152 results on '"Tirino V"'
Search Results
2. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer
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Ferri, C, Di Biase, A, Bocchetti, M, Zappavigna, S, Wagner, S, Le Vu, P, Luce, A, Cossu, AM, Vadakekolathu, J, Miles, A, Boocock, DJ, Robinson, A, Schwerdtfeger, M, Tirino, V, Papaccio, F, Caraglia, M, Regad, T, Desiderio, V, Ferri, C., Di Biase, A., Bocchetti, M., Zappavigna, S., Wagner, S., Le Vu, P., Luce, A., Cossu, A. M., Vadakekolathu, J., Miles, A., Boocock, D. J., Robinson, A., Schwerdtfeger, M., Tirino, V., Papaccio, F., Caraglia, M., Regad, T., and Desiderio, V.
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Male ,Cancer Research ,Molecular biology ,lncRNAs ,Mice, Nude ,Transfection ,miR-423-5p ,Mice ,Malat-1 ,lncRNA ,Animals ,Humans ,Cellular biology ,Neoplasm Metastasis ,RC254-282 ,miRNA ,Cell Proliferation ,Cancer ,Research ,Prostate ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prostatic Neoplasms ,Gene expression ,miRNAs ,MicroRNAs ,Oncology - Abstract
Background The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs). Methods Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa. Results Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model. Conclusions We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.
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- 2022
3. Flow cytometric evaluation of measurable residual disease in chronic lymphocytic leukemia: Where do we stand?
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D'Arena, G., Sgambato, Alessandro, Volpe, S., Coppola, G., Amodeo, R., Tirino, V., D'Auria, F., Statuto, T., Valvano, L., Pietrantuono, G., Deaglio, S., Efremov, Dimitar, Laurenti, Luca, Aiello, Antimo, Sgambato A. (ORCID:0000-0002-9487-4563), Efremov D., Laurenti L. (ORCID:0000-0002-8327-1396), Aiello A., D'Arena, G., Sgambato, Alessandro, Volpe, S., Coppola, G., Amodeo, R., Tirino, V., D'Auria, F., Statuto, T., Valvano, L., Pietrantuono, G., Deaglio, S., Efremov, Dimitar, Laurenti, Luca, Aiello, Antimo, Sgambato A. (ORCID:0000-0002-9487-4563), Efremov D., Laurenti L. (ORCID:0000-0002-8327-1396), and Aiello A.
- Abstract
Measurable residual disease (MRD) has emerged as a relevant parameter of response to therapy in chronic lymphocytic leukemia (CLL). Although several methods have been developed, flow cytometry has emerged as the most useful and standardized approach to measure and quantify MRD. The improved sensitivity of MRD measurements has been paralleled by the development of more effective therapeutic strategies for CLL, increasing the applicability of MRD detection in this setting. Chemotherapy and chemoimmunotherapy have firstly demonstrated their ability to obtain a deep MRD. Combined targeted therapies are also demonstrating a high molecular response rate and prospective trials are exploring the role of MRD to guide the duration of treatment in this setting. In this review we briefly summarize what we have learned about MRD with emphasis on its flow cytometric detection.
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- 2022
4. Erratum: Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis in Vitro Model Based on Human Synoviocytes and Chondrocytes (BioMed Research International (2019) 2019 (4328219) DOI: 10.1155/2019/4328219)
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Stellavato A., Vassallo V., La Gatta A., Pirozzi A. V. A., De Rosa M., Balato G., D'addona A., Tirino V., Ruosi C., Schiraldi C., Stellavato, A., Vassallo, V., La Gatta, A., Pirozzi, A. V. A., De Rosa, M., Balato, G., D'Addona, A., Tirino, V., Ruosi, C., and Schiraldi, C.
- Abstract
In the article titled "Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes" [1], there was an error in Figure 6. In the part of Figure 6(a), "HCC 24h" is incorrect. The corrected figure is shown below, and is listed as (Figure present).
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- 2020
5. 3-O-methylfunicone, from Penicillium pinophilum, is a selective inhibitor of breast cancer stem cells
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Buommino, E., Tirino, V., De Filippis, A., Silvestri, F., Nicoletti, R., Ciavatta, M. L., Pirozzi, G., and Tufano, M. A.
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- 2011
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6. 1951P Niraparib and irinotecan combination in ATM-mutated colorectal cancer
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Vitiello, P.P., primary, Martini, G., additional, Mele, L., additional, Giunta, E.F., additional, De Falco, V., additional, Ciardiello, D., additional, Belli, V., additional, Cardone, C., additional, Matrone, N., additional, Poliero, L., additional, Tirino, V., additional, Selvaggi, F., additional, Papaccio, G., additional, Troiani, T., additional, Desiderio, V., additional, Ciardiello, F., additional, and Martinelli, E., additional
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- 2020
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7. The osteoblastic differentiation of human dental pulp stem cells and bone formation on two different titanium surface textures: 363
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Mangano, C, Mangano, F, De Rosa, A, Desiderio, V, dʼAquino, R, Piattelli, A, de Francesco, F, Tirino, V, and Papaccio, G
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- 2010
8. Elementi di istologia e cenni di embriologia
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Adamo, S., Bernardini, N., Boitani, C., Bonsi, L., Bouché, M., Brun, P., Canipari, R., Castriconi, R., Castrogiovanni, P., Ciccarelli, C., DE ANGELIS, L., D’Alessio, A., DE CESARIS, P., DE FELICI, M., DE MATTEI, M., Desiderio, V., DI ROSA, M., Dolfi, A., Dupont, S., Fazi, F., Filippini, A., Gagliano, N., Grano, M., Imbesi, R., Marcenaro, E., Musarò, A., Nervi, C., Papaccio, G. P., Ricci, G., Riccioli, A., Salustri, A., Scicchitano, B. M., Sivori, S., Tirino, V., Vicini, E., Virgintino, D., and Ziparo, E.
- Published
- 2019
9. Effetti e meccanismi molecolari della Curcumina nelle leucemie linfoblasti che acute dell’età pediatrica
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D’Angelo, V., PICA, ALESSANDRA, Iannotta, A., Di Massa, L., Ramaglia, M., Tirino, V., Di Martino, M., Pota, E., Di Pinto, D., Boccieri, E., MANCA, ROSA, Perrotta, S., Indolfi, P., Casale, F. ., D’Angelo, V., Pica, Alessandra, Iannotta, A., Di Massa, L., Ramaglia, M., Tirino, V., Di Martino, M., Pota, E., Di Pinto, D., Boccieri, E., Manca, Rosa, Perrotta, S., Indolfi, P., and Casale, F. .
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curcumina, daunoblastina, linee cellulari leucemiche, SUP-B15, Jurkat - Abstract
La curcumina, componente della curcuma presente nei rizomi della Curcuma Longa, sembra avere effetti antineoplastici per cui è stata studiata quale potenziale agente per la prevenzione e il trattamento di varie neoplasie in quanto bloccherebbe la trasformazione cellulare, proliferazione delle cellule neoplastiche inducendo apoptosi. Ci proponiamo di studiare l’effetto della curcumina su cellule leucemiche della linea B e T, in singolo e combinato con farmaci convenzionali utilizzati nei protocolli delle leucemie e con DZnep inibitore indiretto del regolatore epigenetico EZH2. .METODI: Sono state utilizzate, come modelli in vitro, due linee cellulari (SuP B-15 e Jurkat) per verificare gli effetti della curcumina a concentrazioni scalari e in combinazione con diversi agenti chemioterapici (Daunoblastina, L-asparaginasi, metotrexate) e con l’ inibitore di EZH2 (DZnep). Abbiamo studiato l’apoptosi, il ciclo cellulare, la produzione cellulare di ROS prima e dopo trattamento e effettuato l’analisi al microscopio confocale. RISuLTATI: I risultati preliminari mostrano che la curcumina inibisce in maniera dose-dipendente la proliferazione delle cellule di entrambe le linee cellulari dopo 24 ore di trattamento (p
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- 2017
10. ISTOLOGIA di Monesi 7
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Adamo, S., De Felici, M., Dolfi, A., Filippini, A., Grano, M., Musarò, A., Nervi, C., Papaccio, G., Salustri, A., Ziparo, E., Bernardini, N., Boitani, C., Bonsi, L., Bouchè, M., Brun, P., Canipari, R., Castriconi, R., Castrogiovanni, P., Ciccarelli, C., De Cesaris, P., De Mattei, M., Desiderio, V., Dupont, S., Fazi, F., Gagliano, N., Imbesi, R., Marcenaro, E., Riccioli, A., Sivori, S., Tirino, V., Vicini, E., and Virgintino, D.
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Citologia Istologia - Published
- 2018
11. Il Citoscheletro
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Adamo, S., DE FELICI, M., Dolfi, A., Filippini, A., Grano, M., Musarò, A., Nervi, C., Papaccio, G., Salustri, A., Ziparo, E., Bernardini, N., Boitani, C., Bonsi, L., Bouché, M., Brun, P., Canipari, R., Castriconi, R., Castrogiovanni, P., Ciccarelli, C., DE CESARIS, P., DE MATTEI, M., Desiderio, V., Dupont, S., Fazi, F., Gagliano, N., Imbesi, R., Marcenaro, E., Riccioli, A., Sivori, S., Tirino, V., Vicini, E., and Virgintino, D.
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- 2018
12. GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
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Vitiello, P.P., primary, Mele, L., additional, Prisco, C., additional, Cardone, C., additional, Ciardiello, D., additional, Poliero, L., additional, Borrelli, C., additional, Zanaletti, N., additional, Vitale, P., additional, Tirino, V., additional, Papaccio, G., additional, Troiani, T., additional, Ciardiello, F., additional, Marampon, F., additional, Desiderio, V., additional, and Martinelli, E., additional
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- 2019
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13. Effects of total antigens of Dicrocoelium dendriticum on human epatocarcinoma cells
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Alfano, Settimia, Della Pepa, Maria Elena, Tirino, V, Desiderio, V, Caraglia, Michele, Galdiero, Marilena, Galdiero, Massimiliano, PEPE, PAOLA, RINALDI, LAURA, CRINGOLI, GIUSEPPE, Italian Society of Microbiology, Alfano, Settimia, Della Pepa, Maria Elena, Pepe, Paola, Rinaldi, Laura, Cringoli, Giuseppe, Tirino, V, Desiderio, V, Caraglia, Michele, Galdiero, Marilena, and Galdiero, Massimiliano
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- 2015
14. Synergistic effect of vismodegib and cisplatin in NSCLC models via autophagy
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Papaccio, F., primary, Mele, L., additional, Della Corte, C.M., additional, Liccardo, D., additional, La Noce, M., additional, Desiderio, V., additional, Tirino, V., additional, Ciardiello, F., additional, and Morgillo, F., additional
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- 2017
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15. 28P - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
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Vitiello, P.P., Mele, L., Prisco, C., Cardone, C., Ciardiello, D., Poliero, L., Borrelli, C., Zanaletti, N., Vitale, P., Tirino, V., Papaccio, G., Troiani, T., Ciardiello, F., Marampon, F., Desiderio, V., and Martinelli, E.
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- 2019
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16. Ingegneria tissulare per la produzione di tessuto adiposo umano: applicazioni per la medicina rigenerativa
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D'ANDREA, FRANCESCO, Ferraro G., De Francesco F., Nicoletti GF, Tirino V., Rossano F., Desiderio V., Lo Sapio B., Papaccio G., D'Andrea, Francesco, Ferraro, G., De Francesco, F., Nicoletti, Gf, Tirino, V., Rossano, F., Desiderio, V., Lo Sapio, B., and Papaccio, G.
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- 2008
17. TREATMENT OF HUMAN OSTEOSARCOMA CELLS WITH 3AB INDUCES THE APPEARANCE OF CD133+ CELL POPULATION CONTAINING A POTENTIALLY STEM-LIKE PHENOTYPE
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DI FIORE, Riccardo, DRAGO FERRANTE, Rosa, CARTA, Patrizia, VENTO, Renza, PIROZZI G, TIRINO V, DI FIORE R, PIROZZI G, TIRINO V, DRAGO FERRANTE R, CARTA P, and VENTO R
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- 2007
18. The osteoblastic differentiation of human dental pulp stem cells and bone formation on two different titanium surface textures
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Mangano, Carlo, Mangano, F, De Rosa, A, Desideio, V, D'Aquino, R, Piattelli, A, De Francesco, F, Tirino, V, and Papaccio, G.
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- 2010
19. GSK2118436 and GSK1120212, effective BRAF and MEK inhibitors for mutated melanoma cell lines
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Gentilcore G, Capone M, Tirino V, Pirozzi G, Colombino M, Manca A, Palmieri G, Mozzillo N, and Ascierto PA.
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- 2010
20. Anti-tumor activity of NBD peptide in melanoma mouse model
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Gentilcore G, Proietti E, Madonna G, Capone M, Spada M, Tirino V, Pirozzi G, Ombra MN, Sini MC, Palmieri G, Mozzillo N., and Ascierto PA.
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- 2010
21. 36P - Synergistic effect of vismodegib and cisplatin in NSCLC models via autophagy
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Papaccio, F., Mele, L., Della Corte, C.M., Liccardo, D., La Noce, M., Desiderio, V., Tirino, V., Ciardiello, F., and Morgillo, F.
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- 2017
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22. Human CD34+/CD90+ ASCs Are Capable of Growing as Sphere Clusters, Producing High Levels of VEGF and Forming Capillaries
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FRANCESCO F., TIRINO V., DESIDERIO V., FERRARO G., GIULIANO M., LIBONDI G., PIROZZI G., DE ROSA A., PAPACCIO G, DE FRANCESCO F., D'ANDREA F., PAPACCIO G., D'ANDREA, FRANCESCO, Francesco, F., Tirino, V., Desiderio, V., Ferraro, G., D'Andrea, Francesco, Giuliano, M., Libondi, G., Pirozzi, G., DE ROSA, A., Papaccio, G, DE FRANCESCO, F., D'Andrea, F., Papaccio, G., De Francesco, F, Tirino, Virginia, Desiderio, Vincenzo, Ferraro, Giuseppe, Giuliano, Mariateresa, Libondi, G, Pirozzi, G, DE ROSA, Alfredo, and Papaccio, Gianpaolo
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Vascular Endothelial Growth Factor A ,Science ,Cellular differentiation ,CD34 ,Adipose tissue ,Antigens, CD34 ,Enzyme-Linked Immunosorbent Assay ,Biology ,HUMAN CD34/CD90 ASCs ,Side population ,Humans ,CD90 ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,Stem Cells ,Mesenchymal stem cell ,Cell Differentiation ,Cell Biology ,Stromal vascular fraction ,Flow Cytometry ,Molecular biology ,Capillaries ,Developmental Biology/Stem Cells ,Adipose Tissue ,Developmental Biology/Cell Differentiation ,Medicine ,Thy-1 Antigens ,Stem cell ,Cell Division ,Research Article - Abstract
BackgroundHuman adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Moreover, it is an easily accessible site producing a considerable amount of stem cells.Methodology/principal findingsIn this study, we have selected and characterized stem cells within the stromal vascular fraction (SVF) of human adult adipose tissue with the aim of understanding their differentiation capabilities and performance. We have found, within the SVF, different cell populations expressing MSC markers--including CD34, CD90, CD29, CD44, CD105, and CD117--and endothelial-progenitor-cell markers--including CD34, CD90, CD44, and CD54. Interestingly, CD34(+)/CD90(+) cells formed sphere clusters, when placed in non-adherent growth conditions. Moreover, they showed a high proliferative capability, a telomerase activity that was significantly higher than that found in differentiated cells, and contained a fraction of cells displaying the phenotype of a side population. When cultured in adipogenic medium, CD34(+)/CD90(+) quickly differentiated into adipocytes. In addition, they differentiated into endothelial cells (CD31(+)/VEGF(+)/Flk-1(+)) and, when placed in methylcellulose, were capable of forming capillary-like structures producing a high level of VEGF, as substantiated with ELISA tests.Conclusions/significanceOur results demonstrate, for the first time, that CD34(+)/CD90(+) cells of human adipose tissue are capable of forming sphere clusters, when grown in free-floating conditions, and differentiate in endothelial cells that form capillary-like structures in methylcellulose. These cells might be suitable for tissue reconstruction in regenerative medicine, especially when patients need treatments for vascular disease.
- Published
- 2009
23. Fighting for territories: time-lapse analysis of dental pulp and dental follicle stem cells in co-culture reveals specific migratory capabilities
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Schiraldi, C, Stellavato, A, D'Agostino, A, Tirino, V, d'Aquino, R, Woloszyk, A, De Rosa, A, Laino, L, Papaccio, G, Mitsiadis, T A, Schiraldi, C, Stellavato, A, D'Agostino, A, Tirino, V, d'Aquino, R, Woloszyk, A, De Rosa, A, Laino, L, Papaccio, G, and Mitsiadis, T A
- Abstract
Stem cell migration is a critical step during the repair of damaged tissues. In order to achieve appropriate cell-based therapies for tooth and periodontal ligament repair it is necessary first to understand the dynamics of tissue-specific stem cell populations such as dental pulp stem cells (DPSC) and dental follicle stem cells (DFSC). Using time-lapse imaging, we analysed migratory and proliferative capabilities of these two human stem cell lines in vitro. When cultured alone, both DPSC and DFSC exhibited low and irregular migration profiles. In co-cultures, DFSC, but not DPSC, spectacularly increased their migration activity and velocity. DFSC rapidly surrounded the DPSC, thus resembling the in vivo developmental process, where follicle cells encircle both dental epithelium and pulp. Cell morphology was dependent on the culture conditions (mono-culture or co-culture) and changed over time. Regulatory genes involved in dental cell migration and differentiation such as TWIST1, MSX1, RUNX2, SFRP1 and ADAM28, were also evaluated in co-cultures. MSX1 up-regulation indicates that DPSC and DFSC retain their odontogenic potential. However, DPSC lose their capacity to differentiate into odontoblasts in the presence of DFSC, as suggested by RUNX2 up-regulation and TWIST1 down-regulation. In contrast, the unchanged levels of SFRP1 expression suggest that DFSC retain their potential to form periodontal tissues even in the presence of DPSC. These findings demonstrate that stem cells behave differently according to their environment, retain their genetic memory, and compete with each other to acquire the appropriate territory. Understanding the mechanisms involved in stem cell migration may lead to new therapeutic approaches for tooth repair.
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- 2012
24. Amniotic fluid-derived mesenchymal stem cells lead to bone differentiation when cocultured with dental pulp stem cells
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De Rosa, A, Tirino, V, Paino, F, Tartaglione, A, Mitsiadis, T A, Feki, A, d'Aquino, R, Laino, L, Colacurci, N, Papaccio, G, De Rosa, A, Tirino, V, Paino, F, Tartaglione, A, Mitsiadis, T A, Feki, A, d'Aquino, R, Laino, L, Colacurci, N, and Papaccio, G
- Abstract
Mesenchymal stem cells are present in many tissues of the human body, including amniotic fluid (AF) and dental pulp (DP). Stem cells of both AF and DP give rise to a variety of differentiated cells. In our experience, DP stem cells (DPSCs) display a high capacity to produce bone. Therefore, our aim was to investigate if AF-derived stem cells (AFSCs) were able to undergo bone differentiation in the presence of DPSCs. AFSCs were seeded under three different conditions: (i) cocultured with DPSCs previously differentiated into osteoblasts; (ii) cultured in the conditioned medium of osteoblast-differentiated DPSCs; (iii) cultured in the osteogenic medium supplemented with vascular endothelial growth factor and bone morphogenetic protein-2 (BMP-2). Results showed that AFSCs were positive for mesenchymal markers, and expressed high levels of Tra1-60, Tra1-80, BMPR1, BMPR2, and BMP-2. In contrast, AFSCs were negative for epithelial and hematopoietic/endothelial markers. When AFSCs were cocultured with DPSCs-derived osteoblasts, they differentiated into osteoblasts. A similar effect was observed when AFSCs were cultured in the presence of a conditioned medium originated from DPSCs. We found that osteoblasts derived from DPSCs released large amounts of BMP-2 and vascular endothelial growth factor into the culture medium and that those morphogens significantly upregulate RUNX-2 gene, stimulating osteogenesis. This study highlights the mechanisms of osteogenesis and strongly suggests that the combination of AFSCs with DPSCs may provide a rich source of soluble proteins useful for bone engineering purposes.
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- 2011
25. TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction
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Tirino, V, primary, Camerlingo, R, additional, Bifulco, K, additional, Irollo, E, additional, Montella, R, additional, Paino, F, additional, Sessa, G, additional, Carriero, M V, additional, Normanno, N, additional, Rocco, G, additional, and Pirozzi, G, additional
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- 2013
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26. Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer
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PIROZZI, G., primary, TIRINO, V., additional, CAMERLINGO, R., additional, LA ROCCA, A., additional, MARTUCCI, N., additional, SCOGNAMIGLIO, G., additional, FRANCO, R., additional, CANTILE, M., additional, NORMANNO, N., additional, and ROCCO, G., additional
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- 2013
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27. P.102 IDENTIFICATION AND CHARACTERIZATION OF CANCER STEM CELLS IN PRIMARY HUMAN GASTRIC CANCER
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Rocco, A., primary, Liguori, E., additional, Pirozzi, G., additional, Tirino, V., additional, Affuso, A., additional, Pollastrone, G., additional, Masone, S., additional, Coppola Bottazzi, E., additional, D'Armiento, F., additional, Fusco, F., additional, Compare, D., additional, and Nardone, G., additional
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- 2010
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28. The stem cell hypothesis in head and neck cancer
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Graziano, A., primary, d'Aquino, R., additional, Tirino, V., additional, Desiderio, V., additional, Rossi, A., additional, and Pirozzi, G., additional
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- 2008
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29. TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction.
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Tirino, V., Camerlingo, R., Bifulco, K., Irollo, E., Montella, R., Paino, F., Sessa, G., Carriero, M. V., Normanno, N., Rocco, G., and Pirozzi, G.
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- 2013
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30. Correction: Detection and Characterization of CD133+ Cancer Stem Cells in Human Solid Tumours
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Tirino V, Desiderio V, d'Aquino R, Francesco De Francesco, Pirozzi G, Graziano A, Galderisi U, Cavaliere C, De Rosa A, Papaccio G, and Giordano A
31. Activating E17K mutation in the gene encoding the protein kinase AKT1 in a subset of squamous cell carcinoma of the lung
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Malanga, D., Scrima, M., Marco, C., Fabiani, F., Rosa, N., Gisi, S., Malara, N., Savino, R., Gaetano Rocco, Chiappetta, G., Franco, R., Tirino, V., Pirozzi, G., Viglietto, G., Malanga, D, Scrima, M, DE MARCO, C, Fabiani, F, DE ROSA, N, DE GISI, S, Malara, N, Savino, R, Rocco, G, Chiappetta, G, Franco, Renato, Tirino, Virginia, Pirozzi, G, and Viglietto, G.
32. Does poor glycaemic control affect the immunogenicity of the COVID-19 vaccination in patients with type 2 diabetes: The CAVEAT study
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Giovanni Napolitano, Gianpaolo Papaccio, Fabrizio Turriziani, Celestino Sardu, Marilena Galdiero, Antonio Papa, Luigi Salemme, Giuseppe Paolisso, Lucia Scisciola, Nicola Coppola, Eugenio Basile, Carmela Papa, Paolo Maggi, Michelangela Barbieri, Ferdinando Carlo Sasso, Ciro Romano, F. Russo, Maria Rosaria Rizzo, Maria Luisa Balestrieri, Raffaele Marfella, Mario Siniscalchi, Claudio Napoli, Vincenzo Messina, Nunzia D'Onofrio, Ludovica Vittoria Marfella, Maria Vittoria Montemurro, Italo F. Angelillo, Virginia Tirino, Marco Boccalatte, Francesco Frascaria, Mauro Maniscalco, Marfella, Raffaele, D'Onofrio, Nunzia, Sardu, Celestino, Scisciola, Lucia, Maggi, Paolo, Coppola, Nicola, Romano, Ciro, Messina, Vincenzo, Turriziani, Fabrizio, Siniscalchi, Mario, Maniscalco, Mauro, Boccalatte, Marco, Napolitano, Giovanni, Salemme, Luigi, Marfella, Ludovica Vittoria, Basile, Eugenio, Montemurro, Maria Vittoria, Papa, Carmela, Frascaria, Francesco, Papa, Antonio, Russo, Ferdinando, Tirino, Virginia, Papaccio, Gianpaolo, Galdiero, Marilena, Sasso, Ferdinando Carlo, Barbieri, Michelangela, Rizzo, Maria Rosaria, Balestrieri, Maria Luisa, Angelillo, Italo Francesco, Napoli, Claudio, Paolisso, Giuseppe, Marfella, R., D'Onofrio, N., Sardu, C., Scisciola, L., Maggi, P., Coppola, N., Romano, C., Messina, V., Turriziani, F., Siniscalchi, M., Maniscalco, M., Boccalatte, M., Napolitano, G., Salemme, L., Marfella, L. V., Basile, E., Montemurro, M. V., Papa, C., Frascaria, F., Papa, A., Russo, F., Tirino, V., Papaccio, G., Galdiero, M., Sasso, F. C., Barbieri, M., Rizzo, M. R., Balestrieri, M. L., Angelillo, I. F., Napoli, C., and Paolisso, G.
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Blood Glucose ,medicine.medical_specialty ,Glycated Hemoglobin A ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,COVID-19 Vaccine ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Type 2 diabetes ,Glycemic Control ,Affect (psychology) ,Endocrinology ,Immunogenicity, Vaccine ,Internal medicine ,Research Letter ,Internal Medicine ,medicine ,Humans ,In patient ,Poor glycaemic control ,Glycated Hemoglobin ,business.industry ,Immunogenicity ,COVID-19 ,medicine.disease ,Research Letters ,Vaccination ,Diabetes Mellitus, Type 2 ,business ,Human - Published
- 2021
33. Gelatin-biofermentative unsulfated glycosaminoglycans semi-interpenetrating hydrogels via microbial-transglutaminase crosslinking enhance osteogenic potential of dental pulp stem cells
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Anna Virginia Adriana Pirozzi, Virginia Tirino, Annalisa La Gatta, Luigi Laino, Marcella La Noce, Gianpaolo Papaccio, Chiara Schiraldi, Antonietta Stellavato, Nadia Diano, Marianna Portaccio, Marcella Cammarota, Gatta, A. L., Tirino, V., Cammarota, M., Noce, M. L., Stellavato, A., Pirozzi, A. V. A., Portaccio, M., Diano, N., Laino, L., Papaccio, G., and Schiraldi, C.
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food.ingredient ,02 engineering and technology ,Matrix (biology) ,Gelatin ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,chemistry.chemical_compound ,food ,Tissue engineering ,Dental pulp stem cells ,Chondroitin ,Bone regeneration ,Biotechnological chondroitin ,Hyaluronan ,030304 developmental biology ,0303 health sciences ,Chemistry ,Human dental pulp stem cell ,technology, industry, and agriculture ,Hydrogels ,021001 nanoscience & nanotechnology ,Self-healing hydrogels ,Biophysics ,human dental pulp stem cells ,AcademicSubjects/SCI01410 ,AcademicSubjects/MED00010 ,0210 nano-technology ,Research Article - Abstract
Gelatin hydrogels by microbial-transglutaminase crosslinking are being increasingly exploited for tissue engineering, and proved high potential in bone regeneration. This study aimed to evaluate, for the first time, the combination of enzymatically crosslinked gelatin with hyaluronan and the newly developed biotechnological chondroitin in enhancing osteogenic potential. Gelatin enzymatic crosslinking was carried out in the presence of hyaluronan or of a hyaluronan–chondroitin mixture, obtaining semi-interpenetrating gels. The latter proved lower swelling extent and improved stiffness compared to the gelatin matrix alone, whilst maintaining high stability. The heteropolysaccharides were retained for 30 days in the hydrogels, thus influencing cell response over this period. To evaluate the effect of hydrogel composition on bone regeneration, materials were seeded with human dental pulp stem cells and osteogenic differentiation was assessed. The expression of osteocalcin (OC) and osteopontin (OPN), both at gene and protein level, was evaluated at 7, 15 and 30 days of culture. Scanning electron microscopy (SEM) and two-photon microscope observations were performed to assess bone-like extracellular matrix (ECM) deposition and to observe the cell penetration depth. In the presence of the heteropolysaccharides, OC and OPN expression was upregulated and a higher degree of calcified matrix formation was observed. Combination with hyaluronan and chondroitin improved both the biophysical properties and the biological response of enzymatically crosslinked gelatin, fastening bone deposition.
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- 2021
34. Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer
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Valentina Belli, Stefania Napolitano, Virginia Tirino, Pietro Paolo Vitiello, Emilio Francesco Giunta, Nunzia Matrone, Carminia Maria Della Corte, Vincenzo Desiderio, Giulia Martini, Claudia Cardone, Davide Ciardiello, Luigi Mele, L. Poliero, Floriana Morgillo, Vincenzo De Falco, Fortunato Ciardiello, Teresa Troiani, Erika Martinelli, Francesco Selvaggi, Gianpaolo Papaccio, Vitiello, P. P., Martini, G., Mele, L., Giunta, E. F., De Falco, V., Ciardiello, D., Belli, V., Cardone, C., Matrone, N., Poliero, L., Tirino, V., Napolitano, S., Della Corte, C., Selvaggi, F., Papaccio, G., Troiani, T., Morgillo, F., Desiderio, V., Ciardiello, F., and Martinelli, E.
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0301 basic medicine ,Cancer Research ,Indazoles ,Colorectal cancer ,DNA damage ,medicine.medical_treatment ,Mice, Nude ,DNA damage response ,Irinotecan ,lcsh:RC254-282 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Piperidines ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Homologous recombination ,Clonogenic assay ,PARP inhibitors ,Chemotherapy ,business.industry ,Research ,Synergism ,Drug interaction ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,Oxaliplatin ,030104 developmental biology ,PARP inhibitor ,Oncology ,030220 oncology & carcinogenesis ,Combination treatment ,Mutation ,Chemopotentiation ,Cancer research ,Female ,business ,Colorectal Neoplasms ,medicine.drug - Abstract
Background Despite the advancements in new therapies for colorectal cancer (CRC), chemotherapy still constitutes the mainstay of the medical treatment. For this reason, new strategies to increase the efficacy of chemotherapy are desirable. Poly-ADP-Ribose Polymerase inhibitors (PARPi) have shown to increase the activity of DNA damaging chemotherapeutics used in the treatment of CRC, however previous clinical trials failed to validate these results and pointed out dose-limiting toxicities that hamper the use of such combinations in unselected CRC patients. Nevertheless, in these studies little attention was paid to the mutational status of homologous recombination repair (HRR) genes. Methods We tested the combination of the PARPi niraparib with either 5-fluorouracil, oxaliplatin or irinotecan (SN38) in a panel of 12 molecularly annotated CRC cell lines, encompassing the 4 consensus molecular subtypes (CMSs). Synergism was calculated using the Chou-Talalay method for drug interaction. A correlation between synergism and genetic alterations in genes involved in homologous recombination (HR) repair was performed. We used clonogenic assays, mice xenograft models and patient-derived 3D spheroids to validate the results. The induction of DNA damage was studied by immunofluorescence. Results We showed that human CRC cell lines, as well as patient-derived 3D spheroids, harboring pathogenic ATM mutations are significantly vulnerable to PARPi/chemotherapy combination at low doses, regardless of consensus molecular subtypes (CMS) and microsatellite status. The strongest synergism was shown for the combination of niraparib with irinotecan, and the presence of ATM mutations was associated to a delay in the resolution of double strand breaks (DSBs) through HRR and DNA damage persistence. Conclusions This work demonstrates that a numerically relevant subset of CRCs carrying heterozygous ATM mutations may benefit from the combination treatment with low doses of niraparib and irinotecan, suggesting a new potential approach in the treatment of ATM-mutated CRC, that deserves to be prospectively validated in clinical trials.
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- 2021
35. Antioxidant and hypolipidemic activity of açai fruit makes it a valuable functional food
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Renata Piccoli, Chiara Schiraldi, Paola Imbimbo, Antonella D’Agostino, Daria Maria Monti, Rosario Finamore, Virginia Tirino, Anna Virginia Adriana Pirozzi, Pirozzi, A. V. A., Imbimbo, P., D'Agostino, A., Tirino, V., Finamore, R., Monti, D. M., Piccoli, R., Schiraldi, C., Pirozzi, Anna Virginia Adriana, Imbimbo, Paola, D'Agostino, Antonella, Tirino, Virginia, Finamore, Rosario, Monti, Daria Maria, Piccoli, Renata, and Schiraldi, Chiara
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0301 basic medicine ,Antioxidant ,Steatosis ,Physiology ,medicine.medical_treatment ,Açai ,MDA ,Clinical Biochemistry ,HepG2 cell ,macromolecular substances ,medicine.disease_cause ,Biochemistry ,Article ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Functional food ,Lipid droplet ,NAFLD ,medicine ,oxidative stress ,Food science ,NF-kB ,Molecular Biology ,HepG2 cells ,PPAR α/γ ,lcsh:RM1-950 ,Fatty liver ,Lipid metabolism ,Cell Biology ,medicine.disease ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Oxidative stre ,Oxidative stress - Abstract
Several plant extracts are acquiring increasing value because of their antioxidant activity and hypolipidemic properties. Among them, great interest has been recently paid to aç, ai fruit as a functional food. The aim of this study was to test the ability of aç, ai extract in reducing oxidative stress and modulating lipid metabolism in vitro using different cell models and different types of stress. In fact, lipid peroxidation as evaluated in a HepG2 model was reduced five-fold when using 0.25 µ, g/mL of extract, and it was further reduced (20-fold) with the concentration increase up to 2.5 µ, g/mL. With the non alcoholic fatty liver disease (NAFLD)in vitro model, all concentrations tested showed at least a two-fold reduced fat deposit. In addition, primary adipocytes challenged with TNF-&alpha, under hypoxic conditions to mimic the persistent subcutaneous fat, treated with aç, ai extract showed an approximately 40% reduction of fat deposit. Overall, our results show that aç, ai is able to counteract oxidative states in all the cell models analysed and to prevent the accumulation of lipid droplets. No toxic effects and high stability overtime were highlighted at the concentrations tested. Therefore, aç, ai can be considered a suitable support in the prevention of different alterations of lipid and oxidative metabolism responsible for fat deposition and metabolic pathological conditions.
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- 2021
36. β2-AR blockade potentiates MEK1/2 inhibitor effect on HNSCC by regulating the Nrf2-mediated defense mechanism
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Melanie Schwerdtfeger, Sabrina Bimonte, Luigi Mele, Davide Liccardo, Michele Caraglia, Antonio Barbieri, Francesco Marampon, Marcella La Noce, Tarik Regad, Vincenzo Desiderio, Laura Mosca, Virginia Tirino, Aldo Giudice, Vitale Del Vecchio, Claudia Prisco, Sarah Wagner, Gianpaolo Papaccio, Mele, Luigi, Del Vecchio, Vitale, Marampon, Francesco, Regad, Tarik, Wagner, Sarah, Mosca, Laura, Bimonte, Sabrina, Giudice, Aldo, Liccardo, Davide, Prisco, Claudia, Schwerdtfeger, Melanie, La Noce, Marcella, Tirino, Virginia, Caraglia, Michele, Papaccio, Gianpaolo, Desiderio, Vincenzo, Barbieri, Antonio, Mele, L., Del Vecchio, V., Marampon, F., Regad, T., Wagner, S., Mosca, L., Bimonte, S., Giudice, A., Liccardo, D., Prisco, C., Schwerdtfeger, M., La Noce, M., Tirino, V., Caraglia, M., Papaccio, G., Desiderio, V., and Barbieri, A.
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MAPK/ERK pathway ,Cancer Research ,Cell Survival ,NF-E2-Related Factor 2 ,p38 mitogen-activated protein kinases ,MAP Kinase Kinase 2 ,Immunology ,MAP Kinase Kinase 1 ,Protein Kinase Inhibitor ,Article ,Propanolamines ,Cellular and Molecular Neuroscience ,Targeted therapies ,Downregulation and upregulation ,Adrenergic beta-2 Receptor Antagonists ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,lcsh:QH573-671 ,Receptor ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Antineoplastic Combined Chemotherapy Protocol ,Adrenergic beta-2 Receptor Antagonist ,lcsh:Cytology ,Head and Neck Neoplasm ,Squamous Cell Carcinoma of Head and Neck ,Chemistry ,Cell growth ,Oral cancer ,Autophagy ,Drug Synergism ,Cell Biology ,Propanolamine ,Head and Neck Neoplasms ,Cancer cell ,Cancer research ,Receptors, Adrenergic, beta-2 ,Human ,Signal Transduction - Abstract
The β2-Adrenergic receptor (β2-AR) is a G protein-coupled receptor (GPCR), involved in the development of many cancers, among which HNSCC. In this contest, β2-AR signaling interacts with different pathways, such as PI3K and MAPK, commonly activated by TK receptors. For this reason, TK blockade is one of the most adopted therapeutic strategies in HNSCC patients. In our study we investigated the effects of the β2-AR blocking in HNSCC cell lines, using the selective inhibitor ICI118,551 (ICI), in combination with the MAPK inhibitor U0126. We found that ICI leads to the blocking of p38 and NF-kB oncogenic pathways, strongly affecting also the ERK and PI3K pathways. Cotreatment with U0126 displays a synergic effect on cell viability and pathway alteration. Interestingly, we found that the β2-AR blockade affects Nrf2-Keap1 stability and its nuclear translocation leading to a drastic ROS increase and oxidative stress. Our results are confirmed by a TCGA dataset analysis, showing that NFE2L2 gene is commonly overexpressed in HNSC, and correlated with a lower survival rate. In our system, the PI3K pathway inhibition culminated in the blocking of pro-survival autophagy, a mechanism normally adopted by cancer cells to became less responsive to the therapies. The mTOR expression, commonly upregulated in HNSC, was reduced in patients with disease-recurrence. It is well known that mTOR has a strong autophagy inhibition effect, therefore its downregulation promoted pro-survival autophagy, with a related increase recurrence rate. Our findings highlight for the first time the key role of β2-AR and related pathway in HNSCC cell proliferation and drug resistance, proposing it as a valuable therapeutic molecular target. The β2-Adrenergic receptor (β2-AR) is a G protein-coupled receptor (GPCR), involved in the development of many cancers, among which HNSCC. In this contest, β2-AR signaling interacts with different pathways, such as PI3K and MAPK, commonly activated by TK receptors. For this reason, TK blockade is one of the most adopted therapeutic strategies in HNSCC patients. In our study we investigated the effects of the β2-AR blocking in HNSCC cell lines, using the selective inhibitor ICI118,551 (ICI), in combination with the MAPK inhibitor U0126. We found that ICI leads to the blocking of p38 and NF-kB oncogenic pathways, strongly affecting also the ERK and PI3K pathways. Cotreatment with U0126 displays a synergic effect on cell viability and pathway alteration. Interestingly, we found that the β2-AR blockade affects Nrf2-Keap1 stability and its nuclear translocation leading to a drastic ROS increase and oxidative stress. Our results are confirmed by a TCGA dataset analysis, showing that NFE2L2 gene is commonly overexpressed in HNSC, and correlated with a lower survival rate. In our system, the PI3K pathway inhibition culminated in the blocking of pro-survival autophagy, a mechanism normally adopted by cancer cells to became less responsive to the therapies. The mTOR expression, commonly upregulated in HNSC, was reduced in patients with disease-recurrence. It is well known that mTOR has a strong autophagy inhibition effect, therefore its downregulation promoted pro-survival autophagy, with a related increase recurrence rate. Our findings highlight for the first time the key role of β2-AR and related pathway in HNSCC cell proliferation and drug resistance, proposing it as a valuable therapeutic molecular target.
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- 2020
37. The role of autophagy in resistance to targeted therapies
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Nirmal Robinson, Melanie Schwerdtfeger, Luigi Mele, Gianpaolo Papaccio, Vitale Del Vecchio, Vincenzo Desiderio, Marcella La Noce, Claudia Prisco, Davide Liccardo, V. Tirino, Mele, Luigi, del Vecchio, Vitale, Liccardo, Davide, Prisco, Claudia, Schwerdtfeger, Melanie, Robinson, Nirmal, Desiderio, Vincenzo, Tirino, Virginia, Papaccio, Gianpaolo, La Noce, Marcella, Del Vecchio, Vitale, Mele, L., del Vecchio, V., Liccardo, D., Prisco, C., Schwerdtfeger, M., Robinson, N., Desiderio, V., Tirino, V., Papaccio, G., and La Noce, M.
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0301 basic medicine ,medicine.medical_treatment ,Cell ,Tyrosine kinase inhibitor ,Drug resistance ,medicine.disease_cause ,Targeted therapy ,Fight-or-flight response ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Neoplasms ,tyrosine kinase inhibitors ,Molecular Targeted Therapy ,Monoclonal antibodie ,Immunotoxins ,Antibodies, Monoclonal ,General Medicine ,targeted therapy ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,monoclonal antibodies ,medicine.symptom ,Human ,autophagy ,Protein Kinase Inhibitor ,Small Molecule Libraries ,03 medical and health sciences ,Small Molecule Librarie ,medicine ,Autophagy ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Protein Kinase Inhibitors ,Tyrosine kinase inhibitors ,Immunotoxin ,drug resistance ,business.industry ,Animal ,Hypoxia (medical) ,030104 developmental biology ,Drug Resistance, Neoplasm ,Cancer research ,Neoplasm ,business ,Homeostasis ,Oxidative stress - Abstract
Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance. In the last years, in addition to standard anti-cancer treatments such as chemotherapies and irradiation, targeted therapy became one of the most adopted strategies in clinical practices, mainly due to high specificity and reduced side effects. However, similar to standard treatments, drug resistance is the main challenge in most patients. Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies. Refereed/Peer-reviewed
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- 2020
38. Comparative Study of NGS Platform Ion Torrent Personal Genome Machine and Therascreen Rotor-Gene Q for the Detection of Somatic Variants in Cancer
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Elvira Moscarella, Andrea Ronchi, Erika Martinelli, Amalia Luce, Giuseppe Argenziano, Anna Maria Grimaldi, Gabriella Misso, Gianpaolo Papaccio, Michele Caraglia, Fortunato Ciardiello, Pasquale Sperlongano, Raffaele Addeo, Virginia Tirino, Margherita Russo, Gennaro Galizia, Andrea Nečasová, Floriana Morgillo, Teresa Troiani, Vincenzo Desiderio, Francesco Iovino, Alois Nečas, Angela Lombardi, Lombardi, A, Russo, M, Luce, A, Morgillo, F, Tirino, V, Misso, G, Martinelli, E, Troiani, T, Desiderio, V, Papaccio, G, Iovino, F, Argenziano, G, Moscarella, E, Sperlongano, P, Galizia, G, Addeo, R, Necas, A, Necasova, A, Ciardiello, F, Ronchi, A, Caragli, M, and Grimaldi, A
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0301 basic medicine ,metastatic colorectal cancer (mCRC) ,Colorectal cancer ,Biomedical Engineering ,non-small cell lung cancer (NSCLC) ,therascreen rotor gene Q ,Bioengineering ,medicine.disease_cause ,Biochemistry ,Article ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,melanoma ,lcsh:Science ,Lung cancer ,lcsh:QH301-705.5 ,Gene ,neoplasms ,business.industry ,Melanoma ,Ion semiconductor sequencing ,medicine.disease ,digestive system diseases ,ion torrent personal genome machine (PGM) ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,lcsh:Q ,KRAS ,business ,Biotechnology - Abstract
Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.
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- 2019
39. Conditioned medium of primary lung cancer cells induces EMT in A549 lung cancer cell line by TGF-ß1 and miRNA21 cooperation
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Camerlingo R1, Miceli R2, Marra L1, Rea G3, D'Agnano I4, 5, Nardella M6, Montella R7, Morabito A8, Normanno N1, Tirino V7, Rocco G9, Camerlingo, R., Miceli, R., Marra, L., Rea, G., D'Agnano, I., Nardella, M., Montella, R., Morabito, A., Normanno, N., Tirino, V., and Rocco, G.
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0301 basic medicine ,Cell signaling ,Lung Neoplasms ,Hydrolases ,Signal transduction ,Biochemistry ,Lung and Intrathoracic Tumors ,Metastasis ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine and Health Sciences ,Multidisciplinary ,microRNA ,EMT ,Signaling cascades ,Enzymes ,Gene Expression Regulation, Neoplastic ,Nucleic acids ,Phenotypes ,Phenotype ,Oncology ,030220 oncology & carcinogenesis ,embryonic structures ,Medicine ,Research Article ,Cell biology ,Epithelial-Mesenchymal Transition ,Nucleases ,Science ,Biology ,Research and Analysis Methods ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Paracrine signalling ,Ribonucleases ,DNA-binding proteins ,Genetics ,medicine ,Humans ,Vimentin ,Antagomir ,Gene Silencing ,Non-coding RNA ,Molecular Biology Techniques ,Lung cancer ,Autocrine signalling ,Cell Shape ,Molecular Biology ,A549 cell ,Natural antisense transcripts ,Biology and life sciences ,Cancers and Neoplasms ,Proteins ,medicine.disease ,extracellular mediators ,Gene regulation ,Non-Small Cell Lung Cancer ,MicroRNAs ,Cytoskeletal Proteins ,lung cancer ,030104 developmental biology ,TGF-beta signaling cascade ,chemistry ,A549 Cells ,Tumor progression ,Culture Media, Conditioned ,Enzymology ,Cancer research ,RNA ,Gene expression ,Cloning - Abstract
The epithelial-mesenchymal transition (EMT) plays a key role in tumor progression, drug resistance and metastasis. Recently, numerous microRNA (miRNA) have been described to regulate EMT in tumor progression. In this study, we found that conditioned medium from the LC212 non-small-cell lung cancer (NSCLC) cell line (LC212-CM) induces morphological changes and overexpression of Vimentin, CD90, SMAD 2/3, SLUG and TWIST in A549 NSCLC cells, consistent with a mesenchymal phenotype. To identify the soluble mediators in LC212-CM involved in this phenomenon, we performed miRNA profiling and TGF-β1 quantification. We found that LC212-CM contains high levels of TGF-β1 as well as different secreted miRNAs. We focused our attention on Homo sapiens-microRNA21 (hsa-miR21), one of most relevant miRNA associated with lung cancer progression, metastasis and EMT. An hsa-miR21 antagomiR was able to prevent the LC212-CM-induced EMT phenotype in A549 cells. Furthermore, we found that TGF-β1 and hsa-miR21 cooperate in the induction of EMT in A549 cells. Intriguingly, TGF-β1 was found to induce hsa-miR21 expression in A549 cell, thus suggesting that the hsa-miR21 mediates at least in part the pro-EMT effects of TGF-β1. In conclusion, hsa-miR21 and TGF-β1 are involved in autocrine and paracrine circuits that regulate the EMT status of lung cancer cells.
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- 2019
40. Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes
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Annalisa La Gatta, Chiara Schiraldi, Alessio D'Addona, Virginia Tirino, Anna Virginia Adriana Pirozzi, Carlo Ruosi, Mario De Rosa, Antonietta Stellavato, Giovanni Balato, Valentina Vassallo, Stellavato, A., Vassallo, V., La Gatta, A., Pirozzi, A. V. A., De Rosa, M., Balato, G., D'Addona, A., Tirino, V., Ruosi, C., Schiraldi, C., Stellavato, Antonietta, Vassallo, Valentina, LA GATTA, Annalisa, Virginia Adriana Pirozzi, Anna, DE ROSA, Mario, Balato, Giovanni, D’Addona, Alessio, Tirino, Virginia, Ruosi, Carlo, and Schiraldi, Chiara
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0301 basic medicine ,Article Subject ,Cytokine profile ,lcsh:Medicine ,Video microscopy ,Inflammation ,Osteoarthritis ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,In vitro model ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chondrocytes ,Hyaluronic acid ,medicine ,Synovial fluid ,Humans ,Hyaluronic Acid ,Cell Proliferation ,General Immunology and Microbiology ,Cartilage ,lcsh:R ,General Medicine ,medicine.disease ,Synoviocytes ,Molecular Weight ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,medicine.symptom ,Inflammation Mediators ,Gels ,Research Article - Abstract
High molecular weight hyaluronan (H-HA) has a pivotal role in the maintenance of normal functions of synovial fluid and structure of the articular joint, but it has been shown that its concentration is reduced in patients affected by degenerative cartilage diseases, such as osteoarthritis (OA). The aim of this study was to investigate the anti-inflammatory effects and properties of hybrid cooperative complexes based on high and low molecular weight hyaluronan (HCC) compared to H-HA on human primary cells derived by pathological joints. In addition, the rheological behavior of HCC was evaluated in order to define their potential as viscosupplement gel in degenerated joints. The experiments were performed using an in vitro model of OA based on human chondrocytes and synoviocytes isolated from degenerated joints of patients hospitalized for surgical replacement. In order to assess the anti-inflammatory effects of HCC, we evaluated NF-kB, COMP-2, IL-6, and IL-8 as specific markers at the transcriptional and/or protein level. Moreover, the proliferative properties of HCC were assessed using time lapse video microscopy. We showed that chondrocytes and synoviocytes clearly presented an altered cytokine profile compatible with a severe ongoing inflammation status. H-HA and, above all, HCC significantly reduced levels of the specific biomarkers evaluated and improved cartilage healing. The rheological profile indicated HCC suitability for intra-articular injection in joint diseases. HCC viscoelastic properties and the protective/anti-inflammatory effect on human chondrocytes and synoviocytes suggest the novel HCC-based gels as a valid support for OA management.
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- 2019
41. Studio morfologico in time-lapse imaging e molecolare della curcumina sul metabolismo dei ROS nelle leucemie linfoblastiche acute dell’età pediatrica
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A. Iannotta, V. D’Angelo, Alessandra Pica, MANCA, ROSA, L. Di Massa, V. Tirino, M. Di Martino, E. Pota, D. Di Pinto, S. Perrotta, F. Rossi, P. Indolfi, F. Casale, Iannotta, A., D’Angelo, V., Pica, Alessandra, Manca, Rosa, Di Massa, L., Tirino, V., Di Martino, M., Pota, E., Di Pinto, D., Perrotta, S., Rossi, F., Indolfi, P., and Casale, F.
- Abstract
INTRODUZIONE: Le proprietà anti-leucemiche di vari farmaci chemioterapici utilizzati per trattare la leucemia, sono state attribuite alla generazione di ROS nelle cellule leucemiche. Sebbene il controllo selettivo dei livelli di ROS intracellulari sia attualmente una delle terapie più promettenti per la soppressione dei tumori,questo obiettivo non è ancora stato raggiunto con successo. Tuttavia, la Curcumina e i suoi analoghi sono potenziali candidati per questo scopo. METODI: La linea cellulare Jurkat è stata utilizzata come modello per analizzare gli effetti della Curcumina in combinazione con diversi agenti chemioterapici (Daunoblastina, L-Asparaginasi, Metotrexate, Vincristina e Desametazone). Abbiamo studiato la proliferazione, l’apoptosi, il ciclo cellulare, la produzione cellulare di ROS prima e dopo trattamento con inibitore dei ROS (NAC) ed effettuato l’analisi al microscopio confocale con registrazione in tempo reale con Time laps Imaging (Juli-Stage). RISULTATI: Lo studio ha mostrato un significativo shift dell’apoptosi da precoce in tardiva con la curcumina in combinato con Daunoblastina, L-ASPA ,Vincristina e Desametazone gia’ a 24h utilizzando le più basse concentrazioni di chemioterapico possibile, rispetto all’utilizzo dei soli chemioterapici: incremento apoptotico medio del 49% + 6.3 (p
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- 2018
42. Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment
- Author
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Concetta Maria Messina, Renza Vento, Giuseppe Pirozzi, Virginia Tirino, Michela Giuliano, Rosa Drago Ferrante, Anna De Blasio, Giovanni Tesoriere, Andrea Santulli, Riccardo Di Fiore, Di Fiore, R, Santulli, A, Drago Ferrante, R, Giuliano, M, De Blasio, A, Messina, CM, Pirozzi, G, Tirino, V, Tesoriere, G, Vento, R, DI FIORE, R, Ferrante, Rd, DE BLASIO, A, Messina, C, Tirino, Virginia, and Vento, R.
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Adult ,Homeobox protein NANOG ,Adolescent ,Physiology ,Cellular differentiation ,Clinical Biochemistry ,Apoptosis ,Biology ,Stem cell marker ,Young Adult ,cancer stemm cells, osteosarcoma, PARP inhibitors ,Cancer stem cell ,Cell Line, Tumor ,Settore BIO/10 - Biochimica ,Humans ,Rhodamine 123 ,Enzyme Inhibitors ,Progenitor cell ,Child ,Induced pluripotent stem cell ,Cell Shape ,Cell potency ,Fluorescent Dyes ,Osteosarcoma ,Cell Differentiation ,Cell Biology ,Calcium Channel Blockers ,Drug Resistance, Multiple ,Gene Expression Regulation, Neoplastic ,Verapamil ,Benzamides ,Immunology ,Neoplastic Stem Cells ,Cancer research ,ATP-Binding Cassette Transporters ,Benzimidazoles ,Stem cell ,Biomarkers - Abstract
A novel cancer stem-like cell line (3AB-OS), expressing a number of pluripotent stem cell markers, was irreversibly selected from human osteosarcoma MG-63 cells by long-term treatment (100 days) with 3-aminobenzamide (3AB). 3AB-OS cells are a heterogeneous and stable cell population composed by three types of fibroblastoid cells, spindle-shaped, polygonal-shaped, and rounded-shaped. With respect to MG-63 cells, 3AB-OS cells are extremely smaller, possess a much greater capacity to form spheres, a stronger self-renewal ability and much higher levels of cell cycle markers which account for G1-S/G2-M phases progression. Differently from MG-63 cells, 3AB-OS cells can be reseeded unlimitedly without losing their proliferative potential. They show an ATP-binding cassette transporter ABCG2-dependent phenotype with high drug efflux capacity, and a strong positivity for CD133, marker for pluripotent stem cells, which are almost unmeasurable in MG-63 cells. 3AB-OS cells are much less committed to osteogenic and adipogenic differentiation than MG-63 cells and highly express genes required for maintaining stem cell state (Oct3/4, hTERT, nucleostemin, Nanog) and for inhibiting apoptosis (HIF-1alpha, FLIP-L, Bcl-2, XIAP, IAPs, and survivin). 3AB-OS may be a novel tumor cell line useful for investigating the mechanisms by which stem cells enrichment may be induced in a tumor cell line. The identification of a subpopulation of cancer stem cells that drives tumorigenesis and chemoresistance in osteosarcoma may lead to prognosis and optimal therapy determination. Expression patterns of stem cell markers, especially CD133 and ABCG2, may indicate the undifferentiated state of osteosarcoma tumors, and may correlate with unfavorable prognosis in the clinical setting.
- Published
- 2009
43. Dicrocoelium dendriticum induces autophagic vacuoles accumulation in human hepatocarcinoma cells
- Author
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P. Pepe, M. Castellano, S. Alfano, M.E. Della Pepa, V. Tirino, M. Piemonte, V. Desiderio, S. Zappavigna, M. Galdiero, M. Caraglia, G. Cringoli, L. Rinaldi, Pepe, Paola, Castellano, M, Alfano, Settimia, Della Pepa, M. E, Tirino, V, Piemonte, M, Desiderio, V, Zappavigna, S, Galdiero, Massimiliano, Caraglia, M, Cringoli, Giuseppe, Rinaldi, Laura, Galdiero, M., Pepe, P, Alfano, S, Tirino, Virginia, Desiderio, Vincenzo, Caraglia, Michele, Cringoli, G, Rinaldi, L, and Galdiero, Marilena
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Programmed cell death ,Carcinoma, Hepatocellular ,Vacuole ,medicine.disease_cause ,Cell Line, Tumor ,Autophagy ,medicine ,Animals ,Humans ,Somatic antigen ,Dicrocoelium ,Autophagic vacuole ,General Veterinary ,biology ,Cell growth ,Liver Neoplasms ,Dicrocoelium dendriticum ,General Medicine ,biology.organism_classification ,Molecular biology ,Stress oxidative ,digestive system diseases ,Oxidative Stress ,Apoptosis ,Vacuoles ,Immunology ,Parasitology ,Glioblastoma ,Oxidative stress ,Intracellular - Abstract
The relationship between Dicrocoelium dendriticum and cancer has been poorly investigated so far, but a large amount of findings suggest that other trematodes can favour cancer in both animals and humans. In this study, the effects of D. dendriticum on cell proliferation, cell death mechanisms and oxidative stress induction were evaluated in hepatocellular carcinoma (HCC) cell lines (HepG2 and HuH7). Results showed that short time exposure to low concentrations of somatic antigens from D. dendriticum caused slight proliferation in both HepG2 and HuH7 cells while high concentrations and long exposure time to extracts from D. dendriticum caused a significant growth inhibition. This effect was, however, not paralleled by apoptosis but it occurred with an about 40% increase of the formation of autophagic vacuoles. In the same experimental conditions, a strong oxidative stress was recorded with an about 100% increase of the intracellular O(2-). These data suggest the occurrence of an escape anti-apoptotic mechanism in HCC cells. In conclusion, these results suggest a role for D. dendriticum in the chronic oxidative stress and in the regulation of transformation processes in HCC warranting additional investigations in this specific area of research.
- Published
- 2015
44. Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues
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Giuseppe A. Ferraro, Gianfranco Nicoletti, Francesco De Francesco, Vincenzo Desiderio, Francesca Paino, Virginia Tirino, Francesco D'Andrea, Ferraro, Giuseppe, De Francesco, F, Nicoletti, Giovanni Francesco, Paino, Francesca, Desiderio, Vincenzo, Tirino, Virginia, D'Andrea, Francesco, Ferraro, Ga, De Francesco, F., Nicoletti, G., Paino, F., Desiderio, V., and Tirino, V.
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Adult ,Adolescent ,Cell Survival ,Adipose tissue macrophages ,Adipose tissue ,Mice, Nude ,Antigens, CD34 ,Biochemistry ,Mice ,Young Adult ,Cell Adhesion ,Animals ,Humans ,Horses ,Progenitor cell ,Molecular Biology ,Stem cell transplantation for articular cartilage repair ,Cell Proliferation ,Adipogenesis ,Tissue Scaffolds ,Chemistry ,Reverse Transcriptase Polymerase Chain Reaction ,Stem Cells ,Mesenchymal stem cell ,3T3-L1 ,Cell Differentiation ,Cell Biology ,Flow Cytometry ,Cell biology ,Adipose Tissue ,Gene Expression Regulation ,Connective Tissue ,Immunology ,Thy-1 Antigens ,Female ,Collagen ,Stem cell ,Adult stem cell ,Stem Cell Transplantation - Abstract
Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34−CD90− cells and was able to differentiate in vitro into adipocytes (PPARγ+ and adiponectin+) and endothelial cells (CD31+VEGF+Flk1+). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34+/CD90+ stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34+/CD90 ASCs are extremely useful for regenerative medicine. J. Cell. Biochem. 114: 1039–1049, 2013. © 2012 Wiley Periodicals, Inc.
- Published
- 2012
45. Human neural crest-derived postnatal cells exhibit remarkable embryonic attributes either in vitro or in vivo
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Sabata Martino, Riccardo d'Aquino, De Angelis Gc, Luigi Laino, De Rosa A, Maurilio Sampaolesi, Tirino, Francesca Paino, Di Nucci D, Gianpaolo Papaccio, Michèle Studer, Desiderio, D'Aquino, R., (co-first Author)tirino, V., Desiderio, V., Studer, M., De Angelis, Gc, Laino, L., De Rosa, A., Di Nucci, D., Martino, S., Paino, F., Sampaolesi, M., Papaccio, G., R, D'Aquino, Tirino, Virginia, Desiderio, Vincenzo, M, Studer, G, CUSELLA DE ANGELIS, Laino, Luigi, DE ROSA, Alfredo, D, DI NUCCI, S, Martino, Paino, Francesca, M, Sanpaolesi, and Papaccio, Gianpaolo
- Subjects
Pathology ,Stage-Specific Embryonic Antigens ,murine blastocysts ,nervous-system ,lcsh:Diseases of the musculoskeletal system ,mesenchymal stem-cells ,neurons ,Embryoid body ,Mice ,pulp ,Telomerase ,Cells, Cultured ,Cell Aggregation ,Neurons ,Teratoma ,embryonic markers ,Cell Differentiation ,differentiation ,Middle Aged ,Flow Cytometry ,Cell biology ,neural stem cell diffrentiation ,Neuroepithelial cell ,Human adult stem cells ,Neural crest ,Embryonic markers ,Differentiation ,Pluripotency ,Embryoid bodies ,Amniotic epithelial cells ,embryonic structures ,Stem cell ,human hair-follicles ,neural crest ,Human adult stem cells, neural crest, embryonic markers, differentiation, pluripotency, embryoid bodies ,Adult stem cell ,human adult stem cells ,KOSR ,Homeobox protein NANOG ,Adult ,medicine.medical_specialty ,lcsh:Surgery ,differentiate ,Biology ,Bone and Bones ,Young Adult ,medicine ,embryoid bodies ,Animals ,Humans ,Dental Sac ,lcsh:RD1-811 ,Embryo, Mammalian ,pluripotency ,Embryonic stem cell ,Blastocyst ,dental follicle cells ,lcsh:RC925-935 ,teratoma formation - Abstract
During human embryonic development, odontogenic tissues, deriving from the neural crest, remain undifferentiated until the adult age. This study was aimed at characterising the cells of the follicle enveloping the dental germ, due to its direct origin from neural crests. Sixty dental follicles were collected from patients aged 18 to 45 years. This research has clarified that dental follicles, if extracted in a very early stage, when dental roots did not start to be formed, contain a lineage of cells, characterised by a high degree of plasticity in comparison with other adult stem cell populations. In particular, we found that these cells share the following features with ES: (i) high levels of embryonic stem cell markers (CD90, TRA1-60, TRA1- 81, OCT-4, CD133, and SSEA-4); (ii) mRNA transcripts for Nanog and Rex-1; (iii) broader potency, being able to differentiate in cell types of all three germ layer, including smooth and skeletal muscle, osteoblasts, neurons, glial cells, and adipocytes; (iv) high levels of telomerase activity; (v) ability to form embryoid bodies; (vi) ability, after injection in murine blastocysts, to be localised within the inner cell mass; (vii) no teratoma formation after injection; (viii) in vivo tissue formation after transplantation. Our results demonstrate that these cells represent a very easy accessible and extraordinary source of pluripotent cells and point out the fact that they own the cardinal feature of embryonic stem cells. During human embryonic development, odontogenic tissues, deriving from the neural crest, remain undifferentiated until the adult age. This study was aimed at characterising the cells of the follicle enveloping the dental germ, due to its direct origin from neural crests. Sixty dental follicles were collected from patients aged 18 to 45 years. This research has clarified that dental follicles, if extracted in a very early stage, when dental roots did not start to be formed, contain a lineage of cells, characterised by a high degree of plasticity in comparison with other adult stem cell populations. In particular, we found that these cells share the following features with ES: (i) high levels of embryonic stem cell markers (CD90, TRA1-60, TRA1-81, OCT-4, CD133, and SSEA-4); (ii) mRNA transcripts for Nanog and Rex-1; (iii) broader potency, being able to differentiate in cell types of all three germ layer, including smooth and skeletal muscle, osteoblasts, neurons, glial cells, and adipocytes; (iv) high levels of telomerase activity; (v) ability to form embryoid bodies; (vi) ability, after injection in murine blastocysts, to be localised within the inner cell mass; (vii) no teratoma formation after injection; (viii) in vivo tissue formation after transplantation. Our results demonstrate that these cells represent a very easy accessible and extraordinary source of pluripotent cells and point out the fact that they own the cardinal feature of embryonic stem cells.
- Published
- 2011
46. Isolamento di cellule staminali da tessuto adiposo adulto umano
- Author
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Libondi G, De Francesco F, TIRINO, Virginia, DESIDERIO, Vincenzo, PAINO, Francesca, Giuliano M, DE ROSA, Alfredo, D'ANDREA, Francesco, Papaccio G., FERRARO, Giuseppe, Libondi, G., De Francesco, F., Tirino, V., Desiderio, V., Ferraro, G., Paino, F., Giuliano, M., De Rosa, A., D'Andrea, Francesco, Papaccio, G., Libondi, G, De Francesco, F, Tirino, Virginia, Desiderio, Vincenzo, Ferraro, Giuseppe, Paino, Francesca, Giuliano, M, and DE ROSA, Alfredo
- Published
- 2009
47. A new method for cryopreserving adipose-derived stem cells: an attractive and suitable large-scale and long-term cell banking technology
- Author
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Vincenzo Desiderio, Francesco D'Andrea, Virginia Tirino, Francesca Paino, Giuseppe A. Ferraro, Giuseppe Pirozzi, Alfredo De Rosa, Francesco De Francesco, Gianpaolo Papaccio, De Rosa, A., De Francesco, F., Tirino, V., Ferraro, Ga, Desiderio, V., Paino, F., Pirozzi, G., D'Andrea, Francesco, Papaccio, G., DE ROSA, Alfredo, De Francesco, F, Tirino, Virginia, Desiderio, Vincenzo, Paino, Francesca, Pirozzi, G, and Papaccio, Gianpaolo
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Adult ,Time Factors ,Annexins ,Cell ,Biomedical Engineering ,Medicine (miscellaneous) ,Adipose tissue ,Apoptosis ,Bioengineering ,Cell Separation ,Tissue Banks ,Biology ,Cryopreservation ,Immunophenotyping ,chemistry.chemical_compound ,Antigen ,Freezing ,Adipocytes ,medicine ,Humans ,Cell Shape ,trehalose ,Cells, Cultured ,Cell Proliferation ,Dimethyl sulfoxide ,Cell potential ,stem cells cryopreservation ,Stem Cells ,adipose stem cell ,Endothelial Cells ,Cell Differentiation ,Flow Cytometry ,Immunohistochemistry ,Cell biology ,medicine.anatomical_structure ,Adipose Tissue ,chemistry ,Immunology ,Female ,Stem cell ,Fetal bovine serum ,Propidium - Abstract
Recent studies have shown potential ways for improving stem cell cryopreservation. The major need for autologous stem cell use is a long-term storage: this arises from the humans' hope of future use of their own cells. Therefore, it is important to evaluate the cell potential of vitality and differentiation before and after cryopreservation. Although several studies have shown a long-term preservation of adipose tissue, a few of them focused their attention to stem cells. The aim of this study was to evaluate the fate of cryopreserved stem cells collected from adipose tissue and stored at low a temperature in liquid nitrogen through an optimal cryopreservation solution (using slowly cooling in 6% threalose, 4% dimethyl sulfoxide, and 10% fetal bovine serum) and to develop a novel approach to efficiently preserve adipose-derived stem cells (ASCs) for future clinical applications. Results showed that stem cells, after being thawed, are still capable of differentiation and express all surface antigens detected before storage, confirming the integrity of their biology. In particular, ASCs differentiated into adipocytes, showed diffuse positivity for PPARγ and adiponectin, and were also able to differentiate into endothelial cells without addition of angiogenic factors. Therefore, ASCs can be long-term cryopreserved, and this, due to their great numbers, is an attractive tool for clinical applications as well as of impact for the derived market. © 2009 Mary Ann Liebert, Inc. Recent studies have shown potential ways for improving stem cell cryopreservation. The major need for autologous stem cell use is a long-term storage: this arises from the humans' hope of future use of their own cells. Therefore, it is important to evaluate the cell potential of vitality and differentiation before and after cryopreservation. Although several studies have shown a long-term preservation of adipose tissue, a few of them focused their attention to stem cells. The aim of this study was to evaluate the fate of cryopreserved stem cells collected from adipose tissue and stored at low a temperature in liquid nitrogen through an optimal cryopreservation solution (using slowly cooling in 6% threalose, 4% dimethyl sulfoxide, and 10% fetal bovine serum) and to develop a novel approach to efficiently preserve adipose-derived stem cells (ASCs) for future clinical applications. Results showed that stem cells, after being thawed, are still capable of differentiation and express all surface antigens detected before storage, confirming the integrity of their biology. In particular, ASCs differentiated into adipocytes, showed diffuse positivity for PPARγ and adiponectin, and were also able to differentiate into endothelial cells without addition of angiogenic factors. Therefore, ASCs can be long-term cryopreserved, and this, due to their great numbers, is an attractive tool for clinical applications as well as of impact for the derived market. © 2009 Mary Ann Liebert, Inc.
- Published
- 2009
48. Rigenerazione tissulare mediante l'utilizzo di cellule staminali adulte da tessuto adiposo e materiali biocompatibili: quali applicazioni clinico-terapeutiche?
- Author
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FERRARO, Giuseppe, De Francesco F, Rossano F, TIRINO, Virginia, DESIDERIO, Vincenzo, Miccoli A, Papaccio G, D'ANDREA, Francesco, Ferraro, G., De Francesco, F., Rossano, F., Tirino, V., Desiderio, V., Miccoli, A., Papaccio, G., D'Andrea, Francesco, Ferraro, Giuseppe, De Francesco, F, Rossano, F, Tirino, Virginia, Desiderio, Vincenzo, Miccoli, A, and Papaccio, G
- Published
- 2009
49. TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells
- Author
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Virginia Tirino, Franca Esposito, Vincenzo Neri, Alberto Fersini, Eleonora Costantino, Serena Calise, Antonio Ambrosi, Francesca Maddalena, Annamaria Piscazzi, Matteo Landriscina, Costantino, E, Maddalena, F, Calise, S, Piscazzi, A, Tirino, Virginia, Fersini, A, Ambrosi, A, Neri, V, Esposito, F, Landriscina, M., Costantino, E., Maddalena, F., Calise, S., Piscazzi, A., Tirino, V., Fersini, A., Ambrosi, A., Vincenzo, Neri, and Esposito, Franca
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Genotype ,Organoplatinum Compounds ,Colorectal cancer ,medicine.medical_treatment ,Antineoplastic Agents ,Apoptosis ,Drug resistance ,Mouse model of colorectal and intestinal cancer ,Irinotecan ,Transfection ,Internal medicine ,medicine ,Humans ,HSP90 Heat-Shock Proteins ,RNA, Messenger ,Aged ,Aged, 80 and over ,Chemotherapy ,Dose-Response Relationship, Drug ,Chemistry ,Carcinoma ,Middle Aged ,medicine.disease ,Phenotype ,digestive system diseases ,Drug Resistance, Multiple ,Peptide Fragments ,Oxaliplatin ,Mitochondria ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Drug Resistance, Neoplasm ,Cancer research ,Camptothecin ,Female ,Fluorouracil ,Colorectal Neoplasms ,HT29 Cells ,medicine.drug - Abstract
TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance. © 2009 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2008
50. Large-Scale Production of Human Adipose Tissue from Stem Cells: A New Tool for Regenerative Medicine and Tissue Banking
- Author
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Vincenzo Desiderio, Alfredo De Rosa, Giuseppe A. Ferraro, Virginia Tirino, Francesco De Francesco, Gianpaolo Papaccio, Francesco D'Andrea, D'Andrea, Francesco, DE FRANCESCO, F., Ferraro, Giuseppe, Desiderio, Vincenzo, Tirino, Virginia, DE ROSA, Alfredo, Papaccio, Gianpaolo, Ferraro, G., Desiderio, V., Tirino, V., DE ROSA, A., Papaccio, G., DE FRANCESCO, F, and Ferraro, Ga
- Subjects
Adult ,Adolescent ,Biomedical Engineering ,Medicine (miscellaneous) ,Adipose tissue ,Antigens, CD34 ,Bioengineering ,Biology ,Regenerative Medicine ,Regenerative medicine ,Biochemistry ,Biomaterials ,Adipocytes ,Humans ,Stem cell transplantation for articular cartilage repair ,Cell Proliferation ,Tissue Engineering ,Stem Cells ,Mesenchymal stem cell ,Soft tissue ,3T3-L1 ,Cell Differentiation ,Human Adipose Tissue ,Cell biology ,Fibronectins ,Adipose Tissue ,Thy-1 Antigens ,Female ,Collagen ,Stem cell ,Tissue Banking ,Biomedical engineering - Abstract
Adipose tissue is an easy, accessible, and abundant source of mesenchymal stem cells (MSCs) for the reconstruction and addition of soft tissue and for restoration of soft-tissue defects associated with trauma, tumor resections, and congenital deformities. A stable source of adipose cells or tissue is needed for autologous grafting. Therefore, the aim of this study was to obtain enough autologous adipose tissue for possible clinical applications. For this purpose, we isolated MSCs (CD34+/CD90+) from human lipoaspirated or resected fat, which differentiated into adipocytes when placed in culture. Human adipose tissue is a paramount source of autologous MSCs were capable of generating a complete adipose tissue in vitro. Differentiated adipocytes expressed a strong positivity for several specific antibodies, including adiponectin and peroxisome proliferator-activated receptor gamma. In addition, fibroblasts (∼10% of the whole sorted-cell population) started to secrete an extracellular matrix after 60 days that was strongly positive for type I collagen and fibronectin. After long-term culture (4 months), an adipose tissue with collagenic fibers and vessels was obtained. This tissue was comparable with adult human adipose tissue and therefore may be a criterion standard for future tissue repair and regeneration and for therapeutic and transplantation purposes. © Copyright 2008, Mary Ann Liebert, Inc.
- Published
- 2008
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