40 results on '"di Somma, Sarah"'
Search Results
2. Humoral Response to 2-dose BNT162b2 mRNA COVID-19 Vaccination in Liver Transplant Recipients
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Pontillo, Giuseppina, Pignata, Luca, Attanasio, Maria Rosaria, Lieto, Raffaele, Cutolo, Francesco, Cuomo, Marianna, Guarino, Maria, Esposito, Ilaria, Portella, Giuseppe, Cossiga, Valentina, Loperto, Ilaria, Tortora, Raffaella, Cennamo, Michele, Capasso, Mario, Terracciano, Daniela, Galeota Lanza, Alfonso, Di Somma, Sarah, Picciotto, Francesco Paolo, and Morisco, Filomena
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- 2022
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3. Self-assembly of bio-inspired heterochiral peptides
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Florio, Daniele, Di Natale, Concetta, Scognamiglio, Pasqualina Liana, Leone, Marilisa, La Manna, Sara, Di Somma, Sarah, Netti, Paolo Antonio, Malfitano, Anna Maria, and Marasco, Daniela
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- 2021
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4. Structural insights into amyloid structures of the C-terminal region of nucleophosmin 1 in type A mutation of acute myeloid leukemia
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Di Natale, Concetta, La Manna, Sara, Malfitano, Anna Maria, Di Somma, Sarah, Florio, Daniele, Scognamiglio, Pasqualina Liana, Novellino, Ettore, Netti, Paolo Antonio, and Marasco, Daniela
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- 2019
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5. Low Interferon-γ Levels in Cord and Peripheral Blood of Pregnant Women Infected with SARS-CoV-2
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Cennamo, Michele, primary, La Civita, Evelina, additional, Sarno, Laura, additional, Carbone, Gianluigi, additional, Di Somma, Sarah, additional, Cabaro, Serena, additional, Troisi, Jacopo, additional, Sirico, Angelo, additional, Improda, Francesco Paolo, additional, Guida, Maurizio, additional, Terracciano, Daniela, additional, and Portella, Giuseppe, additional
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- 2023
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6. Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer
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Napolitano, Fabiana, primary, Di Somma, Sarah, additional, Castellano, Giuliano, additional, Amato, Jussara, additional, Pagano, Bruno, additional, Randazzo, Antonio, additional, Portella, Giuseppe, additional, and Malfitano, Anna Maria, additional
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- 2022
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7. Humoral Response to 2-dose BNT162b2 mRNA COVID-19 Vaccination in Liver Transplant Recipients
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Guarino, Maria, primary, Esposito, Ilaria, additional, Portella, Giuseppe, additional, Cossiga, Valentina, additional, Loperto, Ilaria, additional, Tortora, Raffaella, additional, Cennamo, Michele, additional, Capasso, Mario, additional, Terracciano, Daniela, additional, Galeota Lanza, Alfonso, additional, Di Somma, Sarah, additional, Picciotto, Francesco Paolo, additional, Morisco, Filomena, additional, Pontillo, Giuseppina, additional, Pignata, Luca, additional, Attanasio, Maria Rosaria, additional, Lieto, Raffaele, additional, Cutolo, Francesco, additional, and Cuomo, Marianna, additional
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- 2022
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8. Humoral response to 2-dose BNT162b2 mRNA vaccine for COVID-19 in liver transplant recipients
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Guarino, Maria, primary, Esposito, Ilaria, additional, Portella, Giuseppe, additional, Cossiga, Valentina, additional, Loperto, Ilaria, additional, Pignata, Luca, additional, Tortora, Raffaella, additional, Attanasio, Maria Rosaria, additional, Cennamo, Michele, additional, Capasso, Mario, additional, Terracciano, Daniela, additional, Cutolo, Francesco Maria, additional, Lanza, Alfonso Galeota, additional, Lieto, Raffaele, additional, di Somma, Sarah, additional, Picciotto, Francesco Paolo, additional, and Morisco, Filomena, additional
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- 2022
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9. Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells
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Gado, Francesca, primary, Ferrisi, Rebecca, additional, Di Somma, Sarah, additional, Napolitano, Fabiana, additional, Mohamed, Kawthar A., additional, Stevenson, Lesley A., additional, Rapposelli, Simona, additional, Saccomanni, Giuseppe, additional, Portella, Giuseppe, additional, Pertwee, Roger G., additional, Laprairie, Robert B., additional, Malfitano, Anna Maria, additional, and Manera, Clementina, additional
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- 2022
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10. Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy
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Di Somma, Sarah, primary, Napolitano, Fabiana, additional, Portella, Giuseppe, additional, and Malfitano, Anna Maria, additional
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- 2021
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11. Proteostasis unbalance of nucleophosmin 1 in Acute Myeloid Leukemia: An aggregomic perspective
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Di Natale, Concetta, primary, Florio, Daniele, additional, Di Somma, Sarah, additional, Di Matteo, Adele, additional, Federici, Luca, additional, Netti, Paolo Antonio, additional, Morelli, Giancarlo, additional, Malfitano, Anna Maria, additional, and Marasco, Daniela, additional
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- 2020
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12. Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines
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Iannuzzi, Carmelina Antonella, primary, Indovina, Paola, additional, Forte, Iris Maria, additional, Di Somma, Sarah, additional, Malfitano, Anna Maria, additional, Bruno, Martina, additional, Portella, Giuseppe, additional, Pentimalli, Francesca, additional, and Giordano, Antonio, additional
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- 2020
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13. Tumor-Associated Macrophage Status in Cancer Treatment
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Malfitano, Anna Maria, primary, Pisanti, Simona, additional, Napolitano, Fabiana, additional, Di Somma, Sarah, additional, Martinelli, Rosanna, additional, and Portella, Giuseppe, additional
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- 2020
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14. Virotherapy: From single agents to combinatorial treatments
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Malfitano, Anna Maria, primary, Di Somma, Sarah, additional, Iannuzzi, Carmelina Antonella, additional, Pentimalli, Francesca, additional, and Portella, Giuseppe, additional
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- 2020
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15. Reply to Comment on “Malfitano, A.M. et al. Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer” Cancers 2019, 11, 1532
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Malfitano, Anna Maria, primary, Di Somma, Sarah, additional, Prevete, Nella, additional, and Portella, Giuseppe, additional
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- 2020
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16. G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells
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Di Somma, Sarah, primary, Amato, Jussara, additional, Iaccarino, Nunzia, additional, Pagano, Bruno, additional, Randazzo, Antonio, additional, Portella, Giuseppe, additional, and Malfitano, Anna Maria, additional
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- 2019
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17. GM-CSF and IL-3 Modulate Human Monocyte TNF-A Production and Renewal in In Vitro Models of Trained Immunity
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Di Somma, Sarah
- Abstract
GM-CSF and IL-3 are hematopoietic cytokines that modulate the effector functions of several immune cell subsets. In particular, GM-CSF and IL-3 exert a significant control on monocyte and macrophage effector functions, as assessed in experimental models of inflammatory and autoimmune diseases and in human studies. Here we sought to investigate the mechanisms and the extent to which GM-CSF and IL-3 modulate the pro-inflammatory, LPS-mediated, activation of human CD14+ monocytes taking into account the new concept of trained immunity (i.e. the priming stimulus modulates the response to subsequent stimuli mainly by enhancing immune activation status). We demonstrate that GM-CSF and IL-3 priming enhances TNF-α production upon subsequent LPS stimulation (short-term model of trained immunity) in a p38- and SIRT2-dependent manner without increasing TNF mRNA or primary transcript levels (a more direct measure of transcription), thus supporting a post-transcriptional regulation of TNF- α in primed monocytes. GM-CSF and IL-3 priming followed by 6 days of resting also results in increased TNF-α production upon LPS stimulation (long-term model of trained immunity). In this case, however, GM-CSF and IL-3 priming induces a c-Myc-dependent monocyte renewal and increase in cell number that is in turn responsible for heightened TNF-α production. Overall, our results provide insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity.
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- 2018
18. The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth
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Di Somma, Sarah, primary, Iannuzzi, Carmelina Antonella, additional, Passaro, Carmela, additional, Forte, Iris Maria, additional, Iannone, Raffaella, additional, Gigantino, Vincenzo, additional, Indovina, Paola, additional, Botti, Gerardo, additional, Giordano, Antonio, additional, Formisano, Pietro, additional, Portella, Giuseppe, additional, Malfitano, Anna Maria, additional, and Pentimalli, Francesca, additional
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- 2019
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19. Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems
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Florio, Daniele, primary, Malfitano, Anna Maria, additional, Di Somma, Sarah, additional, Mügge, Carolin, additional, Weigand, Wolfgang, additional, Ferraro, Giarita, additional, Iacobucci, Ilaria, additional, Monti, Maria, additional, Morelli, Giancarlo, additional, Merlino, Antonello, additional, and Marasco, Daniela, additional
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- 2019
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20. Potential involvement of neutrophils in human thyroid cancer
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Galdiero, Maria Rosaria, primary, Varricchi, Gilda, additional, Loffredo, Stefania, additional, Bellevicine, Claudio, additional, Lansione, Tiziana, additional, Ferrara, Anne Lise, additional, Iannone, Raffaella, additional, di Somma, Sarah, additional, Borriello, Francesco, additional, Clery, Eduardo, additional, Triassi, Maria, additional, Troncone, Giancarlo, additional, and Marone, Gianni, additional
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- 2018
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21. Neutrophils Involvement in Human Thyroid Cancer
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Galdiero, Maria Rosaria, primary, Varricchi, Gilda, additional, Loffredo, Stefania, additional, Bellevicine, Claudio, additional, Lansione, Tiziana, additional, Ferrara, Anne Lise, additional, Iannone, Raffaella, additional, Di Somma, Sarah, additional, Borriello, Francesco, additional, Clery, Eduardo, additional, Triassi, Maria, additional, Troncone, Giancarlo, additional, and Marone, Gianni, additional
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- 2018
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22. LPS-elicited TSLPR expression enriches a functionally discrete subset of human CD14+ CD1c+ monocytes
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Borriello, Francesco, primary, Iannone, Raffaella, additional, Di Somma, Sarah, additional, Vastolo, Viviana, additional, Petrosino, Giuseppe, additional, Visconte, Feliciano, additional, Raia, Maddalena, additional, Scalia, Giulia, additional, Loffredo, Stefania, additional, Varricchi, Gilda, additional, Galdiero, Maria Rosaria, additional, Granata, Francescopaolo, additional, Del Vecchio, Luigi, additional, Portella, Giuseppe, additional, and Marone, Gianni, additional
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- 2017
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23. GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity
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Borriello, Francesco, primary, Iannone, Raffaella, additional, Di Somma, Sarah, additional, Loffredo, Stefania, additional, Scamardella, Eloise, additional, Galdiero, Maria Rosaria, additional, Varricchi, Gilda, additional, Granata, Francescopaolo, additional, Portella, Giuseppe, additional, and Marone, Gianni, additional
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- 2017
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24. The Oncolytic Virus dl 922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.
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Di Somma, Sarah, Iannuzzi, Carmelina Antonella, Passaro, Carmela, Forte, Iris Maria, Iannone, Raffaella, Gigantino, Vincenzo, Indovina, Paola, Botti, Gerardo, Giordano, Antonio, Formisano, Pietro, Portella, Giuseppe, Malfitano, Anna Maria, and Pentimalli, Francesca
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HIGH mobility group proteins ,CELL death ,CELL cycle ,MESOTHELIOMA ,VASCULAR endothelial growth factors - Abstract
Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl 922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl 922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl 922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl 922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl 922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl 922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl 922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl 922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus. [ABSTRACT FROM AUTHOR]
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- 2019
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25. The oncolytic virusdl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma
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Passaro, Carmela, primary, Borriello, Francesco, additional, Vastolo, Viviana, additional, Di Somma, Sarah, additional, Scamardella, Eloise, additional, Gigantino, Vincenzo, additional, Franco, Renato, additional, Marone, Gianni, additional, and Portella, Giuseppe, additional
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- 2015
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26. Early Targets of miR-34a in Neuroblastoma
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De Antonellis, Pasqualino, primary, Carotenuto, Marianeve, additional, Vandenbussche, Jonathan, additional, De Vita, Gennaro, additional, Ferrucci, Veronica, additional, Medaglia, Chiara, additional, Boffa, Iolanda, additional, Galiero, Alessandra, additional, Di Somma, Sarah, additional, Magliulo, Daniela, additional, Aiese, Nadia, additional, Alonzi, Alessandro, additional, Spano, Daniela, additional, Liguori, Lucia, additional, Chiarolla, Cristina, additional, Verrico, Antonio, additional, Schulte, Johannes H., additional, Mestdagh, Pieter, additional, Vandesompele, Jo, additional, Gevaert, Kris, additional, and Zollo, Massimo, additional
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- 2014
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27. Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer.
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Malfitano, Anna Maria, Di Somma, Sarah, Prevete, Nella, and Portella, Giuseppe
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METABOLISM in viruses , *IMMUNOTHERAPY , *THERAPEUTICS , *THYROID gland tumors , *VIRUSES , *PROTEIN kinase inhibitors , *ANAPLASTIC thyroid cancer - Abstract
Virotherapy is a novel cancer treatment based on oncolytic viruses (OVs), which selectively infect and lyse cancer cells, without harming normal cells or tissues. Several viruses, either naturally occurring or developed through genetic engineering, are currently under investigation in clinical studies. Emerging reports suggesting the immune-stimulatory property of OVs against tumor cells further support the clinical use of OVs for the treatment of lesions lacking effective therapies. Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), have a poor prognosis and limited treatment options. Therefore, several groups investigated the therapeutic potential of OVs in PDTC/ATC models producing experimental data sustaining the potential clinical efficacy of OVs in these cancer models. Moreover, the presence of an immunosuppressive microenvironment further supports the potential use of OVs in ATC. In this review, we present the results of the studies evaluating the efficacy of OVs alone or in combination with other treatment options. In particular, their potential therapeutic combination with multiple kinases inhibitors (MKIs) or immune checkpoint inhibitors are discussed. [ABSTRACT FROM AUTHOR]
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- 2019
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28. Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes.
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Borriello, Francesco, Iannone, Raffaella, Di Somma, Sarah, Vastolo, Viviana, Petrosino, Giuseppe, Visconte, Feliciano, Raia, Maddalena, Scalia, Giulia, Loffredo, Stefania, Varricchi, Gilda, Galdiero, Maria Rosaria, Granata, Francescopaolo, Del Vecchio, Luigi, Portella, Giuseppe, and Marone, Gianni
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THYMIC stromal lymphopoietin , *LIPOPOLYSACCHARIDES , *EPITHELIAL cells , *CYTOKINES , *CD14 antigen , *MONOCYTES - Abstract
Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14+ monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14+ CD16- monocytes, TSLPR+ monocytes (TSLPR+ mono), expresses TSLPR complex upon LPS stimulation in an NF-κB- and p38-dependent manner. Phenotypic, functional, and transcriptomic analysis revealed specific features of TSLPR+ mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e., GAS6, ALOX15B, FCGR2B, LAIR1). Strikingly, TSLPR+ mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14+ CD1c+ cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared with healthy control subjects. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14+ CD16- monocytes and prompt further ontogenetic and functional analysis of CD14+ CD1c+ and LPS-activated CD14+ CD1c+ TSLPR+ mono. [ABSTRACT FROM AUTHOR]
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- 2017
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29. Low Interferon-γ Levels in Cord and Peripheral Blood of Pregnant Women Infected with SARS-CoV-2
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Michele Cennamo, Evelina La Civita, Laura Sarno, Gianluigi Carbone, Sarah Di Somma, Serena Cabaro, Jacopo Troisi, Angelo Sirico, Francesco Paolo Improda, Maurizio Guida, Daniela Terracciano, Giuseppe Portella, Cennamo, Michele, LA CIVITA, Evelina, Sarno, Laura, Carbone, Gianluigi, DI SOMMA, Sarah, Cabaro, Serena, Troisi, Jacopo, Sirico, Angelo, Improda, FRANCESCO PAOLO, Guida, Maurizio, Daniela, and Portella, Giuseppe
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Microbiology (medical) ,immune system ,SARS-CoV-2 ,Virology ,anti-Interferon antibody ,cord blood ,Interferon-γ ,pregnancy ,Microbiology - Abstract
COVID-19 is characterized by the immune system’s overreaction resulting in a ‘cytokine storm’, consisting in a massive release of cytokine into the bloodstream, leading to local and systemic inflammatory response. This clinical picture is further complicated in case of infection of patients with a peculiar immunological status, such as pregnancy. In this paper, we focused on Interferon-γ, which plays a pivotal immunomodulatory role in normal pregnancy and fetal development, as well as in defense against pathogens. In this study, we compared the levels of Interferon-γ and the Interferon autoantibodies of the peripheral and cord blood of pregnant women with confirmed mild COVID-19 and healthy pregnant women. The Interferon-γ was significantly lower both in the peripheral and cord blood of SARS-CoV-2-positive mothers, suggesting that infection can affect the fetal microenvironment even without severe maternal symptoms. In conclusion, further studies are needed to clarify whether lower levels of Interferon-γ due to SARS-CoV-2 infection affect the development or infection susceptibility of infants born to SARS-CoV-2-infected mothers.
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- 2023
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30. Targeting G-quadruplex motifs interferes with differentiation of adipose-derived mesenchymal stem cells
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Maria Rosaria Ambrosio, Teresa Migliaccio, Fabiana Napolitano, Sarah Di Somma, Giovanni Maneli, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, Pietro Formisano, Anna Maria Malfitano, Ambrosio, Maria Rosaria, Migliaccio, Teresa, Napolitano, Fabiana, Di Somma, Sarah, Maneli, Giovanni, Amato, Jussara, Pagano, Bruno, Randazzo, Antonio, Portella, Giuseppe, Formisano, Pietro, and Malfitano, Anna Maria
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Adipocyte ,G-quadruplex ,Differentiation ,Molecular Medicine ,Medicine (miscellaneous) ,Mesenchymal stem cells ,Cell Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
Background G-quadruplex (G4) motifs are nucleic acid secondary structures observed in mammalian genomes and transcriptomes able to regulate various cellular processes. Several small molecules have been developed so far to modulate G4 stability, frequently associated with anticancer activity. However, how G4 structures are regulated over homeostatic conditions is mostly unexplored. Here, we used human adipose-derived mesenchymal stem cells (ASCs) to address the role of G4 motifs during adipogenic differentiation. Methods Adipocyte differentiation of ASCs was investigated in the presence or absence of a well-known G4 ligand, Braco-19. Cell viability was determined by sulforhodamine B assay. Cell dimension and granularity, DNA G4 motifs and cell cycle were detected by flow cytometry. Lipid droplet accumulation was assessed by Oil Red O staining. Cell senescence was evaluated by β-galactosidase staining. Gene expression was measured by qPCR. Protein release in the extracellular medium was quantified by ELISA. Results Braco-19 used at non-cytotoxic concentrations induced morphological changes in mature adipocytes partially restoring an undifferentiated-like status. Braco-19 reduced lipid vacuolization and PPARG, AP2, LEP and TNFA mRNA levels in terminally differentiated cells. No effect was observed in cell senescence, fibrotic markers, IL-6 and IL-8 production, while the secretion of VEGF was dose-dependently reduced. Interestingly, G4 structures were increased in differentiated adipocytes compared to their precursors. Braco-19 treatment reduced G4 content in mature adipocytes. Conclusions Our data highlight a new role of G4 motifs as genomic structural elements related to human ASC differentiation into mature adipocytes, with potential implications in physio-pathological processes.
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- 2023
31. Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer
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Fabiana Napolitano, Sarah Di Somma, Giuliano Castellano, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, Anna Maria Malfitano, Napolitano, Fabiana, Di Somma, Sarah, Castellano, Giuliano, Amato, Jussara, Pagano, Bruno, Randazzo, Antonio, Portella, Giuseppe, and Malfitano, Anna Maria
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Male ,senescence ,G-quadruplex ,adenoviru ,Animal ,Adenoviridae Infection ,oncolytic virus ,adenovirus ,breast cancer ,STING ,Mice, Nude ,General Medicine ,DNA ,Adenoviridae ,G-Quadruplexes ,Mice ,oncolytic viru ,Breast Neoplasm ,Human - Abstract
G-quadruplexes (G4s) are nucleic secondary structures characterized by G-tetrads. G4 motif stabilization induces DNA damage and cancer cell death; therefore, G4-targeting small molecules are the focus of clinical investigation. DNA destabilization induced by G4 ligands might potentiate the anticancer activity of agents targeting DNA or inhibiting its repair such as oncolytic viruses. This study represents the first approach combining G4 ligands, BRACO-19 (B19), pyridostatin (PDS), and the adenovirus dl922-947 in breast cancer cells. We demonstrated that G4 binders and dl922-947 induce cytotoxicity in breast cancer cells (MDA-MB-231 and MCF-7) and at higher doses in other neoplastic cell lines of thyroid (BHT-101 cells) and prostate (PC3 cells). G4 binders induce G4 motifs distributed in the S and G2/M phases in MCF-7 cells. G4 binder/dl922-947 combination increases cell cytotoxicity and the accumulation in subG0/G1. Indeed, G4 binders favor viral entry and replication with no effect on coxsackie and adenovirus receptor. Notably, dl922-947 induces G4 motifs and its combination with PDS potentiates this effect in MCF-7 cells. The agents alone or in combination similarly enhanced cell senescence. Additionally, PDS/dl922-947 combination inactivates STING signaling in MDA-MB-231 cells. Our results suggest that G4 binder/virotherapy combination may represent a novel therapeutic anticancer approach.
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- 2022
32. Platinum(II) O,S Complexes Inhibit the Aggregation of Amyloid Model Systems
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Antonello Merlino, Daniela Marasco, Wolfgang Weigand, Maria Chiara Monti, Daniele Florio, Ilaria Iacobucci, Giarita Ferraro, Anna Maria Malfitano, Carolin Mügge, Giancarlo Morelli, Sarah Di Somma, Florio, Daniele, Malfitano, Anna Maria, Di Somma, Sarah, Mügge, Carolin, Weigand, Wolfgang, Ferraro, Giarita, Iacobucci, Ilaria, Monti, Maria, Morelli, Giancarlo, Merlino, Antonello, and Marasco, Daniela
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Circular dichroism ,amyloid aggregation ,Amyloid ,Stereochemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Physical Chemistry ,Catalysis ,Cinnamic acid ,Adduct ,Inorganic Chemistry ,anti-aggregation properties ,lcsh:Chemistry ,chemistry.chemical_compound ,Physical and Theoretical Chemistry ,Cytotoxicity ,Molecular Biology ,platinum complexe ,lcsh:QH301-705.5 ,Spectroscopy ,anti-aggregation propertie ,Nucleophosmin ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,General Medicine ,0104 chemical sciences ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,Thioflavin ,Platinum ,platinum complexes - Abstract
Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.
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- 2019
33. G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells
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Nunzia Iaccarino, Bruno Pagano, Jussara Amato, Sarah Di Somma, Anna Maria Malfitano, Giuseppe Portella, Antonio Randazzo, DI SOMMA, Sarah, Amato, Jussara, Iaccarino, Nunzia, Pagano, Bruno, Randazzo, Antonio, Portella, Giuseppe, and Malfitano, Anna Maria
- Subjects
0301 basic medicine ,Cancer Research ,T cell ,Cell ,lcsh:RC254-282 ,Article ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,breast cancer ,immunogenic cell death markers ,medicine ,Cytotoxicity ,medicine.diagnostic_test ,G-quadruplex ,Chemistry ,T cell activation ,Cell cycle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Immunogenic cell death ,Intracellular - Abstract
Background: DNA G-quadruplex (G4) structures represent potential anti-cancer targets. In this study, we compared the effect of two G4-targeting compounds, C066-3108 and the gold standard BRACO-19. Methods: In breast and prostate cancer cells, cytotoxicity induced by both molecules was measured by a sulforhodamine B assay. In breast cancer cells, cycle, apoptosis, the formation of G4 structures, calreticulin and high mobility group box 1 (HMGB1), as well as T cell activation, were analyzed by flow cytometry and adenosine triphosphate (ATP) by luminescence. Results: Both ligands inhibited cell survival and induced DNA damage. In MCF-7 cells, G4 ligands increased the subG0/G1 phase of the cell cycle inducing apoptosis and reduced intracellular ATP. In untreated MCF-7 cells, we observed a slight presence of G4 structures associated with the G2/M phase. In MDA-MB231 cells, G4 ligands decreased the G1 and enhanced the G2/M phase. We observed a decrease of intracellular ATP, calreticulin cell surface exposure and an increase of HMGB1, accompanied by T cell activation. Both compounds induced G4 structure formation in the subG0/G1 phase. Conclusions: Our data report similar effects for both compounds and the first evidence that G4 ligands induce the release of danger signals associated with immunogenic cell death and induction of T cell activation.
- Published
- 2019
34. Potential involvement of neutrophils in human thyroid cancer
- Author
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Raffaella Iannone, Sarah Di Somma, Francesco Borriello, Gianni Marone, Tiziana Lansione, Stefania Loffredo, Maria Rosaria Galdiero, Gilda Varricchi, Claudio Bellevicine, Maria Triassi, Giancarlo Troncone, Eduardo Clery, Anne Lise Ferrara, Galdiero, Maria Rosaria, Varricchi, Gilda, Loffredo, Stefania, Bellevicine, Claudio, Lansione, Tiziana, Ferrara, ANNE LISE, Iannone, Raffaella, DI SOMMA, Sarah, Borriello, Francesco, Clery, Eduardo, Triassi, Maria, Troncone, Giancarlo, and Marone, Gianni
- Subjects
0301 basic medicine ,Neutrophils ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Lung and Intrathoracic Tumors ,White Blood Cells ,Spectrum Analysis Techniques ,0302 clinical medicine ,Animal Cells ,Thymic Tumors ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,lcsh:Science ,Endocrine Tumors ,Immune Response ,CD11b Antigen ,Multidisciplinary ,biology ,Cell adhesion molecule ,Chemistry ,Chemotaxis ,Flow Cytometry ,3. Good health ,Cell Motility ,Oncology ,Neutrophil Infiltration ,Integrin alpha M ,Spectrophotometry ,030220 oncology & carcinogenesis ,Cytophotometry ,Cellular Types ,medicine.symptom ,Research Article ,Cell Survival ,Immune Cells ,Immunology ,Inflammation ,Research and Analysis Methods ,GPI-Linked Proteins ,Carcinomas ,Proinflammatory cytokine ,03 medical and health sciences ,Signs and Symptoms ,Downregulation and upregulation ,Diagnostic Medicine ,Antigens, CD ,Cell Line, Tumor ,medicine ,Humans ,Thyroid Neoplasms ,Interleukin 8 ,Immunoassays ,Molecular Biology Techniques ,Molecular Biology ,Blood Cells ,Innate immune system ,Biochemistry, Genetics and Molecular Biology (all) ,lcsh:R ,Interleukin-8 ,Biology and Life Sciences ,Cancers and Neoplasms ,Cell Biology ,Coculture Techniques ,Immunity, Innate ,030104 developmental biology ,Agricultural and Biological Sciences (all) ,Immunologic Techniques ,Cancer research ,biology.protein ,lcsh:Q ,Thyroid Carcinomas ,Reactive Oxygen Species ,Cell Adhesion Molecules ,Cloning - Abstract
Background Neutrophil functions have long been regarded as limited to acute inflammation and the defense against microbes. The role(s) of neutrophils in cancer remain poorly understood. Neutrophils infiltrate tumors and are key effector cells in the orchestration of inflammatory responses. Thyroid cancer (TC) is the most recurrent endocrine malignant tumor and is responsible for 70% of deaths due to endocrine cancers. No studies are so far available on the role of neutrophils in TC. Objective Our purpose was to study the involvement of tumor-associated neutrophils in TC. Methods Highly purified human neutrophils (>99%) from healthy donors were stimulated in vitro with conditioned media derived from TC cell lines TPC1 and 8505c (TC-CMs). Neutrophil functions (e.g., chemotaxis, activation, plasticity, survival, gene expression, and protein release) were evaluated. Results TC-derived soluble factors promoted neutrophil chemotaxis and survival. Neutrophil chemotaxis toward a TC-CM was mediated, at least in part, by CXCL8/IL-8, and survival was mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, each TC-CM induced morphological changes and activation of neutrophils (e.g., CD11b and CD66b upregulation and CD62L shedding) and modified neutrophils' kinetic properties. Furthermore, each TC-CM induced production of reactive oxygen species, expression of proinflammatory and angiogenic mediators (CXCL8/IL-8, VEGF-A, and TNF-α), and a release of matrix metalloproteinase 9 (MMP-9). Moreover, in TC patients, tumor-associated neutrophils correlated with larger tumor size. Conclusions TC cell lines produce soluble factors able to "educate" neutrophils toward an activated functional state. These data will advance the understanding of the molecular and cellular mechanisms of innate immunity in TC.
- Published
- 2018
35. Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14(+) CD1c(+) Monocytes
- Author
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Raffaella Iannone, Francesco Borriello, Maria Rosaria Galdiero, Francescopaolo Granata, Viviana Vastolo, Feliciano Visconte, Giuseppe Petrosino, Luigi Del Vecchio, Sarah Di Somma, Maddalena Raia, Giulia Scalia, Stefania Loffredo, Gianni Marone, Gilda Varricchi, Giuseppe Portella, Borriello, Francesco, Iannone, Raffaella, Di Somma, Sarah, Vastolo, Viviana, Petrosino, Giuseppe, Visconte, Feliciano, Raia, Maddalena, Scalia, Giulia, Loffredo, Stefania, Varricchi, Gilda, Galdiero, Maria Rosaria, Granata, Francescopaolo, Del Vecchio, Luigi, Portella, Giuseppe, and Marone, Gianni
- Subjects
0301 basic medicine ,Thymic stromal lymphopoietin ,Sepsi ,CD14 ,Immunology ,Population ,Lipopolysaccharide ,CD16 ,Biology ,Antigens, CD14 ,Monocyte ,Immunophenotyping ,Antigens, CD1 ,03 medical and health sciences ,medicine ,Intercellular Signaling Peptides and Protein ,Immunology and Allergy ,Arachidonate 15-Lipoxygenase ,Receptors, Cytokine ,Receptors, Immunologic ,Interleukin-7 receptor ,education ,Cytokine ,Interleukin 4 ,Cells, Cultured ,education.field_of_study ,Receptors, IgG ,Cell Differentiation ,Dendritic cell ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Chemokine CCL17 ,Interleukin-4 ,Human - Abstract
Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14+ monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14+ CD16− monocytes, TSLPR+ monocytes (TSLPR+ mono), expresses TSLPR complex upon LPS stimulation in an NF-κB– and p38-dependent manner. Phenotypic, functional, and transcriptomic analysis revealed specific features of TSLPR+ mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e., GAS6, ALOX15B, FCGR2B, LAIR1). Strikingly, TSLPR+ mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14+ CD1c+ cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared with healthy control subjects. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14+ CD16− monocytes and prompt further ontogenetic and functional analysis of CD14+ CD1c+ and LPS-activated CD14+ CD1c+ TSLPR+ mono.
- Published
- 2017
36. GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity
- Author
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Raffaella Iannone, Gilda Varricchi, Gianni Marone, Giuseppe Portella, Sarah Di Somma, Eloise Scamardella, Francescopaolo Granata, Stefania Loffredo, Francesco Borriello, Maria Rosaria Galdiero, Borriello, Francesco, Iannone, Raffaella, Di Somma, Sarah, Loffredo, Stefania, Scamardella, Eloise, Galdiero, Maria Rosaria, Varricchi, Gilda, Granata, Francescopaolo, Portella, Giuseppe, and Marone, Gianni
- Subjects
0301 basic medicine ,CD14 ,Immunology ,immunometabolism ,Priming (immunology) ,Inflammation ,macrophage ,Biology ,innate immune memory ,03 medical and health sciences ,Immune system ,Immunity ,TLR ,medicine ,Immunology and Allergy ,Monocyte ,IL-3 ,GM-CSF ,3. Good health ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,inflammation ,monocyte ,Tumor necrosis factor alpha ,medicine.symptom - Abstract
GM-CSF and IL-3 are hematopoietic cytokines that also modulate the effector functions of several immune cell subsets. In particular, GM-CSF and IL-3 exert a significant control on monocyte and macrophage effector functions, as assessed in experimental models of inflammatory and autoimmune diseases and also in human studies. Here, we sought to investigate the mechanisms and the extent to which GM-CSF and IL-3 modulate the pro-inflammatory, LPS-mediated, activation of human CD14(+) monocytes taking into account the new concept of trained immunity (i.e., the priming stimulus modulates the response to subsequent stimuli mainly by inducing chromatin remodeling and increased transcription at relevant genetic loci). We demonstrate that GM-CSF and IL-3 priming enhances TNF-α production upon subsequent LPS stimulation (short-term model of trained immunity) in a p38- and SIRT2-dependent manner without increasing TNF primary transcript levels (a more direct measure of transcription), thus supporting a posttranscriptional regulation of TNF-α in primed monocytes. GM-CSF and IL-3 priming followed by 6 days of resting also results in increased TNF-α production upon LPS stimulation (long-term model of trained immunity). In this case, however, GM-CSF and IL-3 priming induces a c-Myc-dependent monocyte renewal and increase in cell number that is in turn responsible for heightened TNF-α production. Overall, our results provide insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity.
- Published
- 2017
37. The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP- 1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma
- Author
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Vincenzo Gigantino, Giuseppe Portella, Gianni Marone, Viviana Vastolo, Renato Franco, Francesco Borriello, Eloise Scamardella, Sarah Di Somma, Carmela Passaro, Passaro, Carmela, Borriello, Francesco, Vastolo, Viviana, Di Somma, Sarah, Scamardella, Eloise, Gigantino, Vincenzo, Franco, Renato, Marone, Gianni, Portella, Giuseppe, and Somma, Sarah Di
- Subjects
0301 basic medicine ,Time Factors ,Monocyte chemotaxis ,Angiogenesis ,medicine.medical_treatment ,Cell Plasticity ,Thyroid Carcinoma, Anaplastic ,0302 clinical medicine ,Tumor-associated macrophage ,Cancer immunotherapy ,Tumor Microenvironment ,Medicine ,Promoter Regions, Genetic ,Chemokine CCL2 ,Oncolytic Virotherapy ,Innate immunity ,Neovascularization, Pathologic ,tumor-associated macrophages ,Chemotaxis ,Gene Expression Regulation, Neoplastic ,Oncolytic Viruses ,Phenotype ,Oncology ,Chemokine ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Female ,Research Paper ,Oncolytic adenovirus ,Down-Regulation ,Mice, Nude ,Transfection ,Adenoviridae ,03 medical and health sciences ,Tumor vasculature ,Cell Line, Tumor ,Animals ,Humans ,Interleukin 8 ,Thyroid Neoplasms ,Virotherapy ,Tumor microenvironment ,Binding Sites ,business.industry ,Macrophages ,Interleukin-8 ,Transcription Factor RelA ,Xenograft Model Antitumor Assays ,Oncolytic virus ,030104 developmental biology ,Immunology ,Cancer research ,business - Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy.
- Published
- 2016
38. Platinum(II) O , S Complexes Inhibit the Aggregation of Amyloid Model Systems.
- Author
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Florio D, Malfitano AM, Di Somma S, Mügge C, Weigand W, Ferraro G, Iacobucci I, Monti M, Morelli G, Merlino A, and Marasco D
- Subjects
- Alzheimer Disease drug therapy, Alzheimer Disease pathology, Amyloid beta-Peptides antagonists & inhibitors, Amyloid beta-Peptides chemical synthesis, Amyloidosis drug therapy, Amyloidosis pathology, Benzothiazoles pharmacology, Cell Line, Cinnamates chemistry, Cinnamates pharmacology, Circular Dichroism, Coordination Complexes chemistry, Humans, Ligands, Nuclear Proteins antagonists & inhibitors, Nucleophosmin, Peptide Termination Factors antagonists & inhibitors, Platinum chemistry, Platinum pharmacology, Protein Aggregation, Pathological genetics, Protein Aggregation, Pathological pathology, Saccharomyces cerevisiae Proteins antagonists & inhibitors, Amyloid beta-Peptides chemistry, Coordination Complexes pharmacology, Nuclear Proteins chemistry, Peptide Termination Factors chemistry, Protein Aggregation, Pathological drug therapy, Saccharomyces cerevisiae Proteins chemistry
- Abstract
Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC
50 values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
- Full Text
- View/download PDF
39. Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14 + CD1c + Monocytes.
- Author
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Borriello F, Iannone R, Di Somma S, Vastolo V, Petrosino G, Visconte F, Raia M, Scalia G, Loffredo S, Varricchi G, Galdiero MR, Granata F, Del Vecchio L, Portella G, and Marone G
- Subjects
- Antigens, CD1 metabolism, Arachidonate 15-Lipoxygenase genetics, Cells, Cultured, Chemokine CCL17 metabolism, Gene Expression Regulation, Humans, Immunophenotyping, Intercellular Signaling Peptides and Proteins genetics, Interleukin-4 immunology, Lipopolysaccharide Receptors metabolism, Lipopolysaccharides immunology, Receptors, Cytokine genetics, Receptors, IgG genetics, Receptors, Immunologic genetics, Thymic Stromal Lymphopoietin, Cell Differentiation, Cytokines metabolism, Monocytes immunology, Receptors, Cytokine metabolism, Sepsis immunology
- Abstract
Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14
+ monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14+ CD16- monocytes, TSLPR+ monocytes (TSLPR+ mono), expresses TSLPR complex upon LPS stimulation in an NF-κB- and p38-dependent manner. Phenotypic, functional, and transcriptomic analysis revealed specific features of TSLPR+ mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e., GAS6 , ALOX15B , FCGR2B , LAIR1 ). Strikingly, TSLPR+ mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14+ CD1c+ cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared with healthy control subjects. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14+ CD16- monocytes and prompt further ontogenetic and functional analysis of CD14+ CD1c+ and LPS-activated CD14+ CD1c+ TSLPR+ mono., (Copyright © 2017 by The American Association of Immunologists, Inc.)- Published
- 2017
- Full Text
- View/download PDF
40. The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma.
- Author
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Passaro C, Borriello F, Vastolo V, Di Somma S, Scamardella E, Gigantino V, Franco R, Marone G, and Portella G
- Subjects
- Animals, Binding Sites, Cell Line, Tumor, Cell Plasticity, Chemokine CCL2 genetics, Chemotaxis, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Host-Pathogen Interactions, Humans, Interleukin-8 genetics, Macrophages virology, Mice, Nude, Phenotype, Promoter Regions, Genetic, Thyroid Carcinoma, Anaplastic metabolism, Thyroid Carcinoma, Anaplastic pathology, Thyroid Carcinoma, Anaplastic virology, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology, Thyroid Neoplasms virology, Time Factors, Transcription Factor RelA metabolism, Transfection, Tumor Microenvironment, Xenograft Model Antitumor Assays, Adenoviridae pathogenicity, Chemokine CCL2 metabolism, Interleukin-8 metabolism, Macrophages metabolism, Neovascularization, Pathologic, Oncolytic Virotherapy, Oncolytic Viruses pathogenicity, Thyroid Carcinoma, Anaplastic therapy, Thyroid Neoplasms therapy
- Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy.
- Published
- 2016
- Full Text
- View/download PDF
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