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https://www.readbyqxmd.com/read/28822917/coexistence-of-aberrant-hematopoietic-and-stromal-elements-in-myelodysplastic-syndromes
#1
Salar Abbas, Archana Kini, Vivi M Srivastava, Marie Therese M, Sukesh C Nair, Aby Abraham, Vikram Mathews, Biju George, Sanjay Kumar, Aparna Venkatraman, Alok Srivastava
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD)...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#2
Patrick M Reeves, Mojgan A Abbaslou, Farah R W Kools, Mark C Poznansky
The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination...
August 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#3
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia-growth-permissive and normal-hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Pre-conditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28811711/fibroblast-derived-cxcl12-sdf-1%C3%AE-promotes-cxcl6-secretion-and-co-operatively-enhances-metastatic-potential-through-the-pi3k-akt-mtor-pathway-in-colon-cancer
#4
Jia-Chi Ma, Xiao-Wen Sun, He Su, Quan Chen, Tian-Kang Guo, Yuan Li, Xiao-Chang Chen, Jin Guo, Zhen-Qiang Gong, Xiao-Dan Zhao, Jian-Bo Qi
AIM: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811579/cxcl12-enhances-angiogenesis-through-cxcr7-activation-in-human-umbilical-vein-endothelial-cells
#5
Min Zhang, Lisha Qiu, Yanyan Zhang, Dongsheng Xu, Jialin C Zheng, Li Jiang
Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809532/transient-and-local-expression-of-chemokine-and-immune-checkpoint-traps-to-treat-pancreatic-cancer
#6
Lei Miao, Jingjing Li, Qi Liu, Richard Feng, Manisit Das, C Michael Lin, Tyler J Goodwin, Oleksandra Dorosheva, Rihe Liu, Leaf Huang
Pancreatic tumor is known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 nM and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and injected IV to mice bearing orthotopic pancreatic cancer...
August 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/28804991/nf-%C3%AE%C2%BAb2-controls-migratory-activity-of-memory-t-cells-by-regulating-expression-of-cxcr4-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#7
Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Jonathan Sprent, Naozumi Ishimaru
OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific chemokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren's syndrome (SS) model. METHODS: T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28801669/balance-between-estrogens-and-proinflammatory-cytokines-regulates-chemokine-production-involved-in-thymic-germinal-center-formation
#8
Nadine Dragin, Patrice Nancy, José Villegas, Régine Roussin, Rozen Le Panse, Sonia Berrih-Aknin
The early-onset form of Myasthenia Gravis (MG) is prevalent in women and associates with ectopic germinal centers (GCs) development and inflammation in the thymus. we aimed to investigate the contribution of estrogens in the molecular processes involved in thymic GCs formation. We examined expression of genes involved in anti-acetylcholine receptor (AChR) response in MG, MHC class II and α-AChR subunit as well as chemokines involved in GC development (CXCL13, CCL21and CXCL12). In resting conditions, estrogens have strong regulatory effects on thymic epithelial cells (TECs), inducing a decreased protein expression of the above molecules...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793338/anti-tumor-activity-of-nanomicelles-encapsulating-cxcr4-peptide-antagonist-e5
#9
Xiaocui Fang, Hanyi Xie, Hongyang Duan, Ping Li, Maryam Yousaf, Haiyan Xu, Yanlian Yang, Chen Wang
Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5)...
2017: PloS One
https://www.readbyqxmd.com/read/28783870/cxcr4-antagonist-delivery-on-decellularized-skin-scaffold-facilitates-impaired-wound-healing-in-diabetic-mice-by-increasing-expression-of-sdf-1-and-enhancing-migration-of-cxcr4-positive-cells
#10
Hao Liu, Hanping Liu, Xiaoyuan Deng, Maosheng Chen, Xue Han, Wenxia Yan, Ning Wang
C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing...
June 8, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28774348/epithelial-to-mesenchymal-transition-in-fhc-silenced-cells-the-role-of-cxcr4-cxcl12-axis
#11
I Aversa, F Zolea, C Ieranò, S Bulotta, A M Trotta, M C Faniello, C De Marco, D Malanga, F Biamonte, G Viglietto, G Cuda, S Scala, F Costanzo
BACKGROUND: Ferritin plays a central role in the intracellular iron metabolism; the molecule is a nanocage of 24 subunits of the heavy and light types. The heavy subunit (FHC) is provided of a ferroxidase activity and thus performs the key transformation of iron in a non-toxic form. Recently, it has been shown that FHC is also involved in additional not iron-related critical pathways including, among the others, p53 regulation, modulation of oncomiRNAs expression and chemokine signalling...
August 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#12
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#13
Raymond H de Wit, Raimond Heukers, Hendrik Brink, Angela Arsova, David Maussang, Pasquale Cutolo, Beatrijs Strubbe, Henry Vischer, Francoise Bachelerie, Martine J Smit
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM mutants have a gain of function in response to its ligand CXCL12, which results in abnormal leukocyte migration and thereby immune system dysfunctions. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses...
August 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28768055/harnessing-cxcr4-antagonists-in-stem-cell-mobilization-hiv-infection-ischemic-diseases-and-oncology
#14
REVIEW
Lun Kelvin Tsou, Ying-Huey Huang, Jen-Shin Song, Yi-Yu Ke, Jing-Kai Huang, Kak-Shan Shia
CXCR4 antagonists (e.g., Plerixafor(TM) ) have been successfully validated as stem cell mobilizers for peripheral blood stem cell transplantation. Applications of the CXCR4 antagonists have heralded the era of cell-based therapy and opened a potential therapeutic horizon for many unmet medical needs such as kidney injury, ischemic stroke, cancer, and myocardial infarction. In this review, we first introduce the central role of CXCR4 in diverse cellular signaling pathways and discuss its involvement in several disease progressions...
August 2, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28765149/changes-in-multiple-cytokine-concentrations-in-the-aqueous-humour-of-neovascular-age-related-macular-degeneration-after-2-months-of-ranibizumab-therapy
#15
Shinichi Sakamoto, Hidenori Takahashi, Xue Tan, Yuji Inoue, Yoko Nomura, Yusuke Arai, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
PURPOSE: To determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD). METHODS: This prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012...
August 1, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28755135/macrophage-derived-hmgb1-as-a-pain-mediator-in-the-early-stage-of-acute-pancreatitis-in-mice-targeting-rage-and-cxcl12-cxcr4-axis
#16
Yuhei Irie, Maho Tsubota, Hiroyasu Ishikura, Fumiko Sekiguchi, Yuka Terada, Toshifumi Tsujiuchi, Keyue Liu, Masahiro Nishibori, Atsufumi Kawabata
Extracellular high mobility group box 1 (HMGB1) activates the receptor for advanced glycation end products (RAGE) or Toll-like receptor 4 (TLR4) and forms a heterocomplex with CXCL12 that strongly activates CXCR4, promoting inflammatory and pain signals. In the present study, we investigated the role of HMGB1 in pancreatic pain accompanying cerulein-induced acute pancreatitis in mice. Abdominal referred hyperalgesia accompanying acute pancreatitis occurred within 1 h after 6 hourly injections of cerulein. The anti-HMGB1 neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, abolished the cerulein-induced referred hyperalgesia, but not pancreatitis itself...
July 28, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28754798/frontline-science-cxcr7-mediates-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-a-potential-therapeutic-target-for-neuroaids
#17
Mike Veenstra, Dionna W Williams, Tina M Calderon, Kathryn Anastos, Susan Morgello, Joan W Berman
CD14(+)CD16(+) monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting >50% of infected individuals...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28753202/targeting-the-cxcr4-cxcl12-axis-in-treating-epithelial-ovarian-cancer
#18
T L Mao, K F Fan, C L Liu
Ovarian carcinoma is the most crucial and difficult target for available therapeutic treatments among gynecological malignancies, and great efforts are required to find an effective solution. Molecular studies showed that the chemokine stromal cell-derived factor (SDF)-1 (also known as CXCL12) and its receptor, CXCR4, are key determinants of tumor initiation, progression, and metastasis in ovarian carcinomas. Hence, it is generally believed that blocking the CXCR4/CXCL12 pathway could serve as a potential therapy for patients with ovarian cancer...
July 28, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28752270/combination-treatment-with-dendrosomal-nanocurcumin-and-doxorubicin-improves-anticancer-effects-on-breast-cancer-cells-through-modulating-cxcr4-nf-%C3%AE%C2%BAb-smo-regulatory-network
#19
Mohammad Amin Mahjoub, Babak Bakhshinejad, Majid Sadeghizadeh, Sadegh Babashah
Despite advantageous antitumor properties of doxorubicin, the considerable cytotoxicity of this chemotherapeutic agent has made it necessary to develop combination treatment strategies. The aim of the current study was to investigate the possible synergism between dendrosomal nanocurcumin (DNC) and doxorubicin in eliciting anticancer effects on MDA-MB-231 metastatic breast cancer cells. The expression levels of CXCL12/CXCR4 axis and Hedgehog pathway genes were evaluated in patient-derived breast carcinoma tissues by qRT-PCR...
July 27, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28749367/genome-wide-association-study-of-susceptibility-to-particulate-matter-associated-qt-prolongation
#20
Rahul Gondalia, Christy L Avery, Melanie D Napier, Raúl Méndez-Giráldez, James D Stewart, Colleen M Sitlani, Yun Li, Kirk C Wilhelmsen, Qing Duan, Jeffrey Roach, Kari E North, Alexander P Reiner, Zhu-Ming Zhang, Lesley F Tinker, Jeff D Yanosky, Duanping Liao, Eric A Whitsel
BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986-2004), longitudinal data on in diameter (), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis...
June 8, 2017: Environmental Health Perspectives
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