765 results match your criteria mobilization homing

The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows ~50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Read More

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Safety and therapeutic potential of human bone marrow-derived mesenchymal stromal cells in regenerative medicine.

Stem Cell Investig 2021 11;8:10. Epub 2021 May 11.

Stempeutics Research Pvt. Ltd, Manipal, Karnataka, India.

Regenerative medicine is considered as an alternative approach to healthcare. Owing to their pluripotent abilities and their relative lack of ethical and legal issues, adult stem cells are considered as optimal candidates for use in the treatment of various diseases. Bone marrow-derived mesenchymal stem cells are among the most promising candidates for clinical applications as they have expressed a higher degree of plasticity . Read More

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Inhibition of SGLT2 Rescues Bone Marrow Cell Traffic for Vascular Repair. Role of Glucose Control and Ketogenesis.

Diabetes 2021 Apr 26. Epub 2021 Apr 26.

Department of Medicine, University of Padova, Padova, Italy

The mechanisms by which sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells with vascular regenerative capacity, at least in part by lowering glycemia. In this study, we used mice with streptozotocin-induced diabetes treated with the SGLT2i dapagliflozin at a dose that reduced glucose levels by 20%. Read More

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The Nlrp3 inflammasome - the evolving story of its positive and negative effects on hematopoiesis.

Curr Opin Hematol 2021 Jul;28(4):251-261

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.

Purpose Of Review: Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the Nlrp3 inflammasome, which is an intracellular innate immunity pattern recognition receptor and sensor of changes in the hematopoietic microenvironment, and focus on its role in hematopoieisis.

Recent Findings: Hematopoietic stem progenitor cells (HSPCs) are exposed to several external mediators of innate immunity. Read More

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Inhibition of CXCR4 ameliorates hypoxia-induced pulmonary arterial hypertension in rats.

Am J Transl Res 2021 15;13(3):1458-1470. Epub 2021 Mar 15.

Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi, Jiangsu Province, China.

Pulmonary vascular remodeling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is the main characteristic of pulmonary arterial hypertension (PAH). CXCR4 is a specific stem cell surface receptor of cytokine CXCL12 which could regulate homing of hematopoietic progenitor cells and their mobilization. There is evidence that bone marrow-derived CXCR4 proangiogenic cell accumulation take an important part in the development of pulmonary arterial hypertension; however, the underlying mechanisms still remain unknown. Read More

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Neurotrophin-3 accelerates reendothelialization through inducing EPC mobilization and homing.

Open Life Sci 2020 11;15(1):241-250. Epub 2020 May 11.

The 8th Medical Center of Chinese PLA General Hospital, Beijing, 100091, China.

Rapid endothelialization is an effective way to treat intimal hyperplasia after intravascular stent implantation. Blood vessels and nerves coordinate with each other in function, while neurotrophin-3 (NT-3) is an important class of nerve growth factors. Our study found that NT-3 promoted endothelial progenitor cell (EPC) mobilization, and the proportion of EPCs in peripheral blood was increased by 1. Read More

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Platelet TSP-1 controls prostate cancer-induced osteoclast differentiation and bone marrow-derived cell mobilization through TGFβ-1.

Am J Clin Exp Urol 2021 15;9(1):18-31. Epub 2021 Feb 15.

Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Cleveland, OH, USA.

The development of distant metastasis is the leading cause of prostate cancer (CaP)-related death, with the skeleton being the primary site of metastasis. While the progression of primary tumors and the growth of bone metastatic tumors are well described, the mechanisms controlling pre-metastatic niche formation and homing of CaP to bone remain unclear. Through prior studies, we demonstrated that platelet secretion was required for ongoing tumor growth and pre-metastatic tumor-induced bone formation. Read More

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February 2021

Danger-associated molecular pattern molecules take unexpectedly a central stage in Nlrp3 inflammasome-caspase-1-mediated trafficking of hematopoietic stem/progenitor cells.

Leukemia 2021 Feb 23. Epub 2021 Feb 23.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Like their homing after transplantation to bone marrow (BM), the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not fully understood, and several overlapping pathways are involved. Several years ago our group proposed that sterile inflammation in the BM microenvironment induced by pro-mobilizing agents is a driving force in this process. In favor of our proposal, both complement cascade (ComC)-deficient and Nlrp3 inflammasome-deficient mice are poor G-CSF and AMD3100 mobilizers. Read More

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February 2021

Extracellular Adenosine Triphosphate (eATP) and Its Metabolite, Extracellular Adenosine (eAdo), as Opposing "Yin-Yang" Regulators of Nlrp3 Inflammasome in the Trafficking of Hematopoietic Stem/Progenitor Cells.

Front Immunol 2020 29;11:603942. Epub 2021 Jan 29.

Stem Cell Institute at Division of Hematology, Department of Medicine and James Graham Brown Cancer Center, University of Louisville, KY, United States.

Nlrp3 inflammasome plays a pleiotropic role in hematopoietic cells. On the one hand, physiological activation of this intracellular protein complex is crucial to maintaining normal hematopoiesis and the trafficking of hematopoietic stem progenitor cells (HSPCs). On the other hand, its hyperactivation may lead to cell death by pyroptosis, and prolonged activity is associated with sterile inflammation of the BM and, as a consequence, with the HSPCs aging and origination of myelodysplasia and leukemia. Read More

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Neovascularization: The Main Mechanism of MSCs in Ischemic Heart Disease Therapy.

Front Cardiovasc Med 2021 26;8:633300. Epub 2021 Jan 26.

Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been shown to effectively limit the infarct area in numerous clinical and preclinical studies. However, the primary mechanism associated with this activity in MSC transplantation therapy remains unclear. Blood supply is fundamental for the survival of myocardial tissue, and the formation of an efficient vascular network is a prerequisite for blood flow. Read More

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January 2021

Poor mobilization of autologous CD34 peripheral blood stem cells in haematology patients undergoing autologous stem cell transplantation is associated with the presence of variants in genes implicated in clonal haematopoiesis of indeterminant potential.

Br J Haematol 2021 May 22;193(4):841-844. Epub 2021 Jan 22.

Department of Haematology and Transfusion, Royal North Shore Hospital, St Leonards, Australia.

Clonal haematopoiesis of indeterminant potential (CHIP) increases in frequency with age. The effect of CHIP on the mobilization of autologous CD34+ peripheral blood stem cells (PBSC) has not been reported. This study uses a DNA-based targeted candidate gene approach to identify the presence of somatic mutations in ASXL1, DNMT3A, JAK2, SF3B1, TET2 and TP53 in CD34+ haematopoietic progenitor cell-apheresis products of 96 patients who undergo PBSC mobilization for autologous stem cell transplantation (ASCT). Read More

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Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells - Clinical and Translational Implications.

Stem Cell Rev Rep 2021 Jun 16;17(3):821-828. Epub 2020 Nov 16.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.

Evidence indicates that bone marrow (BM)-residing hematopoietic stem/progenitor cells (HSPCs) are released into peripheral blood (PB) after administration of pro-mobilizing drugs, which induce a state of sterile inflammation in the BM microenvironment. In the reverse process, as seen after hematopoietic transplantation, intravenously injected HSPCs home and engraft into BM niches. Here again, conditioning for transplantation by myeloablative chemo- or radiotherapy induces a state of sterile inflammation that promotes HSPC seeding to BM stem cell niches. Read More

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The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative.

Nathan Karin

Front Immunol 2020 26;11:557586. Epub 2020 Oct 26.

Department of Immunology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells. Under normal conditions, they differentiate into macrophages, dendritic cells, and granulocytes. Under pathological conditions, such as chronic inflammation, or cancer, they tend to maintain their immature state as immature myeloid cells that, within the tumor microenvironment, become suppressor cells and assist tumor escape from immune eradication. Read More

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Ultrasound combined with SDF-1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model.

J Cell Mol Med 2020 09 17;24(18):10816-10829. Epub 2020 Aug 17.

Department of Medical Ultrasound, Laboratory of Ultrasound Imaging Drug, West China Hospital of Sichuan University, Chengdu, China.

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Read More

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September 2020

SDF-1 mediates mesenchymal stem cell recruitment and migration via the SDF-1/CXCR4 axis in bone defect.

J Bone Miner Metab 2021 Mar 20;39(2):126-138. Epub 2020 Oct 20.

Department of Geriatric Medicine, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130041, Jilin, People's Republic of China.

Introduction: Recent studies have indicated the potential of stem cell therapy in combination with cytokines to restore the bone repair via migration and homing of stem cells to the defected area. The present study aimed to investigate the mobilization and recruitment of mesenchymal stem cells (MSCs) in response to SDF-1.

Materials And Methods: Herein, the knockout rat model of the bone defect (BD) was treated with the induced membrane technique. Read More

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Subcutaneous Administration of AMD3100 into Mice Models of Alzheimer's Disease Ameliorated Cognitive Impairment, Reduced Neuroinflammation, and Improved Pathophysiological Markers.

J Alzheimers Dis 2020 ;78(2):653-671

The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Background: Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifest simultaneously, leading to cognitive impairment and death. Amyloid-β (Aβ) accumulation in the brain triggers the onset of AD, accompanied by neuroinflammatory response and pathological changes. The CXCR4/CXCL12 (SDF1) axis is one of the major signal transduction cascades involved in the inflammation process and regulation of homing of hematopoietic stem cells (HSCs) within the bone marrow niche. Read More

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CD81 knockout promotes chemosensitivity and disrupts in vivo homing and engraftment in acute lymphoblastic leukemia.

Blood Adv 2020 09;4(18):4393-4405

Nemours Center for Childhood Cancer Research, Cancer and Blood Disorders, Alfred I. duPont Hospital for Children, Wilmington, DE; and.

Relapse remains a major obstacle to achieving 100% overall survival rate in pediatric hematologic malignancies like acute lymphoblastic leukemia (ALL). Relapse often results from the development of chemoresistance. One of the mechanisms of chemoresistance involves ALL cell interactions with the bone marrow (BM) microenvironment, providing a sanctuary. Read More

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September 2020

"Protocol for a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-myocardial infarction": study protocol for a randomized controlled trial.

Trials 2020 Aug 26;21(1):744. Epub 2020 Aug 26.

Department of Cardiology, Medical University of Graz, Graz, Austria.

Background: Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Previous trials using bone marrow cells, selected stem cell populations, or cardiac stem cell progenitors require invasive procedures and had so far inconclusive results. A less invasive approach utilizes granulocyte-colony stimulating factor (G-CSF) to mobilize stem cells to circulating blood and induce neovascularization and differentiation into endothelial cells and cardiomyocytes. Read More

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Leukemia Stem Cell Release From the Stem Cell Niche to Treat Acute Myeloid Leukemia.

Front Cell Dev Biol 2020 9;8:607. Epub 2020 Jul 9.

Stem Cell Aging and Cancer Research Group, Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Tromsø, Norway.

Acute myeloid leukemia (AML) is a heterogeneous, complex, and deadly disease, whose treatment has hardly evolved for decades and grounds on the use of intensive chemotherapy regimens. Chemotherapy helps reduce AML bulk, but promotes relapse in the long-run by selection of chemoresistant leukemia stem cells (LSC). These may diversify and result in progression to more aggressive forms of AML. Read More

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Multiple Roles for Chemokines in Neutrophil Biology.

Front Immunol 2020 9;11:1259. Epub 2020 Jul 9.

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.

Chemokines are recognized as the most critical mediators for selective neutrophil recruitment during inflammatory conditions. Furthermore, they are considered fundamental regulators of neutrophil mobilization from the bone marrow (BM) to the bloodstream and for their homing back at the end of their life for apoptosis and clearance. However, chemokines are also important mediators of neutrophil effector functions including oxidative burst, degranulation, neutrophil extracellular trap (NET)osis, and production of inflammatory mediators. Read More

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Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice.

Stem Cells Int 2020 30;2020:6938620. Epub 2020 Jun 30.

Department of Cardiology and Hypertension, Yanbian University Hospital, Yanji, Jilin 133000, China.

Background: Aging is a major risk factor for cardiovascular disease. Cysteine protease cathepsin K (CatK) has been implicated in the process of angiogenesis, but the exact roles of individual CatK in vessel formation during aging are poorly understood.

Methods And Results: To study the putative role of CatK in ischemia-induced angiogenesis, we applied a hindlimb ischemia model to aged wild-type (CatK) and CatK-deficient (CatK) mice. Read More

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Pannexin-1 channel "fuels" by releasing ATP from bone marrow cells a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells.

Purinergic Signal 2020 09 12;16(3):313-325. Epub 2020 Jun 12.

Center for Preclinical Studies and Technology, Department of Regenerative Medicine, Medical University of Warsaw, ul. Żwirki i Wigury 61, 02-091, Warsaw, Poland.

An efficient harvest of hematopoietic stem/progenitor cells (HSPCs) after pharmacological mobilization from the bone marrow (BM) into peripheral blood (PB) and subsequent proper homing and engraftment of these cells are crucial for clinical outcomes from hematopoietic transplants. Since extracellular adenosine triphosphate (eATP) plays an important role in both processes as an activator of sterile inflammation in the bone marrow microenvironment, we focused on the role of Pannexin-1 channel in the secretion of ATP to trigger both egress of HSPCs out of BM into PB as well as in reverse process that is their homing to BM niches after transplantation into myeloablated recipient. We employed a specific blocking peptide against Pannexin-1 channel and noticed decreased mobilization efficiency of HSPCs as well as other types of BM-residing stem cells including mesenchymal stroma cells (MSCs), endothelial progenitors (EPCs), and very small embryonic-like stem cells (VSELs). Read More

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September 2020

Stem cell homing: From physiology to therapeutics.

Stem Cells 2020 10 21;38(10):1241-1253. Epub 2020 Jul 21.

James P. Wilmot Cancer Institute, Department of Medicine, University of Rochester, Rochester, New York, USA.

Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization. Read More

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October 2020

Innate immunity orchestrates the mobilization and homing of hematopoietic stem/progenitor cells by engaging purinergic signaling-an update.

Purinergic Signal 2020 06 15;16(2):153-166. Epub 2020 May 15.

Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Professor Lineu Prestes 748, Sao Paulo, SP, 05508-000, Brazil.

Bone marrow (BM) as an active hematopoietic organ is highly sensitive to changes in body microenvironments and responds to external physical stimuli from the surrounding environment. In particular, BM tissue responds to several cues related to infections, strenuous exercise, tissue/organ damage, circadian rhythms, and physical challenges such as irradiation. These multiple stimuli affect BM cells to a large degree through a coordinated response of the innate immunity network as an important guardian for maintaining homeostasis of the body. Read More

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Adipose mesenchymal stromal/stem cells expanded by a GMP compatible protocol displayed improved adhesion on cancer cells in flow conditions.

Ann Transl Med 2020 Apr;8(8):533

Stem Cell Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy.

Background: Adipose tissue derived mesenchymal stromal/stem cells (ASC) can be expanded using supernatant rich in growth factors (SRGF) as Good Manufacturing Practice compatible additive, instead of fetal bovine serum (FBS). After transendothelial migration, ASC can migrate to cancer masses where they can release active substances. Due to their homing and secretion properties ASC can be used as targeted drug delivery vehicles. Read More

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The Nlrp3 inflammasome as a "rising star" in studies of normal and malignant hematopoiesis.

Leukemia 2020 06 20;34(6):1512-1523. Epub 2020 Apr 20.

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Recent investigations indicate that hematopoiesis is coregulated by innate immunity signals and by pathways characteristic of the activation of innate immunity cells that also operate in normal hematopoietic stem progenitor cells (HSPCs). This should not be surprising because of the common developmental origin of these cells from a hemato/lymphopoietic stem cell. An important integrating factor is the Nlrp3 inflammasome, which has emerged as a major sensor of changes in body microenvironments, cell activation, and cell metabolic activity. Read More

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Low-Energy Shockwave Treatment Promotes Endothelial Progenitor Cell Homing to the Stenotic Pig Kidney.

Cell Transplant 2020 Jan-Dec;29:963689720917342

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.

Endothelial progenitor cells (EPCs) patrols the circulation and contributes to endothelial cell regeneration. Atherosclerotic renal artery stenosis (ARAS) induces microvascular loss in the stenotic kidney (STK). Low-energy shockwave therapy (SW) can induce angiogenesis and restore the STK microcirculation, but the underlying mechanism remains unclear. Read More

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GRASP55 Is Dispensable for Normal Hematopoiesis but Necessary for Myc-Dependent Leukemic Growth.

J Immunol 2020 05 30;204(10):2685-2696. Epub 2020 Mar 30.

Equipe Labellisée Ligue contre le Cancer, Aix Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, Cancerology Research Center of Marseille, Marseille 13009, France; and

Grasp55 is a ubiquitous Golgi stacking protein involved in autophagy, protein trafficking, and glucose deprivation sensing. The function of Grasp55 in protein trafficking has been attributed to its PDZ-mediated interaction with the C-terminal PDZ-binding motifs of protein cargos. We have recently shown that such an interaction occurs between Grasp55 and the adhesion molecule Jam-C, which plays a central role in stemness maintenance of hematopoietic and spermatogenic cells. Read More

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Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8 T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma.

Clin Cancer Res 2020 07 27;26(14):3791-3802. Epub 2020 Mar 27.

Cancer Center Amsterdam (CCA), Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands.

Purpose: Adenocarcinoma of the uterine cervix is the second most common type of cervical cancer after squamous cell carcinoma (SCC). Although both subtypes are treated similarly, patients with adenocarcinoma have a worse prognosis. In this study, immunologic features of the tumor microenvironment in these two subsets were pursued with potential therapeutic implications. Read More

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Differentiation and activation of eosinophils in the human bone marrow during experimental human endotoxemia.

J Leukoc Biol 2020 11 10;108(5):1665-1671. Epub 2020 Jan 10.

Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.

Acute infection is characterized by eosinopenia. However, the underlying mechanism(s) are poorly understood and it is unclear whether decreased mobilization/production of eosinophils in the bone marrow (BM) and/or increased homing to the tissues play a role. The objective of this study was to investigate the differentiation and activation status of eosinophils in the human BM and blood upon experimental human endotoxemia, a standardized, controlled, and reproducible model of acute systemic inflammation. Read More

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November 2020