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https://www.readbyqxmd.com/read/28875842/targeting-cxcl12-cxcr4-axis-in-tumor-immunotherapy
#1
Weiqiang Zhou, Shanchun Guo, Mingli Liu, Matthew E Burow, Guangdi Wang
Chemokines, which have chemotactic abilities, are comprised of over 50 family members. Through binding to the 7-transmembrane domain of G-protein-coupled receptors (GPCR), they function in immune cells by trafficking and regulating cell prolif¬eration, differentiation, activation, and migration, homing under both physiologic and pathologic conditions. The alpha-chemokine receptor CXCR4 for the alpha-chemokine stromal cell-derived-factor-1 (SDF-1) is most widely expressed by tumors. CXCL12/CXCR4 axis is a major culprit for human tumor because of its crucial role in tumor initiation and progression by activating a number of signaling pathways, such as ERK1/2, ras, PLC/ MAPK, p38 MAPK, and SAPK/ JNK, as well as regulating cancer stem cells...
August 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28868340/e-selectin-and-sdf-1-regulate-metastatic-trafficking-of-breast-cancer-cells-within-the-bone
#2
Trevor T Price, Dorothy A Sipkins
E-selectin is a key mediator of breast cancer cell (BCC) metastatic entry into the bone and stromal-derived factor 1 (SDF-1) is a critical molecular anchor for BCCs within discrete pro-dormancy bone marrow (BM) niches. Small-molecule inhibitors blocked metastatic entry and mobilized established disease from BM, suggesting a new treatment strategy to prevent breast cancer relapse.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28846922/interaction-of-zap70-and-cxcr4-receptor-at-lamellipodia-that-determines-the-directionality-during-jurkat-t-cells-chemotaxis
#3
Chia-Yun Wu, Yi-Ying Tsai, Sheng-Yi Chen, Yu-Ping Lin, Jyh-Wei Shin, Chia-Ching Wu, Bei-Chang Yang
Directional migration of T-lymphocytes is a key process during immune activation and is tightly regulated both temporally and spatially. The initial cell membrane protrusion at a particular site is critical for determining the direction of cell migration. In this study, we found that ZAP-70 protein appeared not only at the margin of the spreading areas of polarized Jurkat T cells but also formed clusters near the center of the cell body on a fibronectin plate. Specifically, some pZAP-70 was located at the lamellipodia/filopodia and was closely associated with the most extended membrane contact...
August 25, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28828731/pharmacological-properties-and-biological-functions-of-the-gpr17-receptor-a-potential-target-for-neuro-regenerative-medicine
#4
Marta Fumagalli, Davide Lecca, Giusy T Coppolino, Chiara Parravicini, Maria P Abbracchio
In 2006, cells heterologously expressing the "orphan" receptor GPR17 were shown to acquire responses to both uracil nucleotides and cysteinyl-leukotrienes, two families of signaling molecules accumulating in brain or heart as a result of hypoxic/traumatic injuries. In subsequent years, evidence of GPR17 key role in oligodendrogenesis and myelination has highlighted it as a "model receptor" for new therapies in demyelinating and neurodegenerative diseases. The apparently contrasting evidence in the literature about the role of GPR17 in promoting or inhibiting myelination can be due to its transient expression in the intermediate stages of differentiation, exerting a pro-differentiating function in early oligodendrocyte precursor cells (OPCs), and an inhibitory role in late stage maturing cells...
August 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28819116/silencing-of-tgf-%C3%AE-1-in-tumor-cells-impacts-mmp-9-in-tumor-microenvironment
#5
Lakisha D Moore-Smith, Tatyana Isayeva, Joo Hyoung Lee, Andra Frost, Selvarangan Ponnazhagan
Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807596/the-role-of-angiotensin-ii-in-parietal-epithelial-cell-proliferation-and-crescent-formation-in-glomerular-diseases
#6
Paola Rizzo, Rubina Novelli, Cinzia Rota, Elena Gagliardini, Barbara Ruggiero, Daniela Rottoli, Ariela Benigni, Giuseppe Remuzzi
Crescentic glomerulonephritis (GN) is a devastating disease with rapidly progressive deterioration in kidney function, which, histologically, manifests as crescent formation in most glomeruli. We previously found that crescents derive from the aberrant proliferation and migration of parietal epithelial cells (PECs)/progenitor cells, and that the angiotensin (ang) II/ang II type-1 (AT1) receptor pathway may participate, together with the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor 4 axis, in the development of those lesions...
August 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28791359/stromal-cell-derived-factor-1-protects-human-periodontal-ligament-stem-cells-against-hydrogen-peroxide-induced-apoptosis
#7
Yimiao Feng, Xiaohui Fu, Xintian Lou, Baiping Fu
Periodontal ligament stem cells (PDLSCs) are considered a promising cell source for dental tissue regeneration. Stromal cell-derived factor 1 [SDF‑1, also known as chemokine (C‑X‑C motif) ligand 12] is regarded as a critical cytokine involved in stem/progenitor cell chemotaxis and homing during tissue regeneration. The present study described a previously unsuspected role for SDF‑1 in the protection of PDLSCs against oxidative stress‑induced apoptosis. In the present study, apoptosis was induced by exposure of PDLSCs to various concentrations of H2O2 for 12 h, following which cell viability was assessed, and cleaved caspase‑3 and ‑9 expression levels were evaluated...
October 2017: Molecular Medicine Reports
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
#8
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/28780431/thermosensitive-chitosan-based-hydrogels-releasing-stromal-cell-derived-factor-1-alpha-recruit-msc-for-corneal-epithelium-regeneration
#9
Qiaomei Tang, Chenqi Luo, Bing Lu, Qiuli Fu, Houfa Yin, Zhenwei Qin, Danni Lyu, Lifang Zhang, Zhi Fang, Yanan Zhu, Ke Yao
Corneal epithelium integrity depends on continuous self-renewing of epithelium and connections between adjacent cells or between the cells and the basement membrane. Self-renewing epithelium cells mainly arise from the continuous proliferation and differentiation of the basal layer and limbal stem cells. The aim of the present study was to generate a bioactive, thermosensitive chitosan-gelatin hydrogel (CHI hydrogel) by incorporating exogenous recombinant human stromal cell-derived factor-1 alpha (SDF-1 alpha) for corneal epithelium regeneration...
August 2, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28774332/baicalin-attenuates-chronic-hypoxia-induced-pulmonary-hypertension-via-adenosine-a2a-receptor-induced-sdf-1-cxcr4-pi3k-akt-signaling
#10
Xiaoying Huang, Peiliang Wu, Feifei Huang, Min Xu, Mayun Chen, Kate Huang, Guo-Ping Li, Manhuan Xu, Dan Yao, Liangxing Wang
BACKGROUND: Baicalin, an important flavonoid in Scutellaria baicalensis Georgi extracts, exerts a variety of pharmacological effects. In this study, we explored the effects of baicalin on chronic hypoxia-induced pulmonary arterial hypertension (PAH) and investigated the mechanism underlying these effects. Moreover, we examined whether the inflammatory response was mediated by the A2A receptor (A2AR) and stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-induced phosphatidyl inositol-3-kinase (PI3K) signaling in vivo...
August 3, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28765024/amd3100-accelerates-reendothelialization-of-neointima-in-rabbit-saccular-aneurysm-after-flow-diverter-treatment
#11
Zifu Li, Rui Zhao, Xinggen Fang, Jiahao Zhou, Guoquan Jiang, Qinghai Huang, Jianmin Liu
OBJECTIVE: To inspect the role of AMD3100 that acts as an antagonist of SDF-1/CXCR4 on the formation of neointima in rabbit saccular aneurysm after flow diverter (FD) treatment. METHODS: Twenty saccular aneurysm models were established by using porcine pancreatic elastase. Three weeks later, a FDs of Tubridge was implanted into the saccular aneurysm. All treated models were immediately divided into two groups: the AMD3100 group was subcutaneously injected with AMD3100 (5 mg/kg per day), while control group with saline...
July 29, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28763008/omega-3-fatty-acids-supplementation-differentially-modulates-the-sdf-1-cxcr-4-cell-homing-axis-in-hypertensive-and-normotensive-rats
#12
Luiza Halmenschlager, Alexandre Machado Lehnen, Aline Marcadenti, Melissa Medeiros Markoski
BACKGROUND: We assessed the effect of acute and chronic dietary supplementation of ω-3 on lipid metabolism and cardiac regeneration, through its influence on the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in normotensive and hypertensive rats. METHODS: Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight animals each), which received daily orogastric administration of ω-3 (1 g) for 24 h, 72 h or 2 weeks...
August 1, 2017: Nutrients
https://www.readbyqxmd.com/read/28754873/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#13
Ning Zheng, Jiahang Chen, Weiqun Liu, Jian Liu, Tao Li, Hongning Chen, Jichuang Wang, Lee Jia
SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753202/targeting-the-cxcr4-cxcl12-axis-in-treating-epithelial-ovarian-cancer
#14
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/28745789/culture-conditions-of-human-embryonic-stem-cells-for-differentiation-into-retinal-vascular-structure
#15
Y-Z Pan, H Wang, F Gao
OBJECTIVE: This study sought to identify the suitable cell culture conditions for the in vitro-induced differentiation of human embryonic stem cells (hESCs) into retinal vascular tissue cell types. MATERIALS AND METHODS: To do this, we established four treatment groups. Group A was designed to culture hESCs in a three-dimensional system. The feeder cells and leukemia inhibitory factor (LIF) were removed in Group B. In group C, hESCs were cultured with a variety of pro-angiogenic growth factors...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28739729/the-axis-of-cxcr4-sdf-1-plays-a-role-in-colon-cancer-cell-adhesion-through-regulation-of-the-akt-and-igf1r-signalling-pathways
#16
Fei Zheng, Zhongtao Zhang, Valentina Flamini, Wen G Jiang, Yuxin Cui
BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer in the world. The high mortality of this tumor is mainly due to its invasive properties, as it forms metastases in multiple organs, preferentially in the liver. There has evidence showing that C-X-C chemokine receptor type 4 (CXCR-4) and its ligand, stromal cell-derived factor-1 (SDF-1), plays an important role in cancer progression and metastasis. However, the molecular mechanism underling the CRCR4-mediated CRC metastasis has not been well characterized...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739546/in-situ-tissue-regeneration-through-sdf-1%C3%AE-driven-cell-recruitment-and-stiffness-mediated-bone-regeneration-in-a-critical-sized-segmental-femoral-defect
#17
Amaia Cipitria, Kathrin Boettcher, Sophia Schoenhals, Daniela S Garske, Katharina Schmidt-Bleek, Agnes Ellinghaus, Anke Dienelt, Anja Peters, Manav Mehta, Christopher M Madl, Nathaniel Huebsch, David J Mooney, Georg N Duda
In-situ tissue regeneration aims to utilize the body's endogenous healing capacity through the recruitment of host stem or progenitor cells to an injury site. Stromal cell-derived factor-1α (SDF-1α) is widely discussed as a potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i) deliver SDF-1α for the recruitment of endogenous bone marrow-derived stromal cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii) induce hydrogel stiffness-mediated osteogenic differentiation in-vivo...
July 21, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28734802/co-transplantation-of-mesenchymal-and-neural-stem-cells-and-overexpressing-stromal-derived-factor-1-for-treating-spinal-cord-injury
#18
Andrew N Stewart, Griffin Kendziorski, Zachary M Deak, Dara J Brown, Matthew N Fini, Katherine L Copely, Julien Rossignol, Gary L Dunbar
Genetic engineering of mesenchymal stem cells (MSCs) and neuronal stem cells (NSCs) has been used to treat spinal cord injuries (SCI). As a mechanism of therapy, MSCs secrete high amounts of anti-inflammatory cytokines and trophic factors, while NSCs can differentiate into neuronal lineages and aid in tissue replacement. Additionally, the forced overexpression of secreted proteins can enhance the secretome of transplanted cells, which can increase therapeutic efficacy. This study utilized a combinational treatment consisting of MSCs, NSCs, and the forced overexpression of the chemokine stromal-derived factor-1 (SDF-1) from MSCs (SDF-1-MSCs), to treat a rat model of SCI...
July 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28715799/resident-arterial-cells-and-circulating-bone-marrow-derived-cells-both-contribute-to-intimal-hyperplasia-in-a-rat-allograft-carotid-transplantation-model
#19
Yi He, Xin Xu, Ting Zhu, Min Tang, Ju Mei, Yi Si
BACKGROUND/AIMS: Neointimal formation following vascular injury remains a major mechanism of restenosis, whereas the precise sources of neointimal cells are still uncertain. We tested the hypothesis that both injured arterial cells and non-arterial cells contribute to intimal hyperplasia. METHODS: Following allograft transplantation of the balloon-injured carotid common artery (n = 3-6), the cellular composition of the transplant grafts and the origins of neointimal cells were measured by immunohistochemistry and immunofluorescence staining...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28711757/cxcr4-and-cxcr7-play-distinct-roles-in-cardiac-lineage-specification-and-pharmacologic-%C3%AE-adrenergic-response
#20
Delaine K Ceholski, Irene C Turnbull, Venu Pothula, Laura Lecce, Andrew A Jarrah, Changwon Kho, Ahyoung Lee, Lahouaria Hadri, Kevin D Costa, Roger J Hajjar, Sima T Tarzami
CXCR4 and CXCR7 are prominent G protein-coupled receptors (GPCRs) for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). This study demonstrates that CXCR4 and CXCR7 induce differential effects during cardiac lineage differentiation and β-adrenergic response in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-CMs were tested for phenotypic and functional properties due to gene knockdown. Gene expression and flow cytometry confirmed the pluripotent and cardiomyocyte phenotype of undifferentiated and differentiated hiPSCs, respectively...
August 2017: Stem Cell Research
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