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https://www.readbyqxmd.com/read/29317253/cxcr4-antagonist-amd3100-enhances-the-response-of-mda-mb-231-triple-negative-breast-cancer-cells-to-ionizing-radiation
#1
K X Zhou, L H Xie, X P, Q M Guo, Q Y Wu, W H Wang, G L Zhang, J F Wu, G J Zhang, C W Du
Radiation therapy (RT) is one of the primary modalities for triple-negative breast cancer (TNBC) treatment. However, due to the pro-metastatic potential of radiation and the intrinsic radiation resistance of some tumors, many patients experience RT failure, which leads to cancer relapse and distant metastasis. This preclinical study evaluated the efficacy of the antagonist of the SDF-1 receptor CXCR4, AMD3100, as a radiosensitizer in TNBC models. The combined effect of ionizing radiation and AMD3100 was determined in vitro by surviving fraction, cell cycle distribution, Bax and Bcl-2 expression, and apoptosis assays in a TNBC cell line (MDA-MB-231)...
January 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29312699/role-of-the-stromal-cell-derived-factor-1-cxc-chemokine-receptor-4-axis-in-the-invasion-and-metastasis-of-lung-cancer-and-mechanism
#2
Yun Zeng, Xinwei Wang, Bijian Yin, Guohao Xia, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
Background: Lung cancer is the most common tumor, and has the highest incidence and mortality rates among all malignant tumors. Since stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) are specific to binding sites, they are more important than other members of the families for tumor invasion and metastasis. We herein aimed to investigate the role of the axis of chemokine SDF-1 and its receptor CXCR4 in the invasion and metastasis of lung cancer. Methods: Sixty clinical non-small cell lung cancer (NSCLC) tissue samples were collected...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29310647/have-dipeptidyl-peptidase-4-inhibitors-ameliorated-the-vascular-complications-of-type-2-diabetes-in-large-scale-trials-the-potential-confounding-effect-of-stem-cell-chemokines
#3
REVIEW
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29299123/inhibition-of-sdf-1-induced-migration-of-oncogene-driven-myeloid-leukemia-by-the-l-rna-aptamer-spiegelmer-nox-a12-and-potentiation-of-tyrosine-kinase-inhibition
#4
Ellen L Weisberg, Martin Sattler, Abdel Kareem Azab, Dirk Eulberg, Anna Kruschinski, Paul W Manley, Richard Stone, James D Griffin
Resistance to targeted tyrosine kinase inhibitors (TKI) remains a challenge for the treatment of myeloid leukemias. Following treatment with TKIs, the bone marrow microenvironment has been found to harbor a small pool of surviving leukemic CD34+ progenitor cells. The long-term survival of these leukemic cells has been attributed, at least in part, to the protective effects of bone marrow stroma. We found that the NOX-A12 'Spiegelmer', an L-enantiomeric RNA oligonucleotide that inhibits SDF-1α, showed in vitro and in vivo activity against BCR-ABL- and FLT3-ITD-dependent leukemia cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296749/high-cd123-levels-enhance-proliferation-in-response-to-il-3-but-reduce-chemotaxis-by-downregulating-cxcr4-expression
#5
Nicole L Wittwer, Gabriela Brumatti, Ceilidh Marchant, Jarrod J Sandow, Melanie K Pudney, Mara Dottore, Richard J D'Andrea, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285291/serum-sdf-1-levels-are-a-reliable-diagnostic-marker-of-feline-mammary-carcinoma-discriminating-her2-overexpressing-tumors-from-other-subtypes
#6
Cláudia S Marques, Maria Soares, Ana Santos, Jorge Correia, Fernando Ferreira
The feline mammary carcinoma (FMC) is the third most common tumor in cat, sharing many clinicopathological features with human breast cancer and thus, considered a suitable model for comparative oncology. Due to its poor prognosis, further studies are required to improve the diagnostic accuracy and treatment of cats with spontaneous mammary carcinoma. Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284451/synovial-inflammation-plays-a-greater-role-in-post-traumatic-osteoarthritis-compared-to-idiopathic-osteoarthritis-in-the-hartley-guinea-pig-knee
#7
Nathan P Thomas, Wesley J Wu, Braden C Fleming, Fangyuan Wei, Qian Chen, Lei Wei
BACKGROUND: The objective of this study was to evaluate the extent of stromal cell-derived factor-1's (SDF-1) involvement in the pathogenesis of idiopathic versus post-traumatic OA by comparing differences in synovial membrane morphology, SDF-1 synovial fluid (SF) concentrations, and matrix metalloproteinase-13 (MMP-13) SF concentrations. METHODS: Thirty-six 3-month-old Hartley guinea pigs were obtained and divided into 6 groups. Upon sacrifice, India Ink staining was used to evaluate gross morphology, Safranin O/Fast green staining was used to assess cartilage damage, H/E staining was employed to visualize the synovium, and SF samples were obtained for biochemical analyses...
December 29, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29259394/characterizing-the-effect-of-supplements-on-the-phenotype-of-cultured-macrophages-from-patients-with-age-related-macular-degeneration
#8
Batya Rinsky, Shira Hagbi-Levi, Sarah Elbaz-Hayoun, Michelle Grunin, Itay Chowers
Purpose: Oral vitamin and mineral supplements reduce the risk of visual loss in age-related macular degeneration (AMD). However, the pathways that mediate this beneficial effect are poorly understood. Macrophages may exert oxidative, inflammatory, and angiogenic effects in the context of AMD. We aim to assess if oral supplements can modulate the macrophage phenotype in this disease. Methods: Monocytes were isolated from patients with neovascular AMD (nvAMD), cultured, matured to macrophages, and polarized to classical [M1 (stimulated by IFNγ and lipopolysaccharide (LPS))] and alternative [M2 (stimulated with IL-4 and IL-13)] phenotypes...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29258450/serum-cytokine-profiles-predict-survival-benefits-in-patients-with-advanced-hepatocellular-carcinoma-treated-with-sorafenib-a-retrospective-cohort-study
#9
Tomoyuki Hayashi, Taro Yamashita, Takeshi Terashima, Tsuyoshi Suda, Hikari Okada, Yoshiro Asahina, Takehiro Hayashi, Yasumasa Hara, Kouki Nio, Hajime Sunagozaka, Hajime Takatori, Kuniaki Arai, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
BACKGROUND: Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles...
December 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29246578/personalized-proteomics-in-proliferative-vitreoretinopathy-implicate-hematopoietic-cell-recruitment-and-mtor-as-a-therapeutic-target
#10
C Nathaniel Roybal, Gabriel Velez, Marcus Toral, Stephen H Tsang, Alexander G Bassuk, Vinit B Mahajan
PURPOSE: To profile vitreous cytokine expression of proliferative vitreoretinopathy (PVR) patients DESIGN: Case-control study. METHODS: Liquid biopsies were collected from two groups: control subjects (n=3) undergoing pars plana vitrectomy to remove an epiretinal membrane (ERM), and test subjects (n=7) with varying degrees of PVR. A high-throughput cytokine screen measured expression of 200 cytokines. Cytokine expression patterns were prospectively validated in separate cohorts of control patients and those with PVR-A, PVR-B, and PVR-C (n=10 for each group)...
December 12, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29242607/the-impact-of-stromal-hic-5-on-the-tumorigenesis-of-colorectal-cancer-through-lysyl-oxidase-induction-and-stromal-remodeling
#11
Tomokatsu Omoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Akira Orimo, Koji Ohnishi, Kosuke Yoshihara, Aya Miyauchi, Shuo Li, Lin Gao, Takahiro Umemoto, Junichi Tanaka, Kenta Nakahara, Motohiro Takeya, Fumio Ishida, Shin-Ei Kudo, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29236198/sdf-1-induces-tnf-mediated-apoptosis-in-cardiac-myocytes
#12
Andrew A Jarrah, Martina Schwarskopf, Edward R Wang, Thomas LaRocca, Ashwini Dhume, Shihong Zhang, Lahouria Hadri, Roger J Hajjar, Alison D Schecter, Sima T Tarzami
Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation. One such chemokine, Stromal cell-derived factor-1 (SDF-1) also known as CXCL12, and its receptor, CXCR4, are expressed and functional in cardiac myocytes. SDF-1 both stimulates and enhances the cellular signal which attracts potentially beneficial stem cells for tissue repair within the ischemic heart. Paradoxically however, this chemokine is known to act in concert with the inflammatory cytokines of the innate immune response which contributes to cellular injury through the recruitment of inflammatory cells during ischemia...
January 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29233725/amd3100-treatment-attenuates-pulmonary-angiogenesis-by-reducing-the-c-kit-cells-and-its-pro-angiogenic-activity-in-cbdl-rat-lungs
#13
Cheng-Cheng Shen, Bing Chen, Jian-Teng Gu, Jiao-Lin Ning, Jing Zeng, Bin Yi, Kai-Zhi Lu
Recent studies have shown that pulmonary angiogenesis is an important pathological process in the development of hepatopulmonary syndrome (HPS), and growing evidence has indicated that Stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis is involved in pulmonary vascular disease by mediating the accumulation of c-kit+ cells. This study aimed to test the effect of AMD3100, an antagonist of CXCR4, in HPS pulmonary angiogenesis. Common bile duct ligation (CBDL) rats were used as experimental HPS model and were treated with AMD3100 (1...
December 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29212254/distinct-mobilization-of-leukocytes-and-hematopoietic-stem-cells-by-cxcr4-peptide-antagonist-ly2510924-and-monoclonal-antibody-ly2624587
#14
Sheng-Bin Peng, Robert D Van Horn, Tinggui Yin, Robin M Brown, William C Roell, Victor H Obungu, Charles Ruegg, Victor J Wroblewski, Eyas Raddad, John R Stille
Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a critical role in mobilization and redistribution of immune cells and hematopoietic stem cells (HSCs). We evaluated effects of two CXCR4-targeting agents, peptide antagonist LY2510924 and monoclonal antibody LY2624587, on mobilizing HSCs and white blood cells (WBCs) in humans, monkeys, and mice. Biochemical analysis showed LY2510924 peptide blocked SDF-1/CXCR4 binding in all three species; LY2624587 antibody blocked binding in human and monkey, with minimal activity in mouse...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207135/bfgf-promotes-sca%C3%A2-1-cardiac-stem-cell-migration-through-activation-of-the-pi3k-akt-pathway
#15
Lin Ling, Shaohua Gu, Yan Cheng, Liucheng Ding
Cardiac stem cells (CSCs) are important for improving cardiac function following myocardial infarction, with CSC migration to infarcted or ischemic myocardium important for cardiac regeneration. Strategies to improve cell migration may improve the efficiency of myocardial regeneration. Basic fibroblast growth factor (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level is too low to be effective. The effect of exogenously delivered bFGF on CSC migration was observed in vitro and in vivo in the present study...
November 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29207021/stromal-cell%C3%A2-derived-factor%C3%A2-1-induces-matrix-metalloproteinase-expression-in-human-endplate-chondrocytes-cartilage-endplate-degradation-in-explant-culture-and-the-amelioration-of-nucleus-pulposus-degeneration-in-vivo
#16
Hua Zhang, Ting Zhu, Li Zhang, Qionghua Wu
Intervertebral disc (IVD) degeneration is a strong etiological factor in chronic lower back pain. Stem cell migration toward the site of IVD degeneration for regeneration is restricted by avascularity and distance. Our previous study indicated that the expression of stromal cell‑derived factor‑1 (SDF‑1) and its receptor, C-X-C chemokine receptor type 4 (CXCR4) was upregulated in degenerated cartilage endplate (CEP) and nucleus pulposus (NP). In the present study, SDF‑1 increased CXCR4 mRNA and protein expression in human endplate chondrocytes in a dose‑dependent manner...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29201496/platelets-prime-hematopoietic-and-vascular-niche-to-drive-angiocrine-mediated-liver-regeneration
#17
Koji Shido, Deebly Chavez, Zhongwei Cao, Jane Ko, Shahin Rafii, Bi-Sen Ding
In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here, we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7+ liver sinusoidal endothelial cell (LSEC) and VEGFR1+ myeloid cell, orchestrating hepatic regeneration. After carbon tetrachloride (CCl4) injection or hepatectomy, platelets and CD11b+VEGFR1+ myeloid cells were recruited LSEC, and liver regeneration in both models was impaired in thrombopoietin-deficient (Thpo-/-) mice lacking circulating platelets...
2017: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29190645/cd105-mesenchymal-stem-cells-migrate-into-osteoarthritis-joint-an-animal-model
#18
Pablo Fernandez-Pernas, Iván Rodríguez-Lesende, Alexandre de la Fuente, Jesús Mateos, Isaac Fuentes, Javier De Toro, Fco J Blanco, M C Arufe
Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model...
2017: PloS One
https://www.readbyqxmd.com/read/29186036/a-new-bone-substitute-developed-from-3d-prints-of-polylactide-pla-loaded-with-collagen-i-an-in-vitro-study
#19
Ulrike Ritz, Rebekka Gerke, Hermann Götz, Stefan Stein, Pol Maria Rommens
Although a lot of research has been performed, large segmental bone defects caused by trauma, infection, bone tumors or revision surgeries still represent big challenges for trauma surgeons. New and innovative bone substitutes are needed. Three-dimensional (3D) printing is a novel procedure to create 3D porous scaffolds that can be used for bone tissue engineering. In the present study, solid discs as well as porous cage-like 3D prints made of polylactide (PLA) are coated or filled with collagen, respectively, and tested for biocompatibility and endotoxin contamination...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29176797/cytokines-hepatic-cell-profiling-and-cell-interactions-during-bone-marrow-cell-therapy-for-liver-fibrosis-in-cholestatic-mice
#20
Daphne Pinheiro, Luana Leirós, Juliana Barbosa Torreão Dáu, Ana Carolina Stumbo, Alessandra Alves Thole, Erika Afonso Costa Cortez, Carlos Alberto Mandarim-de-Lacerda, Lais de Carvalho, Simone Nunes de Carvalho
Bone marrow cells (BMC) migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation...
2017: PloS One
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