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https://www.readbyqxmd.com/read/28821477/tgf-%C3%AE-induced-intracellular-pai-1-is-responsible-for-retaining-hematopoietic-stem-cells-in-the-niche
#1
Takashi Yahata, Abd Aziz Ibrahim, Yukari Muguruma, Mesut Eren, Alexander M Shaffer, Nobuo Watanabe, Satoko Kaneko, Tetsuo Nakabayashi, Takashi Dan, Noriaki Hirayama, Douglas E Vaughan, Toshio Miyata, Kiyoshi Ando
Hematopoietic stem and progenitor cells (HSPCs) reside in the supportive stromal niche in bone marrow (BM); when needed, however, they are rapidly mobilized into the circulation, suggesting that HSPCs are intrinsically highly motile but are usually stayed in the niche. We questioned what determines the motility of HSPCs. Here we show that transforming growth factor (TGF)-β-induced intracellular plasminogen activator inhibitor (PAI)-1 activation is responsible for keeping HSPCs in the BM niche. We found that the expression of PAI-1, a downstream target of TGF-β-signaling, was selectively augmented in niche-residing HSPCs...
August 18, 2017: Blood
https://www.readbyqxmd.com/read/28819198/regulation-of-ccr7-dependent-cell-migration-through%C3%A2-ccr7-homodimer-formation
#2
Daichi Kobayashi, Masataka Endo, Hirotaka Ochi, Hironobu Hojo, Masayuki Miyasaka, Haruko Hayasaka
The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#3
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/28815665/pharmacological-modulation-of-c-x-c-motif-chemokine-receptor-4-influences-development-of-acute-respiratory-distress-syndrome-after-lung-ischemia-reperfusion-injury
#4
Sean P Nassoiy, Favin S Babu, Heather M LaPorte, Matthias Majetschak
Activation of CXC motif chemokine receptor 4 (CXCR4) has been reported to result in lung protective effects in various experimental models. The effects of pharmacological CXCR4 modulation on the development of acute respiratory distress syndrome (ARDS) after lung injury, however, are unknown. Thus, we studied whether blockade and activation of CXCR4 influences development of ARDS in a unilateral lung ischemia-reperfusion injury rat model. Anesthetized, mechanically ventilated animals underwent right lung ischemia (series 1: 30 min; series 2: 60 min) followed by reperfusion for 300 min...
August 16, 2017: Clinical and Experimental Pharmacology & Physiology
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/28810154/synthesis-and-evaluation-of-a-99m-tc-labeled-chemokine-receptor-antagonist-peptide-for-imaging-of-chemokine-receptor-expressing-tumors
#6
Azadeh Mikaeili, Mostafa Erfani, Omid Sabzevari
OBJECTIVE: The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. In the present study, we report on the evaluation of a new radiopharmaceutical peptide for its potential to visualization for CXCR4-expressing tumors in vivo. METHODS: A CXCR4 antagonist analogue was synthesized using a standard Fmoc solid phase strategy and labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands. In addition, stability in human serum, receptor binding internalization, in vivo tumor uptake, and tissue biodistribution were evaluated...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28807596/the-role-of-angiotensin-ii-in-parietal-epithelial-cell-proliferation-and-crescent-formation-in-glomerular-diseases
#7
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)/CXCR4 axis, in the development of those lesions...
August 11, 2017: American Journal of Pathology
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
#8
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/28804668/impaired-mrna-expression-of-the-migration-related-chemokine-receptor-cxcr4-in-mesenchymal-stem-cells-of-copd-patients
#9
K Karagiannis, A Proklou, E Tsitoura, I Lasithiotaki, C Kalpadaki, D Moraitaki, I Sperelakis, G Kontakis, K M Antoniou, N Tzanakis
Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. CXCR4/SDF1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BM-MSCs obtained from twelve COPD patients and seven healthy donors...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28802167/induction-of-senescence-in-cancer-cells-by-5-aza-2-deoxycytidine-bioinformatics-and-experimental-insights-to-its-targets
#10
Jayarani F Putri, Nashi Widodo, Kazuichi Sakamoto, Sunil C Kaul, Renu Wadhwa
5'-Aza-2'-deoxycytidine (5-Aza-dC) is a demethylating drug that causes genome-wide hypomethylation resulting in the expression of several tumor suppressor genes causing growth arrest of cancer cells. Cancer is well established as a multifactorial disease and requires multi-module therapeutics. Search for new drugs and their approval by FDA takes a long time. Keeping this in view, research on new functions of FDA-approved anticancer drugs is desired to expand the list of multi-module functioning drugs for cancer therapy...
August 2, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28797111/angiogenic-t-cell-expansion-correlates-with-severity-of-peripheral-vascular-damage-in-systemic-sclerosis
#11
Mirko Manetti, Sara Pratesi, Eloisa Romano, Silvia Bellando-Randone, Irene Rosa, Serena Guiducci, Bianca Saveria Fioretto, Lidia Ibba-Manneschi, Enrico Maggi, Marco Matucci-Cerinic
The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay...
2017: PloS One
https://www.readbyqxmd.com/read/28793338/anti-tumor-activity-of-nanomicelles-encapsulating-cxcr4-peptide-antagonist-e5
#12
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/28790053/progenitor-cells-and-clinical-outcomes-in-patients-with-heart-failure
#13
Ayman Samman Tahhan, Muhammad Hammadah, Pratik B Sandesara, Salim S Hayek, Andreas P Kalogeropoulos, Ayman Alkhoder, Heval Mohamed Kelli, Matthew Topel, Nima Ghasemzadeh, Kaavya Chivukula, Yi-An Ko, Hiroshi Aida, Iraj Hesaroieh, Ernestine Mahar, Jonathan H Kim, Peter Wilson, Leslee Shaw, Viola Vaccarino, Edmund K Waller, Arshed A Quyyumi
BACKGROUND: Endogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, their predictive role in heart failure (HF) remains controversial. We assessed the relationship between the number of circulating PCs and the pathogenesis and severity of HF and their impact on incident HF events. METHODS AND RESULTS: We recruited 2049 adults of which 651 had HF diagnosis...
August 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28789988/the-use-of-retronectin-in-studies-requiring-in-vitro-hiv-1-infection-of-human-hematopoietic-stem-progenitor-cells
#14
Tetsuo Tsukamoto, Seiji Okada
Human immunodeficiency virus (HIV) causes damage, directly or indirectly, to the whole hematopoietic system, including CD34(+) hematopoietic stem/progenitor cells (HSPCs). CXCR4-tropic strains of HIV-1 may affect the function of CD34(+)CXCR4(+) progenitor cells either by infecting the cells or modifying the dynamics of more differentiated hematopoietic cells. However, CD34(+) cells are known for their resistance to HIV-1 infection in vitro, which restricts any detailed analysis of the impact of HIV on HSPCs...
August 5, 2017: Journal of Virological Methods
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
#15
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/28782391/in-vitro-expansion-of-cd-133-cells-derived-from-umbilical-cord-blood-in-poly-l-lactic-acid-plla-scaffold-coated-with-fibronectin-and-collagen
#16
Maryam Islami, Yousef Mortazavi, Masoud Soleimani, Samad Nadri
CONTEXT: Due to their renewal and potency, umbilical cord blood (UCB) stem cells have the ability to proliferate and serve as an attractive alternative source for bone marrow transplantation. However, insufficient number of haematopoietic stem cells (HSCs) in UCB is still a major constraint in clinical applications. OBJECTIVE: In vitro expansion of stem cells on fibronectin (Fn)-coated poly-L-lactic acid (PLLA) scaffold can be a proper way to overcome this limitation...
August 6, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28780431/thermosensitive-chitosan-based-hydrogels-releasing-stromal-cell-derived-factor-1-alpha-recruit-msc-for-corneal-epithelium-regeneration
#17
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/28775206/clinical-molecular-imaging-of-chemokine-receptor-cxcr4-expression-in-atherosclerotic-plaque-using-68-ga-pentixafor-pet-correlation-with-cardiovascular-risk-factors-and-calcified-plaque-burden
#18
Desiree Weiberg, James T Thackeray, Guenter Daum, Jan M Sohns, Saskia Kropf, Hans-Jürgen Wester, Tobias L Ross, Frank M Bengel, Thorsten Derlin
The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4+ cell types in cardiovascular diseases including atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of (68)Ga-Pentixafor, a specific CXCR4 ligand for positron emission tomography (PET). Methods: Data of fifty-one patients who underwent (68)Ga-Pentixafor PET/computed tomography (PET/CT) for non-cardiovascular indications were retrospectively analyzed...
August 3, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#19
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28774348/epithelial-to-mesenchymal-transition-in-fhc-silenced-cells-the-role-of-cxcr4-cxcl12-axis
#20
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
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