidis is an opportunistic pathogen involved in hospital-acquired infections, particularly in those related to medical devices. This study characterized 50 genetically unrelated S. epidermidis isolates from bloodstream infections (BSIs, n = 31) and nares (n = 19) of neonates in relation to staphylococcal chromosomal cassette mec (SCCmec) type, biofilm production and associated genes, and the arginine catabolic mobile elements (ACME), in order to detect virulence factors that could discriminate a potential invasiveness isolate or predict an increasing pathogenicity...
January 13, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28076416/the-ccr2-inhibitor-propagermanium-attenuates-diet-induced-insulin-resistance-adipose-tissue-inflammation-and-non-alcoholic-steatohepatitis
#3
Petra Mulder, Anita M van den Hoek, Robert Kleemann
BACKGROUND AND AIM: Obese patients with chronic inflammation in white adipose tissue (WAT) have an increased risk of developing non-alcoholic steatohepatitis (NASH). The C-C chemokine receptor-2 (CCR2) has a crucial role in the recruitment of immune cells to WAT and liver, thereby promoting the inflammatory component of the disease. Herein, we examined whether intervention with propagermanium, an inhibitor of CCR2, would attenuate tissue inflammation and NASH development. METHODS: Male C57BL/6J mice received a high-fat diet (HFD) for 0, 6, 12 and 24 weeks to characterize the development of early disease symptoms of NASH, i...
2017: PloS One
https://www.readbyqxmd.com/read/28073847/identification-of-ccr2-and-cd180-as-robust-pharmacodynamic-tumor-and-blood-biomarkers-for-clinical-use-with-brd4-bet-inhibitors
#4
Tammie C Yeh, Greg O'Connor, Philip Petteruti, Austin Dulak, Maureen Hattersley, J Carl Barrett, Huawei Chen
PURPOSE: AZD5153 is a novel BRD4/BET inhibitor with a distinctive bivalent bromodomain binding mode. To support its clinical development, we identified pharmacodynamic (PD) biomarkers for use in clinical trials to establish target engagement. EXPERIMENTAL DESIGN: CCR2 and CD180 mRNAs, initially identified from whole transcriptome profiling, were further evaluated by quantitative PCR in hematologic cell lines, xenografts, and whole blood from rat, healthy volunteers, and patients with cancer...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28069536/m2-macrophages-infusion-ameliorates-obesity-and-insulin-resistance-by-remodeling-inflammatory-macrophages-homeostasis-in-obese-mice
#5
Qi Zhang, Haojie Hao, Zongyan Xie, Yu Cheng, Yaqi Yin, Min Xie, Hong Huang, Jieqing Gao, Hongyu Liu, Chuan Tong, Li Zang, Yiming Mu, Weidong Han
OBJECTIVE: The role of M2 macrophages infusion in dealing with obesity is still little known. In this study, the therapeutic effects of M2 macrophages infusion were investigated. METHODS: High fat diet (HFD) was used to induce obesity in C57BL/6N mice. 5 × 10(5) M2 macrophages, derived from the bone marrow, were injected into obese mice through the tail vein twice with an interval of one week. RESULTS: One week after the second injection, weight of inguinal adipose pad was significantly decreased...
January 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28059456/comprehensive-computational-analysis-of-gwas-loci-identifies-ccr2-as-a-candidate-gene-for-celiac-disease-pathogenesis
#6
Babajan Banaganapalli, Omran Rashidi, Omar Saadah, Jun Wang, Imran Ali Khan Muhammed, Jumana Y Al-Aama, Noor Ahmad Shaik, Ramu Elango
Celiac disease (CD) is a gluten intolerance disorder with known genetic contribution. The recent fine mapping andgenome-wide association studies (GWAS) have identified up to 57 non-HLA CD susceptibility SNPs, majority of which are non-coding variants lacking any functional annotation. Therefore, we adopted multidimensional computational approach for uncovering the plausible mechanisms through which these GWAS SNPs are connected to CD pathogenesis. At initial phase, we identified that 25 (43.85%) out of 57 CD-SNPs lies in evolutionarily constrained genetic element regions...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28045930/the-ccl2-ccr2-axis-affects-transmigration-and-proliferation-but-not-resistance-to-chemotherapy-of-acute-myeloid-leukemia-cells
#7
Patricia Macanas-Pirard, Thomas Quezada, Leonardo Navarrete, Richard Broekhuizen, Andrea Leisewitz, Bruno Nervi, Pablo A Ramírez
Acute myeloid leukemia (AML) has a high mortality rate despite chemotherapy and transplantation. Both CXCR4/SDF-1 and VLA-4/VCAM1 axes are involved in leukemia protection but little is known about the role of CCL2/CCR2 in AML biology and protection against chemotherapy. We measured CCR2 expression in AML cell lines and primary AML cells by flow cytometry (FCM), real time PCR (RT-PCR) and western blot (WB). CCL2 production was quantified by solid phase ELISA in peripheral blood (PB) and bone marrow (BM) serum...
2017: PloS One
https://www.readbyqxmd.com/read/28045644/pet-based-imaging-of-chemokine-receptor-2-in-experimental-and-disease-related-lung-inflammation
#8
Yongjian Liu, Sean P Gunsten, Deborah H Sultan, Hannah P Luehmann, Yongfeng Zhao, T Scott Blackwell, Zachary Bollermann-Nowlis, Jie-Hong Pan, Derek E Byers, Jeffrey J Atkinson, Daniel Kreisel, Michael J Holtzman, Robert J Gropler, Christophe Combadiere, Steven L Brody
Purpose To characterize a chemokine receptor type 2 (CCR2)-binding peptide adapted for use as a positron emission tomography (PET) radiotracer for noninvasive detection of lung inflammation in a mouse model of lung injury and in human tissues from subjects with lung disease. Materials and Methods The study was approved by institutional animal and human studies committees. Informed consent was obtained from patients. A 7-amino acid CCR2 binding peptide (extracellular loop 1 inverso [ECL1i]) was conjugated to tetraazacyclododecane tetraacetic acid (DOTA) and labeled with copper 64 ((64)Cu) or fluorescent dye...
January 3, 2017: Radiology
https://www.readbyqxmd.com/read/28039457/tumor-associated-macrophages-promote-prostate-cancer-migration-through-activation-of-the-ccl22-ccr4-axis
#9
Aerken Maolake, Kouji Izumi, Kazuyoshi Shigehara, Ariunbold Natsagdorj, Hiroaki Iwamoto, Suguru Kadomoto, Yuta Takezawa, Kazuaki Machioka, Kazutaka Narimoto, Mikio Namiki, Wen-Jye Lin, Guzailinuer Wufuer, Atsushi Mizokami
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032600/the-function-of-cancer-shed-gangliosides-in-macrophage-phenotype-involvement-with-angiogenesis
#10
Tae-Wook Chung, Hee-Jung Choi, Mi-Ju Park, Hee-Jin Choi, Syng-Ook Lee, Keuk-Jun Kim, Cheorl-Ho Kim, Changwan Hong, Kyun-Ha Kim, Myungsoo Joo, Ki-Tae Ha
Tumor-derived gangliosides in the tumor microenvironment are involved in the malignant progression of cancer. However, the molecular mechanisms underlying the effects of gangliosides shed from tumors on macrophage phenotype remain unknown. Here, we showed that ganglioside GM1 highly induced the activity and expression of arginase-1 (Arg-1), a major M2 macrophage marker, compared to various gangliosides in bone marrow-derived macrophages (BMDM), peritoneal macrophages and Raw264.7 macrophage cells. We found that GM1 bound to macrophage mannose receptor (MMR/CD206) and common gamma chain (γc)...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025034/ccl2-ccr2-signaling-pathway-in-glioblastoma-multiforme
#11
REVIEW
Alireza Vakilian, Hossein Khorramdelazad, Parisa Heidari, Zahra Sheikh Rezaei, Gholamhossein Hassanshahi
Glioblastoma multiform (GBM) is described as one of the most frequent primary brain tumors. These types of malignancies constitute only 15% of all primary brain tumors. Despite, extensive developments on effective therapeutic methods during the 20th century as well as the first decade of the present century (21st), the median survival rate for patients suffering from GBM is only approximately 15 months, even in response to multi-modal therapy. numerous types of reticuloendothelial system cells such as macrophages and microglial cells occupied within both GBM and also normal surrounding tissues...
December 24, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/28018174/neurogenesis-promoting-natural-product-%C3%AE-asarone-modulates-morphological-dynamics-of-activated-microglia
#12
Qing Cai, Yuanyuan Li, Jianxin Mao, Gang Pei
α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 μM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28011675/cx3cr1-dependent-endothelial-margination-modulates-ly6chigh-monocyte-systemic-deployment-upon-inflammation-in-mice
#13
Pauline Hamon, Pierre-Louis Loyher, Camille Baudesson de Chanville, Fabrice Licata, Christophe Combadière, Alexandre Boissonnas
Two subsets of blood monocytes are commonly described in mice and humans; the classical inflammatory monocytes which are rapidly mobilized upon inflammation in a CC-chemokine receptor 2 (CCR2)-dependent manner, and the non-classical blood resident monocyte subset that patrol the intraluminal side of the endothelium. Old reports suggest that blood monocytes are distributed into circulating and marginating pools but no direct evidence of the latter has been obtained so far. Using a combination of in vivo real-time imaging and blood/tissue partitioning by intravascular staining of leukocytes, we showed that both inflammatory and resident monocytes are retained in the bone marrow vasculature, representing an important reservoir of marginated monocytes...
December 23, 2016: Blood
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in-active-and-resolved-psoriasis
#14
Elisa Martini, Maria Wiken, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), phenotypically distinct from dermal DCs, were strictly confined to lesional psoriasis. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28002729/the-heterogeneity-of-ly6c-hi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells
#15
Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, Juan Dubrot, Rajen Patel, Emmanuel L Gautier, Stéphanie Hugues, M Paula Longhi, Jake Y Henry, Sergio A Quezada, Grégoire Lauvau, Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martínez, Alain Bessis, Elisa Gomez-Perdiguero, Christian E Jacome-Galarza, Hannah Garner, Frederic Geissmann, Rachel Golub, Michel C Nussenzweig, Pierre Guermonprez
Inflammation triggers the differentiation of Ly6C(hi) monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3(+)CD11c(-)MHCII(+)PU.1(hi) subset...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27995603/role-of-gamma-interferon-and-inflammatory-monocytes-in-driving-colonic-inflammation-during-acute-c-difficile-infection-in-mice
#16
Andrew J McDermott, Nicole R Falkowski, Roderick A McDonald, Charles R Frank, Chinmay R Pandit, Vincent B Young, Gary B Huffnagle
The inflammatory response to the colonic pathogen Clostridium difficile is characterized by the induction of inflammatory cytokines including Interleukin-23 (IL-23) and interferon gamma (IFNγ) and the recruitment of myeloid cells including Ly6C(H)(igh) monocytes. IL-23KO mice showed reduced expression of the monocyte chemokines Ccl4 and Ccl7, but not Ccl2, as well as reduced Ly6C(H)(igh) Ly6G(M)(id) monocyte recruitment to the colon in response to C. difficile colitis. C. difficile-infected CCR2(-/-) (CCR2KO) mice showed a significant defect in Ly6C(H)(igh) Ly6G(M)(id) monocyte recruitment to the colon in response to C...
December 20, 2016: Immunology
https://www.readbyqxmd.com/read/27982503/t-cells-promote-bronchial-epithelial-cells-secretion-of-matrix-metalloproteinase-9-via-a-c-c-chemokine-receptor-type-2-pathway-implications-for-chronic-lung-allograft-dysfunction
#17
M Pain, P-J Royer, J Loy, A Girardeau, A Tissot, P Lacoste, A Roux, M Reynaud-Gaubert, R Kessler, S Mussot, C Dromer, O Brugière, J-F Mornex, R Guillemain, M Dahan, C Knoop, K Botturi, C Pison, R Danger, S Brouard, A Magnan
Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation (LT). CLAD manifests as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity on epithelial cell differentiation. Primary human bronchial epithelial cells (BEC) were treated with activated T cells in the presence or absence of TGF-β...
December 16, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#18
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar Wani, Juan Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma (HCC), a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in HCC patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and HCC in the miR-122 knockout (aka KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to HCC with age...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27974221/cell-based-delivery-of-interleukin-13-directs-alternative-activation-of%C3%A2-macrophages-resulting-in-improved-functional-outcome-after%C3%A2-spinal%C3%A2-cord%C3%A2-injury
#19
Dearbhaile Dooley, Evi Lemmens, Tim Vangansewinkel, Debbie Le Blon, Chloé Hoornaert, Peter Ponsaerts, Sven Hendrix
The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27965260/ccl2-ccr2-but-not-ccl5-ccr5-mediates-monocyte-recruitment-inflammation-and-cartilage-destruction-in-osteoarthritis
#20
Harini Raghu, Christin M Lepus, Qian Wang, Heidi H Wong, Nithya Lingampalli, Francesca Oliviero, Leonardo Punzi, Nicholas J Giori, Stuart B Goodman, Constance R Chu, Jeremy B Sokolove, William H Robinson
OBJECTIVES: While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/CCR5 chemokine axes in OA pathogenesis. METHODS: Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA...
December 13, 2016: Annals of the Rheumatic Diseases
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