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https://www.readbyqxmd.com/read/29627981/discovery-of-a-novel-small-molecule-modulator-of-c-x-c-chemokine-receptor-type-7-as-a-treatment-for-cardiac-fibrosis
#1
Elnaz Menhaji-Klotz, Kevin D Hesp, Allyn Timothy Londregan, Amit S Kalgutkar, David W Piotrowski, Markus Boehm, Kun Song, Tim Ryder, Kevin Beaumont, Rhys M Jones, Karen Atkinson, Janice A Brown, John Litchfield, Jun Xiao, Daniel P Canterbury, Kristen Burford, Benjamin A Thuma, Chris Limberakis, Wenhua Jiao, Scott W Bagley, Saket Agarwal, Danielle Crowell, Stephen Pazdziorko, Jessica Ward, David A Price, Valerie Clerin
C-X-C chemokine receptor type 7 (CXCR7) is involved in cardiac and immune pathophysiology. We report the discovery of a novel 1,4-diazepine CXCR7 modulator, demonstrating for the first time, the role of pharmacological CXCR7 intervention in cardiac repair. Structure-activity relationship (SAR) studies demonstrated that a net reduction in lipophilicity (logD) and incorporation of saturated ring systems yielded compounds with good CXCR7 potency and improvements in oxidative metabolic stability in human liver microsomes (HLM)...
April 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29614310/cxcl12-gene-engineered-endothelial-progenitor-cells-further-improve-the-functions-of-oligodendrocyte-precursor-cells
#2
Fang Yuan, Shuang Chang, Longlong Luo, Yaning Li, Liping Wang, Yaying Song, Meijie Qu, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang
Oligodendrocyte precursor cells (OPCs) are needed for white matter repair after various brain injury. Means that promote OPC functions could benefit white matter recovery after injury. Chemokine CXCL12 and endothelial progenitor cells (EPCs) both have been shown to promote remyelination. We hypothesize that the beneficial effects of EPCs and CXCL12 can be harnessed by genetically modifying EPCs with cxcl12 to synergistically improve the functions of OPCs. In this work, CXCL12-EPC was generated using virus-mediated gene transfer...
March 31, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29608300/structure-activity-relationship-study-of-cyclic-pentapeptide-ligands-for-atypical-chemokine-receptor-3-ackr3
#3
Haruka Sekiguchi, Tomoko Kuroyanagi, David Rhainds, Kazuya Kobayashi, Yuka Kobayashi, Hiroaki Ohno, Nikolaus Heveker, Kenichi Akaji, Nobutaka Fujii, Shinya Oishi
The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in a ACKR3-selective ligand, FC313 [cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal(2)-L-Pro-)], for the devel-opment of highly active ACKR3 ligands. Notably, modification at the L-Pro position with a bulky hydrophobic side chain led to improved bioactivity toward ACKR3...
April 2, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29606504/a-chimeric-antibody-against-ackr3-cxcr7-in-combination-with-tmz-activates-immune-responses-and-extends-survival-in-mouse-gbm-models
#4
Nicole Salazar, Jeffrey C Carlson, Kexin Huang, Yayue Zheng, Cecilia Oderup, Julia Gross, Andrew D Jang, Thomas M Burke, Susanna Lewén, Alexander Scholz, Serina Huang, Leona Nease, Jon Kosek, Michel Mittelbronn, Eugene C Butcher, Hua Tu, Brian A Zabel
Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG1 ) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells...
March 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29587613/g-protein-coupled-receptor-cxcr7-is-overexpressed-in-human-and-murine-endometriosis
#5
Nicola Pluchino, Ramanaiah Mamillapalli, Irene Moridi, Reshef Tal, Hugh S Taylor
Endometriosis is a chronic inflammatory disease. Dysfunctional regulation of chemokines and chemokine receptors is a crucial aspect of endometriosis pathogenesis. Chemokine G-protein-coupled receptors (GPCRs) are important drug targets that regulate inflammation and immunity. Recently, CXCR7, a C-X-C motif containing GPCR, has been identified as a receptor for chemokine ligand CXCL12, one of the best characterized chemokines for cell trafficking, angiogenesis, and cell proliferation in cancer and inflammation...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29581772/cxcr4-cxcr7-cxcl12-axis-in-follicular-thyroid-carcinoma
#6
Thomas Artur Werner, Christina Maria Forster, Levent Dizdar, Pablo Emilio Verde, Katharina Raba, Matthias Schott, Wolfram Trudo Knoefel, Andreas Krieg
Background: Follicular thyroid carcinoma's (FTC) often benign course is partially due to adjuvant radioactive iodine (RAI) treatment. However, once the tumour has spread and fails to retain RAI, the therapeutic options are limited and the outcome is poor. In this subset of patients, the identification of novel druggable biomarkers appears invaluable. Here, we investigated the stage dependent expression and functional role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in FTC. Methods: CXCR4/7 expression was examined in 44 FTC and corresponding non-neoplastic thyroid specimens as well as 10 FTC distant metastases and 18 follicular adenomas using tissue microarray technology...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29570832/development-of-mimokines-chemokine-n-terminus-based-cxcr4-inhibitors-optimized-by-phage-display-and-rational-design
#7
Virginie Fievez, Martyna Szpakowska, Amor Mosbah, Karthik Arumugam, Julie Mathu, Manuel Counson, Nadia Beaupain, Carole Seguin-Devaux, Sabrina Deroo, Michèle Baudy-Floc'h, Andy Chevigné
The chemokine receptor CXCR4 (C-X-C chemokine receptor type 4 also known as fusin or CD184 (cluster of differentiation 184)) is implicated in various biological and pathological processes of the hematopoietic and immune systems. CXCR4 is also one of the major coreceptors for HIV-1 entry into target cells and is overexpressed in many cancers, supporting cell survival, proliferation, and migration. CXCR4 is thus an extremely relevant drug target. Among the different strategies to block CXCR4, chemokine-derived peptide inhibitors hold great therapeutic potential...
March 23, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29560468/cxcr7-ackr3-targeting-ligands-interfere-with-x7-hiv-1-and-hiv-2-entry-and-replication-in-human-host-cells
#8
Thomas D'huys, Sandra Claes, Tom Van Loy, Dominique Schols
Chemokine receptors CCR5 and CXCR4 are considered the main coreceptors for initial HIV infection, replication and transmission, and subsequent AIDS progression. Over the years, other chemokine receptors, belonging to the family of G protein-coupled receptors, have also been identified as candidate coreceptors for HIV entry into human host cells. Amongst them, CXCR7, also known as atypical chemokine receptor 3 (ACKR3), was suggested as a coreceptor candidate capable of facilitating both HIV-1 and HIV-2 entry in vitro ...
March 2018: Heliyon
https://www.readbyqxmd.com/read/29551920/relationship-between-expression-of-cxcr7-and-nf-%C3%AE%C2%BAb-in-breast-cancer-tissue-and-occurrence-of-breast-cancer-and-lymphatic-metastasis
#9
Cheng-Liang Yuan, Zhao-Hong Liu, Ning Zou, Ya-Li Wang, Zhong-Yao Chen
It is designed to discuss the relationship between the expression of chemokine receptor 7 (chemokine receptor 7, CXCR7) and nuclear transcription factor-κB (nuclear factor kappa B, NF-κB) and the occurrence of the breast cancer and lymphatic metastasis. METHOD: 80 samples were excised and confirmed as breast cancer through our hospital pathology from January 2014 to December 2016 and tumor tissues and normal mammary tissues 2 cm from the tumor edges were taken as an experimental group and a control group, respectively...
December 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29541196/assessment-of-cxc-ligand-12-mediated-calcium-signalling-and-its-regulators-in-basal-like-breast-cancer-cells
#10
S Y N Jamaludin, I Azimi, F M Davis, A A Peters, T J Gonda, E W Thompson, S J Roberts-Thomson, G R Monteith
CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29537098/cxcl12-mediated-feedback-from-granule-neurons-regulates-generation-and-positioning-of-new-neurons-in-the-dentate-gyrus
#11
Philipp Abe, Hannah M Wüst, Sebastian J Arnold, Serge A van de Pavert, Ralf Stumm
Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed...
March 14, 2018: Glia
https://www.readbyqxmd.com/read/29530506/mutational-analysis-of-the-extracellular-disulphide-bridges-of-the-atypical-chemokine-receptor-ackr3-cxcr7-uncovers-multiple-binding-and-activation-modes-for-its-chemokine-and-endogenous-non-chemokine-agonists
#12
Martyna Szpakowska, Max Meyrath, Nathan Reynders, Manuel Counson, Julien Hanson, Jan Steyaert, Andy Chevigné
The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor...
March 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29526013/correction-to-biological-pathological-functions-of-the-cxcl12-cxcr4-cxcr7-axes-in-the-pathogenesis-of-bladder-cancer
#13
Alireza Nazari, Hossein Khorramdelazad, Gholamhossein Hassanshahi
Following the publication from the original article, it came to our attention that we unintentionally neglected to acknowledge some text overlap with previous publications.
March 10, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29499763/modulatory-effects-of-trophoblast-secreted-cxcl12-on-the-migration-and-invasion-of-human-first-trimester-decidual-epithelial-cells-are-mediated-by-cxcr4-rather-than-cxcr7
#14
Jiayi Zheng, Haiping Wang, Wenhui Zhou
BACKGROUND: Maternal-fetal crosstalk during embryo implantation is complex and regulated by local signaling molecules. Chemokines and their receptors are critical signaling components required for implantation and the process of pregnancy. This study aimed to explore whether human first-trimester trophoblast cells (TCs) were capable of modulating the migration and invasion of human first-trimester decidual epithelial cells (DECs) via CXCL12/CXCR4/CXCR7 signaling. METHOD: The expression of CXCR4 and CXCR7 in DECs was examined by immunohistochemistry, immunocytochemistry, immunofluorescence, flow cytometry, real-time polymerase chain reactions and western blotting...
March 2, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29497024/atypical-chemokine-receptor-ccrl2-is-overexpressed-in-prostate-cancer-cells
#15
Reyes Niradiz, Benedetti Ines, Rebollo Juan, Correa Oscar, Geliebter Jan
Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6, ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29422961/microrna-100-suppresses-human-gastric-cancer-cell-proliferation-by-targeting-cxcr7
#16
Yongfeng Cao, Jiaye Song, Jianjuan Ge, Zhuchen Song, Jia Chen, Changping Wu
microRNAs (miRs) are a class of small non-coding RNAs that have been demonstrated to have a crucial role in tumorigenesis of human cancers, including gastric cancer (GC). Previous results have established that miR-100 participated in the development of GC; however, the underlying mechanism remains largely unknown. The preesent study utilized reverse transcription-quantitative polymerase chain reaction to analyze the expression of miR-100 in GC tissues and adjacent normal tissues. The present results indicated that the expression of miR-100 was downregulated in GC tissues when compared to the adjacent normal tissues...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29420253/the-c-x-c-signalling-system-in-the-rodent-vs-primate-testis-impact-on-germ-cell-niche-interaction
#17
Laura Heckmann, Tim Pock, Ina Tröndle, Nina Neuhaus
In zebrafish, action of the chemokine Cxcl12 is mediated through its G-protein coupled seven-transmembrane domain receptor Cxcr4 and the atypical receptor Cxcr7. Employing this animal model it was revealed that this Cxcl12 signalling system plays a crucial role for directed migration of primordial germ cells (PGC) during early testicular development. Importantly, subsequent studies indicated that this regulatory mechanism is evolutionarily conserved also in mice. What is more, the functional role of the CXCL12 system does not seem to be limited to early phases of testicular development...
February 2, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29408206/the-5t4-oncofetal-glycoprotein-does-not-act-as-a-general-organizer-of-the-cxcl12-system-in-cancer-cells
#18
Malte Puchert, Christian Koch, Jürgen Engele
The chemokine, CXCL12, promotes cancer growth and metastasis through interaction with either CXCR4 and/or CXCR7. This tumor-specific organization of the CXCL12 system obscures current therapeutic approaches, aiming at the selective inactivation of CXCL12 receptors. Since it has been previously suggested that the cellular use of CXCR4 or CXCR7 is dictated by the 5T4 oncofetal glycoprotein, we have now tested whether 5T4 would represent a general and reliable marker for the organization of the CXCL12 system in cancer cells...
February 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29393458/microrna-126-stromal-cell-derived-factor-1-c-x-c-chemokine-receptor-type-7-signaling-pathway-promotes-post-stroke-angiogenesis-of-endothelial-progenitor-cell-transplantation
#19
Caiyun Shan, Yongsheng Ma
Stroke is the most common cause of mortality worldwide. Post-stroke angiogenesis is of great significance to the treatment of strokes. The aim of the present study was to investigate the mechanism underlying the angiogenesis-promoting effect of microRNA‑126 (miR‑126)‑associated signaling pathways using a stroke model in vivo and a cell migration model in vitro. Bone marrow‑derived endothelial progenitor cells (EPCs) were extracted and identified using a density gradient method. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to examine the expression levels of miR‑126 and C‑X‑C chemokine receptor type 7 (CXCR7)...
January 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29390073/lyg-202-inhibits-activation-of-endothelial-cells-and-angiogenesis-through-cxcl12-cxcr7-pathway-in-breast-cancer
#20
Kai Zhao, Yuyuan Yao, Xuwei Luo, Binyan Lin, Yujie Huang, Yuxin Zhou, Zhiyu Li, Qinglong Guo, Na Lu
Angiogenesis is critical for the growth and metastasis of triple-negative breast cancer (TNBC) and its inhibition reduces the risk of progression of metastatic TNBC. In this study, we investigated that LYG-202, a flavonoid with a piperazine substitution, inhibited angiogenesis induced by conditioned media (CM) from MDA-MB-231 cells under hypoxia and revealed its underlying mechanism. The results showed that LYG-202 decreased CXCL12 secretion and CXCR7 expression, leading to suppression of its downstream ERK/AKT/NF-κB signaling, which eventually decreased the expression of MMP-2, MMP-9, RhoA and increased VE-cadherin expression in EA...
January 30, 2018: Carcinogenesis
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