130 results on '"De Cesare D"'
Search Results
2. Routes of Transcriptional Activation in the Testis: CREM and its Co-Activator ACT
- Author
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De Cesare, D., Fimia, G. M., Morlon, A., Sassone-Corsi, P., Stock, G., editor, Lessl, M., editor, Jégou, B., editor, Pineau, C., editor, and Saez, J., editor
- Published
- 2000
- Full Text
- View/download PDF
3. 1719P Decentralized clinical trials: Is there a space in Italy?
- Author
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Cagnazzo, C., Mannozzi, F., Stabile, S., Sgarbossa, C., De Cesare, D., Carrera, A., and Testoni, S.
- Published
- 2023
- Full Text
- View/download PDF
4. Change Management for Digital Innovation: Towards an Ecosystem Perspective
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Locatelli, P., Gastaldi, L., Cirilli, F., De Cesare, D., and Scardigno, A. J.
- Published
- 2020
5. CREM, a master-switch of the transcriptional cascade in male germ cells
- Author
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De Cesare, D., Fimia, G. M., and Sassone-Corsi, P.
- Published
- 2000
- Full Text
- View/download PDF
6. High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis
- Author
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Cipollone, F, Fazia, M, Iezzi, A, Pini, B, Costantini, F, De Cesare, D, Paloscia, L, Materazzo, G, D’Annunzio, E, Bucciarelli, T, Vecchiet, J, Chiarelli, F, Cuccurullo, F, and Mezzetti, A
- Published
- 2003
7. Role of microRNA-155 in the pathogenesis and treatment of psoriatic arthritis
- Author
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Bucci, M., primary, Ianni, U., additional, Celletti, E., additional, Sabatini, E., additional, De Cesare, D., additional, and Cipollone, F., additional
- Published
- 2017
- Full Text
- View/download PDF
8. Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum
- Author
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D'Aniello, C., Habibi, E., Cermola, F., Paris, D., Russo, F., Fiorenzano, A., Di Napoli, G., Melck, D.J., Cobellis, G., Angelini, C., Fico, A., Blelloch, R., Motta, A., Stunnenberg, H.G., De Cesare, D., Patriarca, E.J., Minchiotti, G., D'Aniello, C., Habibi, E., Cermola, F., Paris, D., Russo, F., Fiorenzano, A., Di Napoli, G., Melck, D.J., Cobellis, G., Angelini, C., Fico, A., Blelloch, R., Motta, A., Stunnenberg, H.G., De Cesare, D., Patriarca, E.J., and Minchiotti, G.
- Abstract
Contains fulltext : 165841.pdf (publisher's version ) (Open Access)
- Published
- 2016
9. Work-related stress in healthcare workers
- Author
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Tomei, G, Ricci, S, Fidanza, L, Sacco, C, De Cesare, D. P, Ricci, P, Pimpinella, B, Giubilati, R, Suppi, A, Anzelmo, Vincenza, Tomei, F, Casale, T, Rosati, M. V., Anzelmo, Vincenza (ORCID:0000-0002-0411-6639), Tomei, G, Ricci, S, Fidanza, L, Sacco, C, De Cesare, D. P, Ricci, P, Pimpinella, B, Giubilati, R, Suppi, A, Anzelmo, Vincenza, Tomei, F, Casale, T, Rosati, M. V., and Anzelmo, Vincenza (ORCID:0000-0002-0411-6639)
- Abstract
BACKGROUND: In the assessment of work-related stress it is crucial to find the factors that generate and increase it in order to identify categories of individuals at risk, to plan interventions for prevention, elimination or reduction of risk. The aim of the study is to assess the subjective stress in 68 workers of a large Italian company dealing with human health, through the use of a questionnaire-indicating tool, elaborated by the Italian National Institute for insurance against accidents at work (INAIL) and developed by the Health and Safety Executive (HSE). METHODS: We studied a final sample of 68 individuals (34 drivers/rescuers and 34 video display unit (VDU) operators). The questionnaire consists of 35 items (divided into six areas) with five possible answers each, that cover working conditions considered potential causes of stress. RESULTS: The drivers/rescuers had a better performance than the VDU operators, especially in the areas "demand", "relationships" and "role". We compared men and women in the two groups, finding that, in VDU operators, women had a better performance than men in all areas, except "role" and "changes", in which the overall scores were the same in men and women. In the drivers/rescuers women showed more critical scores in the items "relationships" and "change". CONCLUSION: The results show that: the questionnaire-indicating tool is useful, with a demonstrated effectiveness for the occupational physician during the visits and proven validity; additional future efforts should focus on understanding the psycho-social, organizational and individual problems related to stress and the consequent implementation of preventive measures. KEYWORDS: Health workers; Psychophysical health; Questionnaire; VDU operators; Work-related
- Published
- 2016
10. Microfabricated sensors for label-free electronic DNA detection
- Author
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GUIDUCCI, CARLOTTA, STAGNI DEGLI ESPOSTI, CLAUDIO, BENINI, LUCA, ZUCCHERI, GIAMPAOLO, SAMORI', BRUNO, RICCO', BRUNO, Caputo D., Nascetti A., De Cesare D., Guiducci C., Stagni C., Benini L., Zuccheri G., Samorì B., Caputo D., Nascetti A., De Cesare D., and Riccò B.
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SENSORS ,MICROELECTRONICS ,DNA DETECTION - Published
- 2005
11. Erratum: A novel autoregulatory loop between the Gcn2-Atf4 pathway and l-Proline metabolism controls stem cell identity
- Author
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D'Aniello, C, primary, Fico, A, additional, Casalino, L, additional, Guardiola, O, additional, Di Napoli, G, additional, Cermola, F, additional, De Cesare, D, additional, Tatè, R, additional, Cobellis, G, additional, Patriarca, E J, additional, and Minchiotti, G, additional
- Published
- 2015
- Full Text
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12. A novel autoregulatory loop between the Gcn2-Atf4 pathway and L-Proline metabolism controls stem cell identity
- Author
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D'Aniello, C, primary, Fico, A, additional, Casalino, L, additional, Guardiola, O, additional, Di Napoli, G, additional, Cermola, F, additional, De Cesare, D, additional, Tatè, R, additional, Cobellis, G, additional, Patriarca, E J, additional, and Minchiotti, G, additional
- Published
- 2015
- Full Text
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13. The Cellmaker: a fully automated robotic platform to identify stem cell regulators
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Casalino L, Comes S, Lambazzi G, De Stefano B, De Cesare D, De Falco S, Filosa S, Minchiotti G, and Patriarca E J.
- Published
- 2009
14. Combined administration of losartan and simvastatin may produce optimal plaque stabilization in humans by maximally suppressing inducible PGE synthase type 1 in macrophages
- Author
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Fazia, Ml, Iezzi, A, Cuccurullo, C, De Cesare, D, Ucchino, S, Spigonardo, F, Ferri, Claudio, Letizia, C, Desideri, Giovambattista, Cuccurullo, F, and Cipollone, F.
- Published
- 2006
15. Correlazione tra benzene e testosterone nei lavoratori esposti a inquinamento urbano.
- Author
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Rosati, M. V., Sancini, A., Tomei, F., Sacco, C., Traversini, V., De Vita, A., De Cesare, D. P., Giammichele, G., De Marco, F., Pagliara, F., Massoni, F., Ricci, L., Tomei, G., and Ricci, S.
- Abstract
Copyright of Clinica Terapeutica is the property of Societa Editrice Universo s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2017
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16. Accumulation of Fra-1 in ras-transformed cells depends on both transcriptional autoregulation and MEK-dependent posttranslational stabilization
- Author
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Casalino L, De Cesare D, and Verde P.
- Subjects
Transcription Factor ,Gene Expression ,MAP kinase ,Ras oncogene ,Posttranslational - Abstract
The AP-1 transcription factor plays an essential role in cell proliferation and tumorigenesis. It was previously shown that the fra-1 gene product is upregulated by various oncogenes and is involved in the in vitro and in vivo transformation of thyroid cells. Here we show that the ras oncogene-dependent accumulation of Fra-1 is mediated by a positive feedback mechanism which requires both transcriptional autoregulation and posttranslational stabilization of the protein. The oncogene-dependent transcriptional activation involves the cooperation between both Raf-dependent and Raf-independent pathways and is mediated by an AP-1 site within the fra-1 first intron, which becomes stably occupied by a transcriptionally active Fra-1-containing complex in ras-transformed cells. The posttranslational stabilization results in a drastic increase in the Fra-1 half-life in ras-transformed cells and is totally dependent on the activity of the MEK/ERK phosphorylation pathway. The analysis of the Fra-1 transactivation potential shows that the protein is able to stimulate a heterologous promoter in a ras-dependent manner, but the transactivating activity requires the recruitment of a heterodimeric partner. These data show that the alteration of multiple regulatory mechanisms is required for the constitutive activation of Fra-1 as a nuclear target of ras transformation.
- Published
- 2003
17. Gamma-glutamyl transpeptidase dependent iron reduction and low density lipoprotein oxidation - characterization of a novel mechanism of atherogenesis
- Author
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Paolicchi, Aldo, Minotti, G., Tonarelli, P., Tongiani, Roberto, DE CESARE, D., Mezzetti, A., Comporti, M., and Pompella, Alfonso
- Published
- 1999
18. Gamma-glutamyl transpeptidase-dependent iron reduction and LDL oxidation--a potential mechanism in atherosclerosis
- Author
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Paolicchi, Aldo, Minotti, G, Tonarelli, P, Tongiani, Roberto, De Cesare, D, Mezzetti, A, Dominici, S, Comporti, M, and Pompella, Alfonso
- Published
- 1999
19. Increased systemic oxidative stress after elective endarterectomy. Relation to vascular remodeling
- Author
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Mezzetti, A, Guglielmi, Md, Pierdomenico, Sd, Costantini, F, Cipollone, F, DE CESARE, D, Bucciarelli, T, Ucchino, S, Chiarelli, F, Cuccurullo, F, and Romano, Ferdinando
- Published
- 1999
20. Copper/zinc ratio and systemic oxidant load: effect of aging and aging-related degenerative disease
- Author
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Mezzetti, A, Pierdomenico, Sd, Costantini, F, Romano, Ferdinando, DE CESARE, D, Cuccurullo, F, Imbastaro, T, RIARIO SFORZA, G, DI GIACOMO, F, and Zuliani, G.
- Published
- 1998
21. EXPRESSION OF CB1 AND CB2 IN HUMAN ATHEROSCLEROTIC PLAQUES
- Author
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Fazia, M.L., primary, Di Francesco, A., additional, De Cesare, D., additional, Bucci, M., additional, Ucchino, S., additional, Spigonardo, F., additional, and Mezzetti, A., additional
- Published
- 2008
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22. PO11-313 SUPPRESSION OF 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE AS A BASIS OF ATHEROSCLEROTIC PLAQUE INSTABILITY IN HUMANS
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Di Francesco, A., primary, Fazia, M.L., additional, Iezzi, A., additional, Cuccurullo, C., additional, De Cesare, D., additional, Dannenberg, A.J., additional, Mezzetti, A., additional, and Cipollone, F., additional
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- 2007
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23. Tu-P7:287 Overexpression of toll like receptor 4 as a basis of cyclooxygenase 2-dependent atherosclerotic plaque instability in humans
- Author
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Iezzi, A., primary, Fazia, M.L., additional, Cuccurullo, C., additional, De Cesare, D., additional, Ucchino, S., additional, Spigonardo, F., additional, Cuccurullo, F., additional, Mezzetti, A., additional, and Cipollone, F., additional
- Published
- 2006
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24. Tu-P7:280 Hur protein as potential modulator of angiotensin II type 1 receptor expression in human atherosclerotic plaque
- Author
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Cuccurullo, C., primary, Fazia, M.L., additional, Iezzi, A., additional, De Cesare, D., additional, Uechino, S., additional, Spigonardo, F., additional, Bucci, M., additional, Cuccurullo, F., additional, Mezzetti, A., additional, and Cipollone, F., additional
- Published
- 2006
- Full Text
- View/download PDF
25. Tu-P7:282 Overexpression of protein AUF1 as a protective mechanism against PGE2-dependent atherosclerotic plaque instability in humans
- Author
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Fazia, M.L., primary, Cuccurullo, C., additional, Iezzi, A., additional, De Cesare, D., additional, Ucchino, S., additional, Spigonardo, F., additional, Cuccurullo, F., additional, Mezzetti, A., additional, and Cipollone, F., additional
- Published
- 2006
- Full Text
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26. Relationship between Reduced BCL-2 Expression in Circulating Mononuclear Cells and Early Nephropathy in Type 1 Diabetes
- Author
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Cipollone, F., primary, Chiarelli, F., additional, Iezzi, A., additional, Fazia, M.L., additional, Cuccurullo, C., additional, Pini, B., additional, De Cesare, D., additional, Torello, M., additional, Tumini, S., additional, Cuccurullo, F., additional, and Mezzetti, A., additional
- Published
- 2005
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27. Heterodimerization of c-Jun with ATF-2 and cFos is required for positive and negative regulation of the human urokinase enhancer
- Author
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De Cesare, D., Vallone, D., Caracciolo, A., Sassone-Corsi, P., Nerlov, C., Verde, P., De Cesare, D., Vallone, D., Caracciolo, A., Sassone-Corsi, P., Nerlov, C., and Verde, P.
- Published
- 1995
28. ACT, un nouveau co-activateur transcriptionnel
- Author
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Fimia, GM, primary, De Cesare, D, additional, Morlon, A, additional, and Sassone Corsi, P, additional
- Published
- 1999
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- View/download PDF
29. Separation and characterization of non-phosphorylated and serine-phosphorylated human urokinase. Catalytic properties and sensitivity to PAI-1
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Franco, P., Mastronicola, M.R., De Cesare, D., Nolli, M.L., Wun, T.-C., Verde, P., Blasi, Francesco, Stopelli, M.P., Franco, P., Mastronicola, M.R., De Cesare, D., Nolli, M.L., Wun, T.-C., Verde, P., Blasi, Francesco, and Stopelli, M.P.
- Published
- 1992
30. Mechanisms of Activation by CREB and CREM: Phosphorylation, CBP, and a Novel Coactivator, ACT
- Author
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FIMIA, G.M., primary, DE CESARE, D., additional, and SASSONE-CORSI, P., additional
- Published
- 1998
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- View/download PDF
31. Le syndrome de Coffin-Lowry : une anomalie de la transduction du signal (voie Ras/MAP kinase)
- Author
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Hanauer, A, primary, Trivier, E, additional, De Cesare, D, additional, Jacquot, S, additional, Pannetier, S, additional, Sassone-Corsi, P, additional, and Mandel, JL, additional
- Published
- 1997
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32. A regulatory element that mediates co-operation between a PEA3-AP-1 element and an AP-1 site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells.
- Author
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Nerlov, C., primary, De Cesare, D., additional, Pergola, F., additional, Caracciolo, A., additional, Blasi, F., additional, Johnsen, M., additional, and Verde, P., additional
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- 1992
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- View/download PDF
33. Separation and characterization of nonphosphorylated and serine-phosphorylated urokinase. Catalytic properties and sensitivity to plasminogen activator inhibitor type 1.
- Author
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Franco, P, primary, Mastronicola, M.R., additional, De Cesare, D, additional, Nolli, M.L., additional, Wun, T.C., additional, Verde, P, additional, Blasi, F, additional, and Stoppelli, M.P., additional
- Published
- 1992
- Full Text
- View/download PDF
34. Glutathione-related enzyme activities and lipoperoxide levels in human internal mammary artery and ascending aorta. Relations with serum lipids.
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Mezzetti, A, primary, Lapenna, D, additional, Calafiore, A M, additional, Proietti-Franceschilli, G, additional, Porreca, E, additional, De Cesare, D, additional, Neri, M, additional, Di Ilio, C, additional, and Cuccurullo, F, additional
- Published
- 1992
- Full Text
- View/download PDF
35. The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques: role of glycemic control.
- Author
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Cipollone F, Iezzi A, Fazia M, Zucchelli M, Pini B, Cuccurullo C, De Cesare D, De Blasis G, Muraro R, Bei R, Chiarelli F, Schmidt AM, Cuccurullo F, Mezzetti A, Cipollone, Francesco, Iezzi, Annalisa, Fazia, Maria, Zucchelli, Mirco, Pini, Barbara, and Cuccurullo, Chiara
- Published
- 2003
36. Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans.
- Author
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Cipollone F, Fazia M, Iezzi A, Zuccelli M, Pini B, De Cesare D, Ucchino S, Spigonardo F, Bajocchi G, Bei R, Muraro R, Artese L, Piatelli A, Chiarelli F, Cuccurullo F, Mezzetti A, Cipollone, Francesco, Fazia, Maria, Iezzi, Annalisa, and Zucchelli, Mirco
- Published
- 2003
37. Characterization of UEF-4, a DNA-binding protein required for transcriptional synergism between two AP-1 sites in the human urokinase enhancer.
- Author
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De Cesare, D, Palazzolo, M, Berthelsen, J, and Blasi, F
- Abstract
The enhancer of the inducible urokinase gene depends on three essential but not sufficient transactivating elements, an upstream PEA3/AP-1A and a downstream AP-1B site. Enhancer activity also requires the interposed 74-base pair-long cooperation mediator (COM) region that allows transcriptional synergism between the transactivating sites. The 5'-half of COM (uCOM) forms four retarded complexes with HeLa or Hep-G2 nuclear proteins (UEF-1-4). We have identified the binding sequence for UEF-4 and generated uCOM elements uniquely mutated in the UEF-4-binding site or uniquely binding UEF-4. Introduction of these and other mutations in the context of the urokinase enhancer showed that all uCOM sites are important for enhancer activity but that UEF-4 and UEF-1 plus UEF-2/3 can substitute for each other, suggesting functional redundancy of urokinase enhancer factors. UEF-4 was purified from HeLa nuclear extract by affinity chromatography and shown to contain two polypeptides of 105 and 65 kDa, respectively, of which at least the former was endowed with DNA binding activity.
- Published
- 1997
38. C007: Low density lipoprotein oxidation and vitamins E and C in dipper and nondipper hypertensive patients.
- Author
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Pierdomenico, S.D., Costantini, F., Bucci, A., De Cesare, D., Cuccurullo, F., and Mezzetti, A.
- Published
- 1998
- Full Text
- View/download PDF
39. G42: Low density lipoprotein oxidation in white coat and sustained hypertension.
- Author
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Pierdomenico, S.D., Costantini, F., Lapenna, D., Bucci, A., De Cesare, D., Cuccurullo, F., and Mezzetti, A.
- Published
- 1997
- Full Text
- View/download PDF
40. A novel autoregulatory loop between the Gcn2-Atf4 pathway and L-Proline metabolism controls stem cell identity
- Author
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G Di Napoli, Gilda Cobellis, Ombretta Guardiola, Annalisa Fico, Eduardo J. Patriarca, Federica Cermola, Cristina D'Aniello, Laura Casalino, Rosarita Tatè, D De Cesare, Gabriella Minchiotti, D'Aniello, C, Fico, A, Casalino, L, Guardiola, O, Di Napoli, G, Cermola, F, De Cesare, D, Tatè, R, Cobellis, G, Patriarca, E J, and Minchiotti, G
- Subjects
L-Proroline ,Proline ,Protein Serine-Threonine Kinases ,Protein-Serine-Threonine Kinase ,Activating Transcription Factor 4 ,Biology ,Mice ,Embryonic Stem Cell ,Stress, Physiological ,Animals ,Induced pluripotent stem cell ,Molecular Biology ,Embryonic Stem Cells ,Feedback, Physiological ,chemistry.chemical_classification ,Original Paper ,Animal ,Cell growth ,Cell Biology ,Embryonic stem cell ,Amino acid ,chemistry ,Biochemistry ,embryonic structures ,Erratum ,Signal transduction ,Stem cell ,Starvation response ,Signal Transduction - Abstract
Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2?-Atf4 amino acid starvation response (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop generates a highly specific intrinsic shortage of L-Pro that restricts proliferation of tightly packed domed-like ESC colonies and safeguards ESC identity. Indeed, alleviation of this nutrient stress condition by exogenously provided L-Pro induces proliferation and modifies the ESC phenotypic and molecular identity towards that of mesenchymal-like, invasive pluripotent stem cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by halofuginone or forced expression of Atf4 antagonises the effects of exogenous L-Pro. Our data provide unprecedented evidence that L-Pro metabolism and the nutrient stress response are functionally integrated to maintain ESC identity.Cell Death and Differentiation advance online publication, 10 April 2015; doi:10.1038/cdd.2015.24.
- Published
- 2015
41. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
- Author
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. 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Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
- Subjects
0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
42. Three-dimensional environment sensitizes pancreatic cancer cells to the anti-proliferative effect of budesonide by reprogramming energy metabolism.
- Author
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Ibello E, Saracino F, Delle Cave D, Buonaiuto S, Amoroso F, Andolfi G, Corona M, Guardiola O, Colonna V, Sainz B Jr, Altucci L, De Cesare D, Cobellis G, Lonardo E, Patriarca EJ, D'Aniello C, and Minchiotti G
- Subjects
- Humans, Mice, Animals, Cell Line, Tumor, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Xenograft Model Antitumor Assays, Cell Movement drug effects, Budesonide pharmacology, Budesonide therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Energy Metabolism drug effects, Cell Proliferation drug effects
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals with severe and long-standing asthma. Here we explored the potential link between PDAC and the glucocorticoid (GC) budesonide, a first-line therapy to treat asthma., Methods: We tested the effect of budesonide and the classical GCs on the morphology, proliferation, migration and invasiveness of patient-derived PDAC cells and pancreatic cancer cell lines, using 2D and 3D cultures in vitro. Furthermore, a xenograft model was used to investigate the effect of budesonide on PDAC tumor growth in vivo. Finally, we combined genome-wide transcriptome analysis with genetic and pharmacological approaches to explore the mechanisms underlying budesonide activities in the different environmental conditions., Results: We found that in 2D culture settings, high micromolar concentrations of budesonide reduced the mesenchymal invasive/migrating features of PDAC cells, without affecting proliferation or survival. This activity was specific and independent of the Glucocorticoid Receptor (GR). Conversely, in a more physiological 3D environment, low nanomolar concentrations of budesonide strongly reduced PDAC cell proliferation in a GR-dependent manner. Accordingly, we found that budesonide reduced PDAC tumor growth in vivo. Mechanistically, we demonstrated that the 3D environment drives the cells towards a general metabolic reprogramming involving protein, lipid, and energy metabolism (e.g., increased glycolysis dependency). This metabolic change sensitizes PDAC cells to the anti-proliferative effect of budesonide, which instead induces opposite changes (e.g., increased mitochondrial oxidative phosphorylation). Finally, we provide evidence that budesonide inhibits PDAC growth, at least in part, through the tumor suppressor CDKN1C/p57Kip2., Conclusions: Collectively, our study reveals that the microenvironment influences the susceptibility of PDAC cells to GCs and provides unprecedented evidence for the anti-proliferative activity of budesonide on PDAC cells in 3D conditions, in vitro and in vivo. Our findings may explain, at least in part, the reason for the lower occurrence of pancreatic cancer in asthmatic patients and suggest a potential suitability of budesonide for clinical trials as a therapeutic approach to fight pancreatic cancer., (© 2024. The Author(s).)
- Published
- 2024
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43. Budesonide Analogues Preserve Stem Cell Pluripotency and Delay 3D Gastruloid Development.
- Author
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Amoroso F, Ibello E, Saracino F, Cermola F, Ponticelli G, Scalera E, Ricci F, Villetti G, Cobellis G, Minchiotti G, Patriarca EJ, De Cesare D, and D'Aniello C
- Abstract
Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as an anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.
- Published
- 2023
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44. Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids.
- Author
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Cermola F, Amoroso F, Saracino F, Ibello E, De Cesare D, Fico A, Cobellis G, Scalera E, Casiraghi C, D'Aniello C, Patriarca EJ, and Minchiotti G
- Subjects
- Cell Adhesion, Embryonic Development, Budesonide pharmacology, Budesonide metabolism, Embryonic Stem Cells metabolism, Embryo, Mammalian metabolism
- Abstract
3D embryonic stem cell (ESC) aggregates self-organize into embryo-like structures named gastruloids that recapitulate the axial organization of post-implantation embryos. Crucial in this process is the symmetry-breaking event that leads to the emergence of asymmetry and spatially ordered structures from homogeneous cell aggregates. Here, we show that budesonide, a glucocorticoid drug widely used to treat asthma, prevents ESC aggregates to break symmetry. Mechanistically, the effect of budesonide is glucocorticoid receptor independent. RNA sequencing and lineage fate analysis reveal that budesonide counteracts exit from pluripotency and modifies the expression of a large set of genes associated with cell migration, A-P axis formation, and WNT signaling. This correlates with reduced phenotypic and molecular cell heterogeneity, persistence of E-CADHERIN at the cell-cell interface, and cell aggregate compaction. Our findings reveal that cell-cell adhesion properties control symmetry breaking and cell fate transition in 3D gastruloids and suggest a potential adverse effect of budesonide on embryo development., Competing Interests: Conflict of interests E.S. and C.C. are employees of Chiesi Farmaceutici S.p.A., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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45. Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.
- Author
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Concistrè A, Petramala L, Circosta F, Romagnoli P, Soldini M, Bucci M, De Cesare D, Cavallaro G, De Toma G, Cipollone F, and Letizia C
- Abstract
Background: Primary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA)., Methods: The quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA)., Results: Real-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA., Conclusion: This study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Concistrè, Petramala, Circosta, Romagnoli, Soldini, Bucci, De Cesare, Cavallaro, De Toma, Cipollone and Letizia.)
- Published
- 2022
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46. Capturing Transitional Pluripotency through Proline Metabolism.
- Author
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Minchiotti G, D'Aniello C, Fico A, De Cesare D, and Patriarca EJ
- Subjects
- Animals, Cell Differentiation, Mice, Proline metabolism, Transcriptome, Blastocyst metabolism, Embryonic Stem Cells
- Abstract
In this paper, we summarize the current knowledge of the role of proline metabolism in the control of the identity of Embryonic Stem Cells (ESCs). An imbalance in proline metabolism shifts mouse ESCs toward a stable naïve-to-primed intermediate state of pluripotency. Proline-induced cells (PiCs), also named primitive ectoderm-like cells (EPLs), are phenotypically metastable, a trait linked to a rapid and reversible relocalization of E-cadherin from the plasma membrane to intracellular membrane compartments. The ESC-to-PiC transition relies on the activation of Erk and Tgfβ/Activin signaling pathways and is associated with extensive remodeling of the transcriptome, metabolome and epigenome. PiCs maintain several properties of naïve pluripotency (teratoma formation, blastocyst colonization and 3D gastruloid development) and acquire a few traits of primed cells (flat-shaped colony morphology, aerobic glycolysis metabolism and competence for primordial germ cell fate). Overall, the molecular and phenotypic features of PiCs resemble those of an early-primed state of pluripotency, providing a robust model to study the role of metabolic perturbations in pluripotency and cell fate decisions.
- Published
- 2022
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47. The Multifaceted Roles of Proline in Cell Behavior.
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Patriarca EJ, Cermola F, D'Aniello C, Fico A, Guardiola O, De Cesare D, and Minchiotti G
- Abstract
Herein, we review the multifaceted roles of proline in cell biology. This peculiar cyclic imino acid is: (i) A main precursor of extracellular collagens (the most abundant human proteins), antimicrobial peptides (involved in innate immunity), salivary proteins (astringency, teeth health) and cornifins (skin permeability); (ii) an energy source for pathogenic bacteria, protozoan parasites, and metastatic cancer cells, which engage in extracellular-protein degradation to invade their host; (iii) an antistress molecule (an osmolyte and chemical chaperone) helpful against various potential harms (UV radiation, drought/salinity, heavy metals, reactive oxygen species); (iv) a neural metabotoxin associated with schizophrenia; (v) a modulator of cell signaling pathways such as the amino acid stress response and extracellular signal-related kinase pathway; (vi) an epigenetic modifier able to promote DNA and histone hypermethylation; (vii) an inducer of proliferation of stem and tumor cells; and (viii) a modulator of cell morphology and migration/invasiveness. We highlight how proline metabolism impacts beneficial tissue regeneration, but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Patriarca, Cermola, D’Aniello, Fico, Guardiola, De Cesare and Minchiotti.)
- Published
- 2021
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48. Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes.
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Santovito D, Toto L, De Nardis V, Marcantonio P, D'Aloisio R, Mastropasqua A, De Cesare D, Bucci M, Paganelli C, Natarelli L, Weber C, Consoli A, Mastropasqua R, and Cipollone F
- Subjects
- Aged, Biomarkers blood, Case-Control Studies, Circulating MicroRNA genetics, Female, Gene Expression Regulation genetics, Gene Ontology, Humans, Male, Middle Aged, Prospective Studies, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 genetics, Diabetic Retinopathy blood, Diabetic Retinopathy genetics, MicroRNAs blood, MicroRNAs genetics
- Abstract
Diabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P < 0.001) in a cohort of patients with T2DM with DR (n = 20), compared with diabetic subjects without DR (n = 10) and healthy individuals (n = 10). These associations persisted significant after adjustment for age, gender, and HbA1c. The circulating levels of these miRNAs correlated with severity of the disease and their concomitant evaluation showed high accuracy for identifying DR (AUROC = 0.93; P < 0.001). Gene ontology analysis of validated targets revealed enrichment in pathways such as regulation of metabolic process (P = 1.5 × 10
-20 ), of cell response to stress (P = 1.9 × 10-14 ), and development of blood vessels (P = 2.7 × 10-14 ). Pending external validation, we anticipate that these miRNAs may serve as putative disease biomarkers and highlight novel molecular targets for improving care of patients with diabetic retinopathy.- Published
- 2021
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49. Gastruloid Development Competence Discriminates Different States of Pluripotency.
- Author
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Cermola F, D'Aniello C, Tatè R, De Cesare D, Martinez-Arias A, Minchiotti G, and Patriarca EJ
- Subjects
- Animals, Cell Differentiation, Epidermal Growth Factor genetics, Membrane Glycoproteins genetics, Mice, Mice, Knockout, Neoplasm Proteins genetics, Embryonic Development, Epidermal Growth Factor metabolism, Germ Layers metabolism, Membrane Glycoproteins metabolism, Mouse Embryonic Stem Cells metabolism, Neoplasm Proteins metabolism, Organogenesis, Organoids embryology, Pluripotent Stem Cells metabolism
- Abstract
Floating spheroidal aggregates of mouse embryonic stem cells can develop into polarized/elongated organoids, namely gastruloids. We set up a high-performing assay to measure gastruloid formation efficiency (GFE), and found that GFE decreases as pluripotency progresses from naive (GFE ≥ 95%) to primed (GFE = 0) state. Specifically, we show that primed EpiSCs fail to generate proper cell aggregates, while early-primed EpiLCs aggregate but eventually fail to develop into elongated gastruloids. Moreover, we characterized proline-induced cells (PiCs), a LIF-dependent reversible early-primed state of pluripotency, and show that PiCs are able to generate gastruloids (GFE ∼ 50%) and are also competent to differentiate into primordial germ cell-like cells. Thus, we propose the GFE assay as a valuable functional tool to discriminate different states of the pluripotency continuum., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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50. High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion.
- Author
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Santovito D, Marcantonio P, Mastroiacovo D, Natarelli L, Mandolini C, De Nardis V, Paganelli C, De Cesare D, Affaitati G, Giamberardino MA, Stellin L, Pinelli M, Weber C, De Blasis G, Occhiuzzi U, Bucci M, Desideri G, and Cipollone F
- Subjects
- ATP Binding Cassette Transporter 1 biosynthesis, Aged, Aged, 80 and over, Anticholesteremic Agents administration & dosage, Dose-Response Relationship, Drug, Female, Humans, Male, ATP Binding Cassette Transporter 1 blood, Cholesterol blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Plaque, Atherosclerotic blood, Plaque, Atherosclerotic drug therapy, Rosuvastatin Calcium administration & dosage
- Abstract
Background: ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques., Methods: Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10 mg/day) or high (40 mg/day) dose rosuvastatin for 12 weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry., Results: Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein., Conclusions: High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin., Trial Registration: ISRCTN16590640., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
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