21 results on '"Artuso, Simona"'
Search Results
2. Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2
- Author
-
Gnani, Daniela, Romito, Ilaria, Artuso, Simona, Chierici, Marco, De Stefanis, Cristiano, Panera, Nadia, Crudele, Annalisa, Ceccarelli, Sara, Carcarino, Elena, D'Oria, Valentina, Porru, Manuela, Giorda, Ezio, Ferrari, Karin, Miele, Luca, Villa, Erica, Balsano, Clara, Pasini, Diego, Furlanello, Cesare, Locatelli, Franco, Nobili, Valerio, Rota, Rossella, Leonetti, Carlo, Alisi, Anna, Miele, Luca (ORCID:0000-0003-3464-0068), Locatelli, Franco (ORCID:0000-0002-7976-3654), Gnani, Daniela, Romito, Ilaria, Artuso, Simona, Chierici, Marco, De Stefanis, Cristiano, Panera, Nadia, Crudele, Annalisa, Ceccarelli, Sara, Carcarino, Elena, D'Oria, Valentina, Porru, Manuela, Giorda, Ezio, Ferrari, Karin, Miele, Luca, Villa, Erica, Balsano, Clara, Pasini, Diego, Furlanello, Cesare, Locatelli, Franco, Nobili, Valerio, Rota, Rossella, Leonetti, Carlo, Alisi, Anna, Miele, Luca (ORCID:0000-0003-3464-0068), and Locatelli, Franco (ORCID:0000-0002-7976-3654)
- Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes. Among these genes, we showed that FAK silencing decreased transcription and nuclear localization of enhancer of zeste homolog 2 (EZH2) and its tri-methylation activity on lysine 27 of histone H3 (H3K27me3). Accordingly, FAK, EZH2 and H3K27me3 were concomitantly upregulated in human HCCs compared to non-tumor livers. In vitro experiments demonstrated that FAK affected EZH2 expression and function by modulating, at least in part, p53 and E2F2/3 transcriptional activity. Moreover, FAK silencing downregulated both EZH2 binding and histone H3K27me3 levels at the promoter of its target gene NOTCH2. Finally, we found that pharmacological inhibition of FAK activity resembled these effects although milder. In summary, we demonstrate that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2. Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies.
- Published
- 2017
3. Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2
- Author
-
Gnani, Daniela, primary, Romito, Ilaria, additional, Artuso, Simona, additional, Chierici, Marco, additional, De Stefanis, Cristiano, additional, Panera, Nadia, additional, Crudele, Annalisa, additional, Ceccarelli, Sara, additional, Carcarino, Elena, additional, D’Oria, Valentina, additional, Porru, Manuela, additional, Giorda, Ezio, additional, Ferrari, Karin, additional, Miele, Luca, additional, Villa, Erica, additional, Balsano, Clara, additional, Pasini, Diego, additional, Furlanello, Cesare, additional, Locatelli, Franco, additional, Nobili, Valerio, additional, Rota, Rossella, additional, Leonetti, Carlo, additional, and Alisi, Anna, additional
- Published
- 2017
- Full Text
- View/download PDF
4. Additional file 2: Figure S1. of Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model
- Author
-
Pessina, Augusto, Leonetti, Carlo, Artuso, Simona, Benetti, Anna, Dessy, Enrico, Pascucci, Luisa, Passeri, Daniela, Orlandi, Augusto, Berenzi, Angiola, Bonomi, Arianna, Coccè, Valentina, Ceserani, Valentina, Ferri, Anna, Dossena, Marta, Mazzuca, Pietro, Ciusani, Emilio, Ceccarelli, Piero, Caruso, Arnaldo, Portolani, Nazario, Sisto, Francesca, Parati, Eugenio, and Alessandri, Giulio
- Abstract
SR4987GFP and SR4987GFP-PTX arrest in the lung of mice upon i.v. administration. Mice were sacrificed at 6 h, 24 h and 48 h after treatments with cells. Panel (A) shows photos taken under fluorescent microscopy immediately upon enzymatic lung tissue disruption, showing the presence of several fluorescent cells until 48 h after their injection. Not significant difference were noted between mice treated with SR4987GFP and SR4987GFP-PTX (10x magnification). Panel (B) shows photos of SR4987GFP and SR4987GFP-PTX cultured for 2 and 7 days upon isolation from mice, indicating that cells maintain their viability (20x magnification). Figure S2. Sca-1 is highly expressed on SR4987 and can be used for their detection in the mice lung. In (A) FC analysis showing the high positivity of the SR4987 for Sca-1. In (B), Immunostaining for anti-Sca-1 of lungs derived from mice treated i.v. with saline , 106 SR4987 and 106 SR4987PTX cells and sacrificed 24 h after treatments. Pictures show the high presence of Sca-1+ cells (black arrows) in the parenchyma and in the lumen of lung vessels in mice treated with both SR4987 and SR4987PTX. Only, very few Sca-1+ cells were detected in control mice (CTRL) (photo 20x, in the box 40x magnifications). Figure S3. Sensibility of SR4987 to PTX and efficacy of SR4987PTX-CM to inhibit B16 proliferation. In (A) the proliferation of SR4987 in the presence of increasing concentration of PTX. The IC50 of PTX was around 34 ng/ml. In (B) is shown that viability of SR4987 is not affected by PTX even at concentration up 5000 ng/ml. In (C) is shown the growth inhibition of Molt-4 tumor cells in the presence of decreasing dilution of SR4987PTX-CM confirming that SR4987PTX release significant amount of PTX in the CM. In (D) the inhibition of proliferation of B16 cells in the presence of increasing concentration of PTX. The IC50 is 7.18 ± 4.99 ng/ml. In (E) is shown the dose dependent efficacy of SR4987PTX-CM to inhibit B16 cells proliferation with an IC50 DIL of around 1/10. Figure S4. Co-culture of SR4987 and SR4987PTX with B16 cells using transwell insert. B16 cells seeded on the top of membrane (0.4 um pore size) insert were co-cultured with different dose of SR4987 and SR4987PTX seeded on the bottom well and cultured for 5 days. The Figure shows that SR4987PTX at 1:5 ratio was able to strongly inhibit B16 proliferation as visualized by crystal violet staining of B16 in the transwell line (A) and on the membrane line (B). In line (C), photos of cultured B16 cells not stained upon co-culture or not with SR4987 and SR4987PTX (20x magnifications). Figure S5. Rosette formed by B16 + SR4987 and B16 + SR4987PTX and their ultrastructural analysis by TEM. In (A) and (B) rosette formed by SR4987GFP + B16 photographed under light and fluorescence microscopy respectively. (C-F) four different panels at TEM showing the interactions between untreated SR4987GFP and B16 cells. Note that B16 cells bound SR4987GFP appear healthy (C); the presence of area of contact between B16 and SR4987 is evident; junctional-like structure and a gap-like junction (D,E) and even nanotubule structure (F) are seen (white arrows). In (G) and (H) rosette formed by SR4987GFP-PTX + B16. Note that most of B16 cells appeared damaged and necrotic under light (G) and fluorescence (H) microscopy observation. In (I-L) four different panels at TEM showing the interaction between SR4987GFP-PTX and B16. The B16 cells bound to SR4987GFP-PTX show varying degrees of degeneration, some cells seemed even emptied of their cytoplasm (I) and, similarly to untreated SR4987, area of contact (white arrows) can be observed (J,K). In (L) a microvescicole that arise from SR4987PTX is photographed. Figure S6. Metastasis in the lung of control mice and after treatment with PTX, SR4987 and SR4987PTX. On day 21 after B16 cells injection, mice were euthanized, lungs removed and fixed in Bouin’s solution. In the figure photos of the lungs, taken under a dissecting stereomicroscope. Note the presence of several melanoma lung nodules (black arrows) in control and SR4987 treated mice. In contrast, at both dosage of SR4987PTX injected, the lung nodules are very few and are significantly less than those detected in PTX treated mice. Figure S7. Chemiotaxis of SR4987 and SR4987PTX in response to B16-CM and expression of the SDF-1 receptors CXCR4 and CXCR7. In (A) migration of SR4987PTX and SR4987 placed on the top of transwell membrane insert and stimulated by different dilution of B16-CM. No significant chemotaxis activity of both SR4987 and SR4987PTX is stimulated by B16-CM at every dilutions tested. Note that the basal migration of SR4987PTX is around three fold lower than untreated SR4987 (* p 90 %), CXCR7 is less expressed (18 %). (DOC 26 kb)
- Published
- 2015
- Full Text
- View/download PDF
5. Additional file 1: of Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model
- Author
-
Pessina, Augusto, Leonetti, Carlo, Artuso, Simona, Benetti, Anna, Dessy, Enrico, Pascucci, Luisa, Passeri, Daniela, Orlandi, Augusto, Berenzi, Angiola, Bonomi, Arianna, Coccè, Valentina, Ceserani, Valentina, Ferri, Anna, Dossena, Marta, Mazzuca, Pietro, Ciusani, Emilio, Ceccarelli, Piero, Caruso, Arnaldo, Portolani, Nazario, Sisto, Francesca, Parati, Eugenio, and Alessandri, Giulio
- Abstract
Supplementary materials and methods. (DOC 45 kb)
- Published
- 2015
- Full Text
- View/download PDF
6. Abstract 266: The G-quadruplex ligand EMICORON potentiates the antitumor efficacy of chemotherapy on colon cancer experimental models
- Author
-
Porru, Manuela, primary, Artuso, Simona, additional, Pompili, Luca, additional, Caruso, Carla, additional, Bianco, Armandodoriano, additional, Mottolese, Marcella, additional, Amoreo, Carla A., additional, Biroccio, Annamaria, additional, and Leonetti, Carlo, additional
- Published
- 2016
- Full Text
- View/download PDF
7. Targeting G-quadruplex DNA Structures by EMICORON has a strong antitumor efficacy against advanced models of human colon cancer
- Author
-
Porru, Manuela, Artuso, Simona, Salvati, Erica, Bianco, Armandodoriano, Franceschin, Marco, Diodoro, Maria Grazia, Passeri, Daniela, Orlandi, Augusto, Savorani, Francesco, D'Incalci, Maurizio, Biroccio, Annamaria, Leonetti, Carlo, Porru, Manuela, Artuso, Simona, Salvati, Erica, Bianco, Armandodoriano, Franceschin, Marco, Diodoro, Maria Grazia, Passeri, Daniela, Orlandi, Augusto, Savorani, Francesco, D'Incalci, Maurizio, Biroccio, Annamaria, and Leonetti, Carlo
- Abstract
We previously identified EMICORON as a novel G-quadruplex (G4) ligand showing high selectivity for G4 structures over the duplex DNA, causing telomere damage and inhibition of cell proliferation in transformed and tumor cells. Here, we evaluated the antitumoral effect of EMICORON on advanced models of human colon cancer that could adequately predict human clinical outcomes. Our results showed that EMICORON was well tolerated in mice, as no adverse effects were reported, and a low ratio of sensitivity across human and mouse bone marrow cells was observed, indicating a good potential for reaching similar blood levels in humans. Moreover, EMICORON showed a marked therapeutic efficacy, as it inhibited the growth of patient-derived xenografts (PDX) and orthotopic colon cancer and strongly reduced the dissemination of tumor cells to lymph nodes, intestine, stomach, and liver. Finally, activation of DNA damage and impairment of proliferation and angiogenesis are proved to be key determinants of EMICORON antitumoral activity. Altogether, our results, performed on advanced experimental models of human colon cancer that bridge the translational gap between preclinical and clinical studies, demonstrated that EMICORON had an unprecedented antitumor activity warranting further studies of EMICORON-based combination treatments. Mol Cancer Ther; 14(11); 2541-51. ©2015 AACR.
- Published
- 2015
8. Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer
- Author
-
Porru, Manuela, primary, Artuso, Simona, additional, Salvati, Erica, additional, Bianco, Armandodoriano, additional, Franceschin, Marco, additional, Diodoro, Maria Grazia, additional, Passeri, Daniela, additional, Orlandi, Augusto, additional, Savorani, Francesco, additional, D'Incalci, Maurizio, additional, Biroccio, Annamaria, additional, and Leonetti, Carlo, additional
- Published
- 2015
- Full Text
- View/download PDF
9. Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance
- Author
-
Zizza, Pasquale, primary, Cingolani, Chiara, additional, Artuso, Simona, additional, Salvati, Erica, additional, Rizzo, Angela, additional, D'Angelo, Carmen, additional, Porru, Manuela, additional, Pagano, Bruno, additional, Amato, Jussara, additional, Randazzo, Antonio, additional, Novellino, Ettore, additional, Stoppacciaro, Antonella, additional, Gilson, Eric, additional, Stassi, Giorgio, additional, Leonetti, Carlo, additional, and Biroccio, Annamaria, additional
- Published
- 2015
- Full Text
- View/download PDF
10. Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model
- Author
-
Pessina, Augusto, primary, Leonetti, Carlo, additional, Artuso, Simona, additional, Benetti, Anna, additional, Dessy, Enrico, additional, Pascucci, Luisa, additional, Passeri, Daniela, additional, Orlandi, Augusto, additional, Berenzi, Angiola, additional, Bonomi, Arianna, additional, Coccè, Valentina, additional, Ceserani, Valentina, additional, Ferri, Anna, additional, Dossena, Marta, additional, Mazzuca, Pietro, additional, Ciusani, Emilio, additional, Ceccarelli, Piero, additional, Caruso, Arnaldo, additional, Portolani, Nazario, additional, Sisto, Francesca, additional, Parati, Eugenio, additional, and Alessandri, Giulio, additional
- Published
- 2015
- Full Text
- View/download PDF
11. Erratum: Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities
- Author
-
Rizzo, Angela, primary, Iachettini, Sara, additional, Zizza, Pasquale, additional, Cingolani, Chiara, additional, Porru, Manuela, additional, Artuso, Simona, additional, Stevens, Malcolm, additional, Hummersone, Marc, additional, Biroccio, Annamaria, additional, Salvati, Erica, additional, and Leonetti, Carlo, additional
- Published
- 2015
- Full Text
- View/download PDF
12. Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities
- Author
-
Rizzo, Angela, primary, Iachettini, Sara, additional, Zizza, Pasquale, additional, Cingolani, Chiara, additional, Porru, Manuela, additional, Artuso, Simona, additional, Stevens, Malcolm, additional, Hummersone, Marc, additional, Biroccio, Annamaria, additional, Salvati, Erica, additional, and Leonetti, Carlo, additional
- Published
- 2014
- Full Text
- View/download PDF
13. Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid
- Author
-
Porru, Manuela, primary, Zappavigna, Silvia, additional, Salzano, Giuseppina, additional, Luce, Amalia, additional, Stoppacciaro, Antonella, additional, Balestrieri, Maria Luisa, additional, Artuso, Simona, additional, Lusa, Sara, additional, De Rosa, Giuseppe, additional, Leonetti, Carlo, additional, and Caraglia, Michele, additional
- Published
- 2014
- Full Text
- View/download PDF
14. A Nitric Oxide-dependent Cross-talk between Class I and III Histone Deacetylases Accelerates Skin Repair
- Author
-
Spallotta, Francesco, primary, Cencioni, Chiara, additional, Straino, Stefania, additional, Nanni, Simona, additional, Rosati, Jessica, additional, Artuso, Simona, additional, Manni, Isabella, additional, Colussi, Claudia, additional, Piaggio, Giulia, additional, Martelli, Fabio, additional, Valente, Sergio, additional, Mai, Antonello, additional, Capogrossi, Maurizio C., additional, Farsetti, Antonella, additional, and Gaetano, Carlo, additional
- Published
- 2013
- Full Text
- View/download PDF
15. Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance.
- Author
-
Zizza, Pasquale, Cingolani, Chiara, Artuso, Simona, Salvati, Erica, Rizzo, Angela, D'Angelo, Carmen, Porru, Manuela, Pagano, Bruno, Amato, Jussara, Randazzo, Antonio, Novellino, Ettore, Stoppacciaro, Antonella, Gilson, Eric, Stassi, Giorgio, Leonetti, Carlo, and Biroccio, Annamaria
- Published
- 2016
- Full Text
- View/download PDF
16. Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals
- Author
-
Goeman, Frauke, primary, Manni, Isabella, additional, Artuso, Simona, additional, Ramachandran, Balaji, additional, Toietta, Gabriele, additional, Bossi, Gianluca, additional, Rando, Gianpaolo, additional, Cencioni, Chiara, additional, Germoni, Sabrina, additional, Straino, Stefania, additional, Capogrossi, Maurizio C., additional, Bacchetti, Silvia, additional, Maggi, Adriana, additional, Sacchi, Ada, additional, Ciana, Paolo, additional, and Piaggio, Giulia, additional
- Published
- 2012
- Full Text
- View/download PDF
17. Transcription Factor NF-Y Induces Apoptosis in Cells Expressing Wild-Type p53 through E2F1 Upregulation and p53 Activation
- Author
-
Gurtner, Aymone, primary, Fuschi, Paola, additional, Martelli, Fabio, additional, Manni, Isabella, additional, Artuso, Simona, additional, Simonte, Giacoma, additional, Ambrosino, Valeria, additional, Antonini, Annalisa, additional, Folgiero, Valentina, additional, Falcioni, Rita, additional, Sacchi, Ada, additional, and Piaggio, Giulia, additional
- Published
- 2010
- Full Text
- View/download PDF
18. Posttranslational Regulation of NF-YA Modulates NF-Y Transcriptional Activity
- Author
-
Manni, Isabella, primary, Caretti, Giuseppina, additional, Artuso, Simona, additional, Gurtner, Aymone, additional, Emiliozzi, Velia, additional, Sacchi, Ada, additional, Mantovani, Roberto, additional, and Piaggio, Giulia, additional
- Published
- 2008
- Full Text
- View/download PDF
19. Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid
- Author
-
Sara Lusa, Simona Artuso, Amalia Luce, Giuseppe De Rosa, Antonella Stoppacciaro, Michele Caraglia, Manuela Porru, Maria Luisa Balestrieri, Silvia Zappavigna, Carlo Leonetti, Giuseppina Salzano, Porru, Manuela, Zappavigna, Silvia, Salzano, Giuseppina, Luce, Amalia, Stoppacciaro, Antonella, Balestrieri, MARIA LUISA, Artuso, Simona, Lusa, Sara, DE ROSA, Giuseppe, Leonetti, Carlo, Caraglia, Michele, Porru, M, Zappavigna, S, Salzano, G, Luce, A, Stoppacciaro, A, Balestrieri, Maria Luisa, Artuso, S, Lusa, S, De Rosa, G, and Leonetti, C
- Subjects
Male ,intracranial xenografts ,Apoptosis ,Pharmacology ,Zoledronic Acid ,Mice, Inbred Strain ,Nitrosourea Compounds ,Mice ,Drug Delivery Systems ,Nanoparticle ,Neoplasm ,chemistry.chemical_classification ,Cell Growth Processe ,Diphosphonates ,calcium phosphate self-assembly nanoparticles ,Brain Neoplasms ,Imidazoles ,Transferrin ,Tumor Burden ,Dacarbazine ,medicine.anatomical_structure ,Diphosphonate ,Oncology ,Blood-Brain Barrier ,Drug delivery ,delivery ,Research Paper ,Human ,medicine.drug ,Glioblastoma ,zoledronic acid ,transferrin ,Mice, Inbred Strains ,Cell Growth Processes ,Nitrosourea Compound ,Blood–brain barrier ,Brain Neoplasm ,Organophosphorus Compounds ,Cell Line, Tumor ,Temozolomide ,medicine ,Animals ,Humans ,Imidazole ,Animal ,business.industry ,technology, industry, and agriculture ,Apoptosi ,medicine.disease ,Xenograft Model Antitumor Assays ,Zoledronic acid ,chemistry ,Drug Resistance, Neoplasm ,Nanoparticles ,Fotemustine ,Organophosphorus Compound ,business ,Drug Delivery System - Abstract
Glioblastomas are highly aggressive adult brain tumors with poor clinical outcome. In the central nervous system (CNS) the blood-brain barrier (BBB) is the most important limiting factor for both development of new drugs and drug delivery. Here, we propose a new strategy to treat glioblastoma based on transferrin (Tf)-targeted self-assembled nanoparticles (NPs) incorporating zoledronic acid (ZOL) (NPs-ZOL-Tf). NPs-ZOL-Tf have been assessed on the glioblastoma cell line U373MG-LUC that showed a refractoriness in vitro to temozolomide (TMZ) and fotemustine (FTM). NPs-ZOL-Tf treatment resulted in higher in vitro cytotoxic activity than free ZOL. However, the potentiation of anti-proliferative activity of NPs-ZOL-Tf was superimposable to that one induced by NPs-ZOL (not armed with Tf). On the other hand, NPs-ZOL-Tf showed a higher antitumor efficacy if compared with that one caused by NPs-ZOL in immunosuppressed mice intramuscularly bearing U373MG-LUC xenografts, inducing a significant tumor weight inhibition (TWI). The experiments performed on mice with intracranial U373MG-LUC xenografts confirmed the efficacy of NPs-ZOL-Tf. These effects were paralleled by a higher intratumour localization of fluorescently-labeled-NPs-Tf both in intramuscular and intracranial xenografts. In conclusion, our results demonstrate that the encapsulation of ZOL increases the antitumor efficacy of this drug in glioblastoma through the acquisition of ability to cross the BBB.
- Published
- 2014
20. A Survey on Clinical and Biological Characteristic and Therapy Management of an Italian Series of 455 Adult Patients with Systemic Mastocytosis on Behalf of Italian Registry of Mastocytosis
- Author
-
Roberta Zanotti, Vittoria Cova, Alberto Bosi, Anna Artuso, Chiara Elena, Simona Muratori, Federica Irene Grifoni, Massimo Triggiani, Omar Perbellini, Serena Merante, Elena Maria Elli, Fabio Almerigogna, Diomira Magliacane, Marina Mauro, Giovanni Martinelli, Cristina Papayannidis, Massimiliano Bonifacio, Lisa Pieri, G Cortellini, L. Lunardon, Caterina De Benedittis, Patrizia Bonadonna, Maurizio Severino, Stefania Girlanda, Agostino Cortelezzi, Simona Soverini, Federica Scarfì, Maria Loredana Iorno, Alessandro M. Vannucchi, Michela Rondoni, and Lisa Pieri, Patrizia Bonadonna, Chiara Elena, Cristina Papayannidis, Federica Irene Grifoni, Michela Rondoni, Stefania Girlanda, Marina Mauro, Diomira Magliacane, Elena Maria Elli, Maria Loredana Iorno, Maurizio Severino, Fabio Almerigogna, Federica Scarfì, Massimiliano Bonifacio, Omar Perbellini, Anna Artuso, Simona Soverini, Caterina De Benedittis, Simona Muratori, Luisa Lunardon, Vittoria Cova, Gabriele Cortellini, Alberto Bosi, Agostino Cortelezzi, Giovanni Martinelli, Massimo Triggiani, Serena Merante, Alessandro Maria Vannucchi, Roberta Zanotti
- Subjects
medicine.medical_specialty ,Pathology ,Thrombocytosis ,business.industry ,Cutaneous Mastocytosis ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,systemic mastocytosis ,medicine.disease ,Biochemistry ,Gastroenterology ,Imatinib mesylate ,epidemiology ,Internal medicine ,Medicine ,Systemic mastocytosis ,business ,Myelofibrosis ,Myeloproliferative neoplasm ,Multiple myeloma ,Mastocytosis - Abstract
Systemic mastocytosis (SM) is a rare myeloproliferative neoplasm characterized by proliferation and hyperactivation of clonal mast cells. Clinical manifestations are heterogeneous and encompass cutaneous lesions, gastrointestinal alterations, osteoporosis, anaphylaxis and involvement of bone marrow and other organs due to neoplastic mast cells (MC) infiltration. As consequence, diagnosis may be difficult and patients (pts) are often evaluated by different specialists before the disease is recognized. To date, only few studies (Lim 2009, Escribano 2009, Cohen 2014) described relatively large series of pts with SM. We performed a multicentre retrospective study to evaluate clinical and biological features and therapeutic management in a large series of pts from 10 Italian centres experienced in management of SM and organized in multidisciplinary groups of specialists. We collected 455 pts diagnosed with SM according to WHO criteria. Additionally 26 pts with mastocytosis in the skin (MIS) evaluated with BM examination did not fulfil criteria for SM, leading to diagnosis of Cutaneous Mastocytosis (CM); however 2/26 pts with CM had both cKITD816V mutation and CD2/CD25 expression on MC in BM, additional 3 showed either cKITD816V or CD2/CD25. Moreover, we found 22 pts without MIS but with features of monoclonal mast cell activation syndrome. Of the 455 pts with WHO-SM (male 56%), 252 (55%) had MIS: median age at MIS diagnosis (dg) was 37 years (y) (range 0-79), while at SM dg it was 46.5 (range 18-82). Time from onset of MIS to dg of SM was 9 y (range 0-43). In 18/252 pts (7%) MIS occurred before age of 18 y (median 9, range 0-17) and persisted over childhood. Median age at dg of SM without MIS (203/455 pts, 45%) was older: 54 y, range 19-79 (p Disclosures Martinelli: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; ARIAD: Consultancy.
21. Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance
- Author
-
Manuela Porru, Bruno Pagano, Eric Gilson, Chiara Cingolani, Annamaria Biroccio, Antonio Randazzo, Ettore Novellino, Simona Artuso, Antonella Stoppacciaro, Jussara Amato, Pasquale Zizza, Carmen D'Angelo, Erica Salvati, Angela Maria Rizzo, Giorgio Stassi, Carlo Leonetti, Zizza, Pasquale, Cingolani, Chiara, Artuso, Simona, Salvati, Erica, Rizzo, Angela, D'Angelo, Carmen, Porru, Manuela, Pagano, Bruno, Amato, Jussara, Randazzo, Antonio, Novellino, Ettore, Stoppacciaro, Antonella, Gilson, Eric, Stassi, Giorgio, Leonetti, Carlo, Biroccio, Annamaria, Zizza P., Cingolani C., Artuso S., Salvati E., Rizzo A., D'Angelo C., Porru M., Pagano B., Amato J., Randazzo A., Novellino E., Stoppacciaro A., Gilson E., Stassi G., Leonetti C., and Biroccio A.
- Subjects
cancer stem cells ,0301 basic medicine ,DNA damage ,Settore BIO/11 - Biologia Molecolare ,Tumor initiation ,Biology ,G-quadruplex ,03 medical and health sciences ,Cancer stem cell ,Antigens, CD ,Cell Line, Tumor ,G-Quadruplexe ,Genetics ,Humans ,Neoplasm Invasiveness ,AC133 Antigen ,Gene ,Glycoproteins ,Cell Proliferation ,Settore MED/04 - Patologia Generale ,Neoplasm Invasivene ,Protein Biosynthesi ,Drug discovery ,Gene regulation, Chromatin and Epigenetics ,Alternative splicing ,Intron ,cd133 ,Molecular biology ,G-Quadruplexes ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Cell Transformation, Neoplastic ,Drug Resistance, Neoplasm ,Protein Biosynthesis ,Peptide ,Neoplastic Stem Cells ,Cancer research ,Neoplastic Stem Cell ,Settore MED/46 - Scienze Tecniche Di Medicina Di Laboratorio ,Glycoprotein ,Peptides ,Human - Abstract
Cancer stem cells (CSCs) have been identified in several solid malignancies and are now emerging as a plausible target for drug discovery. Beside the questionable existence of CSCs specific markers, the expression of CD133 was reported to be responsible for conferring CSC aggressiveness. Here, we identified two G-rich sequences localized within the introns 3 and 7 of the CD133 gene able to form G-quadruplex (G4) structures, bound and stabilized by small molecules. We further showed that treatment of patient-derived colon CSCs with G4-interacting agents triggers alternative splicing that dramatically impairs the expression of CD133. Interestingly, this is strongly associated with a loss of CSC properties, including self-renewing, motility, tumor initiation and metastases dissemination. Notably, the effects of G4 stabilization on some of these CSC properties are uncoupled from DNA damage response and are fully recapitulated by the selective interference of the CD133 expression. In conclusion, we provided the first proof of the existence of G4 structures within the CD133 gene that can be pharmacologically targeted to impair CSC aggressiveness. This discloses a class of potential antitumoral agents capable of targeting the CSC subpopulation within the tumoral bulk.
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.