A5047764985- Bone health and treatments
- Bone Metabolism and Diseases
- Extracellular vesicles in disease
- Bone and Joint Diseases
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Osteomyelitis and Bone Disorders Research
- Nicotinic Acetylcholine Receptors Study
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Stock Market Forecasting Methods
- Immune cells in cancer
- Fullerene Chemistry and Applications
- Synthesis of Tetrazole Derivatives
- Immunodeficiency and Autoimmune Disorders
- Systemic Lupus Erythematosus Research
- Blood disorders and treatments
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Bone health and osteoporosis research
- Diabetes Treatment and Management
- Synthesis and Reactivity of Heterocycles
- Prostate Cancer Treatment and Research
- Balkans: History, Politics, Society
Semmelweis University
2013-2024
Babraham Institute
2016-2018
Hungarian Academy of Sciences
2014
Redundancy and compensation provide robustness to biological systems but may contribute therapy resistance. Both tumor-associated macrophages (TAMs) Foxp3+ regulatory T (Treg) cells promote tumor progression by limiting antitumor immunity. Here we show that genetic ablation of CSF1 in colorectal cancer reduces the influx immunosuppressive CSF1R+ TAMs within tumors. This reduction CSF1-dependent resulted increased CD8+ cell attack on tumors, its effect growth was limited a compensatory...
Abstract CD4 + regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target immunosuppressive function of Treg cells within tumours without disrupting their systemic anti‐inflammatory function. High levels expression chemokine (C‐C motif) receptor 8 (CCR8) discriminate from those found lymphoid tissues. It has recently been...
An effective immune response to the ubiquitous fungus Aspergillus fumigatus is dependent upon production of reactive oxygen species (ROS) by NADPH oxidase. This evidenced acute sensitivity oxidase-deficient humans and mice invasive aspergillosis. Neutrophils are recruited lungs shortly postinfection respond phagocytosing conidia mediating extracellular killing germinated hyphae in a ROS-dependent manner. However, signaling mechanisms regulating generation ROS poorly understood. PI3Ks...
Multiple modes of immunosuppression restrain immune function within tumors. We previously reported that phosphoinositide 3-kinase δ (PI3Kδ) inactivation in mice confers resistance to a range tumor models by disrupting mediated regulatory T cells (Tregs). The PI3Kδ inhibitor idelalisib has proven highly effective the clinical treatment chronic lymphocytic leukemia and potential extend use inhibitors nonhematological cancers is being evaluated. In this work, we demonstrate antitumor effect...
Background: Our aim was to investigate the role of nicotinic acetylcholine receptors (nAChRs) in in-vitro osteoclastogenesis and in-vivo bone homeostasis. Methods:The presence nAChR subunits as well effects agonists were investigated by ex vivo assays, real-time polymerase chain reaction, Western blot flow cytometry murine marrow-derived macrophages differentiated recombinant receptor activator nuclear factor kappa B ligand (RANKL) macrophage colony-stimulating (M-CSF).The phenotype mice...
Osteoclasts play a central role in cancer-cell-induced osteolysis, but the molecular mechanisms of osteoclast activation during bone metastasis formation are incompletely understood. By performing RNA sequencing on mouse breast carcinoma cell line with higher bone-metastatic potential, here we identify enzyme CYP11A1 strongly upregulated osteotropic tumor cells. Genetic deletion Cyp11a1 cells leads to decreased number metastases does not alter primary growth and lung mice. The product...
While phosphoinositide 3-kinases (PI3Ks) are involved in various intracellular signal transduction processes, the specific functions of different PI3K isoforms poorly understood. We have previously shown that PI3Kβ isoform is required for arthritis development K/BxN serum-transfer model. Since osteoclasts play a critical role pathologic bone loss during inflammatory and other diseases, we undertook this study to test osteoclast function using combined genetic pharmacologic approach.The...
Eur J Clin Invest 2012; 42 (1): 49–60 Abstract Background Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule diverse haematopoietic lineages. Here, we tested the of PLCγ2 and ovariectomy‐induced resorption, as well vitro osteoclast cultures using PLCγ2‐deficient (PLCγ2 −/− ) mice. Materials methods The...
Syk is a nonreceptor tyrosine kinase critically involved in signaling by various immunoreceptors including B-cell-receptors and activating Fc-receptors. We have previously shown that also mediates immunoreceptor-like signals required for the vitro development function of osteoclasts. However, perinatal lethality Syk–/– mice precluded analysis role vivo bone metabolism. To overcome problem, we generated with osteoclast-specific (SykΔOC) or hematopoietic (SykΔHaemo) deficiency conditional...
Steroid hormone production by adrenal cortex, gonads and placenta (so called glandular steroidogenesis) is responsible for the endocrine control of body’s homeostasis organized a feedback regulatory mechanism based on hypothalamus-pituitary-steroidogenic gland axis. On other hand, recently discovered extraglandular steroidogenesis occurring locally in different tissues rather linked to paracrine or autocrine signaling it independent hypothalamus pituitary. Bone cells, such as bone-forming...
Tumors often metastasize to the bone and osteolytic metastases, where bone-resorbing osteoclasts are activated, leading pathological fractures increased mortality in patients. Osteoclasts play a central role cancer cell-induced osteolysis, but molecular mechanisms of osteoclast activation during metastasis formation incompletely understood. Solid tumors were previously considered induce differentiation indirectly via osteoblasts, however, based on our results, cell-derived soluble factors...
Osteoclasts are multinucleated cells of hematopoietic origin which critically involved in physiological and pathological bone resorption. They develop from myeloid progenitors through characteristic gene expression changes intercellular fusion. This process is directed by M-CSF RANKL also able to trigger osteoclast development marrow vitro . conventionally visualized histochemical staining followed manual counting, hinders kinetic studies automated quantification. Here we describe two...
<h3>Background/Objectives</h3> We have previously shown that nicotinic acetylcholine receptors (nAChRs) are key regulators of osteoclastogenesis (1)<b>.</b> NAChRs permit the movement Ca2+, intracellular oscillation which is known to play an essential role in mediating effects RANKL on osteoclastogenesis. therefore elucidated potential nAChR ligands RANKL-induced Ca2+ oscillation. To assess downstream elements RANK pathway, we also evaluated their effect transcription factors NFATc1 and...
<h3>Introduction</h3> Extracellular vesicles (EV) are subcellular sized intercellular messengers, which present in various biological fluids. EVs carry a wide variety of biomolecules and they may alter the recipient cells' functions. The microvesicles plasma membrane derived EVs; exosomes, smallest vesicles, originate from endosome. Our objectives were to investigate effect on human <i>in vitro</i> osteoclastogenesis, characterise serum EV profile healthy donors, rheumatoid arthritis (RA)...
<h3>Background and objectives</h3> Osteoclasts are the unique bone-resorbing cells of hematopoietic origin; their development is regulated primarily by M-CSF, RANKL integrin-mediated interactions. Our workgroup has previously tested thousands Src-family kinase inhibitors produced Vichem Ltd on neutrophil granulocytes, which show many similarities with osteoclasts regarding signalling pathways. One most effective was PD166326, an anti-leukaemia drug candidate. Here we effect PD166326...
<h3>Background</h3> Extracellular vesicles (EVs) like microvesicles (MVs) and exosomes (EXOs) are released in an evolutionary conserved manner by cells. EVs mediate intercellular communication with the transmission of molecules from their parent cell to targets. <h3>Objectives</h3> Our objective was investigate effect on human <i>in vitro</i> osteoclastogenesis healthy donors, rheumatoid arthritis (RA) psoriatic (PsA) patients. <h3>Methods</h3> Blood samples volunteers, RA patients PsA...