46 results on '"Marotta, Pina"'
Search Results
2. Heterogeneity of Adult Cardiac Stem Cells
- Author
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Scalise, Mariangela, Marino, Fabiola, Cianflone, Eleonora, Mancuso, Teresa, Marotta, Pina, Aquila, Iolanda, Torella, Michele, Nadal-Ginard, Bernardo, Torella, Daniele, COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Birbrair, Alexander, editor
- Published
- 2019
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3. An optimised method for intact nuclei isolation from diatoms
- Author
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Annunziata, Rossella, Balestra, Cecilia, Marotta, Pina, Ruggiero, Antonella, Manfellotto, Francesco, Benvenuto, Giovanna, Biffali, Elio, and Ferrante, Maria Immacolata
- Published
- 2021
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4. Prenatal expression of d-aspartate oxidase causes early cerebral d-aspartate depletion and influences brain morphology and cognitive functions at adulthood
- Author
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De Rosa, Arianna, Mastrostefano, Francesca, Di Maio, Anna, Nuzzo, Tommaso, Saitoh, Yasuaki, Katane, Masumi, Isidori, Andrea M., Caputo, Viviana, Marotta, Pina, Falco, Geppino, De Stefano, Maria Egle, Homma, Hiroshi, Usiello, Alessandro, and Errico, Francesco
- Published
- 2020
- Full Text
- View/download PDF
5. Editorial: Unicellular organisms as an evolutionary snapshot toward multicellularity
- Author
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Marotta, Pina, primary, Ruggiero, Antonella, additional, and Bilcke, Gust, additional
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- 2023
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- View/download PDF
6. Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia
- Author
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Bellelli, Roberto, Vitagliano, Donata, Federico, Giorgia, Marotta, Pina, Tamburrino, Anna, Salerno, Paolo, Paciello, Orlando, Papparella, Serenella, Knauf, Jeffrey A., Fagin, James A., Refetoff, Samuel, Troncone, Giancarlo, and Santoro, Massimo
- Published
- 2018
- Full Text
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7. Kitcre knock-in mice fail to fate-map cardiac stem cells
- Author
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Vicinanza, Carla, Aquila, Iolanda, Cianflone, Eleonora, Scalise, Mariangela, Marino, Fabiola, Mancuso, Teresa, Fumagalli, Francesca, Giovannone, Emilia Dora, Cristiano, Francesca, Iaccino, Enrico, Marotta, Pina, Torella, Annalaura, Latini, Roberto, Agosti, Valter, Veltri, Pierangelo, Urbanek, Konrad, Isidori, Andrea M., Saur, Dieter, Indolfi, Ciro, Nadal-Ginard, Bernardo, and Torella, Daniele
- Subjects
Stem cells -- Physiological aspects ,Heart cells -- Physiological aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): Carla Vicinanza [1]; Iolanda Aquila [1]; Eleonora Cianflone [1]; Mariangela Scalise [1]; Fabiola Marino [1]; Teresa Mancuso [1]; Francesca Fumagalli [2]; Emilia Dora Giovannone [3]; Francesca Cristiano [4]; Enrico [...]
- Published
- 2018
- Full Text
- View/download PDF
8. Mate Perception and Gene Networks Regulating the Early Phase of Sex in Pseudo-nitzschia multistriata
- Author
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Marotta, Pina, primary, Borgonuovo, Camilla, additional, Santin, Anna, additional, Russo, Monia Teresa, additional, Manfellotto, Francesco, additional, Montresor, Marina, additional, De Luca, Pasquale, additional, and Ferrante, Maria Immacolata, additional
- Published
- 2022
- Full Text
- View/download PDF
9. EphA3 targeting reduces in vitro adhesion and invasion and in vivo growth and angiogenesis of multiple myeloma cells
- Author
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La Rocca, Francesco, Airoldi, Irma, Di Carlo, Emma, Marotta, Pina, Falco, Geppino, Simeon, Vittorio, Laurenzana, Ilaria, Trino, Stefania, De Luca, Luciana, Todoerti, Katia, Villani, Oreste, Lackmann, Martin, D’Auria, Fiorella, Frassoni, Francesco, Neri, Antonino, Del Vecchio, Luigi, Musto, Pellegrino, Cilloni, Daniela, and Caivano, Antonella
- Published
- 2017
- Full Text
- View/download PDF
10. The use and abuse of Cre/Lox recombination to identify adult cardiomyocyte renewal rate and origin
- Author
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Aquila, Iolanda, Marino, Fabiola, Cianflone, Eleonora, Marotta, Pina, Torella, Michele, Mollace, Vincenzo, Indolfi, Ciro, Nadal-Ginard, Bernardo, and Torella, Daniele
- Published
- 2018
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- View/download PDF
11. Biolistic transformation of Pseudo-nitzschia multistriata v1
- Author
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Santin, Anna, primary, Teresa Russo, Monia, additional, Marotta, Pina, additional, Manfellotto, Francesco, additional, Ruggiero, Antonella, additional, and Ferrante, Mariella, additional
- Published
- 2022
- Full Text
- View/download PDF
12. Trade-off between sex and growth in diatoms: Molecular mechanisms and demographic implications
- Author
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Annunziata, Rossella, primary, Mele, Bruno Hay, additional, Marotta, Pina, additional, Volpe, Massimiliano, additional, Entrambasaguas, Laura, additional, Mager, Svenja, additional, Stec, Krzysztof, additional, d’Alcalà, Maurizio Ribera, additional, Sanges, Remo, additional, Finazzi, Giovanni, additional, Iudicone, Daniele, additional, Montresor, Marina, additional, and Ferrante, Maria Immacolata, additional
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- 2022
- Full Text
- View/download PDF
13. Silencing of a Pseudo‐nitzschia arenysensis lipoxygenase transcript leads to reduced oxylipin production and impaired growth
- Author
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Sabatino, Valeria, primary, Orefice, Ida, additional, Marotta, Pina, additional, Ambrosino, Luca, additional, Chiusano, Maria Luisa, additional, d'Ippolito, Giuliana, additional, Romano, Giovanna, additional, Fontana, Angelo, additional, and Ferrante, Maria Immacolata, additional
- Published
- 2021
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14. Genomic DNA extraction from the diatom Pseudo-nitzschia multistriata for Illumina sequencing v2
- Author
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Manfellotto, Francesco, primary, Teresa Russo, Monia, additional, Marotta, Pina, additional, Annunziata, Rossella, additional, Santin, Anna, additional, Ruggiero, Antonella, additional, and Ferrante, Mariella, additional
- Published
- 2021
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15. ZFP36L2 Role in Thyroid Functionality
- Author
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Albano, Francesco, primary, Tucci, Valeria, additional, Blackshear, Perry J., additional, Reale, Carla, additional, Roberto, Luca, additional, Russo, Filomena, additional, Marotta, Pina, additional, Porreca, Immacolata, additional, Colella, Marco, additional, Mallardo, Massimo, additional, de Felice, Mario, additional, and Ambrosino, Concetta, additional
- Published
- 2021
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16. The Ascidia Ciona robusta Provides Novel Insights on the Evolution of the AP-1 Transcriptional Complex
- Author
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Marotta, Pina, primary, Salatiello, Federica, additional, Ambrosino, Luca, additional, Berruto, Federica, additional, Chiusano, Maria Luisa, additional, and Locascio, Annamaria, additional
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- 2021
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17. Detection of bacteria in antibiotic-treated diatom cultures and cell harvesting v1
- Author
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Manfellotto, Francesco, primary, Teresa Russo, Monia, additional, Marotta, Pina, additional, Ruggiero, Antonella, additional, and Ferrante, Mariella, additional
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- 2021
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18. Silencing of a Pseudo‐nitzschia arenysensis lipoxygenase transcript leads to reduced oxylipin production and impaired growth.
- Author
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Sabatino, Valeria, Orefice, Ida, Marotta, Pina, Ambrosino, Luca, Chiusano, Maria Luisa, d'Ippolito, Giuliana, Romano, Giovanna, Fontana, Angelo, and Ferrante, Maria Immacolata
- Subjects
PHAEODACTYLUM tricornutum ,PSEUDO-nitzschia ,STRUCTURAL frame models ,EICOSAPENTAENOIC acid ,OXYLIPINS ,PROTEIN models - Abstract
Summary: Because of their importance as chemical mediators, the presence of a rich and varied family of lipoxygenase (LOX) products, collectively named oxylipins, has been investigated thoroughly in diatoms, and the involvement of these products in important processes such as bloom regulation has been postulated. Nevertheless, little information is available on the enzymes and pathways operating in these protists.Exploiting transcriptome data, we identified and characterized a LOX gene, PaLOX, in Pseudo‐nitzschia arenysensis, a marine diatom known to produce different species of oxylipins by stereo‐ and regio‐selective oxidation of eicosapentaenoic acid (EPA) at C12 and C15.PaLOX RNA interference correlated with a decrease of the lipid‐peroxidizing activity and oxylipin synthesis, as well as with a reduction of growth of P. arenysensis. In addition, sequence analysis and structure models of the C‐terminal part of the predicted protein closely fitted with the data for established LOXs from other organisms.The presence in the genome of a single LOX gene, whose downregulation impairs both 12‐ and 15‐oxylipins synthesis, together with the in silico 3D protein modelling suggest that PaLOX encodes for a 12/15S‐LOX with a dual specificity, and provides additional support to the correlation between cell growth and oxylipin biosynthesis in diatoms. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
19. An optimised method for intact nuclei isolation from diatoms v1
- Author
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Annunziata, Rossella, primary, Balestra, Cecilia, additional, Marotta, Pina, additional, Ruggiero, Antonella, additional, Manfellotto, Francesco, additional, Benvenuto, Giovanna, additional, Biffali, Elio, additional, and Ferrante, Mariella, additional
- Published
- 2020
- Full Text
- View/download PDF
20. RNA extraction from low amount of diatom cells v1
- Author
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Annunziata, Rossella, primary, Manfellotto, Francesco, additional, Marotta, Pina, additional, Ruggiero, Antonella, additional, Santin, Anna, additional, Teresa Russo, Monia, additional, and Ferrante, Mariella, additional
- Published
- 2020
- Full Text
- View/download PDF
21. Genomic DNA extraction from low amount of diatom cells v1
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Annunziata, Rossella, primary, Manfellotto, Francesco, additional, Marotta, Pina, additional, Ruggiero, Antonella, additional, Santin, Anna, additional, Teresa Russo, Monia, additional, and Ferrante, Mariella, additional
- Published
- 2020
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22. Erratum. miRNA Regulation of the Hyperproliferative Phenotype of Vascular Smooth Muscle Cells in Diabetes. Diabetes 2018;67:2554–2568
- Author
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Torella, Daniele, primary, Iaconetti, Claudio, additional, Tarallo, Roberta, additional, Marino, Fabiola, additional, Giurato, Giorgio, additional, Veneziano, Claudia, additional, Aquila, Iolanda, additional, Scalise, Mariangela, additional, Mancuso, Teresa, additional, Cianflone, Eleonora, additional, Valeriano, Chiara, additional, Marotta, Pina, additional, Tammè, Laura, additional, Vicinanza, Carla, additional, Sasso, Ferdinando C., additional, Cozzolino, Domenico, additional, Torella, Michele, additional, Weisz, Alessandro, additional, and Indolfi, Ciro, additional
- Published
- 2020
- Full Text
- View/download PDF
23. Insight into Nephrocan Function in Mouse Endoderm Patterning
- Author
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Addeo, Martina, primary, Buonaiuto, Silvia, additional, Guerriero, Ilaria, additional, Amendola, Elena, additional, Visconte, Feliciano, additional, Marino, Antonio, additional, De Angelis, Maria Teresa, additional, Russo, Filomena, additional, Roberto, Luca, additional, Marotta, Pina, additional, Russo, Nicola Antonino, additional, Iervolino, Anna, additional, Amodio, Federica, additional, De Felice, Mario, additional, Lucci, Valeria, additional, and Falco, Geppino, additional
- Published
- 2019
- Full Text
- View/download PDF
24. miRNA Regulation of the Hyperproliferative Phenotype of Vascular Smooth Muscle Cells in Diabetes
- Author
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Torella, Daniele, primary, Iaconetti, Claudio, additional, Tarallo, Roberta, additional, Marino, Fabiola, additional, Giurato, Giorgio, additional, Veneziano, Claudia, additional, Aquila, Iolanda, additional, Scalise, Mariangela, additional, Mancuso, Teresa, additional, Cianflone, Eleonora, additional, Valeriano, Chiara, additional, Marotta, Pina, additional, Tammè, Laura, additional, Vicinanza, Carla, additional, Sasso, Ferdinando C., additional, Cozzolino, Domenico, additional, Torella, Michele, additional, Weisz, Alessandro, additional, and Indolfi, Ciro, additional
- Published
- 2018
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- View/download PDF
25. Molecular basis of functional myogenic specification ofBona Fidemultipotent adult cardiac stem cells
- Author
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Cianflone, Eleonora, primary, Aquila, Iolanda, additional, Scalise, Mariangela, additional, Marotta, Pina, additional, Torella, Michele, additional, Nadal-Ginard, Bernardo, additional, and Torella, Daniele, additional
- Published
- 2018
- Full Text
- View/download PDF
26. Combining cell and gene therapy to advance cardiac regeneration
- Author
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Marotta, Pina, primary, Cianflone, Eleonora, additional, Aquila, Iolanda, additional, Vicinanza, Carla, additional, Scalise, Mariangela, additional, Marino, Fabiola, additional, Mancuso, Teresa, additional, Torella, Michele, additional, Indolfi, Ciro, additional, and Torella, Daniele, additional
- Published
- 2018
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27. Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification
- Author
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Vicinanza, Carla, primary, Aquila, Iolanda, additional, Scalise, Mariangela, additional, Cristiano, Francesca, additional, Marino, Fabiola, additional, Cianflone, Eleonora, additional, Mancuso, Teresa, additional, Marotta, Pina, additional, Sacco, Walter, additional, Lewis, Fiona C, additional, Couch, Liam, additional, Shone, Victoria, additional, Gritti, Giulia, additional, Torella, Annalaura, additional, Smith, Andrew J, additional, Terracciano, Cesare MN, additional, Britti, Domenico, additional, Veltri, Pierangelo, additional, Indolfi, Ciro, additional, Nadal-Ginard, Bernardo, additional, Ellison-Hughes, Georgina M, additional, and Torella, Daniele, additional
- Published
- 2017
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28. Molecular basis of functional myogenic specification of Bona Fide multipotent adult cardiac stem cells.
- Author
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Cianflone, Eleonora, Aquila, Iolanda, Scalise, Mariangela, Marotta, Pina, Torella, Michele, Nadal-Ginard, Bernardo, and Torella, Daniele
- Abstract
Ischemic Heart Disease (IHD) remains the developed world’s number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
29. Kitcre knock-in mice fail to fate-map cardiac stem cells.
- Author
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Vicinanza, Carla, Aquila, Iolanda, Cianflone, Eleonora, Scalise, Mariangela, Marino, Fabiola, Mancuso, Teresa, Fumagalli, Francesca, Giovannone, Emilia Dora, Cristiano, Francesca, Iaccino, Enrico, Marotta, Pina, Torella, Annalaura, Latini, Roberto, Agosti, Valter, Veltri, Pierangelo, Urbanek, Konrad, Isidori, Andrea M., Saur, Dieter, Indolfi, Ciro, and Nadal-Ginard, Bernardo
- Published
- 2018
- Full Text
- View/download PDF
30. EphA3 targeting reduces in vitro adhesion and invasion and in vivo growth and angiogenesis of multiple myeloma cells.
- Author
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Rocca, Francesco, Airoldi, Irma, Carlo, Emma, Marotta, Pina, Falco, Geppino, Simeon, Vittorio, Laurenzana, Ilaria, Trino, Stefania, Luca, Luciana, Todoerti, Katia, Villani, Oreste, Lackmann, Martin, D'Auria, Fiorella, Frassoni, Francesco, Neri, Antonino, Vecchio, Luigi, Musto, Pellegrino, Cilloni, Daniela, and Caivano, Antonella
- Subjects
PROTEIN-tyrosine kinases ,MULTIPLE myeloma treatment ,MULTIPLE myeloma ,PLASMA cells ,BONE marrow ,PATIENTS ,THERAPEUTICS - Abstract
Purpose: Multiple myeloma (MM) is a hematologic malignancy characterized by a clonal expansion of plasma cells (PCs) in the bone marrow (BM). Since MM has so far remained incurable, further insights into its pathogenesis and the concomitant identification of new therapeutic targets are urgently needed. The tyrosine kinase receptor EphA3 is known to be involved in various cellular processes including cell viability, cell movement and cell-cell interactions. Recently, EphA3 has emerged as a potential therapeutic target in several hematologic and solid tumors. Here, we aimed to uncover the role of EphA3 in MM. Methods: EphA3 mRNA and protein expression in primary MM bone marrow plasma cells (BMPCs), in MM-derived cell lines and in healthy controls (HCs) was assessed using qRT-PCR, Western blotting and flow cytometry. The effects of siRNA-mediated EphA3 silencing and anti EphA3 antibody (EphA3mAb) treatment on MM PC trafficking and viability were evaluated using in vitro assays. The effects of EphA3mAb treatment were also assessed in two MM-derived mouse xenograft models. Results: We found that EphA3 was overexpressed in primary MM BMPCs and MM-derived cell lines compared to HCs. We also found that siRNA-mediated EphA3 silencing and EphA3mAb treatment significantly inhibited the ability of MM PCs to adhere to fibronectin and stromal cells and to invade in vitro, without affecting cell proliferation and viability. Gene expression profiling showed that EphA3 silencing resulted in expression modulation of several molecules that regulate adhesion, migration and invasion processes. Importantly, we found that EphA3mAb treatment significantly inhibited in vivo tumor growth and angiogenesis in two MM-derived mouse xenograft models. Conclusions: Our findings suggest that EphA3 plays an important role in the pathogenesis of MM and provide support for the notion that its targeting may represent a novel therapeutic opportunity for MM. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
31. Role of Pax8 transcriptional factor in the differentiated thyroid
- Author
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Marotta, Pina
- Subjects
endocrine system ,endocrine system diseases - Abstract
In Pax8-/- mice the thyroid anlage disappears around E11.5. At birth the gland appears as a rudimentary structure composed only of C cells while thyroid follicular cells are undetectable. Thus, this model does not allow the study of Pax8 function in the postnatal thyroid. To address the role of Pax8 in the differentiated thyroid, I established novel strains amenable to thyroid follicular cell-specific conditional knockout of Pax8 gene using the Cre/lox system. A genetically modified mouse strain (Pax8fl/fl) harbouring a floxed allele of Pax8 was generated. These mice were crossed with two different Cre mice, a Pax8Cre/+ strain expressing constitutively Cre recombinase by embryonic day 8.5 and a Tg-CreER strain in which Cre is active in thyroid follicular cells following tamoxifen injection. Pax8Cre/fl mice do not display an overt phenotype during embryonic life. However, 3-week old Pax8Cre/fl pups show a hypothyroid phenotype characterized by both an increased serum TSH value and a significant reduction in body weight when compared with their wild type littermates. In Pax8Cre/fl animals the thyroid gland is hypoplastic and shows the absence of the follicular structure; moreover, the expression of many thyroid specific genes, required for both hormone production and regulative functions, is completely abolished. In addition, survival of follicular cells is impaired. The disruption of Pax8 in adult life (Pax8ko/fl;Tg-CreER strain) seems to be not efficient and thyroid structure appears comparable to that of wild type. However, the absence of a clear phenotype in the Pax8ko/fl;TgCreER thyroid could be due to the compensatory proliferation of cells in which Pax8 has not been inactivated. In conclusion, in my thesis work I demonstrated in vivo that Pax8 plays a key role in controlling both the expression of many thyroid specific genes and the survival of thyroid follicular cells.
- Published
- 2010
- Full Text
- View/download PDF
32. The paired box transcription factor Pax8 is essential for function and survival of adult thyroid cells
- Author
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Marotta, Pina, primary, Amendola, Elena, additional, Scarfò, Marzia, additional, De Luca, Pasquale, additional, Zoppoli, Pietro, additional, Amoresano, Angela, additional, De Felice, Mario, additional, and Di Lauro, Roberto, additional
- Published
- 2014
- Full Text
- View/download PDF
33. Identification of a Novel Gene Signature of ES Cells Self-Renewal Fluctuation through System-Wide Analysis
- Author
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Cerulo, Luigi, primary, Tagliaferri, Daniela, additional, Marotta, Pina, additional, Zoppoli, Pietro, additional, Russo, Filomena, additional, Mazio, Claudia, additional, DeFelice, Mario, additional, Ceccarelli, Michele, additional, and Falco, Geppino, additional
- Published
- 2014
- Full Text
- View/download PDF
34. Molecular basis of functional myogenic specification of Bona Fidemultipotent adult cardiac stem cells
- Author
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Cianflone, Eleonora, Aquila, Iolanda, Scalise, Mariangela, Marotta, Pina, Torella, Michele, Nadal-Ginard, Bernardo, and Torella, Daniele
- Abstract
ABSTRACTIschemic Heart Disease (IHD) remains the developed world’s number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment.
- Published
- 2018
- Full Text
- View/download PDF
35. Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning
- Author
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Fagman, Henrik, primary, Amendola, Elena, additional, Parrillo, Luca, additional, Zoppoli, Pietro, additional, Marotta, Pina, additional, Scarfò, Marzia, additional, De Luca, Pasquale, additional, de Carvalho, Denise Pires, additional, Ceccarelli, Michele, additional, De Felice, Mario, additional, and Di Lauro, Roberto, additional
- Published
- 2011
- Full Text
- View/download PDF
36. A Neutralizing RNA Aptamer against EGFR Causes Selective Apoptotic Cell Death
- Author
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Esposito, Carla Lucia, primary, Passaro, Diana, additional, Longobardo, Immacolata, additional, Condorelli, Gerolama, additional, Marotta, Pina, additional, Affuso, Andrea, additional, de Franciscis, Vittorio, additional, and Cerchia, Laura, additional
- Published
- 2011
- Full Text
- View/download PDF
37. Insight into Nephrocan Function in Mouse Endoderm Patterning.
- Author
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Addeo, Martina, Buonaiuto, Silvia, Guerriero, Ilaria, Amendola, Elena, Visconte, Feliciano, Marino, Antonio, De Angelis, Maria Teresa, Russo, Filomena, Roberto, Luca, Marotta, Pina, Russo, Nicola Antonino, Iervolino, Anna, Amodio, Federica, De Felice, Mario, Lucci, Valeria, and Falco, Geppino
- Subjects
ENDODERM ,EPIBLAST ,PANCREAS ,EMBRYONIC stem cells ,MICE ,ORGANS (Anatomy) - Abstract
Endoderm-derived organs as liver and pancreas are potential targets for regenerative therapies, and thus, there is great interest in understanding the pathways that regulate the induction and specification of this germ layer. Currently, the knowledge of molecular mechanisms that guide the in vivo endoderm specification is restricted by the lack of early endoderm specific markers. Nephrocan (Nepn) is a gene whose expression characterizes the early stages of murine endoderm specification (E7.5–11.5) and encodes a secreted N-glycosylated protein. In the present study, we report the identification of a new transcript variant that is generated through alternative splicing. The new variant was found to have differential and tissue specific expression in the adult mouse. In order to better understand Nepn role during endoderm specification, we generated Nepn knock-out (KO) mice. Nepn
−/− mice were born at Mendelian ratios and displayed no evident phenotype compared to WT mice. In addition, we produced nullizygous mouse embryonic stem cell (mESC) line lacking Nepn by applying (CRISPR)/CRISPR-associated systems 9 (Cas9) and employed a differentiation protocol toward endoderm lineage. Our in vitro results revealed that Nepn loss affects the endoderm differentiation impairing the expression of posterior foregut-associated markers. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
38. Trade-off between sex and growth in diatoms: Molecular mechanisms and demographic implications
- Author
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Rossella Annunziata, Bruno Hay Mele, Pina Marotta, Massimiliano Volpe, Laura Entrambasaguas, Svenja Mager, Krzysztof Stec, Maurizio Ribera d’Alcalà, Remo Sanges, Giovanni Finazzi, Daniele Iudicone, Marina Montresor, Maria Immacolata Ferrante, Stazione Zoologica Anton Dohrn (SZN), Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Light Photosynthesis & Metabolism (Photosynthesis), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Italian Flagship Program RITMARE, The Gordon and Betty Moore Foundation through grant no. 7978 t, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), European Project: 833184, ChloroMito, Annunziata, Rossella, Mele, Bruno Hay, Marotta, Pina, Volpe, Massimiliano, Entrambasaguas, Laura, Mager, Svenja, Stec, Krzysztof, D'Alcalà, Maurizio Ribera, Sanges, Remo, Finazzi, Giovanni, Iudicone, Daniele, Montresor, Marina, and Ferrante, Maria Immacolata
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Diatoms ,Multidisciplinary ,Earth, Environmental, Ecological, and Space Sciences ,Ecology ,Reproduction ,Cell Cycle ,SciAdv r-articles ,Cell Biology ,Plankton ,[SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems ,Settore BIO/13 - Biologia Applicata ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Demography ,Research Article - Abstract
Diatoms are fast-growing and winning competitors in aquatic environments, possibly due to optimized growth performance. However, their life cycles are complex, heteromorphic, and not fully understood. Here, we report on the fine control of cell growth and physiology during the sexual phase of the marine diatom Pseudo-nitzschia multistriata. We found that mating, under nutrient replete conditions, induces a prolonged growth arrest in parental cells. Transcriptomic analyses revealed down-regulation of genes related to major metabolic functions from the early phases of mating. Single-cell photophysiology also pinpointed an inhibition of photosynthesis and storage lipids accumulated in the arrested population, especially in gametes and zygotes. Numerical simulations revealed that growth arrest affects the balance between parental cells and their siblings, possibly favoring the new generation. Thus, in addition to resources availability, life cycle traits contribute to shaping the species ecological niches and must be considered to describe and understand the structure of plankton communities., Description, Growth control of vegetative cells during sexual reproduction favors offspring survival success.
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- 2022
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39. Silencing of a Pseudo-nitzschia arenysensis lipoxygenase transcript leads to reduced oxylipin production and impaired growth
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Angelo Fontana, Giovanna Romano, Maria Luisa Chiusano, Ida Orefice, Luca Ambrosino, Maria Immacolata Ferrante, Valeria Sabatino, Pina Marotta, Giuliana d'Ippolito, Sabatino, Valeria, Orefice, Ida, Marotta, Pina, Ambrosino, Luca, Chiusano, Maria Luisa, D'Ippolito, Giuliana, Romano, Giovanna, Fontana, Angelo, and Ferrante, Maria Immacolata
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0106 biological sciences ,Physiology ,In silico ,Lipoxygenase ,Oxylipin ,Pseudo-nitzschia arenysensi ,Plant Science ,01 natural sciences ,Transcriptome ,03 medical and health sciences ,biosynthesi ,Downregulation and upregulation ,RNA interference ,algal growth ,Gene silencing ,Oxylipins ,Gene ,030304 developmental biology ,Diatoms ,0303 health sciences ,Pseudo-nitzschia arenysensis ,biology ,Chemistry ,RNA-interference ,diatom ,gene function ,Biochemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,biosynthesis ,010606 plant biology & botany - Abstract
Because of their importance as chemical mediators, the presence of a rich and varied family of lipoxygenase (LOX) products, collectively named oxylipins, has been investigated thoroughly in diatoms, and the involvement of these products in important processes such as bloom regulation has been postulated. Nevertheless, little information is available on the enzymes and pathways operating in these protists. Exploiting transcriptome data, we identified and characterized a LOX gene, PaLOX, in Pseudo-nitzschia arenysensis, a marine diatom known to produce different species of oxylipins by stereo- and regio-selective oxidation of eicosapentaenoic acid (EPA) at C12 and C15. PaLOX RNA interference correlated with a decrease of the lipid-peroxidizing activity and oxylipin synthesis, as well as with a reduction of growth of P. arenysensis. In addition, sequence analysis and structure models of the C-terminal part of the predicted protein closely fitted with the data for established LOXs from other organisms. The presence in the genome of a single LOX gene, whose downregulation impairs both 12- and 15-oxylipins synthesis, together with the in silico 3D protein modelling suggest that PaLOX encodes for a 12/15S-LOX with a dual specificity, and provides additional support to the correlation between cell growth and oxylipin biosynthesis in diatoms.
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- 2022
40. The Ascidia Ciona robusta Provides Novel Insights on the Evolution of the AP-1 Transcriptional Complex
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Pina Marotta, Federica Salatiello, Luca Ambrosino, Federica Berruto, Maria Luisa Chiusano, Annamaria Locascio, Marotta, Pina, Salatiello, Federica, Ambrosino, Luca, Berruto, Federica, Chiusano, Maria Luisa, and Locascio, Annamaria
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animal structures ,bZIP protein ,QH301-705.5 ,Population ,Gene redundancy ,mesenchyme ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,Biology (General) ,education ,Gene ,Transcription factor ,Jun ,transcription factor ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,biology ,Fos ,bZIP domain ,notochord ,Cell Biology ,biology.organism_classification ,Cell biology ,Ciona ,Fo ,Ectopic expression ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The Activator Protein-1 transcription factor family (AP-1) transcriptional complex is historically defined as an early response group of transcription factors formed by dimeric complexes of the Jun, Fos, Atf, and Maf bZIP proteins that control cell proliferation and differentiation by regulating gene expression. It has been greatly investigated in many model organisms across metazoan evolution. Nevertheless, its complexity and variability of action made its multiple functions difficult to be defined. Here, we place the foundations for understanding the complexity of AP-1 transcriptional members in tunicates. We investigated the gene members of this family in the ascidian Ciona robusta and identified single copies of Jun, Fos, Atf3, Atf2/7, and Maf bZIP-related factors that could have a role in the formation of the AP-1 complex. We highlight that mesenchyme is a common cellular population where all these factors are expressed during embryonic development, and that, moreover, Fos shows a wider pattern of expression including also notochord and neural cells. By ectopic expression in transgenic embryos of Jun and Fos genes alone or in combination, we investigated the phenotypic alterations induced by these factors and highlighted a degree of functional conservation of the AP-1 complex between Ciona and vertebrates. The lack of gene redundancy and the first pieces of evidence of conserved functions in the control of cell movements and structural organization exerted by these factors open the way for using Ciona as a helpful model system to uncover the multiple potentialities of this highly complex family of bZIP transcription factors.
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- 2021
41. Molecular basis of functional myogenic specification ofBona Fidemultipotent adult cardiac stem cells
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Michele Torella, Iolanda Aquila, Mariangela Scalise, Bernardo Nadal-Ginard, Daniele Torella, Pina Marotta, Eleonora Cianflone, Cianflone, Eleonora, Aquila, Iolanda, Scalise, Mariangela, Marotta, Pina, Torella, Michele, Nadal-Ginard, Bernardo, and Torella, Daniele
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0301 basic medicine ,medicine.medical_treatment ,Population ,Review ,myogenic differentiation ,Biology ,Muscle Development ,Bioinformatics ,Cardiac stem cell ,03 medical and health sciences ,medicine ,Animals ,Humans ,Myocardial infarction ,education ,Molecular Biology ,Heart transplantation ,Myocardial Degeneration ,education.field_of_study ,Multipotent Stem Cells ,Myocardium ,Regeneration (biology) ,Cell Cycle ,cardiac regeneration ,Cell Biology ,medicine.disease ,Embryonic stem cell ,Adult Stem Cells ,Phenotype ,030104 developmental biology ,Heart failure ,Stem cell ,Developmental Biology - Abstract
Ischemic Heart Disease (IHD) remains the developed world's number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment.
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- 2018
42. Combining cell and gene therapy to advance cardiac regeneration
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Daniele Torella, Mariangela Scalise, Teresa Mancuso, Michele Torella, Iolanda Aquila, Pina Marotta, Carla Vicinanza, Eleonora Cianflone, Fabiola Marino, Ciro Indolfi, Marotta, Pina, Cianflone, Eleonora, Aquila, Iolanda, Vicinanza, Carla, Scalise, Mariangela, Marino, Fabiola, Mancuso, Teresa, Torella, Michele, Indolfi, Ciro, and Torella, Daniele
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0301 basic medicine ,RNA, Untranslated ,Somatic cell ,Genetic enhancement ,non-coding RNA ,education ,Clinical Biochemistry ,Cell ,Cell- and Tissue-Based Therapy ,Myocardial Infarction ,Endogeny ,Biology ,complex mixtures ,Cardiac regeneration ,03 medical and health sciences ,Genome editing ,Drug Discovery ,medicine ,genome editing ,Animals ,Humans ,Regeneration ,Pharmacology ,Gene Editing ,Stem Cells ,Heart ,somatic reprogramming ,Cellular Reprogramming ,humanities ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Stem cell ,cardiac stem cell ,Reprogramming - Abstract
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair. Expert opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure.
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- 2018
43. The use and abuse of Cre/Lox recombination to identify adult cardiomyocyte renewal rate and origin
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Pina Marotta, Eleonora Cianflone, Michele Torella, Fabiola Marino, Iolanda Aquila, Ciro Indolfi, Bernardo Nadal-Ginard, Daniele Torella, Vincenzo Mollace, Aquila, Iolanda, Marino, Fabiola, Cianflone, Eleonora, Marotta, Pina, Torella, Michele, Mollace, Vincenzo, Indolfi, Ciro, Nadal-Ginard, Bernardo, and Torella, Daniele
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0301 basic medicine ,Endogeny ,Biology ,Cardiac stem cell ,03 medical and health sciences ,Animals ,Humans ,Regeneration ,Myocytes, Cardiac ,Progenitor cell ,Recombination, Genetic ,Pharmacology ,Integrases ,Mechanism (biology) ,Stem Cells ,Regeneration (biology) ,Anatomy ,Cell biology ,Transplantation ,Clinical trial ,030104 developmental biology ,Cre-Lox recombination ,Cardiac regeneration ,Stem cell ,Myocyte regeneration ,Homeostasis - Abstract
The adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan. This endogenous regenerative potential increases after various forms of injury. Nevertheless, the degree/significance and more importantly the origin of adult new cardiomyocytes remains strongly disputed. Evidence from independent laboratories has shown that the adult myocardium harbours bona-fide tissue-specific cardiac stem cells (CSCs). Their transplantation and in situ activation have demonstrated the CSCs regenerative potential and have been used to develop regeneration protocols which in pre-clinical tests have shown to be effective in the prevention and treatment of heart failure. Recent reports purportedly tracking the c-kit+CSC’s fate using Cre/lox recombination in the mouse have challenged the existence and regenerative potential of the CSCs and have raised scepticism about their role in myocardial homeostasis and regeneration. The validity of these reports, however, is controversial because they failed to show that the experimental approach used is capable to both identify and tract the fate of the CSCs. Despite these serious shortcomings, in contraposition to the CSCs, these publications have proposed the proliferation of existing adult fully-matured cardiomyocytes as the relevant mechanism to explain cardiomyocyte renewal in the adult. This review critically ponders the available evidence showing that the adult mammalian heart possesses a definable myocyte-generating progenitor cell of biological significance. This endogenous regenerative potential is expected to provide the bases for novel approaches of myocardial repair in the near future.
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- 2018
44. EphA3 targeting reduces in vitro adhesion and invasion and in vivo growth and angiogenesis of multiple myeloma cells
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Pina Marotta, Fiorella D'Auria, Stefania Trino, Luciana De Luca, Emma Di Carlo, Katia Todoerti, Daniela Cilloni, Martin Lackmann, Oreste Villani, Vittorio Simeon, Francesco La Rocca, Antonella Caivano, Antonino Neri, Irma Airoldi, Francesco Frassoni, Pellegrino Musto, Ilaria Laurenzana, Luigi Del Vecchio, Geppino Falco, La Rocca, Francesco, Airoldi, Irma, Di Carlo, Emma, Marotta, Pina, Falco, Geppino, Simeon, Vittorio, Laurenzana, Ilaria, Trino, Stefania, De Luca, Luciana, Todoerti, Katia, Villani, Oreste, Lackmann, Martin, D'Auria, Fiorella, Frassoni, Francesco, Neri, Antonino, Del Vecchio, Luigi, Musto, Pellegrino, Cilloni, Daniela, Caivano, Antonella, and D’Auria, Fiorella
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0301 basic medicine ,Cancer Research ,Angiogenesis ,Plasma cell ,Mice, SCID ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Multiple myeloma ,Monoclonal ,Cells, Cultured ,Plasma cells ,Tumor ,Cultured ,Neovascularization, Pathologic ,Receptor, EphA3 ,Antibodies, Monoclonal ,General Medicine ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,RNA Interference ,Receptor ,Stromal cell ,Anti EphA3 monoclonal antibody ,Cell movement ,EphA3 ,Animals ,Cell Adhesion ,Cell Line, Tumor ,Cell Movement ,Gene Expression Profiling ,Humans ,Multiple Myeloma ,Xenograft Model Antitumor Assays ,Cells ,Biology ,SCID ,Antibodies ,Cell Line ,03 medical and health sciences ,In vivo ,medicine ,Gene silencing ,Viability assay ,Cell adhesion ,Neovascularization ,Pathologic ,Neoplastic ,Cell growth ,Molecular biology ,030104 developmental biology ,Gene Expression Regulation ,Cancer research ,Inbred NOD ,Bone marrow - Abstract
Purpose: Multiple myeloma (MM) is a hematologic malignancy characterized by a clonal expansion of plasma cells (PCs) in the bone marrow (BM). Since MM has so far remained incurable, further insights into its pathogenesis and the concomitant identification of new therapeutic targets are urgently needed. The tyrosine kinase receptor EphA3 is known to be involved in various cellular processes including cell viability, cell movement and cell-cell interactions. Recently, EphA3 has emerged as a potential therapeutic target in several hematologic and solid tumors. Here, we aimed to uncover the role of EphA3 in MM. Methods: EphA3 mRNA and protein expression in primary MM bone marrow plasma cells (BMPCs), in MM-derived cell lines and in healthy controls (HCs) was assessed using qRT-PCR, Western blotting and flow cytometry. The effects of siRNA-mediated EphA3 silencing and anti EphA3 antibody (EphA3mAb) treatment on MM PC trafficking and viability were evaluated using in vitro assays. The effects of EphA3mAb treatment were also assessed in two MM-derived mouse xenograft models. Results: We found that EphA3 was overexpressed in primary MM BMPCs and MM-derived cell lines compared to HCs. We also found that siRNA-mediated EphA3 silencing and EphA3mAb treatment significantly inhibited the ability of MM PCs to adhere to fibronectin and stromal cells and to invade in vitro, without affecting cell proliferation and viability. Gene expression profiling showed that EphA3 silencing resulted in expression modulation of several molecules that regulate adhesion, migration and invasion processes. Importantly, we found that EphA3mAb treatment significantly inhibited in vivo tumor growth and angiogenesis in two MM-derived mouse xenograft models. Conclusions: Our findings suggest that EphA3 plays an important role in the pathogenesis of MM and provide support for the notion that its targeting may represent a novel therapeutic opportunity for MM.
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- 2017
45. Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia
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Massimo Santoro, Anna Tamburrino, Samuel Refetoff, Giorgia Federico, Donata Vitagliano, Pina Marotta, Jeffrey A. Knauf, Orlando Paciello, James A. Fagin, Paolo Salerno, Serenella Papparella, Giancarlo Troncone, Roberto Bellelli, Bellelli, Roberto, Vitagliano, Donata, Federico, Giorgia, Marotta, Pina, Tamburrino, Anna, Salerno, Paolo, Paciello, Orlando, Papparella, Serenella, Knauf, Jeffrey A., Fagin, James A., Refetoff, Samuel, Troncone, Giancarlo, and Santoro, Massimo
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0301 basic medicine ,MAPK/ERK pathway ,Male ,endocrine system diseases ,Thyroid Gland ,Thyrotropin ,Apoptosis ,medicine.disease_cause ,Biochemistry ,Endocrinology ,Phosphorylation ,Thyroid cancer ,Cellular Senescence ,Thyroid ,Forkhead Transcription Factors ,medicine.anatomical_structure ,RET oncogene ,Female ,Senescence ,medicine.medical_specialty ,endocrine system ,DNA damage ,Mice, Transgenic ,Biology ,Article ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Thyroid Neoplasms ,Protein kinase B ,Molecular Biology ,Hyperplasia ,AKT ,Oncogene-induced senescence ,Oncogenes ,medicine.disease ,Enzyme Activation ,Disease Models, Animal ,Thyroxine ,030104 developmental biology ,Thyroid Epithelial Cells ,Cancer research ,Cattle ,Carcinogenesis ,Proto-Oncogene Proteins c-akt ,DNA Damage - Abstract
Here we describe a conditional doxycycline-dependent mouse model of RET/PTC3 (NCOA4-RET) oncogene-induced thyroid tumorigenesis. In these mice, after 10 days of doxycycline (dox) administration, RET/PTC3 expression induced mitogen activated protein kinase (MAPK) stimulation and a proliferative response which resulted in the formation of hyperplastic thyroid lesions. This was followed, after 2 months, by growth arrest accompanied by typical features of oncogene-induced senescence (OIS), including upregulation of p16INK4A and p21CIP, positivity at the Sudan black B, activation of the DNA damage response (DDR) markers γH2AX and pChk2 T68, and induction of p53 and p19ARF. After 5 months, about half of thyroid lesions escaped OIS and formed tumors that remained dependent on RET/ PTC3 expression. This progression was accompanied by activation of AKT-FOXO1/3a pathway and increased serum TSH levels.
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- 2015
46. A Neutralizing RNA Aptamer against EGFR Causes Selective Apoptotic Cell Death
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Vittorio de Franciscis, Pina Marotta, Laura Cerchia, Gerolama Condorelli, Immacolata Longobardo, Andrea Affuso, Diana Passaro, Carla Lucia Esposito, Esposito, C. L., Passaro, D., Longobardo, Immmacolata, Condorelli, Gerolama, Marotta, Pina, Affuso, A., de Franciscis, V., and Cerchia, Laura
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Lung Neoplasms ,lcsh:Medicine ,Cetuximab ,Apoptosis ,Biochemistry ,Lung and Intrathoracic Tumors ,Synthetic Nucleic Acids ,Mice ,0302 clinical medicine ,Nucleic Acids ,Molecular Cell Biology ,Membrane Receptor Signaling ,Epidermal growth factor receptor ,lcsh:Science ,Caspase 8 ,0303 health sciences ,Multidisciplinary ,Cell Death ,biology ,Caspase 3 ,Antibodies, Monoclonal ,Aptamers, Nucleotide ,Flow Cytometry ,Caspase 9 ,3. Good health ,ErbB Receptors ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Tyrosine kinase ,Research Article ,Signal Transduction ,medicine.drug ,Cell Survival ,medicine.drug_class ,Aptamer ,Immunoblotting ,Mice, Nude ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,03 medical and health sciences ,Gefitinib ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Biology ,030304 developmental biology ,lcsh:R ,Cancers and Neoplasms ,Molecular biology ,Non-Small Cell Lung Cancer ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,biology.protein ,RNA ,lcsh:Q ,Systematic evolution of ligands by exponential enrichment - Abstract
Nucleic acid aptamers have been developed as high-affinity ligands that may act as antagonists of disease-associated proteins. Aptamers are non immunogenic and characterised by high specificity and low toxicity thus representing a valid alternative to antibodies or soluble ligand receptor traps/decoys to target specific cancer cell surface proteins in clinical diagnosis and therapy. The epidermal growth factor receptor (EGFR) has been implicated in the development of a wide range of human cancers including breast, glioma and lung. The observation that its inhibition can interfere with the growth of such tumors has led to the design of new drugs including monoclonal antibodies and tyrosine kinase inhibitors currently used in clinic. However, some of these molecules can result in toxicity and acquired resistance, hence the need to develop novel kinds of EGFR-targeting drugs with high specificity and low toxicity. Here we generated, by a cell-Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach, a nuclease resistant RNA-aptamer that specifically binds to EGFR with a binding constant of 10 nM. When applied to EGFR-expressing cancer cells the aptamer inhibits EGFR-mediated signal pathways causing selective cell death. Furthermore, at low doses it induces apoptosis even of cells that are resistant to the most frequently used EGFR-inhibitors, such as gefitinib and cetuximab, and inhibits tumor growth in a mouse xenograft model of human non-small-cell lung cancer (NSCLC). Interestingly, combined treatment with cetuximab and the aptamer shows clear synergy in inducing apoptosis in vitro and in vivo. In conclusion, we demonstrate that this neutralizing RNA-aptamer is a promising bio-molecule that can be developed as a more effective alternative to the repertoire of already existing EGFR-inhibitors.
- Published
- 2011
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