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https://www.readbyqxmd.com/read/28231592/cxcr4-a-new-player-in-an-old-scene
#1
Andreas Knopf, Marie Kristin Fritsche, Yin Li
Transmembrane C-X-C chemokine receptor 4 (CXCR4) and its ligand C-X-C motif chemokine 12 (CXCL12) came into focus in many solid cancers, allowing a more fundamental diagnostic and therapeutic approach by modulating the immune response against cancer cells. CXCR4 and CXCL12 mediate cell proliferation, migration, and metastatic outgrowth in head and neck squamous cell carcinoma (HNSCC) and are strongly associated with cancer recurrence and patient survival. Despite recent advances in molecular imaging and cancer therapy in lymphoma using CXCL12 analogues, clinical trials evaluating the diagnostic and therapeutic impact on HNSCC are missing...
February 24, 2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28223138/foxc1-and-foxc2-are-necessary-to-maintain-glomerular-podocytes
#2
Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreER(T2)) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreER(T2) was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreER(T2); Foxc1(+/flox); Foxc2(flox/flox) mice developed microalbuminuria, while ROSA26-Cre ER(T2); Foxc1(flox/flox); Foxc2(+/flox) mice had no microalbuminuria...
February 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28222766/increased-cortical-lesion-load-and-intrathecal-inflammation-is-associated-with-oligoclonal-bands-in-multiple-sclerosis-patients-a-combined-csf-and-mri-study
#3
Gabriele Farina, Roberta Magliozzi, Marco Pitteri, Richard Reynolds, Stefania Rossi, Alberto Gajofatto, Maria Donata Benedetti, Francesco Facchiano, Salvatore Monaco, Massimiliano Calabrese
BACKGROUND: Although IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) are a frequent phenomenon in multiple sclerosis (MS) patients, their relationship with grey matter lesions, intrathecal/meningeal inflammation and clinical evolution has not been clarified yet. The aim of our study was to assess the relationship between the OCBs, the inflammatory/neurodegenerative CSF profile at diagnosis, the cortical lesion load and the clinical evolution after 10 years. METHODS: This is a 10-year observational, cross-sectional study based on a combined MRI, cognitive and CSF profiling of the examined patients...
February 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28220507/relationships-between-inflammation-and-immunity-related-transcript-abundance-in-the-rumen-and-jejunum-of-beef-steers-with-divergent-average-daily-gain
#4
J G Reynolds, A P Foote, H C Freetly, W T Oliver, A K Lindholm-Perry
The bovine rumen papillae are in contact with a wide array of microorganisms and the metabolites they produce, which may activate an inflammatory and/or immune response. Cytokines, chemokines and their receptor genes were tested for differential expression in the rumen and jejunum of beef steers with greater and lesser average daily body weight gain (ADG) near the average daily dry matter intake (DMI) for the population. Angus-sired steers (n = 16) were used to represent the greater (ADG = 2.2 ± 0.07 kg/day; DMI = 10...
February 21, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28220184/cxcl12a-cxcr4b-acts-to-retain-neutrophils-in-caudal-hematopoietic-tissue-and-to-antagonize-recruitment-to-an-injury-site-in-the-zebrafish-larva
#5
Susana Paredes-Zúñiga, Rodrigo A Morales, Salomé Muñoz-Sánchez, Carlos Muñoz-Montecinos, Margarita Parada, Karina Tapia, Carlos Rubilar, Miguel L Allende, Oscar A Peña
Neutrophils are a major component of the innate immune response and the most abundant circulating cell type in humans and zebrafish. The CXCL12/CXCR4 ligand receptor pair plays a key role in neutrophil homeostasis, controlling definitive hematopoiesis and neutrophil release into circulation. Neutrophils overexpressing CXCR4 respond by migrating towards sources of CXCL12, which is abundant in hematopoietic tissues. However, the physiological role of CXCL12/CXCR4 signaling during inflammatory responses remains unknown...
February 20, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28219003/targeting-the-cxcl12-cxcr4-axis-in-acute-myeloid-leukemia-from-bench-to-bedside
#6
Byung-Sik Cho, Hee-Je Kim, Marina Konopleva
The interactions between the cancerous cells of acute myeloid leukemia (AML) and the bone marrow (BM) microenvironment have been postulated to be important for resistance to chemotherapy and disease relapse in AML. The chemokine receptor CXC chemokine receptor 4 (CXCR4) and its ligand, CXC motif ligand 12 (CXCL12), also known as stromal cell-derived factor 1α, are key mediators of this interaction. CXCL12 is produced by the BM microenvironment, binds and activates its cognate receptor CXCR4 on leukemic cells, facilitates leukemia cell trafficking and homing in the BM microenvironment, and keeps leukemic cells in close contact with the stromal cells and extracellular matrix that constitutively generate growth-promoting and anti-apoptotic signals...
February 21, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28218906/differential-cytokine-contributions-of-perivascular-haematopoietic-stem-cell-niches
#7
Noboru Asada, Yuya Kunisaki, Halley Pierce, Zichen Wang, Nicolas F Fernandez, Alexander Birbrair, Avi Ma'ayan, Paul S Frenette
Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#8
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#9
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28209525/stromal-vascular-fraction-shows-robust-wound-healing-through-high-chemotactic-and-epithelialization-property
#10
Dong-Sic Chae, Seongho Han, Mina Son, Sung-Whan Kim
BACKGROUND: Although human stromal vascular fraction (SVF) has been regarded as an attractive stem cell source, its therapeutic mechanism in wound healing has not been fully elucidated. AIMS: In this study, we investigated the molecular characteristics and therapeutic property of SVF for wound healing. METHODS: Microarray data showed that SVF cells are enriched with a higher level of wound healing or epithelium development-related genes and micro RNA...
February 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28207860/effect-of-human-cytomegalovirus-hcmv-us27-on-cxcr4-receptor-internalization-measured-by-fluorogen-activating-protein-fap-biosensors
#11
Jordan M Boeck, Juliet V Spencer
Human cytomegalovirus (HCMV) is a widespread pathogen and a member of the Herpesviridae family. HCMV has a large genome that encodes many genes that are non-essential for virus replication but instead play roles in manipulation of the host immune environment. One of these is the US27 gene, which encodes a protein with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs). The US27 protein has no known chemokine ligands but can modulate the signaling activity of host receptor CXCR4...
2017: PloS One
https://www.readbyqxmd.com/read/28202459/il-4-cxcl12-loop-is-a-key-regulator-of-lymphoid-stroma-function-in-follicular-lymphoma
#12
Shubham Pandey, Frédéric Mourcin, Tony Marchand, Saba Nayar, Marion Guirriec, Céline Pangault, Céline Monvoisin, Patricia Amé-Thomas, Fabien Guilloton, Joelle Dulong, Mark Coles, Thierry Fest, Anja Mottok, Francesca Barone, Karin Tarte
Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the accumulation of germinal center-derived malignant B cells engaged in a bidirectional crosstalk with their supportive microenvironment in invaded lymph nodes (LN) and bone marrow (BM). T follicular helper cells (TFH) and infiltrating stromal cells have been shown to favor FL B-cell growth but the mechanisms of their protumoral effect and how LN/BM microenvironment is converted into a lymphoma-permissive cell niche remain poorly understood...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28197019/inflammation-and-cancer-extra-and-intracellular-determinants-of-tumor-associated-macrophages-as-tumor-promoters
#13
REVIEW
Gabor J Szebeni, Csaba Vizler, Klara Kitajka, Laszlo G Puskas
One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28193907/stem-cell-autocrine-cxcl12-cxcr4-stimulates-invasion-and-metastasis-of-esophageal-cancer
#14
Xingwei Wang, Yan Cao, Shirong Zhang, Zhihui Chen, Ling Fan, Xiaochun Shen, Shiwen Zhou, Dongfeng Chen
Esophageal cancer is one of the most common malignant tumors of the digestive tract. The greatest obstacle to the curing of esophageal cancer is its propensity to spread and metastasize. Esophageal cancer stem cells are considered the source for recurrence and metastasis of the tumors. While clinical evidence suggested that continuous up-regulation of CXCL12/CXCR4 was significantly associated with poor prognosis in patients with esophageal cancer, but the role and mechanism of CXCL12/CXCR4 in the invasion and metastasis of esophageal cancer has not been reported by far...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193885/essential-role-of-immobilized-chemokine-cxcl12-in-the-regulation-of-the-humoral-immune-response
#15
Aleksandr Barinov, Lingjie Luo, Pamela Gasse, Vannary Meas-Yedid, Emmanuel Donnadieu, Fernando Arenzana-Seisdedos, Paulo Vieira
Chemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptor-binding domain is distinct and does not overlap with the immobilization domains...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28187313/il-20-contributes-to-low-grade-inflammation-and-weight-gain-in-the-psammomys-obesus
#16
Helena Cucak, Lise Høj Thomsen, Alexander Rosendahl
The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To determine the importance of inflammation in obesity and diabetes, in a normal non-genetically modified species, an intervention study with neutralizing anti-IL-20 antibodies was conducted in the spontaneous T2D model Psammomys obesus. All IL-20 receptor chains were expressed on protein level in the Psammomys obesus. Neutralization of IL-20 did not modulate blood glucose, HbA1c, insulin levels or lymphocyte numbers after five weeks treatment although a trend to reduced weight gain rate was observed upon anti-IL-20 treatment...
February 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28186979/osteotropism-of-neuroendocrine-tumors-role-of-the-cxcl12-cxcr4-pathway-in-promoting-emt-in-vitro
#17
Mauro Cives, Davide Quaresmini, Francesca Maria Rizzo, Claudia Felici, Stella D'Oronzo, Valeria Simone, Franco Silvestris
Neuroendocrine tumors (NETs) metastasize to the skeleton in approximately 20% of patients. We have previously shown that the epithelial-mesenchymal transition (EMT) regulates the NET osteotropism and that CXCR4 overexpression predicts bone spreading. Here, we unravel the molecular mechanisms linking the activation of the CXCL12/CXCR4 axis to the bone colonization of NETs using cell lines representative of pancreatic (BON1, CM, QGP1), intestinal (CNDT 2.5), and bronchial origin (H727). By combining flow cytometry and ELISA, BON1, CM and QGP1 cells were defined as CXCR4high/CXCL12low, while H727 and CNDT 2...
6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179498/loss-of-twist1-in-the-mesenchymal-compartment-promotes-increased-fibrosis-in-experimental-lung-injury-by-enhanced-expression-of-cxcl12
#18
Jiangning Tan, John R Tedrow, Mehdi Nouraie, Justin A Dutta, David T Miller, Xiaoyun Li, Shibing Yu, Yanxia Chu, Brenda Juan-Guardela, Naftali Kaminski, Kritika Ramani, Partha S Biswas, Yingze Zhang, Daniel J Kass
Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the accumulation of apoptosis-resistant fibroblasts in the lung. We have previously shown that high expression of the transcription factor Twist1 may explain this prosurvival phenotype in vitro. However, this observation has never been tested in vivo. We found that loss of Twist1 in COL1A2(+) cells led to increased fibrosis characterized by very significant accumulation of T cells and bone marrow-derived matrix-producing cells. We found that Twist1-null cells expressed high levels of the T cell chemoattractant CXCL12...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28176874/cxcl12-cxcr4-axis-induced-mir-125b-promotes-invasion-and-confers-5-fluorouracil-resistance-through-enhancing-autophagy-in-colorectal-cancer
#19
Xinfeng Yu, Wenna Shi, Yuhang Zhang, Xiaohui Wang, Shiyue Sun, Zhiyu Song, Man Liu, Qiao Zeng, Shuxiang Cui, Xianjun Qu
The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelial-mesenchymal transition (EMT) and concurrent upregulation of miR-125b...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174416/microrna-155-promotes-g-csf-induced-mobilization-of-murine-hematopoietic-stem-and-progenitor-cells-via-propagation-of-cxcl12-signaling
#20
T Itkin, A Kumari, E Schneider, S Gur-Cohen, C Ludwig, R Brooks, O Kollet, K Golan, E Khatib-Massalha, C M Russo, J D Chisholm, A Rouhi, H Geiger, E Hornstein, W G Kerr, F Kuchenbauer, T Lapidot
Leukemia accepted article preview online, 08 February 2017. doi:10.1038/leu.2017.50.
February 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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