23 results on '"De Marinis, Elisabetta"'
Search Results
2. Biomarkers in acute myeloid leukemia: From state of the art in risk classification to future challenges of RNA editing as disease predictor and therapy target
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Quattrocchi, Alberto, Cappelli, Luca Vincenzo, De Simone, Giovanna, De Marinis, Elisabetta, Gentile, Martina, Gasperi, Tecla, Pulsoni, Alessandro, Ascenzi, Paolo, and Nervi, Clara
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- 2023
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3. Nuclear miRNAs: Gene Regulation Activities.
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Billi, Monia, De Marinis, Elisabetta, Gentile, Martina, Nervi, Clara, and Grignani, Francesco
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GENETIC regulation , *MICRORNA , *GENE enhancers , *MESSENGER RNA , *NON-coding RNA , *GENE expression - Abstract
MicroRNAs (miRNAs) are small non-coding RNAs which contribute to the regulation of many physiological and pathological processes. Conventionally, miRNAs perform their activity in the cytoplasm where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. miRNAs recruit different protein complexes to these regions, resulting in activation or repression of transcription, through a number of molecular mechanisms. Hematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs can influence gene expression by affecting nuclear mRNA processing and by regulating pri-miRNA maturation, thus impacting the biogenesis of miRNAs themselves. Overall, nuclear miRNAs are biologically active molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Ruxolitinib binding to human serum albumin: bioinformatics, biochemical and functional characterization in JAK2V617F+ cell models
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De Marinis, Elisabetta, Ceccherelli, Alessia, Quattrocchi, Alberto, Leboffe, Loris, Polticelli, Fabio, Nervi, Clara, and Ascenzi, Paolo
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- 2019
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5. Retinoic acid receptors: From molecular mechanisms to cancer therapy
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di Masi, Alessandra, Leboffe, Loris, De Marinis, Elisabetta, Pagano, Francesca, Cicconi, Laura, Rochette-Egly, Cécile, Lo-Coco, Francesco, Ascenzi, Paolo, and Nervi, Clara
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- 2015
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6. Neuroglobin and neuronal cell survival
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Fiocchetti, Marco, De Marinis, Elisabetta, Ascenzi, Paolo, and Marino, Maria
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- 2013
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7. Human platelet lysate‐derived extracellular vesicles enhance angiogenesis through miR‐126.
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Bordin, Antonella, Chirivì, Maila, Pagano, Francesca, Milan, Marika, Iuliano, Marco, Scaccia, Eleonora, Fortunato, Orazio, Mangino, Giorgio, Dhori, Xhulio, De Marinis, Elisabetta, D'Amico, Alessandra, Miglietta, Selenia, Picchio, Vittorio, Rizzi, Roberto, Romeo, Giovanna, Pulcinelli, Fabio, Chimenti, Isotta, Frati, Giacomo, and De Falco, Elena
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EXTRACELLULAR vesicles ,BLOOD platelets ,NEOVASCULARIZATION ,UMBILICAL veins ,NON-coding RNA ,VESICLES (Cytology) ,EXOSOMES - Abstract
Objectives: Extracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here, we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL. Methods: We tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL‐derived EVs. Results: A subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in human umbilical vein endothelial cells (HUVECs) and increasing the angiogenic tubularly‐like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched with small RNAs and a high amount of miR‐126, the most abundant angiogenic miRNA in platelets. The transfer of miR‐126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as a downstream target in this system. Conclusion: PL is a biological source of available EVs with angiogenic effects involving a miRNAs‐based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Omega-3 as well as caloric restriction prevent the age-related modifications of cholesterol metabolism
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Martini, Chiara, Pallottini, Valentina, De Marinis, Elisabetta, Marino, Maria, Cavallini, Gabriella, Donati, Alessio, Straniero, Sara, and Trentalance, Anna
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- 2008
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9. Serum albumin and nucleic acids biodistribution: From molecular aspects to biotechnological applications.
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Vita, Gian Marco, De Simone, Giovanna, De Marinis, Elisabetta, Nervi, Clara, Ascenzi, Paolo, and di Masi, Alessandra
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SERUM albumin ,BLOOD proteins ,POST-translational modification ,RIBONUCLEOTIDES ,RNA ,DNA - Abstract
Serum albumin (SA) is the most abundant protein in plasma and represents the main carrier of endogenous and exogenous compounds. Several evidence supports the notion that SA binds single and double‐stranded deoxynucleotides and ribonucleotides at two sites, with values of the dissociation equilibrium constant (i.e., Kd) ranging from micromolar to nanomolar values. This can be relevant from a physiological and pathological point of view, as in human plasma circulates cell‐free nucleic acids (cfNAs), released by different tissues via apoptosis, necrosis, and secretions, circulates as single and double‐stranded NAs. Albeit SA shows low hydrolytic reactivity toward DNA and RNA, the high plasma concentration of this protein and the occurrence of several SA receptors may be pivotal for sequestering and hydrolyzing cfNAs. Therefore, pathological conditions like cancer, characterized by altered levels of human SA or by altered SA post‐translational modifications, may influence cfNAs distribution and metabolism. Besides, the stability, solubility, biocompatibility, and low immunogenicity make SA a golden share for biotechnological applications related to the delivery of therapeutic NAs (TNAs). Indeed, pre‐clinical studies report the therapeutic potential of SA:TNAs complexes in precision cancer therapy. Here, the molecular and biotechnological implications of SA:NAs interaction are discussed, highlighting new perspectives on SA plasmatic functions. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Treatment of Insulin Resistance in the Neurodegeneration
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Stefanelli, Manuela, Martocchia, Antonio, De Marinis, Elisabetta Adele, Falaschi, Giulia Maria, Romano, Gloria, Rufo, Maddalena, and Falaschi, Paolo
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- 2014
11. Epigenetic role of miRNAs in normal and leukemic hematopoiesis
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Pagano, Francesca, De Marinis, Elisabetta, Grignani, Francesco, and Nervi, Clara
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- 2013
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12. Genetic lesions disrupting calreticulin 3′‐untranslated region in JAK2 mutation‐negative polycythemia vera.
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Quattrocchi, Alberto, Maiorca, Carlo, Billi, Monia, Tomassini, Simona, De Marinis, Elisabetta, Cenfra, Natalia, Equitani, Francesco, Gentile, Martina, Ceccherelli, Alessia, Banella, Cristina, Mecarocci, Sergio, Scerpa, Maria Cristina, Pisanò, Stefania, Pacilli, Annalisa, Di Cristofano, Claudio, Mancini, Massimiliano, Guglielmelli, Paola, Vannucchi, Alessandro Maria, Noguera, Nelida, and Grignani, Francesco
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- 2020
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13. PB1787: PLZF‐RARΑ ENHANCES METABOLIC PLASTICITY AND ROS SCAVENGING IN AML CELLS.
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Zaza, Alessandra, Gallo, Mariana, Biscussi, Brunella, Angelini, Daniela F., Pasqualini, Gloria, Catalano, Gianfranco, De Marinis, Elisabetta, Pertinhez, Thelma, Voso, Maria Teresa, Venditti, Adriano, Nervi, Clara, and Noguera, Nelida Ines
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- 2023
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14. Therapeutic Drug Monitoring in the Management of HIV-Infected Patients
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Jelena, Ivanovic, Ivanovic, Jelena, Emanuele, Nicastri, Nicastri, Emanuele, Paolo, Ascenzi, Ascenzi, Paolo, Rita, Bellagamba, Bellagamba, Rita, Elisabetta, De Marinis, De Marinis, Elisabetta, Stefania, Notari, Notari, Stefania, Leopoldo Paolo, Pucillo, Pucillo Leopoldo, Paolo, Valerio, Tozzi, Tozzi, Valerio, Giuseppe, Ippolito, Ippolito, Giuseppe, Pasquale, Narciso, and Narciso, Pasquale
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Drug ,medicine.medical_specialty ,Anti-HIV Agents ,media_common.quotation_subject ,HIV Infections ,Therapeutic drug monitoring ,Sensitivity and Specificity ,Biochemistry ,Mass Spectrometry ,Immunoenzyme Techniques ,Efficacy ,Acquired immunodeficiency syndrome (AIDS) ,Pharmacokinetics ,Drug Discovery ,medicine ,Humans ,Drug Interactions ,Intensive care medicine ,Chromatography, High Pressure Liquid ,Ultraviolet ,media_common ,Pharmacology ,Chromatography ,Clinical Trials as Topic ,medicine.diagnostic_test ,Genotypic inhibitory quotient ,business.industry ,Organic Chemistry ,HIV ,virus diseases ,medicine.disease ,Clinical trial ,Spectrophotometry ,High Pressure Liquid ,Pharmacogenomics ,Immunology ,HIV-1 ,Anti-retroviral therapy ,Spectrophotometry, Ultraviolet ,Drug Monitoring ,Molecular Medicine ,business ,Pharmacogenetics - Abstract
The rate of HIV-positive patients that fails to reach or to maintain a durable virological suppression under anti-retroviral (ARV) therapy might be as high as 50%, therefore new tools to improve ARV drug efficacy are urgently needed. Among others, therapeutic drug monitoring (TDM) is a strategy by which the dosing regimen for a patient is guided by measurement of plasma drug levels, enabling physicians to optimize ARV drug efficacy and to avoid drug-related toxicity. The most used analytical methods to determine plasma levels of ARV drugs are HPLC-UV and HPLC-MS(/MS), recently MALDI-based methods and enzyme immunoassay (EIA) technologies have been also employed. The wide inter-patient variability in ARV drug pharmacokinetic supports the application of TDM to the clinical management of HIV-infected patients. Drug-drug and drug-food interactions, drug binding to plasma proteins, drug sequestering by erythrocytes, hepatic impairment, sex, age, pregnancy, and host genetic factors are sources of inter-patient variability affecting ARV drug pharmacokinetics. Combining the information of TDM and resistance tests in genotypic inhibitory quotient (GIQ) is likely to be of great clinical utility. Indeed, only two clinical trials on GIQ, both conducted using ARV drugs not more commonly in use, have shown clinical benefits. The design of new trials with long follow-up and sample size representative of the current HIV prevalence is urgently needed to give indications for GIQ as an early predictor of virological response. Here, the basic principles and the available methods for TDM in the management of HIV-infected patients are reviewed.
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- 2008
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15. Epigenetic treatment of solid tumours: a review of clinical trials.
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Nervi, Clara, De Marinis, Elisabetta, and Codacci-Pisanelli, Giovanni
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TUMOR treatment , *EPIGENETICS , *CLINICAL trials - Abstract
Epigenetic treatment has been approved by regulatory agencies for haematological malignancies. The success observed in cutaneous lymphomas represents a proof of principle that similar results may be obtained in solid tumours. Several agents that interfere with DNA methylation-demethylation and histones acetylation/deacetylation have been studied, and some (such as azacytidine, decitabine, valproic acid and vorinostat) are already in clinical use. The aim of this review is to provide a brief overview of the molecular events underlying the antitumour effects of epigenetic treatments and to summarise data available on clinical trials that tested the use of epigenetic agents against solid tumours. We not only list results but also try to indicate how the proper evaluation of this treatment might result in a better selection of effective agents and in a more rapid development. We divided compounds in demethylating agents and HDAC inhibitors. For each class, we report the antitumour activity and the toxic side effects. When available, we describe plasma pharmacokinetics and pharmacodynamic evaluation in tumours and in surrogate tissues (generally white blood cells). Epigenetic treatment is a reality in haematological malignancies and deserves adequate attention in solid tumours. A careful consideration of available clinical data however is required for faster drug development and possibly to re-evaluate some molecules that were perhaps discarded too early. [ABSTRACT FROM AUTHOR]
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- 2015
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16. 17β-Estradiol - A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H2O2-Induced Toxicity.
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De Marinis, Elisabetta, Ascenzi, Paolo, Pellegrini, Marco, Galluzzo, Paola, Bulzomi, Pamela, Arevalo, Maria Angeles, Garcia-Segura, Luis Miguel, and Marino, Maria
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- 2011
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17. Neuroglobin, estrogens, and neuroprotection.
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De Marinis, Elisabetta, Marino, Maria, and Ascenzi, Paolo
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GLOBIN , *NEUROPROTECTIVE agents , *ESTROGEN receptors , *STEROID hormones , *NEUROTOXICOLOGY , *MITOCHONDRIA - Abstract
Globins have been found in glial cells and neurons of invertebrates and vertebrates. The first nerve globin has been recognized in the nerve cord of the polychaete annelid Aphrodite aculeata in 1872. In some invertebrates, the nerve globin reaches a millimolar concentration which is likely sufficient to sustain the aerobic metabolism and thus the excitability of the nervous system. In 2000, the first vertebrate nerve globin, named neuroglobin (Ngb), has been identified in neuronal tissues of mice and humans. In contrast to invertebrate nerve globins, the concentration of Ngb, the prototype of vertebrate nerve globins, is low (μM), reaching a maximum of 100 μM in retina cells. Therefore, Ngb appears unlikely to act primarily as an O buffer and to facilitate O diffusion to the mitochondria. Indeed, Ngb has been hypothesized to catalyze the formation/decomposition of reactive nitrogen and/or oxygen species and to be part of intracellular signaling pathways enhancing cell survival. Here, we report that neuronal Ngb levels are strongly induced by the steroid hormone 17β-estradiol. Furthermore, Ngb participates to mechanisms involved in 17β-estradiol-induced protective effects against HO-induced neurotoxicity. © 2011 IUBMB IUBMB Life, 63(3): 140-145, 2011 [ABSTRACT FROM AUTHOR]
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- 2011
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18. Peroxynitrite scavenging by ferryl sperm whale myoglobin and human hemoglobin
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Ascenzi, Paolo, De Marinis, Elisabetta, di Masi, Alessandra, Ciaccio, Chiara, and Coletta, Massimo
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NITRITES , *SPERM whale , *MYOGLOBIN , *HEMOGLOBINS , *OXIDATIVE stress , *CELL death , *HYDROGEN-ion concentration , *CARBON dioxide - Abstract
Globins protect from the oxidative and nitrosative cell damage. Here, kinetics of peroxynitrite scavenging by ferryl sperm whale myoglobin (Mb—Fe(IV)ꘌO) and human hemoglobin (Hb—Fe(IV)ꘌO), between pH 5.8 and 8.3 at 20.0 °C, are reported. In the absence of CO2, values of the second-order rate constant for peroxynitrite scavenging by Mb—Fe(IV)ꘌO and Hb—Fe(IV)ꘌO (i.e., for Mb—Fe(III) and Hb—Fe(III) formation; kon) are 4.6 × 104 M−1 s−1 and 3.3 × 104 M−1 s−1, respectively, at pH 7.1. Values of kon increase on decreasing pH with pKa values of 6.9 and 6.7, this suggests that the ONOOH species reacts preferentially with Mb—Fe(IV)ꘌO and Hb—Fe(IV)ꘌO. In the presence of CO2 (=1.2 × 10−3 M), values of kon for peroxynitrite scavenging by Mb—Fe(IV)ꘌO and Hb—Fe(IV)ꘌO are essentially pH-independent, the average kon values are 7.1 × 104 M−1 s−1 and 1.2 × 105 M−1 s−1, respectively. As a whole, Mb—Fe(IV)ꘌO and Hb—Fe(IV)ꘌO, obtained by treatment with H2O2, undertake within the same cycle H2O2 and peroxynitrite detoxification. [Copyright &y& Elsevier]
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- 2009
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19. Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O
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Ascenzi, Paolo, De Marinis, Elisabetta, Visca, Paolo, Ciaccio, Chiara, and Coletta, Massimo
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METABOLIC detoxification , *HEMOPROTEINS , *MYCOBACTERIUM leprae , *REACTIVE oxygen species , *OXIDATIVE stress , *ANTIOXIDANTS - Abstract
Abstract: During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO−) detoxification by ferryl Ml-trHbO (Ml-trHbO:glyph name="dbnd" />O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO:glyph name="dbnd" />O (i.e., of Ml-trHbOormation; k on), at pH 7.2 and 22.0°C, are 1.5×104 M−1 s−1, and 2.2×104 M−1 s−1, in the absence of and presence of physiological levels of CO2 (∼1.2×10−3 M), respectively. Values of k on increase on decreasing pH with a pK a value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbO:glyph name="dbnd" />O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO:glyph name="dbnd" />O, which could be responsible for the oxidative damage of the mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification. [Copyright &y& Elsevier]
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- 2009
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20. Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins.
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De Marinis, Elisabetta, Casella, Luigi, Ciaccio, Chiara, Coletta, Massimo, Visca, Paolo, and Ascenzi, Paolo
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PEROXIDATION , *GLOBIN , *LIGANDS (Biochemistry) , *METAZOA , *NITROGEN , *OXYGEN - Abstract
Globins are generally considered as carriers of diatomic gaseous ligands (e.g., O2 and NO) in metazoa. Recently, the (pseudo-)enzymatic activity of globins towards reactive nitrogen and oxygen species has been elucidated. In particular, some globins (e.g., hemoglobin and myoglobin) catalyze the enzymatic scavenging of NO and peroxynitrite in the presence of H2O2. Indeed, H2O2 oxidizes some globins leading to the formation of water and of the heme-protein ferryl derivative, which, in turn, oxidizes NO and peroxynitrite leading to the formation of the globin ferric species, NO2-, and NO3-. Here, we hypothesize that NO, peroxynitrite, and H2O2 are co-substrates for the peroxidase activity of some globins, this catalytic activity was reported in 1900 for the first time, even though the substrates have never been identified firmly up to now. © 2008 IUBMB IUBMB Life, 61(1): 62–73, 2009 [ABSTRACT FROM AUTHOR]
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- 2009
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21. H2O2 and NO scavenging by Mycobacterium leprae truncated hemoglobin O
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Ascenzi, Paolo, De Marinis, Elisabetta, Coletta, Massimo, and Visca, Paolo
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MYCOBACTERIUM leprae , *HEMOGLOBINS , *ANTIOXIDANTS , *BLOOD proteins - Abstract
Abstract: Kinetics of ferric Mycobacterium leprae truncated hemoglobin O (trHbOoxidation by H2O2 and of trHbO:glyph name="dbnd" />O reduction by NO and NO2 − are reported. The value of the second-order rate constant for H2O2-mediated oxidation of trHbOs 2.4×103 M−1 s−1. The value of the second-order rate constant for NO-mediated reduction of trHbO:glyph name="dbnd" />O is 7.8×106 M−1 s−1. The value of the first-order rate constant for trHbOe:glyph name="sbnd" />ONO decay to the resting form trHbOs 2.1×101 s−1. The value of the second-order rate constant for NO2 −-mediated reduction of trHbO:glyph name="dbnd" />O is 3.1×103 M−1 s−1. As a whole, trHbO:glyph name="dbnd" />O, generated upon reaction with H2O2, catalyzes NO reduction to NO2 −. In turn, NO and NO2 − act as antioxidants of trHbO:glyph name="dbnd" />O, which could be responsible for the oxidative damage of the mycobacterium. Therefore, Mycobacterium leprae trHbO could be involved in both H2O2 and NO scavenging, protecting from nitrosative and oxidative stress, and sustaining mycobacterial respiration. [Copyright &y& Elsevier]
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- 2008
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22. Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells.
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Albanesi, Jacopo, Noguera, Nelida Ines, Banella, Cristina, Colangelo, Tommaso, De Marinis, Elisabetta, Leone, Stefano, Palumbo, Orazio, Voso, Maria Teresa, Ascenzi, Paolo, Nervi, Clara, Bianchi, Fabrizio, and di Masi, Alessandra
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ACUTE promyelocytic leukemia ,ONCOGENIC proteins ,CHIMERIC proteins ,TRANSCRIPTION factors ,ARSENIC trioxide ,DNA repair - Abstract
Acute promyelocytic leukemia (APL) is a hematological disease characterized by a balanced reciprocal translocation that leads to the synthesis of the oncogenic fusion protein PML-RARα. APL is mainly managed by a differentiation therapy based on the administration of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, therapy resistance, differentiation syndrome, and relapses require the development of new low-toxicity therapies based on the induction of blasts differentiation. In keeping with this, we reasoned that a better understanding of the molecular mechanisms pivotal for ATRA-driven differentiation could definitely bolster the identification of new therapeutic strategies in APL patients. We thus performed an in-depth high-throughput transcriptional profile analysis and metabolic characterization of a well-established APL experimental model based on NB4 cells that represent an unevaluable tool to dissect the complex mechanism associated with ATRA-induced granulocytic differentiation. Pathway-reconstruction analysis using genome-wide transcriptional data has allowed us to identify the activation/inhibition of several cancer signaling pathways (e.g., inflammation, immune cell response, DNA repair, and cell proliferation) and master regulators (e.g., transcription factors, epigenetic regulators, and ligand-dependent nuclear receptors). Furthermore, we provide evidence of the regulation of a considerable set of metabolic genes involved in cancer metabolic reprogramming. Consistently, we found that ATRA treatment of NB4 cells drives the activation of aerobic glycolysis pathway and the reduction of OXPHOS-dependent ATP production. Overall, this study represents an important resource in understanding the molecular "portfolio" pivotal for APL differentiation, which can be explored for developing new therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Remote Adipose Tissue-Derived Stromal Cells of Patients with Lung Adenocarcinoma Generate a Similar Malignant Microenvironment of the Lung Stromal Counterpart.
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De Falco, Elena, Bordin, Antonella, Menna, Cecilia, Dhori, Xhulio, Picchio, Vittorio, Cozzolino, Claudia, De Marinis, Elisabetta, Floris, Erica, Maria Giorgiano, Noemi, Rosa, Paolo, Angelo Rendina, Erino, Ibrahim, Mohsen, and Calogero, Antonella
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ADENOCARCINOMA , *LUNG cancer , *INTERLEUKINS , *EPIDERMAL growth factor , *MICRORNA , *STROMAL cells , *BIOINFORMATICS , *RESEARCH funding , *TUMOR necrosis factors , *CELL proliferation , *ADIPOSE tissues , *MESENCHYMAL stem cells - Abstract
Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumors may alter distant niches of stromal cells is still unclear, especially at early stages. In this short report, we attempt to better understand the biology of this cross-talk. In our "autologous stromal experimental setting," we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases such as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC for up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similar to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analyzed by arrays, a small pool of 5 upregulated molecules including IL1-β, IL-3, MCP-1, TNF-α, and EGF, was commonly shared by both malignant-like autologous A- and L-MSC derived microenvironments vs those benign. The bioinformatics analysis revealed that these proteins were strictly and functionally interconnected to lung fibrosis and proinflammation and that miR-126, 101, 486, and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively. When the miR-126-3p was silenced in A549 treated with AMSC-derived conditioned media from patients with lung adenocarcinoma, cell proliferation decreased compared to control media. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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