127 results on '"Piva, F"'
Search Results
2. Review on the degradation of GaN-based lateral power transistors
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De Santi, C., Buffolo, M., Rossetto, I., Bordignon, T., Brusaterra, E., Caria, A., Chiocchetta, F., Favero, D., Fregolent, M., Masin, F., Modolo, N., Nardo, A., Piva, F., Rampazzo, F., Sharma, C., Trivellin, N., Zhan, G., Meneghini, M., Zanoni, E., and Meneghesso, G.
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- 2021
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3. Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies
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Casulari, L.A., Dondi, D., Pratesi, G., Piva, F., Milani, M., Piccolella, M., and Maggi, R.
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- 2020
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4. Modeling the degradation mechanisms of AlGaN-based UV-C LEDs: from injection efficiency to mid-gap state generation
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Piva, F., primary, De Santi, C., additional, Deki, M., additional, Kushimoto, M., additional, Amano, H., additional, Tomozawa, H., additional, Shibata, N., additional, Meneghesso, G., additional, Zanoni, E., additional, and Meneghini, M., additional
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- 2020
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5. P-117 Prognostic role of plasmatic exosomal and tissue caveolin-1 in metastatic pancreatic cancer patients
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Bittoni, A., primary, Pecci, F., additional, Giulia, M., additional, Pellei, C., additional, Zizzi, A., additional, Mandolesi, A., additional, Piva, F., additional, Murrone, A., additional, Cantini, L., additional, Lanese, A., additional, Giglio, E., additional, Meletani, T., additional, Baleani, M., additional, Crocetti, S., additional, Lenci, E., additional, Copparoni, C., additional, Lupi, A., additional, Giampieri, R., additional, and Berardi, R., additional
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- 2020
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6. LHRF, LHRH, GnRH: what controls the secretion of this hormone?
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Martini, L, Motta, M, Piva, F, and Zanisi, M
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- 1997
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7. Expression of Prostacyclin Receptors in Luteinizing Hormone-Releasing Hormone Immortalized Neurons: Role in the Control of Hormone Secretion*
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Pimpinelli, F., Rovati, G. E., Capra, V., Piva, F., Martini, L., and Maggi, R.
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- 1999
8. BRCA mutations and IGF-R1 expression in modulating sensitivity to trastuzumab in HER2-positive breast cancer
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Pistelli, M., primary, Santinelli, A., additional, Santoni, M., additional, Piva, F., additional, Bianchi, F., additional, Belvederesi, L., additional, Biscotti, T., additional, De Lisa, M., additional, Ballatore, Z., additional, Occhipinti, G., additional, Pagliacci, A., additional, Maccaroni, E., additional, Bracci, R., additional, Battelli, N., additional, Cantini, L., additional, Bastianelli, L., additional, Berardi, R., additional, and Cascinu, S., additional
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- 2016
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9. BRCA mutations and IGF-R1 expression in modulating sensitivity to Trastuzumab in patients with HER2-positive breast cancer
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Pistelli, M., primary, Santinelli, A., additional, Santoni, M., additional, Piva, F., additional, Bianchi, F., additional, Biscotti, T., additional, Belvederesi, L., additional, Ballatore, Z., additional, Occhipinti, G., additional, De Lisa, M., additional, Pagliacci, A., additional, Battelli, N., additional, Bracci, R., additional, Maccaroni, E., additional, Bastinelli, L., additional, Cantini, L., additional, Berardi, R., additional, and Cascinu, S., additional
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- 2016
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10. Pathogenic and prognostic role of VEGF and VEGFR single nucleotide polymorphisms in gastroenteropancreatic neuroendocrine neoplasms
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Torniai, M., primary, Piva, F., additional, Rinaldi, S., additional, Santoni, M., additional, Pagliaretta, S., additional, Partelli, S., additional, Savini, A., additional, Morgese, F., additional, Caramanti, M., additional, Pistelli, M., additional, Bittoni, A., additional, Giampieri, R., additional, Onofri, A., additional, Pezzulla, D., additional, Principato, G., additional, Falconi, M., additional, and Berardi, R., additional
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- 2016
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11. Expression and differential effects of the activation of glucocorticoid receptors in mouse gonadotropin-releasing hormone neurons
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Dondi D, Piccolella M, Messi E, Demissie M, Cariboni A, Selleri S, Piva F, Samara A, Maggi R., CONSALEZ , GIAN GIACOMO, Dondi, D, Piccolella, M, Messi, E, Demissie, M, Cariboni, A, Selleri, S, Piva, F, Samara, A, Consalez, GIAN GIACOMO, and Maggi, R.
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- 2005
12. Factors involved in the migration of neuroendocrine hypothalamic neurons
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Maggi, R., Cariboni, A., Zaninetti, R., Samara, A., Stossi, F., Pimpinelli, F., Giacobini, P., Gian Giacomo Consalez, Rugarli, E., Piva, F., Maggi, R, Cariboni, A, Zaninetti, R, Samara, A, Stossi, F, Pimpinelli, F, Giacobini, P, Consalez, GIAN GIACOMO, Rugarli, E, and Piva, F.
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Gonadotropin-Releasing Hormone ,Neurons ,Hypothalamo-Hypophyseal System ,Cell Movement ,Hypothalamus ,Animals ,Gene Expression Regulation, Developmental ,Humans ,Nerve Growth Factors ,Neurosecretory Systems ,Signal Transduction - Abstract
Neuroendocrine control of physiological functions needs a complex developmental organisation of the hypothalamic parvicellular neurons, which synthesise and release hypophysiotropic hormones. Among the hypothalamic neuroendocrine cells, Gonadotropin-releasing hormone (GnRH) neurons represent a unique class; they are generated in the olfactory placode and, during embryonic life, migrate to the septo/hypothalamic region along terminal and vomeronasal nerves. At this level GnRH neurons undergo terminal differentiation and start to release GnRH to modulate the secretion of pituitary gonadotropins. All these steps are under the strict control of several developmental cues and their defect might represent a cause of clinical disorders. A number of factors have been proposed to be involved in the migration of GnRH neurons, but their role is still unclear. By using gene knockout techniques it has been found that mice carrying a targeted deletion of Ebf2 gene, a component of Olf/Ebf bHLH transcription factors, show a defective migration of GnRH neurons, providing the first evidence of a mouse model of such defect. Since the investigation of GnRH neurons is hindered by their peculiar anatomical distribution, other studies has been forwarded by the availability of immortalized GnRH-expressing neurons (GN11 cells) that retain a strong chemomigratory response "in vitro". Among the factors analysed, we found that hepatocyte growth factor/scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF) induce specific chemotaxis of GN 11 neurons, suggesting that migratory signals can arise from nasal mesenchyme and from the concomitant vasculogenesis. Finally, anosmin-1 (the product of the gene responsible of the X-linked form of Kallmann's disease) was found to induce a significant chemotactic response of GN11 cells, confirming a permissive/instructive role of KAL1 gene product in the migratory behaviour of GnRH neurons. In conclusion, the migration of the GnRH neurons appears to be a complex process, which involves the interplay of multiple molecular cues. These studies may provide new insights on the etiopathogenesis of the large proportion of reproductive dysfunctions that affect humans and could provide novel insights on common biochemical events controlling neuronal development and migration.
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- 2005
13. F19 - BRCA mutations and IGF-R1 expression in modulating sensitivity to Trastuzumab in patients with HER2-positive breast cancer
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Pistelli, M., Santinelli, A., Santoni, M., Piva, F., Bianchi, F., Biscotti, T., Belvederesi, L., Ballatore, Z., Occhipinti, G., De Lisa, M., Pagliacci, A., Battelli, N., Bracci, R., Maccaroni, E., Bastinelli, L., Cantini, L., Berardi, R., and Cascinu, S.
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- 2016
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14. B27 - Pathogenic and prognostic role of VEGF and VEGFR single nucleotide polymorphisms in gastroenteropancreatic neuroendocrine neoplasms
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Torniai, M., Piva, F., Rinaldi, S., Santoni, M., Pagliaretta, S., Partelli, S., Savini, A., Morgese, F., Caramanti, M., Pistelli, M., Bittoni, A., Giampieri, R., Onofri, A., Pezzulla, D., Principato, G., Falconi, M., and Berardi, R.
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- 2016
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15. Cancer Stem Cell Genetic Profile as Predictor of Relapse in Radically Resected Colorectal Cancer
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Giampieri, R., primary, Scartozzi, M., additional, Piva, F., additional, Loretelli, C., additional, Mandolesi, A., additional, Faloppi, L., additional, Bianconi, M., additional, Bittoni, A., additional, Bearzi, I., additional, and Cascinu, S., additional
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- 2012
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16. Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH
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Casulari, L.A., primary, Dondi, D., additional, Maggi, R., additional, Demissie, M., additional, Piccolella, M., additional, and Piva, F., additional
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- 2006
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17. Factors released by rat type 1 astrocytes exert different effects on the proliferation of human neuroblastoma cells (SH-SY5Y) in vitro.
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Casulari, L A, primary, Melcangi, R C, additional, Piva, F, additional, Martini, L, additional, and Maggi, R, additional
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- 2000
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18. Neurotransmitters and the control of hypophyseal gonadal functions: possible implications of endocrine disruptors
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Piva, F., primary and Martini, L., additional
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- 1998
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19. Use of the land snail Helix aspersa as sentinel organism for monitoring ecotoxicologic effects of urban pollution: an integrated approach.
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Regoli F, Gorbi S, Fattorini D, Tedesco S, Notti A, Machella N, Bocchetti R, Benedetti M, and Piva F
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Atmospheric pollution from vehicular traffic is a matter of growing interest, often leading to temporary restrictions in urban areas. Although guidelines indicate limits for several parameters, the real toxicologic impacts remain largely unexplored in field conditions. In this study our aim was to validate an ecotoxicologic approach to evaluate both bioaccumulation and toxicologic effects caused by airborne pollutants. Specimens of the land snail Helix aspersa were caged in five sites in the urban area of Ancona, Italy. After 4 weeks, trace metals (cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc) and polycyclic aromatic hydrocarbons (PAHs) were measured and these data integrated with the analyses of molecular and biochemical responses. Such biomarkers reflected the induction of detoxification pathways or the onset of cellular toxicity caused by pollutants. Biomarkers that correlated with contaminant accumulation included levels of metallothioneins, activity of biotransformation enzymes (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase), and peroxisomal proliferation. More general responses were investigated as oxidative stress variations, including efficiency of antioxidant defenses (catalase, glutathione reductase, glutathione S-transferases, glutathione peroxidases, and total glutathione) and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals, onset of cellular damages (i.e., lysosomal destabilization), and loss of DNA integrity. Results revealed a marked accumulation of metals and PAHs in digestive tissues of organisms maintained in more traffic-congested sites. The contemporary appearance of several alterations confirmed the cellular reactivity of these chemicals with toxicologic effects of potential concern for human health. The overall results of this exploratory study suggest the utility of H. aspersa as a sentinel organism for biomonitoring the biologic impact of atmospheric pollution in urban areas. Key words: atmospheric pollutants, bioindicators, biomarkers, DNA integrity, lysosomes, metallothioneins, oxidative stress, peroxisomes, polycyclic aromatic hydrocarbons, trace metals. [ABSTRACT FROM AUTHOR]
- Published
- 2006
20. La Quête du bonheur et l'expression de la douleur dans la littérature et la pensée françaises. Mélanges offerts à Corrado Rosso (review)
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Piva, Franco
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- 2011
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21. Séminaire Robert Challe. «Les Illustres Françaises» (review)
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Piva, Franco
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- 2011
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22. Continuation de l'Histoire de l'admirable Don Quichotte de la Manche (review)
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Piva, Franco
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- 2011
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23. Effects of progesterone on the central nervous system
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Motta, M., Piva, F., Martini, L., Motta, M., Piva, F., and Martini, L.
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- 1969
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24. Effects of epidermal growth factor on the [3H]-thymidine uptake in the SK-N-SH and SH-SY5Y human neuroblastoma cell lines
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Da Motta, L. A., Galli, P., Piva, F., and Roberto Maggi
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neuroblastoma ,epidermal growth factor ,cultura de células ,growth factors ,fator de crescimento epidérmico ,fatores de crescimento ,cells cultured - Abstract
The studies on the factors that regulate the biology of the neuroblastoma cell lines may offer important information on the development of tissues and organs that derive from the neural crest. In the present paper we study the action of epidermal growth factor (EGF) on two human neuroblastoma cell lines: SK-N-SH which is composed at least of two cellular phenotypes (neuroblastic and melanocytic/glial cells), and its pure neuroblastic subclone SH-SY5Y. The results show that EGF (10 ng/ml) significantly stimulates the incorporation of [3H]-thymidine in the SK-N-SH cells only in the presence of fetal bovine serum (FBS) (control = 58285 ± 9327 cpm; EGF =75523 ± 4457; p
25. Hypothalamic and Extrahypothalamic Mechanisms Controlling Adrenocorticotrophin Secretion
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Motta, M, primary, Fraschini, F, additional, Piva, F, additional, and Martini, L, additional
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- 1967
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26. Brain Receptors Sensitive to Indole Compounds: Function in Control of Luteinizing Hormone Secretion
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Fraschini, F., primary, Mess, B., additional, Piva, F., additional, and Martini, L., additional
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- 1968
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27. Le Dialogue dans le roman français de Sorel à Sarraute (review)
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Piva, Franco
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- 2011
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28. Robert Challe: Un Destin, une œuvre (review)
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Piva, Franco
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- 2011
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29. Defects in III-N LEDs: experimental identification and impact on electro-optical characteristics
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Matteo Buffolo, Nicola Roccato, Francesco Piva, Carlo De Santi, Riccardo Brescancin, Claudia Casu, Alessandro Caria, Kalparupa Mukherjee, Camille Haller, Jean Francois Carlin, Nicolas Grandjean, Marco Vallone, Alberto Tibaldi, Francesco Bertazzi, Michele Goano, Giovanni Verzellesi, Mauro Mosca, Gaudenzio Meneghesso, Enrico Zanoni, Matteo Meneghini, Strassburg, Martin, Buffolo M., Roccato N., Piva F., De Santi C., Brescancin R., Casu C., Caria A., Mukherjee K., Haller C., Carlin J.F., Grandjean N., Vallone M., Tibaldi A., Bertazzi F., Goano M., Verzellesi G., Mosca M., Meneghesso G., Zanoni E., and Meneghini M.
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reliability ,gallium nitride ,defects ,indium ,trap-assisted tunneling ,gallium nitride, defects, indium, reliability, trap-assisted tunneling ,Settore ING-INF/01 - Elettronica - Abstract
III-N light-emitting-diodes (LEDs) are subject of intense investigations, thanks to their high efficiency and great reliability. The quality of the semiconductor material has a significant impact on the electro-optical performance of LEDs: for this reason, a detailed characterization of defect properties and the modeling of the impact of defects on device performance are of fundamental importance. This presentation addresses this issue, by discussing a set of recent case studies on the topic; specifically, we focus on the experimental characterization of defects, and on the modeling of their impact on the electro-optical characteristics of the devices.
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- 2022
30. Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors
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Alessia Cimadamore, Camillo Porta, Giacomo Cartenì, Paolo Andrea Zucali, Cinzia Ortega, Roberto Iacovelli, Matteo Santoni, Daniele Santini, Alessandra Mosca, Erin Pierce, Marc R. Matrana, Elena Verzoni, Orazio Caffo, Michele Milella, Rodolfo Montironi, Sebastiano Buti, Jeffrey Graham, Sara Merler, Francesco Carrozza, Sergio Bracarda, Marina Scarpelli, Umberto Basso, Francesco Massari, Francesco Piva, Liang Cheng, Vittorio Paolucci, Angelo Martignetti, Franco Morelli, Cristina Masini, Fabio Calabrò, Giuseppe Fornarini, Sarah Scagliarini, Lorena Incorvaia, Nuno Vau, Mimma Rizzo, Francesco Atzori, Alain Gelibter, Riccardo Ricotta, Antonio Lopez-Beltran, Maria Giuseppa Vitale, Ugo De Giorgi, Simon J. Crabb, Giulia Sorgentoni, Pierangela Sepe, Luca Galli, Giuseppe Procopio, Daniel Y. Heng, Alessandro Conti, Nicola Battelli, Santoni M., Heng D.Y., Bracarda S., Procopio G., Milella M., Porta C., Matrana M.R., Carteni G., Crabb S.J., De Giorgi U., Basso U., Masini C., Calabro F., Vitale M.G., Santini D., Massari F., Galli L., Fornarini G., Ricotta R., Buti S., Zucali P., Caffo O., Morelli F., Carrozza F., Martignetti A., Gelibter A., Iacovelli R., Mosca A., Atzori F., Vau N., Incorvaia L., Ortega C., Scarpelli M., Lopez-Beltran A., Cheng L., Paolucci V., Graham J., Pierce E., Scagliarini S., Sepe P., Verzoni E., Merler S., Rizzo M., Sorgentoni G., Conti A., Piva F., Cimadamore A., Montironi R., and Battelli N.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,renal cell carcinoma ,Cabozantinib ,Prognosi ,Context (language use) ,urologic and male genital diseases ,lcsh:RC254-282 ,Article ,Pazopanib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,cabozantinib ,Internal medicine ,medicine ,Progression-free survival ,Nivolumab ,Prognosis ,Real-world data ,Targeted therapy ,nivolumab ,real-world data ,business.industry ,Sunitinib ,Retrospective cohort study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,targeted therapy ,Axitinib ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,prognosis ,business ,medicine.drug - Abstract
Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan&ndash, Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51&ndash, 10.88) and 11.57 months (95% CI 10.90&ndash, not reached (NR)) as second-line and 11.38 months (95% CI 5.79&ndash, NR) and NR (95% CI 11.51&ndash, NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib&ndash, nivolumab and 25.64 months and NR with nivolumab&ndash, cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39, 95% CI 1.24&ndash, 4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04&ndash, 2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33, 95%CI, 1.16&ndash, 4.69, p = 0.018) and Hb levels (HR = 3.12, 95%CI 1.18&ndash, 8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72, 95%CI 1.04&ndash, 7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.
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- 2019
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31. Clinical impact of different exosomes’ protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy
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Giulia Ricci, Alessandra Righetti, Alberto Murrone, Francesca Bianchi, Francesco Piva, Consuelo Amantini, Riccardo Giampieri, Giulia Occhipinti, Silvia Pagliaretta, Alessandro Bittoni, Rossana Berardi, Stefano Cascinu, Giovanni Principato, Matteo Giulietti, Giorgio Santoni, Giampieri, R., Piva, F., Occhipinti, G., Bittoni, A., Righetti, A., Pagliaretta, S., Murrone, A., Bianchi, F., Amantini, C., Giulietti, M., Ricci, G., Principato, G., Santoni, G., Berardi, R., and Cascinu, S.
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0301 basic medicine ,Oncology ,Male ,Integrins ,Colorectal cancer ,medicine.medical_treatment ,Cancer Treatment ,Gene Expression ,Kaplan-Meier Estimate ,Exosomes ,Biochemistry ,Metastasis ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Enzyme-Linked Immunoassays ,Multidisciplinary ,Pharmaceutics ,Liver Diseases ,Middle Aged ,Prognosis ,Epithelial Cell Adhesion Molecule ,Extracellular Matrix ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Sample collection ,Cellular Structures and Organelles ,Research Article ,Carcinoma, Pancreatic Ductal ,Clinical Oncology ,Adult ,medicine.medical_specialty ,Science ,Gastroenterology and Hepatology ,Adenocarcinoma ,Research and Analysis Methods ,Disease-Free Survival ,03 medical and health sciences ,Cancer Chemotherapy ,Drug Therapy ,Diagnostic Medicine ,Internal medicine ,Pancreatic cancer ,Carcinoma ,Cell Adhesion ,Biomarkers, Tumor ,Chemotherapy ,Humans ,Progression-free survival ,Vesicles ,Immunoassays ,Aged ,business.industry ,Cancer ,Biology and Life Sciences ,Cell Biology ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,Immunologic Techniques ,Clinical Medicine ,business ,Transcriptome ,Biomarkers - Abstract
IntroductionPancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy.Patients and methodsPatients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis.ResultsNineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137andConclusionsPancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.
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- 2019
32. Key role of obesity in genitourinary tumors with emphasis on urothelial and prostate cancers
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Matteo Santoni, Antonio Lopez-Beltran, Rodolfo Montironi, Francesco Massari, Lidia Gatto, Liang Cheng, Alessia Cimadamore, Vincenzo Di Nunno, Francesco Piva, Angelo Martignetti, Nicola Battelli, Gaetano Aurilio, Marina Scarpelli, Santoni M., Cimadamore A., Massari F., Piva F., Aurilio G., Martignetti A., Scarpelli M., Di Nunno V., Gatto L., Battelli N., Cheng L., Lopez-Beltran A., and Montironi R.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adipose tissue ,Disease ,Review ,lcsh:RC254-282 ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,BMI ,0302 clinical medicine ,Internal medicine ,medicine ,Urothelial cancer ,Enzalutamide ,Obesity ,business.industry ,Abiraterone acetate ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Response to therapy ,030104 developmental biology ,Docetaxel ,chemistry ,Cabazitaxel ,030220 oncology & carcinogenesis ,business ,Body mass index ,medicine.drug - Abstract
Background: In human populations, a certain amount of data correlate obesity/body mass index (BMI) with urothelial cancer (UC) and prostate cancer (PCa) occurrence, however this is not fully elucidated at all stages of disease. In an attempt to shed light on uncertain areas in such field, in the present review we illustrate the main molecular mechanisms linking obesity and cancer, focusing on the correlation between obesity and tumor risk, disease progression and response to chemo- and immunotherapy in patients with UC and the predictive/prognostic role of obesity in PCa patients treated with the currently available therapeutic approaches. Methods: We did a large-scale literature search on existing scientific websites focusing on keywords “obesity”, “body mass index (BMI)”, “urothelial cancer”, “prostate cancer”, “docetaxel”, “cabazitaxel”, “abiraterone acetate”, “enzalutamide”, and “radium223”. Results: Many adipocytes-induced molecules support tumor proliferation through activation of various cellular pathways. The available evidence in the postoperative setting do the role of BMI in oncological outcomes prediction still not completely clear. Likewise, in metastatic UC patients controversial results link the role of obesity/BMI with clinical outcomes of tumor response to chemotherapy. Adipose stromal cells recruitment, induced by PCa cells, from white adipose tissue to the tumor sites inducing cell invasiveness was associated with poor survival. Conflicting data, although more oriented towards a better survival outcome, resulted in obese patients treated with docetaxel. In PCa cell-lines a certain cabazitaxel chemo resistance adipose stromal cells (ASC)-mediated was demonstrated. In metastatic castration-resistant PCa patients with high BMI (>25 kg/m2) receiving abiraterone acetate there were significant worse survival outcomes, while in enzalutamide patients BMI did not affect survival outcome. In radium 223 patients higher BMI significantly correlated with favorable overall survival. Conclusions: The main focus of this review was to understand the interplay between obesity/BMI and UC/PCa. Several pathogenic cellular pathways exploring the issue are discussed, opening the way to challenging tailored treatments on the basis of BMI. Improving the knowledge of molecular connections between obesity and UC and PCa could favor the development of new therapies likely reducing chemo- and immunotherapy drug resistance.
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- 2019
33. Phosphorylated mTOR is associated to androgen receptor expression in early triple-negative breast cancer
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F. Piva, Nicola Battelli, M. De Lisa, L. Bastianelli, Mirco Pistelli, Giulia Occhipinti, Stefano Cascinu, Alfredo Santinelli, Zelmira Ballatore, Tommasina Biscotti, R. Bracci, A. Della Mora, Elena Maccaroni, A. Pagliacci, Rossana Berardi, Pistelli, M., Ballatore, Z., Santinelli, A., Biscotti, T., Piva, F., Occhipinti, G., Della Mora, A., Pagliacci, A., Battelli, N., Bastianelli, L., De Lisa, M., Bracci, R., Maccaroni, E., Berardi, R., and Cascinu, S.
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Adult ,0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Triple Negative Breast Neoplasms ,Biology ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Androgen Receptor Antagonists ,medicine ,Humans ,Phosphorylation ,PI3K/AKT/mTOR pathway ,Triple-negative breast cancer ,Aged ,Cell Proliferation ,Retrospective Studies ,Aged, 80 and over ,Oncogene ,MTOR ,TOR Serine-Threonine Kinases ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Molecular medicine ,Androgen receptor ,030104 developmental biology ,Oncology ,Receptors, Androgen ,Tumor progression ,030220 oncology & carcinogenesis ,Triple-negative ,Disease Progression ,Cancer research ,Female - Abstract
The significance of phosphorylated mTOR (p-mTOR) expression is unknown in triple-negative breast carcinoma (TNBC). The aims of the present study were to assess the expression of p-mTOR in early TNBC and to evaluate possible correlations between androgen receptor (AR) expression, clinicopathological parameters and disease outcome. Between January 2009 and December 2013, all consecutive patients who were diagnosed and completed the treatment of invasive TNBC at our institution were eligible for this analysis. Patients with stage IV disease were excluded. The evaluation of p-mTOR immunohistochemical staining was semi-quantitatively considering both the percentage of positive tumor cells (range, 0-100%) and staining intensity (range, 0-3+). Ninety-eight TNBC patients were included. Approximately 33% of cases were p-mTOR positive and there was no association between positive immunostaining for p-mTOR and DFS (p=0.74) and OS (p=0.81). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). High expression of p-mTOR may drive tumor proliferation in almost one third of TNBC. The biological association between mTOR activation and AR pathway suggests that there may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumor progression.
- Published
- 2016
34. KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma
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Matteo Santoni, Giovanni Principato, Marina Scarpelli, Alessandro Conti, Alessandra Mandolesi, Francesco Piva, Cristian Loretelli, Alessandro Bittoni, Andrea Lanese, Kalliopi Andrikou, Stefano Cascinu, Chiara Pellei, Bittoni, A., Piva, F., Santoni, M., Andrikou, K., Conti, A., Loretelli, C., Mandolesi, A., Lanese, A., Pellei, C., Scarpelli, M., Principato, G., and Cascinu, S.
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Adult ,Male ,Cancer Research ,endocrine system diseases ,overall survival ,Mutant ,pancreatic ductal adenocarcinoma ,Adenocarcinoma ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,splicing ,Gene expression ,KRAS ,Humans ,Medicine ,neoplasms ,Gene ,Aged ,Aged, 80 and over ,Mutation ,business.industry ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,digestive system diseases ,Neoplasm Proteins ,respiratory tract diseases ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Vascular endothelial growth factor B ,Oncology ,Cancer research ,nucleotide variations ,Female ,business - Abstract
ABSTRACT Aims: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations. Materials & methods: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients’ survival. Results: MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors. Conclusion: KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.
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- 2015
35. HER family receptor expression and prognosis in pancreatic cancer
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Chiara Pellei, Simona Alfonsi, Stefano Cascinu, Marina Scarpelli, Cristian Loretelli, Alessandro Bittoni, Francesco Piva, Andrea Lanese, Kalliopi Andrikou, Alessandra Mandolesi, Matteo Santoni, Bittoni, A., Mandolesi, A., Andrikou, K., Santoni, M., Alfonsi, S., Lanese, A., Loretelli, C., Pellei, C., Piva, F., Scarpelli, M., and Cascinu, S.
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Male ,Cancer Research ,Receptor expression ,EGFR ,Clinical Biochemistry ,Kaplan-Meier Estimate ,Adenocarcinoma ,Pathology and Forensic Medicine ,Breast cancer ,Pancreatectomy ,Pancreatic cancer ,medicine ,Humans ,Single-Blind Method ,Molecular Targeted Therapy ,Receptor ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Lung ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,Neoplasm Proteins ,ErbB Receptors ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Oncology ,Tumor progression ,HER-2 ,Immunology ,Cancer research ,HER-3 ,Female ,business ,Pancreatic adenocarcinoma ,Dimerization - Abstract
BackgroundHER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients’ clinical outcomes.MethodsTissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+ or 3+ were assigned to each sample based on the intensity of staining for HER receptors. Scores of 2+ or 3+ were defined as positive staining.ResultsHER-1 overexpression was observed in 41 out of 91 samples (45.1%), while HER-2 was not overexpressed in any of the analyzed samples. HER-3 was overexpressed in 37 samples (40.7%) and was found to be associated with advanced TNM stage. In particular, HER-3 was overexpressed in 12 out of 16 stage IV patients (75%) compared with only 33.3% of stage I-III patients (p = 0.02). Among 79 patients with available survival data, the 6 patients with strong HER-3 expression (score 3+) had a shorter survival compared with remaining patients (median overall survival 6.9 months vs. 12.3 months, respectively).ConclusionsHER-1 and HER-3 were found to be expressed in a significant proportion of PC patients. Strong HER-3 expression represents an indicator of poor prognosis in PC patients, being associated with advanced stage and shorter survival.
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- 2015
36. Metabolic alterations in renal cell carcinoma
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Rodolfo Montironi, Alessandra Modena, Chiara Ciccarese, Stefano Cascinu, Matteo Santoni, Giampaolo Tortora, Daniele Santini, Liang Cheng, Emanuela Fantinel, Francesco Massari, Francesco Piva, Davide Bimbatti, Matteo Brunelli, Massari, F., Ciccarese, C., Santoni, M., Brunelli, M., Piva, F., Modena, A., Bimbatti, D., Fantinel, E., Santini, D., Cheng, L., Cascinu, S., Montironi, R., and Tortora, G.
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medicine.medical_specialty ,Nutrient sensing ,Biology ,Pentose phosphate pathway ,urologic and male genital diseases ,medicine.disease_cause ,Internal medicine ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,RCC carcinogenesis ,Carcinoma, Renal Cell ,AMPK ,General Medicine ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,Citric acid cycle ,Metabolic pathway ,Endocrinology ,Oncology ,Anaerobic glycolysis ,Metabolic pathways ,Lipogenesis ,Therapeutic strategies ,Cancer research ,Carcinogenesis ,Metabolic Networks and Pathways - Abstract
Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.
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- 2015
37. Re: Johan Lindberg, Anna Kristiansen, Peter Wiklund, Henrik Gronberg, Lars Egevad. Tracking the Origin of Metastatic Prostate Cancer. Eur Urol 2015; 67: 819-22
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Rodolfo Montironi, Francesco Montorsi, Alberto Briganti, Marina Scarpelli, Francesco Piva, Matteo Santoni, Piva, F, Santoni, M, Scarpelli, M, Briganti, Alberto, Montorsi, Francesco, and Montironi, R.
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Male ,business.industry ,Biopsy ,Urology ,Prostate ,DNA ,medicine.disease ,Carcinoma, Ductal ,Neoplasm Metastasi ,Prostate cancer ,Prostatic Neoplasm ,medicine ,Religious studies ,business ,Human - Published
- 2015
38. PD-1 blockade therapy in renal cell carcinoma. Current studies and future promises
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Rodolfo Montironi, Matteo Santoni, Guido Martignoni, Giampaolo Tortora, Daniele Santini, Matteo Brunelli, Francesco Massari, Chiara Ciccarese, Stefano Cascinu, Camillo Porta, Salvatore Alfieri, F. Piva, Rossana Berardi, Massari, F., Santoni, M., Ciccarese, C., Santini, D., Alfieri, S., Martignoni, G., Brunelli, M., Piva, F., Berardi, R., Montironi, R., Porta, C., Cascinu, Stefano, and Tortora, G.
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Vascular Endothelial Growth Factor A ,T-Lymphocytes ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Cell ,B7-H1 Antigen ,PD-1 ,Immunotherapy ,PDL-1 ,Renal cell carcinoma ,Cytotoxicity ,Clinical Trials as Topic ,renal cell carcinoma ,immunotherapy ,Antibodies, Monoclonal ,General Medicine ,Prognosis ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,Nivolumab ,medicine.anatomical_structure ,Oncology ,Signal Transduction ,medicine.drug ,Down-Regulation ,Antineoplastic Agents ,Ipilimumab ,Antibodies, Monoclonal, Humanized ,Immune system ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Carcinoma, Renal Cell ,Cell Proliferation ,Neoplasm Staging ,business.industry ,Antibody-Dependent Cell Cytotoxicity ,Cancer ,medicine.disease ,Receptors, Vascular Endothelial Growth Factor ,Immunology ,Cancer research ,Neoplasm Grading ,business - Abstract
RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.
- Published
- 2015
39. Cancer stem cell gene profile as predictor of relapse in high risk stage II and stage III, radically resected colon cancer patients
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Michela Del Prete, Francesco Piva, Giovanni Lezoche, Italo Bearzi, Riccardo Giampieri, Mario Scartozzi, Maristella Bianconi, Luca Cecchini, Alessandro Bittoni, Alessandra Mandolesi, Stefano Cascinu, Luca Faloppi, Cristian Loretelli, Mario Guerrieri, Giampieri, R, Scartozzi, M, Loretelli, C, Piva, F, Mandolesi, A, Lezoche, G, Del Prete, M, Bittoni, A, Faloppi, L, Bianconi, M, Cecchini, L, Guerrieri, M, Bearzi, I, and Cascinu, Stefano
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Pathology ,Abcg2 ,Colorectal cancer ,Science ,Disease ,Cancer stem cell ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Stage (cooking) ,ALCAM ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Multidisciplinary ,biology ,business.industry ,CD44 ,Middle Aged ,Prognosis ,medicine.disease ,Colonic Neoplasms ,Neoplastic Stem Cells ,biology.protein ,Female ,Neoplasm Recurrence, Local ,Stem cell ,business ,Research Article - Abstract
Clinical data indicate that prognostic stratification of radically resected colorectal cancer based on disease stage only may not be always be adequate. Preclinical findings suggest that cancer stem cells may influence the biological behaviour of colorectal cancer independently from stage: objective of the study was to assess whether a panel of stemness markers were correlated with clinical outcome in resected stage II and III colon cancer patients. A panel of 66 markers of stemness were analysed and thus patients were divided into two groups (A and B) with most patients clustering in a manner consistent with different time to relapse by using a statistical algorithm. A total of 62 patients were analysed. Thirty-six (58%) relapsed during the follow-up period (range 1.63–86.5 months). Twelve (19%) and 50 (81%) patients were allocated into group A and B, respectively. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p = 0.0296). Among of all genes tested, those with the higher “weight” in determining different prognosis were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis supports the idea that, other than stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients.
- Published
- 2013
40. TRAM (Transcriptome Mapper): database-driven creation and analysis of transcriptome maps from multiple sources
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Federica Facchin, Francesco Piva, Alessandro Coppe, Lorenza Vitale, Gian Antonio Danieli, Raffaella Casadei, Maria Chiara Pelleri, Stefania Bortoluzzi, Flavia Frabetti, Luca Lenzi, Silvia Canaider, Matteo Giulietti, Giovanni Principato, Sergio Ferrari, Pierluigi Strippoli, Lenzi L., Facchin F., Piva F., Giulietti M., Pelleri M.C., Frabetti F., Vitale L., Casadei R., Canaider S., Bortoluzzi S., Coppe A., Danieli G.A., Principato G., Ferrari S., and Strippoli P.
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lcsh:QH426-470 ,lcsh:Biotechnology ,Genomics ,Context (language use) ,TRANSCRIPTOME MAP ,Biology ,computer.software_genre ,Models, Biological ,transcriptome map ,bioinformatics ,hematopoietic cells ,Transcriptome ,User-Computer Interface ,lcsh:TP248.13-248.65 ,Gene cluster ,Databases, Genetic ,Genetics ,Cluster Analysis ,Humans ,Quantile normalization ,Internet ,GENE CLUSTER ,GENE EXPRESSION PROFILE ,Gene Expression Profiling ,Computational Biology ,Gene expression profiling ,lcsh:Genetics ,Data format ,Database Management Systems ,Data mining ,DNA microarray ,computer ,GENOMICS ,Biotechnology ,Research Article - Abstract
Background Several tools have been developed to perform global gene expression profile data analysis, to search for specific chromosomal regions whose features meet defined criteria as well as to study neighbouring gene expression. However, most of these tools are tailored for a specific use in a particular context (e.g. they are species-specific, or limited to a particular data format) and they typically accept only gene lists as input. Results TRAM (Transcriptome Mapper) is a new general tool that allows the simple generation and analysis of quantitative transcriptome maps, starting from any source listing gene expression values for a given gene set (e.g. expression microarrays), implemented as a relational database. It includes a parser able to assign univocal and updated gene symbols to gene identifiers from different data sources. Moreover, TRAM is able to perform intra-sample and inter-sample data normalization, including an original variant of quantile normalization (scaled quantile), useful to normalize data from platforms with highly different numbers of investigated genes. When in 'Map' mode, the software generates a quantitative representation of the transcriptome of a sample (or of a pool of samples) and identifies if segments of defined lengths are over/under-expressed compared to the desired threshold. When in 'Cluster' mode, the software searches for a set of over/under-expressed consecutive genes. Statistical significance for all results is calculated with respect to genes localized on the same chromosome or to all genome genes. Transcriptome maps, showing differential expression between two sample groups, relative to two different biological conditions, may be easily generated. We present the results of a biological model test, based on a meta-analysis comparison between a sample pool of human CD34+ hematopoietic progenitor cells and a sample pool of megakaryocytic cells. Biologically relevant chromosomal segments and gene clusters with differential expression during the differentiation toward megakaryocyte were identified. Conclusions TRAM is designed to create, and statistically analyze, quantitative transcriptome maps, based on gene expression data from multiple sources. The release includes FileMaker Pro database management runtime application and it is freely available at http://apollo11.isto.unibo.it/software/, along with preconfigured implementations for mapping of human, mouse and zebrafish transcriptomes.
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- 2011
41. Il cantiere navale Breda (1928-1942)
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FELTRIN, PAOLO, Piva F., Tattara G., and Feltrin, Paolo
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Veneto ,mercato del lavoro ,occupazione - Published
- 1983
42. A Comparison of Tools That Identify Tumor Cells by Inferring Copy Number Variations from Single-Cell Experiments in Pancreatic Ductal Adenocarcinoma.
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Oketch DJA, Giulietti M, and Piva F
- Abstract
Single-cell RNA sequencing (scRNA-seq) technique has enabled detailed analysis of gene expression at the single cell level, enhancing the understanding of subtle mechanisms that underly pathologies and drug resistance. To derive such biological meaning from sequencing data in oncology, some critical processing must be performed, including identification of the tumor cells by markers and algorithms that infer copy number variations (CNVs). We compared the performance of sciCNV, InferCNV, CopyKAT and SCEVAN tools that identify tumor cells by inferring CNVs from scRNA-seq data. Sequencing data from Pancreatic Ductal Adenocarcinoma (PDAC) patients, adjacent and healthy tissues were analyzed, and the predicted tumor cells were compared to those identified by well-assessed PDAC markers. Results from InferCNV, CopyKAT and SCEVAN overlapped by less than 30% with InferCNV showing the highest sensitivity (0.72) and SCEVAN the highest specificity (0.75). We show that the predictions are highly dependent on the sample and the software used, and that they return so many false positives hence are of little use in verifying or filtering predictions made via tumor biomarkers. We highlight how critical this processing can be, warn against the blind use of these software and point out the great need for more reliable algorithms.
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- 2024
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43. Effects of Eribulin on the RNA Content of Extracellular Vesicles Released by Metastatic Breast Cancer Cells.
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Giulietti M, Piva F, Cecati M, Maggio S, Guescini M, Saladino T, Scortichini L, Crocetti S, Caramanti M, Battelli N, and Romagnoli E
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- Humans, Female, Furans, Breast Neoplasms pathology, MicroRNAs genetics, Extracellular Vesicles metabolism, Polyether Polyketides, Ketones
- Abstract
Extracellular vesicles (EVs) are small lipid particles secreted by almost all human cells into the extracellular space. They perform the essential function of cell-to-cell communication, and their role in promoting breast cancer progression has been well demonstrated. It is known that EVs released by triple-negative and highly aggressive MDA-MB-231 breast cancer cells treated with paclitaxel, a microtubule-targeting agent (MTA), promoted chemoresistance in EV-recipient cells. Here, we studied the RNA content of EVs produced by the same MDA-MB-231 breast cancer cells treated with another MTA, eribulin mesylate. In particular, we analyzed the expression of different RNA species, including mRNAs, lncRNAs, miRNAs, snoRNAs, piRNAs and tRNA fragments by RNA-seq. Then, we performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and miRNA-target identification. Our findings demonstrate the possible involvement of EVs from eribulin-treated cells in the spread of chemoresistance, prompting the design of strategies that selectively target tumor EVs.
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- 2024
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44. Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?
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Giannella L, Piva F, Delli Carpini G, Di Giuseppe J, Grelloni C, Giulietti M, Sopracordevole F, Giorda G, Del Fabro A, Clemente N, Gardella B, Bogani G, Brasile O, Martinello R, Caretto M, Ghelardi A, Albanesi G, Stevenazzi G, Venturini P, Papiccio M, Cannì M, Barbero M, Fambrini M, Maggi V, Uccella S, Spinillo A, Raspagliesi F, Greco P, Simoncini T, Petraglia F, and Ciavattini A
- Abstract
Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH., Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN)., Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC., Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.
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- 2023
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45. Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility.
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Oketch DJA, Giulietti M, and Piva F
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- Humans, DNA Copy Number Variations genetics, Precision Medicine, Gene Dosage, Pancreatic Neoplasms genetics, Carcinoma, Pancreatic Ductal genetics
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, characterized by high tumor heterogeneity and a poor prognosis. Inter- and intra-tumoral heterogeneity in PDAC is a major obstacle to effective PDAC treatment; therefore, it is highly desirable to explore the tumor heterogeneity and underlying mechanisms for the improvement of PDAC prognosis. Gene copy number variations (CNVs) are increasingly recognized as a common and heritable source of inter-individual variation in genomic sequence. In this review, we outline the origin, main characteristics, and pathological aspects of CNVs. We then describe the occurrence of CNVs in PDAC, including those that have been clearly shown to have a pathogenic role, and further highlight some key examples of their involvement in tumor development and progression. The ability to efficiently identify and analyze CNVs in tumor samples is important to support translational research and foster precision oncology, as copy number variants can be utilized to guide clinical decisions. We provide insights into understanding the CNV landscapes and the role of both somatic and germline CNVs in PDAC, which could lead to significant advances in diagnosis, prognosis, and treatment. Although there has been significant progress in this field, understanding the full contribution of CNVs to the genetic basis of PDAC will require further research, with more accurate CNV assays such as single-cell techniques and larger cohorts than have been performed to date.
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- 2023
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46. Maxillary Anterior Teeth Dimensions and Relative Width Proportions: A Narrative Literature Review.
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Cinelli F, Piva F, Bertini F, Russo DS, and Giachetti L
- Abstract
Predictable results in the aesthetic treatment of anterior teeth can be obtained by resorting to the concept of dental aesthetics and, in particular, defining the ideal tooth dimensions and proportions to obtain a harmonious smile. Considering the great variety of articles dealing with the topic, and the lack of updated reviews, this narrative literature review aims to evaluate current knowledge on anterior teeth dimensions and to verify the existence and the potential applications of the anterior teeth proportioning theories (Golden Proportion, Golden Percentage, RED Proportion, and Golden Rectangle). PubMed, Embase, Cochrane Library, and Google Scholar databases were comprehensively searched using different keywords and term combinations. The research includes articles published up to June 2023, no time limits were set, and only articles in English were included. Inclusion criteria comprehended reviews, clinical studies, and in-vitro studies. A total of 66 articles were selected. Two main topics were identified: "Anterior teeth dimensions", "Golden Proportions, Golden Percentage, RED Proportions, and Golden Rectangle". As far as tooth dimensions are concerned, different width ranges are recognized for men and women and for different ethnic groups. Perfectly symmetric contralateral elements are found in low percentages of subjects. The correlation between dental dimensions and facial parameters is not always present, and it strongly depends on the sample's ethnicity and gender. Ideal tooth proportions were only partially identified.
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- 2023
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47. Gut-Joint Axis: Impact of Bifidobacterial Cell Wall Lipoproteins on Arthritis Development.
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Piva F, Gervois P, Karrout Y, Sané F, and Romond MB
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- Mice, Animals, Interleukin-10, Bifidobacterium, Escherichia coli, Mice, Inbred DBA, Collagen, Cell Wall, Arthritis, Experimental chemically induced, Arthritis, Rheumatoid
- Abstract
Gut microbiota affect progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg of Lpps/L, but not 0.25 and 1 mg of Lpps/L, significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. The arthritis index (AI) was also reduced in CAIA mice. In the CIA-protected group, colon Ligilactobacillus murinus , caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher cecal and colon E. coli and lower caecal L. murinus . Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA-protected mice triggered by LPS secreted higher Il-10 than control ones. However, a higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs' recruitment. Labeled bacteria with the Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16 h post-gavage but not in Peyer's patches and the spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24 h. An FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.
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- 2023
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48. Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression.
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Lazzarini R, Tartaglione MF, Ciarapica V, Piva F, Giulietti M, Fulgenzi G, Martelli M, Ledda C, Vitale E, Malavolta M, Santarelli L, and Bracci M
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- Humans, Aldo-Keto Reductase Family 1 Member C3, Cell Line, Tumor, G2 Phase Cell Cycle Checkpoints, Keratinocytes metabolism, Light, Oxidative Stress, Reactive Oxygen Species metabolism, Thioredoxin Reductase 1 metabolism, Apoptosis radiation effects, Proteomics
- Abstract
Several cell-signaling mechanisms are activated by visible light radiation in human keratinocytes, but the key regulatory proteins involved in this specific cellular response have not yet been identified. Human keratinocytes (HaCaT cells) were exposed to blue or red light at low or high irradiance for 3 days in cycles of 12 h of light and 12 h of dark. The cell viability, apoptotic rate and cell cycle progression were analyzed in all experimental conditions. The proteomic profile, oxidative stress and mitochondrial morphology were additionally evaluated in the HaCaT cells following exposure to high-irradiance blue or red light. Low-irradiance blue or red light exposure did not show an alteration in the cell viability, cell death or cell cycle progression. High-irradiance blue or red light reduced the cell viability, induced cell death and cell cycle G2/M arrest, increased the reactive oxygen species (ROS) and altered the mitochondrial density and morphology. The proteomic profile revealed a pivotal role of Cytoplasmic thioredoxin reductase 1 (TXNRD1) and Aldo-keto reductase family 1 member C3 (AKR1C3) in the response of the HaCaT cells to high-irradiance blue or red light exposure. Blue or red light exposure affected the viability of keratinocytes, activating a specific oxidative stress response and inducing mitochondrial dysfunction. Our results can help to address the targets for the therapeutic use of light and to develop adequate preventive strategies for skin damage. This in vitro study supports further in vivo investigations of the biological effects of light on human keratinocytes.
- Published
- 2023
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49. Free lipoproteins from Bifidobacterium longum alleviate osteoarthritis through modulation of the gut microbiome.
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Sane F, Piva F, and Romond MB
- Abstract
Aim: The "gut-joint" axis is suspected to be involved in the pathophysiology of osteoarthritis (OA). The present study aims at investigating the potential of lipoproteins (Lpps) secreted by Bifidobacterium longum to alleviate OA progression in the rat. Methods: Experimental OA was induced in rats harbouring Schaedler Flora maintained in SPF conditions. Two weeks post-injection, 20 rats were randomized to water ( n = 10) or 0.3 mg/L Lpps solution ( n = 10). Weight and food intake were monitored for 6 weeks. At sacrifice, joints were scored using macroscopic and histological criteria. Serum LPS, Schaedler flora as well as selected intestinal bacteria were analyzed. Results: Lpps intake prevents OA progression. The protected rats showed a significant increase in lactobacilli along the intestine as well as in Mucispirillum schaedleri in the colon and a significant decrease in Parabacteroides goldsteini and Akkermansia in caecum and colon, respectively. There was no significant difference in serum lipopolysaccharide or bacteria translocating in Peyer's patches. Labelled Lpps were not detected in bone marrow of the OA joint. The principal component analysis points out that OA prevention is primarily associated with bacteria involved in the tryptophane degradation pathway and SCFA formation. Conclusion: In rats deprived of bifidobacteria, intake of B.longum Lpps prevented OA development and modulated the intestinal microbiome with a possible impact on the bacterial end-products. The link between Lpps and the gut microbial metabolome warrants further investigation., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2023.)
- Published
- 2023
- Full Text
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50. Meldonium Inhibits Cell Motility and Wound-Healing in Trabecular Meshwork Cells and Scleral Fibroblasts: Possible Applications in Glaucoma.
- Author
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Minnelli C, Piva F, Cecati M, Armeni T, Mobbili G, Galeazzi R, Melecchi A, Cristaldi M, Corsaro R, and Rusciano D
- Abstract
Meldonium (MID) is a synthetic drug designed to decrease the availability of L-carnitine-a main player in mitochondrial energy generation-thus modulating the cell pathways of energy metabolism. Its clinical effects are mostly evident in blood vessels during ischemic events, when the hyperproduction of endogenous carnitine enhances cell metabolic activities, leading to increased oxidative stress and apoptosis. MID has shown vaso-protective effects in model systems of endothelial dysfunction induced by high glucose or by hypertension. By stimulating the endothelial nitric oxide synthetase (eNOS) via PI3 and Akt kinase, it has shown beneficial effects on the microcirculation and blood perfusion. Elevated intraocular pressure (IOP) and endothelial dysfunction are major risk factors for glaucoma development and progression, and IOP remains the main target for its pharmacological treatment. IOP is maintained through the filtration efficiency of the trabecular meshwork (TM), a porous tissue derived from the neuroectoderm. Therefore, given the effects of MID on blood vessels and endothelial cells, we investigated the effects of the topical instillation of MID eye drops on the IOP of normotensive rats and on the cell metabolism and motility of human TM cells in vitro. Results show a significant dose-dependent decrease in the IOP upon topic treatment and a decrease in TM cell motility in the wound-healing assay, correlating with an enhanced expression of vinculin localized in focal adhesion plaques. Motility inhibition was also evident on scleral fibroblasts in vitro. These results may encourage a further exploration of MID eye drops in glaucoma treatment.
- Published
- 2023
- Full Text
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