120 results on '"Pisati, F"'
Search Results
2. Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer
- Author
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Frittoli E., Palamidessi A., Iannelli F., Zanardi F., Villa S., Barzaghi L., Abdo H., Cancila V., Beznoussenko G. V., Della Chiara G., Pagani M., Malinverno C., Bhattacharya D., Pisati F., Yu W., Galimberti V., Bonizzi G., Martini E., Mironov A. A., Gioia U., Ascione F., Li Q., Havas K., Magni S., Lavagnino Z., Pennacchio F. A., Maiuri P., Caponi S., Mattarelli M., Martino S., d'Adda di Fagagna F., Rossi C., Lucioni M., Tancredi R., Pedrazzoli P., Vecchione A., Petrini C., Ferrari F., Lanzuolo C., Bertalot G., Nader G., Foiani M., Piel M., Cerbino R., Giavazzi F., Tripodo C., Scita G., Frittoli, E., Palamidessi, A., Iannelli, F., Zanardi, F., Villa, S., Barzaghi, L., Abdo, H., Cancila, V., Beznoussenko, G. V., Della Chiara, G., Pagani, M., Malinverno, C., Bhattacharya, D., Pisati, F., Yu, W., Galimberti, V., Bonizzi, G., Martini, E., Mironov, A. A., Gioia, U., Ascione, F., Li, Q., Havas, K., Magni, S., Lavagnino, Z., Pennacchio, F. A., Maiuri, P., Caponi, S., Mattarelli, M., Martino, S., d'Adda di Fagagna, F., Rossi, C., Lucioni, M., Tancredi, R., Pedrazzoli, P., Vecchione, A., Petrini, C., Ferrari, F., Lanzuolo, C., Bertalot, G., Nader, G., Foiani, M., Piel, M., Cerbino, R., Giavazzi, F., Tripodo, C., and Scita, G.
- Abstract
The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma.
- Published
- 2023
3. Author Correction: Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer (Nature Materials, (2022), 10.1038/s41563-022-01431-x)
- Author
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Frittoli E., Palamidessi A., Iannelli F., Zanardi F., Villa S., Barzaghi L., Abdo H., Cancila V., Beznoussenko G. V., Della Chiara G., Pagani M., Malinverno C., Bhattacharya D., Pisati F., Yu W., Galimberti V., Bonizzi G., Martini E., Mironov A. A., Gioia U., Ascione F., Li Q., Havas K., Magni S., Lavagnino Z., Pennacchio F. A., Maiuri P., Caponi S., Mattarelli M., Martino S., d'Adda di Fagagna F., Rossi C., Lucioni M., Tancredi R., Pedrazzoli P., Vecchione A., Petrini C., Ferrari F., Lanzuolo C., Bertalot G., Nader G., Foiani M., Piel M., Cerbino R., Giavazzi F., Tripodo C., Scita G., Frittoli E., Palamidessi A., Iannelli F., Zanardi F., Villa S., Barzaghi L., Abdo H., Cancila V., Beznoussenko G.V., Della Chiara G., Pagani M., Malinverno C., Bhattacharya D., Pisati F., Yu W., Galimberti V., Bonizzi G., Martini E., Mironov A.A., Gioia U., Ascione F., Li Q., Havas K., Magni S., Lavagnino Z., Pennacchio F.A., Maiuri P., Caponi S., Mattarelli M., Martino S., d'Adda di Fagagna F., Rossi C., Lucioni M., Tancredi R., Pedrazzoli P., Vecchione A., Petrini C., Ferrari F., Lanzuolo C., Bertalot G., Nader G., Foiani M., Piel M., Cerbino R., Giavazzi F., Tripodo C., and Scita G.
- Subjects
c-gas ,Settore MED/05 - Patologia Clinica ,Settore MED/08 - Anatomia Patologica - Abstract
In the version of this article initially published, the first name of Flora Ascione was listed as “Floriana”; the error has been corrected in the HTML and PDF versions of the article.
- Published
- 2023
4. Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
- Author
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Della Chiara, G, Gervasoni, F, Fakiola, M, Godano, C, D'Oria, C, Azzolin, L, Bonnal, R, Moreni, G, Drufuca, L, Rossetti, G, Ranzani, V, Bason, R, De Simone, M, Panariello, F, Ferrari, I, Fabbris, T, Zanconato, F, Forcato, M, Romano, O, Caroli, J, Gruarin, P, Sarnicola, M, Cordenonsi, M, Bardelli, A, Zucchini, N, Ceretti, A, Mariani, N, Cassingena, A, Sartore-Bianchi, A, Testa, G, Gianotti, L, Opocher, E, Pisati, F, Tripodo, C, Macino, G, Siena, S, Bicciato, S, Piccolo, S, Pagani, M, Della Chiara G., Gervasoni F., Fakiola M., Godano C., D'Oria C., Azzolin L., Bonnal R. J. P., Moreni G., Drufuca L., Rossetti G., Ranzani V., Bason R., De Simone M., Panariello F., Ferrari I., Fabbris T., Zanconato F., Forcato M., Romano O., Caroli J., Gruarin P., Sarnicola M. L., Cordenonsi M., Bardelli A., Zucchini N., Ceretti A. P., Mariani N. M., Cassingena A., Sartore-Bianchi A., Testa G., Gianotti L., Opocher E., Pisati F., Tripodo C., Macino G., Siena S., Bicciato S., Piccolo S., Pagani M., Della Chiara, G, Gervasoni, F, Fakiola, M, Godano, C, D'Oria, C, Azzolin, L, Bonnal, R, Moreni, G, Drufuca, L, Rossetti, G, Ranzani, V, Bason, R, De Simone, M, Panariello, F, Ferrari, I, Fabbris, T, Zanconato, F, Forcato, M, Romano, O, Caroli, J, Gruarin, P, Sarnicola, M, Cordenonsi, M, Bardelli, A, Zucchini, N, Ceretti, A, Mariani, N, Cassingena, A, Sartore-Bianchi, A, Testa, G, Gianotti, L, Opocher, E, Pisati, F, Tripodo, C, Macino, G, Siena, S, Bicciato, S, Piccolo, S, Pagani, M, Della Chiara G., Gervasoni F., Fakiola M., Godano C., D'Oria C., Azzolin L., Bonnal R. J. P., Moreni G., Drufuca L., Rossetti G., Ranzani V., Bason R., De Simone M., Panariello F., Ferrari I., Fabbris T., Zanconato F., Forcato M., Romano O., Caroli J., Gruarin P., Sarnicola M. L., Cordenonsi M., Bardelli A., Zucchini N., Ceretti A. P., Mariani N. M., Cassingena A., Sartore-Bianchi A., Testa G., Gianotti L., Opocher E., Pisati F., Tripodo C., Macino G., Siena S., Bicciato S., Piccolo S., and Pagani M.
- Abstract
Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues.
- Published
- 2021
5. 2235P Chemotherapy priming leads to hypermutability and immune surveillance in colorectal cancer
- Author
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Vitiello, P.P., Chilà, R., Battuello, P., Battaglieri, V., Amodio, V., Grasso, G., Rospo, G., Lamba, S., Pisati, F., Rousseau, B.J-C., Diaz, L.A., Crisafulli, G., Di Nicolantonio, F., Germano, G., and Bardelli, A.
- Published
- 2023
- Full Text
- View/download PDF
6. 1068P Fasting mimicking diet reduces anti-OX40/anti PD-L1 and anti-PD-1/anti-CTLA-4 cardiovascular side effects in melanoma and lung cancer models
- Author
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Cortellino, S., Quagliariello, V., Delfanti, G., O. blazevits, Chiodoni, C., Maurea, N., Di Mauro, A., Tatangelo, F., Pisati, F., A. shmahala, Lazzeri, S., Spagnolo, V., Visco, E., Tripodo, C., Casorati, G., Della Bona, P., and Longo, V.
- Published
- 2023
- Full Text
- View/download PDF
7. Pre- and Post-Zygotic TP53 De Novo Mutations in SHH-Medulloblastoma
- Author
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Azzollini, J, Schiavello, E, Buttarelli, F, Clerici, C, Tizzoni, L, Vecchi, G, Capra, F, Pisati, F, Biassoni, V, Runza, L, Carrabba, G, Giangaspero, F, Massimino, M, Pensotti, V, Manoukian, S, Azzollini, Jacopo, Schiavello, Elisabetta, Buttarelli, Francesca Romana, Clerici, Carlo Alfredo, Tizzoni, Laura, Vecchi, Giovanna De, Capra, Fabio, Pisati, Federica, Biassoni, Veronica, Runza, Letterio, Carrabba, Giorgio, Giangaspero, Felice, Massimino, Maura, Pensotti, Valeria, Manoukian, Siranoush, Azzollini, J, Schiavello, E, Buttarelli, F, Clerici, C, Tizzoni, L, Vecchi, G, Capra, F, Pisati, F, Biassoni, V, Runza, L, Carrabba, G, Giangaspero, F, Massimino, M, Pensotti, V, Manoukian, S, Azzollini, Jacopo, Schiavello, Elisabetta, Buttarelli, Francesca Romana, Clerici, Carlo Alfredo, Tizzoni, Laura, Vecchi, Giovanna De, Capra, Fabio, Pisati, Federica, Biassoni, Veronica, Runza, Letterio, Carrabba, Giorgio, Giangaspero, Felice, Massimino, Maura, Pensotti, Valeria, and Manoukian, Siranoush
- Abstract
Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder caused by mutations in the TP53 gene, predisposing to a wide spectrum of early-onset cancers, including brain tumors. In medulloblastoma patients, the role of TP53 has been extensively investigated, though the prevalence of de novo mutations has not been addressed. We characterized TP53 mutations in a monocentric cohort of consecutive Sonic Hedgehog (SHH)-activated medulloblastoma patients. Germline testing was offered based on tumor p53 immunostaining positivity. Among 24 patients, three (12.5%) showed tumor p53 overexpression, of whom two consented to undergo germline testing and resulted as carriers of TP53 mutations. In the first case, family history was uneventful and the mutation was not found in either of the parents. The second patient, with a family history suggestive of LFS, unexpectedly resulted as a carrier of the mosaic mutation c.742=/C>T p.(Arg248=/Trp). The allele frequency was 26% in normal tissues and 42–77% in tumor specimens. Loss of heterozygosity (LOH) in the tumor was also confirmed. Notably, the mosaic case has been in complete remission for more than one year, while the first patient, as most TP53-mutated medulloblastoma cases from other cohorts, showed a severe and rapidly progressive disease. Our study reported the first TP53 mosaic mutation in medulloblastoma patients and confirmed the importance of germline testing in p53 overexpressed SHH-medulloblastoma, regardless of family history.
- Published
- 2020
8. Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells
- Author
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Orzan, F., Pellegatta, S., Poliani, P. L., Pisati, F., Caldera, V., Menghi, F., Kapetis, D., Marras, C., Schiffer, D., and Finocchiaro, G.
- Published
- 2011
- Full Text
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9. ROLE OF SKIN DERIVED STEM CELLS IN PERIPHERAL NERVE REGENERATION
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Marchesi, C, Pluderi, M, Belicchi, M, Gavina, M, Meregalli, M, Draghi, L, Pisati, F, Gaini, S M, Bresolin, N, Grimoldi, N, and Torrente, Y
- Published
- 2005
10. Altered function of the glutamate–aspartate transporter GLAST, a potential therapeutic target in glioblastoma
- Author
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Corbetta, C, Di Ianni, N, Bruzzone, M, Patanè, M, Pollo, B, Cantini, G, Cominelli, M, Zucca, I, Pisati, F, Poliani, P, Finocchiaro, G, Pellegatta, S, Bruzzone, MG, Poliani, PL, Corbetta, C, Di Ianni, N, Bruzzone, M, Patanè, M, Pollo, B, Cantini, G, Cominelli, M, Zucca, I, Pisati, F, Poliani, P, Finocchiaro, G, Pellegatta, S, Bruzzone, MG, and Poliani, PL
- Abstract
In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate–aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration compared to GLAST-depleted glioma. Despite their GLAST expression, GBM stem-like cells (GSCs) released rather than taking up glutamate due to their lack of Na+/K+-ATPase. Overexpression of Na+/K+-ATPase in these cells restored glutamate uptake and induced apoptosis. The therapeutic relevance of targeting GLAST in gliomas was assessed using the inhibitor UCPH-101. In glioma-bearing mice, a single intratumoral injection of UCPH-101 significantly increased survival by decreasing GLAST expression and inducing apoptosis. Thus, GLAST has a novel role in GBM that appears to have crucial relevance in glutamate trafficking and may thus be a new therapeutic target.
- Published
- 2019
11. Human skin-derived stem cells inhibit brain tumor growth
- Author
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Acerbi, F, Giussani, C, Pisati, F, Carrabba, G, Belicchi, M, Lucini, V, Gaini, S, Bikfalvi, A, Torrente, Y, Bello, L, Acerbi F, Giussani C, Pisati F, Carrabba G, Belicchi M, Lucini V, Gaini SM, Bikfalvi A, Torrente Y, Bello L, Acerbi, F, Giussani, C, Pisati, F, Carrabba, G, Belicchi, M, Lucini, V, Gaini, S, Bikfalvi, A, Torrente, Y, Bello, L, Acerbi F, Giussani C, Pisati F, Carrabba G, Belicchi M, Lucini V, Gaini SM, Bikfalvi A, Torrente Y, and Bello L
- Published
- 2005
12. Human skin-derived stem cells inhibit brain tumor growth
- Author
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Acerbi, F, Giussani, C, Carrabba, G, Costa, F, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, Bello, L, Pisati F, Belicchi M, Acerbi, F, Giussani, C, Carrabba, G, Costa, F, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, Bello, L, Pisati F, and Belicchi M
- Published
- 2004
13. p63 Sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling.
- Author
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Memmi, E.M., Sanarico, A.G., Giacobbe, A., Peschiaroli, A., Frezza, V., Cicalese, A., Pisati, F., Tosoni, D., Zhou, Huiqing, Tonon, G., Antonov, A., Melino, G., Pelicci, P.G., Bernassola, F., Memmi, E.M., Sanarico, A.G., Giacobbe, A., Peschiaroli, A., Frezza, V., Cicalese, A., Pisati, F., Tosoni, D., Zhou, Huiqing, Tonon, G., Antonov, A., Melino, G., Pelicci, P.G., and Bernassola, F.
- Abstract
Item does not contain fulltext
- Published
- 2015
14. Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells
- Author
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Orzan, F, Pellegatta, S, Poliani, Pietro Luigi, Pisati, F, Caldera, V, Menghi, F, Kapetis, D, Marras, C, Schiffer, D, and Finocchiaro, G.
- Subjects
ENHANCER OF ZESTE 2 (EZH2) ,GLIOMAS ,CANCER STEM-LIKE CELLS - Published
- 2011
15. Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma
- Author
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Favaro, R, Appolloni, I, Pellegatta, S, Sanga, A, Pagella, P, Gambini, E, Pisati, F, Ottolenghi, S, Foti, M, Finocchiaro, G, Malatesta, P, Nicolis, S, FAVARO, REBECCA, PELLEGATTA, SERENA, GAMBINI, ELISA, OTTOLENGHI, SERGIO, FOTI, MARIA, NICOLIS, SILVIA KIRSTEN, Favaro, R, Appolloni, I, Pellegatta, S, Sanga, A, Pagella, P, Gambini, E, Pisati, F, Ottolenghi, S, Foti, M, Finocchiaro, G, Malatesta, P, Nicolis, S, FAVARO, REBECCA, PELLEGATTA, SERENA, GAMBINI, ELISA, OTTOLENGHI, SERGIO, FOTI, MARIA, and NICOLIS, SILVIA KIRSTEN
- Abstract
The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells.
- Published
- 2014
16. Erratum to “Fate of autologous dermal stem cells transplanted into the spinal cord after traumatic injury (TSCI)” [Neuroscience 125 (2004) 179–189]
- Author
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Gorio, A., primary, Torrente, Y., additional, Madaschi, L., additional, Di Stefano, A.B., additional, Pisati, F., additional, Marchesi, C., additional, Belicchi, M., additional, Di Giulio, A.M., additional, and Bresolin, N., additional
- Published
- 2014
- Full Text
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17. Rai is a New Regulator of Neural Progenitor Migration and Glioblastoma Invasion
- Author
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Ortensi, B, Osti, D, Pellegatta, S, Pisati, F, Brescia, P, Fornasari, L, Levi, D, Gaetani, P, Colombo, P, Ferri, A, Nicolis, S, Finocchiaro, G, Pelicci, G, FERRI, ANNA LUCIA MARIA, NICOLIS, SILVIA KIRSTEN, Pelicci, G., Ortensi, B, Osti, D, Pellegatta, S, Pisati, F, Brescia, P, Fornasari, L, Levi, D, Gaetani, P, Colombo, P, Ferri, A, Nicolis, S, Finocchiaro, G, Pelicci, G, FERRI, ANNA LUCIA MARIA, NICOLIS, SILVIA KIRSTEN, and Pelicci, G.
- Abstract
The invasive nature of glioblastoma is one important reason of treatment failure. Glioblastoma stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knock-down impairs progenitor migration to the olfactory bulb. Its expression is retained in glioblastoma stem/progenitor cells where it exerts the same promigratory activity. Rai-silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple signaling pathways, yet it always leads to reduced expression of proinvasive genes.
- Published
- 2012
18. Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models
- Author
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Pisati, F, Belicchi, M, Acerbi, F, Marchesi, C, Giussani, C, Gavina, M, Javerzat, S, Hagedorn, M, Carrabba, G, Lucini, V, Gaini, S, Bresolin, N, Bello, L, Bikfalvi, A, Torrente, Y, Gaini, SM, Torrente, Y., GIUSSANI, CARLO GIORGIO, Pisati, F, Belicchi, M, Acerbi, F, Marchesi, C, Giussani, C, Gavina, M, Javerzat, S, Hagedorn, M, Carrabba, G, Lucini, V, Gaini, S, Bresolin, N, Bello, L, Bikfalvi, A, Torrente, Y, Gaini, SM, Torrente, Y., and GIUSSANI, CARLO GIORGIO
- Abstract
Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-beta1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation
- Published
- 2007
19. Studio di inibitori endogeni di angiogenesi in un modello murino transgenico di tumore cerebrale.
- Author
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Colleoni, F, Pisati, F, Carrabba, G, Giussani, C, Acerbi, F, Bertani, G, Lucini, V, Pannacci, M, Scaglione, F, Pineau, R, Javerzat, S, Bikfalvi, A, Torrente, Y, Bello, L, Colleoni, F, Pisati, F, Carrabba, G, Giussani, C, Acerbi, F, Bertani, G, Lucini, V, Pannacci, M, Scaglione, F, Pineau, R, Javerzat, S, Bikfalvi, A, Torrente, Y, and Bello, L
- Published
- 2006
20. Human skin-derived stem cells interfer with brain tumor growth by reducing angiogenesis and invasion
- Author
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Borsa, S, Giussani, C, Acerbi, F, Carrabba, G, Costa, F, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, Bello, L, Borsa, S, Giussani, C, Acerbi, F, Carrabba, G, Costa, F, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, and Bello, L
- Published
- 2005
21. LAB-CELL BIOLOGY AND SIGNALING
- Author
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Kijima, N., primary, Hosen, N., additional, Kagawa, N., additional, Hashimoto, N., additional, Chiba, Y., additional, Kinoshita, M., additional, Sugiyama, H., additional, Yoshimine, T., additional, Kim, Y. Z., additional, Kim, K. H., additional, Lee, E. H., additional, Hu, B., additional, Sim, H., additional, Mohan, N., additional, Agudelo-Garcia, P., additional, Nuovo, G., additional, Cole, S., additional, Viapiano, M. S., additional, McFarland, B. C., additional, Hong, S. W., additional, Rajbhandari, R., additional, Twitty, G. B., additional, Kenneth Gray, G., additional, Yu, H., additional, Langford, C. P., additional, Yancey Gillespie, G., additional, Benveniste, E. N., additional, Nozell, S. E., additional, Nitta, R., additional, Mitra, S., additional, Bui, T., additional, Li, G., additional, Munoz, J. L., additional, Rodriguez-Cruz, V., additional, Rameshwar, P., additional, See, W. L., additional, Mukherjee, J., additional, Shannon, K. M., additional, Pieper, R. O., additional, Floyd, D. H., additional, Xiao, A., additional, Purow, B. W., additional, Lavon, I., additional, Zrihan, D., additional, Refael, M., additional, Bier, A., additional, Canello, T., additional, Siegal, T., additional, Granit, A., additional, Xie, Q., additional, Wang, X., additional, Gong, Y., additional, Mao, Y., additional, Chen, X., additional, Zhou, L., additional, Lee, S. X., additional, Tunkyi, A., additional, Wong, E. T., additional, Swanson, K. D., additional, Zhang, K., additional, Chen, L., additional, Zhang, J., additional, Shi, Z., additional, Han, L., additional, Pu, P., additional, Kang, C., additional, Cho, W. H., additional, Ogawa, D., additional, Godlewski, J., additional, Bronisz, A., additional, Antonio Chiocca, E., additional, Mustafa, D. A. M., additional, Sieuwerts, A. M., additional, Smid, M., additional, de Weerd, V., additional, Martens, J. W., additional, Foekens, J. A., additional, Kros, J. M., additional, McCulloch, C., additional, Graff, J., additional, Sui, Y., additional, Dinn, S., additional, Huang, Y., additional, Li, Q., additional, Fiona, G., additional, Nakashima, H., additional, Leiss, L., additional, Manini, I., additional, Enger, P. O., additional, Yang, C., additional, Iyer, R., additional, Yu, A. C. H., additional, Li, S., additional, Ikejiri, B. L., additional, Zhuang, Z., additional, Lonser, R., additional, Massoud, T. F., additional, Paulmurugan, R., additional, Gambhir, S. S., additional, Merrill, M. J., additional, Sun, M., additional, Chen, M., additional, Edwards, N. A., additional, Shively, S. B., additional, Lonser, R. R., additional, Baia, G. S., additional, Caballero, O. L., additional, Orr, B. A., additional, Lal, A., additional, Ho, J. S., additional, Cowdrey, C., additional, Tihan, T., additional, Mawrin, C., additional, Riggins, G. J., additional, Lu, D., additional, Leo, C., additional, Wheeler, H., additional, McDonald, K., additional, Schulte, A., additional, Zapf, S., additional, Stoupiec, M., additional, Kolbe, K., additional, Riethdorf, S., additional, Westphal, M., additional, Lamszus, K., additional, Timmer, M., additional, Rohn, G., additional, Koch, A., additional, Goldbrunner, R., additional, Ruggieri, R., additional, Vanan, I., additional, Dong, Z., additional, Sarkaria, J. N., additional, Tran, N. L., additional, Berens, M. E., additional, Symons, M., additional, Rowther, F. B., additional, Dawson, T., additional, Ashton, K., additional, Darling, J., additional, Warr, T., additional, Okamoto, M., additional, Palanichamy, K., additional, Gordon, N., additional, Patel, D., additional, Walston, S., additional, Krishanan, T., additional, Chakravarti, A., additional, Kalinina, J., additional, Carroll, A., additional, Wang, L., additional, Yu, Q., additional, Mancheno, D. E., additional, Wu, S., additional, Liu, F., additional, Ahn, J., additional, He, M., additional, Mao, H., additional, Van Meir, E. G., additional, Debinski, W., additional, Gonzales, O., additional, Beauchamp, A., additional, Gibo, D. M., additional, Seals, D. F., additional, Speranza, M. C., additional, Frattini, V., additional, Kapetis, D., additional, Pisati, F., additional, Eoli, M., additional, Pellegatta, S., additional, Finocchiaro, G., additional, Maherally, Z., additional, Smith, J. R., additional, Pilkington, G. J., additional, Zhu, W., additional, Wang, Q., additional, Clark, P. A., additional, Yang, S.-S., additional, Lin, S.-H., additional, Kahle, K. T., additional, Kuo, J. S., additional, Sun, D., additional, Hossain, M. B., additional, Cortes-Santiago, N., additional, Gururaj, A., additional, Thomas, J., additional, Gabrusiewicz, K., additional, Gumin, J., additional, Xipell, E., additional, Lang, F., additional, Fueyo, J., additional, Yung, W. K. A., additional, Gomez-Manzano, C., additional, Cook, N. J., additional, Lawrence, J. E., additional, Rovin, R. A., additional, Belton, R. J., additional, Winn, R. J., additional, Ferluga, S., additional, Lee, S.-H., additional, Khwaja, F. W., additional, Zerrouqi, A., additional, Devi, N. S., additional, Drucker, K. L., additional, Lee, H. K., additional, Finniss, S., additional, Cazacu, S., additional, Poisson, L., additional, Xiang, C., additional, Rempel, S. A., additional, Mikkelsen, T., additional, Brodie, C., additional, Shen, J., additional, Kenchappa, R. S., additional, Valadez, J. G., additional, Cooper, M. K., additional, Carter, B. D., additional, Forsyth, P. A., additional, Lee, J. S., additional, Erdreich-Epstein, A., additional, Song, H.-R., additional, Lawn, S., additional, Kenchappa, R., additional, Forsyth, P., additional, Lim, K. J., additional, Bar, E. E., additional, Eberhart, C. G., additional, Blough, M., additional, Alnajjar, M., additional, Chesnelong, C., additional, Weiss, S., additional, Chan, J., additional, Cairncross, G., additional, Wykosky, J., additional, Cavenee, W., additional, Furnari, F., additional, Brown, K. E., additional, Keir, S. T., additional, Sampson, J. H., additional, Bigner, D. D., additional, Kwatra, M. M., additional, Kotipatruni, R. P., additional, Thotala, D. K., additional, Jaboin, J., additional, Taylor, T. E., additional, Schinzel, A. C., additional, Hahn, W. C., additional, Cavenee, W. K., additional, Furnari, F. B., additional, Kapoor, G. S., additional, Macyszyn, L., additional, Bi, Y., additional, Fetting, H., additional, Poptani, H., additional, Ittyerah, R., additional, Davuluri, R. V., additional, O'Rourke, D., additional, Pitter, K. L., additional, Hosni-Ahmed, A., additional, Colevas, K., additional, Holland, E. C., additional, Jones, T. S., additional, Malhotra, A., additional, Potts, C., additional, Fernandez-Lopez, A., additional, Kenney, A. M., additional, Cheng, S., additional, Feng, H., additional, Jarzynka, M. J., additional, Li, Y., additional, Keezer, S., additional, Johns, T. G., additional, Hamilton, R. L., additional, Vuori, K., additional, Nishikawa, R., additional, Fenton, T., additional, Cheng, T., additional, Mikheev, A. M., additional, Mikheeva, S. A., additional, Silber, J. R., additional, Horner, P. J., additional, Rostomily, R., additional, Henson, E. S., additional, Brown, M., additional, Eisenstat, D. D., additional, Gibson, S. B., additional, Price, R. L., additional, Song, J., additional, Bingmer, K., additional, Oglesbee, M., additional, Cook, C., additional, Kwon, C.-H., additional, Nguyen, T. T., additional, Chiocca, E. A., additional, Lukiw, W. J., additional, Culicchia, F., additional, Jones, B. M., additional, Zhao, Y., additional, and Bhattacharjee, S., additional
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- 2012
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22. LAB-IMMUNOLOGY RESEARCH
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Fujita, M., primary, Zhang, R., additional, Nakata, S., additional, Kuzushima, K., additional, Wainwright, D. A., additional, Balyasnikova, I. V., additional, Auffinger, B., additional, Ahmed, A. U., additional, Han, Y., additional, Lesniak, M. S., additional, Knight, A., additional, Arnouk, H., additional, Gillespie, G. Y., additional, Britt, W., additional, Su, Y., additional, Lowdell, M. W., additional, Lamb, L. S., additional, Wang, J., additional, Leiss, L., additional, Choi, B. D., additional, Kuan, C.-T., additional, Cai, M., additional, Bigner, D. D., additional, Sampson, J. H., additional, Shibahara, I., additional, Saito, R., additional, Kanamori, M., additional, Sonoda, Y., additional, Kumabe, T., additional, Kikuchi, T., additional, So, T., additional, Ishii, N., additional, Tominaga, T., additional, Zhang, L., additional, Wang, H., additional, Zhang, I., additional, Chen, X., additional, Da Fonseca, A., additional, Fan, H., additional, Badie, B., additional, Sayour, E. J., additional, McLendon, P., additional, Reynolds, R., additional, McLendon, R., additional, Mitchell, D. A., additional, Sanchez-Perez, L., additional, Pham, C., additional, Snyder, D., additional, Xie, W., additional, Cui, X., additional, McConnell, M. J., additional, Broadley, K. W., additional, Farrand, K., additional, Authier, A., additional, Brown, J. H., additional, Hunn, M., additional, Hermans, I., additional, Cantini, G., additional, Pisati, F., additional, Pessina, S., additional, Finocchiaro, G., additional, Pellegatta, S., additional, Yeung, J. T., additional, Hamilton, R., additional, Pollack, I., additional, Jakacki, R., additional, Okada, H., additional, Choi, B., additional, Schmittling, R. J., additional, Flores, C., additional, Johnson, L., additional, Archer, G. A., additional, Raychaudhuri, B., additional, Rayman, P., additional, Huang, P., additional, Ireland, J., additional, Donnola, S., additional, Hamburdzumyan, D., additional, Finke, J., additional, Vogelbaum, M. A., additional, Batich, K., additional, Reap, E., additional, Archer, G., additional, Sampson, J., additional, Mitchell, D., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Cohen, K. J., additional, Pardoll, D. M., additional, Drake, C. G., additional, Lim, M., additional, Rutledge, W. C., additional, Kong, J., additional, Gao, J., additional, Gutman, D. A., additional, Cooper, L. A., additional, Chisolm, C., additional, Scarpace, L., additional, Mikkelsen, T., additional, Saltz, J. H., additional, Moreno, C. S., additional, Brat, D. J., additional, Everson, R. G., additional, Lisiero, D. N., additional, Soto, H., additional, Liau, L. M., additional, Prins, R. M., additional, Gonzalez, G. C., additional, Chae, M., additional, Peterson, T. E., additional, Parney, I. F., additional, and Johnson, A. J., additional
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- 2012
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23. Human skin-derived stem cells inhibit brain tumor growth.
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Giussani, C, Carrabba, G, Pluderi, M, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, Bello, L, Giussani, C, Carrabba, G, Pluderi, M, Pisati, F, Belicchi, M, Lucini, V, Bikfalvi, A, Torrente, Y, and Bello, L
- Published
- 2004
24. Immunology Research
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Wu, A., primary, Wei, J., additional, Kong, L.-Y., additional, Wang, Y., additional, Priebe, W., additional, Sawaya, R., additional, Heimberger, A. B., additional, Wu, A., additional, Heimberger, A., additional, Doucette, T., additional, Yang, J., additional, Rao, G., additional, Shimato, S., additional, Meier, L. M., additional, Castelli, M., additional, Canoll, P., additional, Asslaber, M., additional, Bruce, J. N., additional, Anderson, D. E., additional, Anderson, R. C., additional, Mahlum, E. W., additional, Jenkins, R. B., additional, Kohanbash, G., additional, Mintz, A. H., additional, McKaveney, K., additional, McDonald, H. A., additional, Ohlfest, J. R., additional, Okada, H., additional, Fujita, M., additional, Zhang, L., additional, Liu, W., additional, Alizadeh, D., additional, Zhao, D., additional, Farrukh, O., additional, Badie, B., additional, Raychaudhuri, B., additional, Pellegatta, S., additional, Cantini, G., additional, Pisati, F., additional, Cuppini, L., additional, Finocchiaro, G., additional, Albesiano, E., additional, Han, J. E., additional, See, A., additional, Jackson, C., additional, Lim, M., additional, Nag, K., additional, White, J., additional, Sippel, T., additional, Klaassen, M., additional, Tsvankin, V., additional, Waziri, A., additional, Mittal, S., additional, Zitron, I. M., additional, Kupsky, W. J., additional, Alkonyi, B., additional, Sood, S., additional, and Juhasz, C., additional
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- 2010
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25. Autologous Transplantation of Muscle-Derived CD133+ Stem Cells in Duchenne Muscle Patients
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Torrente, Y., primary, Belicchi, M., additional, Marchesi, C., additional, D'antona, G., additional, Cogiamanian, F., additional, Pisati, F., additional, Gavina, M., additional, Giordano, R., additional, Tonlorenzi, R., additional, Fagiolari, G., additional, Lamperti, C., additional, Porretti, L., additional, Lopa, R., additional, Sampaolesi, M., additional, Vicentini, L., additional, Grimoldi, N., additional, Tiberio, F., additional, Songa, V., additional, Baratta, P., additional, Prelle, A., additional, Forzenigo, L., additional, Guglieri, M., additional, Pansarasa, O., additional, Rinaldi, C., additional, Mouly, V., additional, Butler-Browne, G. S., additional, Comi, G. P., additional, Biondetti, P., additional, Moggio, M., additional, Gaini, S. M., additional, Stocchetti, N., additional, Priori, A., additional, D'angelo, M. G., additional, Turconi, A., additional, Bottinelli, R., additional, Cossu, G., additional, Rebulla, P., additional, and Bresolin, N., additional
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- 2007
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26. Fate of autologous dermal stem cells transplanted into the spinal cord after traumatic injury (TSCI)
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Gorio, A, primary, Torrente, Y, additional, Madaschi, L, additional, Di Stefano, A.B, additional, Pisati, F, additional, Marchesi, C, additional, Belicchi, M, additional, Di Giulio, A.M, additional, and Bresolin, N, additional
- Published
- 2004
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27. Tumor Necrosis Factor-α (TNF-α) Stimulates Chemotactic Response in Mouse Myogenic Cells
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Torrente, Y., primary, Fahime, E. El, additional, Caron, N. J., additional, Del Bo, R., additional, Belicchi, M., additional, Pisati, F., additional, Tremblay, J. P., additional, and Bresolin, N., additional
- Published
- 2003
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28. Enhancer of Zeste 2 (EZH2) is up?regulated in malignant gliomas and in glioma stem?like cells.
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Orzan, F., Pellegatta, S., Poliani, P. L., Pisati, F., Caldera, V., Menghi, F., Kapetis, D., Marras, C., Schiffer, D., and Finocchiaro, G.
- Subjects
GLIOMAS ,PROTEINS ,ONCOGENIC viruses ,IMMUNOHISTOCHEMISTRY ,NEUROLOGICAL disorders - Abstract
F. Orzan, S. Pellegatta, P. L. Poliani, F. Pisati, V. Caldera, F. Menghi, D. Kapetis, C. Marras, D. Schiffer and G. Finocchiaro (2011) Neuropathology and Applied Neurobiology 381-394 ? Proteins of the Polycomb repressive complex 2 (PRC2) are epigenetic gene silencers and are involved in tumour development. Their oncogenic function might be associated with their role in stem cell maintenance. The histone methyltransferase Enhancer of Zeste 2 ( EZH2) is a key member of PRC2 function: we have investigated its expression and function in gliomas. EZH2 expression was studied in grade II-IV gliomas and in glioma stem?like cells (GSC) by quantitative PCR and immunohistochemistry. Effects of EZH2 down?regulation were analysed by treating GSC with the histone deacetylase (HDAC) inhibitor suberoylanide hydroxamic acid (SAHA) and by shRNA. DNA microarray analysis showed that EZH2 is highly expressed in murine and human GSC. Real?time PCR on gliomas of different grade ( n?=?66) indicated that EZH2 is more expressed in glioblastoma multiforme (GBM) than in low?grade gliomas ( P?=?0.0013). This was confirmed by immunohistochemistry on an independent set of 106 gliomas. Treatment with SAHA caused significant up?regulation of PRC2 predicted target genes, GSC disruption and decreased expression of EZH2 and of the stem cell marker CD133. Inhibition of EZH2 expression by shRNA was associated with a significant decrease of glioma proliferation. The data suggest that EZH2 plays a role in glioma progression and encourage the therapeutic targeting of these malignancies by HDAC inhibitors. [ABSTRACT FROM AUTHOR]
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- 2011
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29. Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients
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Torrente, Y., Belicchi, M., Marchesi, C., D Antona, G., Cogiamanian, F., Pisati, F., Gavina, M., Giordano, R., Tonlorenzi, R., Fagiolari, G., Lamperti, C., Porretti, L., Lopa, R., Sampaolesi, M., Vicentini, L., Grimoldi, N., Tiberio, F., Songa, V., Baratta, P., Prelle, A., Forzenigo, L., Guglieri, M., Pansarasa, O., Rinaldi, C., Vincent Mouly, Butler-Browne, G. S., Comi, G. P., Biondetti, P., Moggio, M., Gaini, S. M., Stocchetti, N., Priori, A., D Angelo, M. G., Turconi, A., Bottinelli, R., Cossu, G., Rebulla, P., and Bresolin, N.
30. GLAST (GLUTAMATE ASPARTATE TRANSPORTER), A POTENTIAL MARKER FOR GLIOMA IMMUNOTHERAPY
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Pellegatta, S., Stucchi, E., Pisati, F., Pietro Luigi POLIANI, Cuppini, L., and Finocchiaro, G.
31. Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
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Giulia Della Chiara, Andrea Cassingena, Valeria Ranzani, Andrea Pisani Ceretti, Francesca Zanconato, Paola Gruarin, Grazisa Rossetti, Michaela Fakiola, Luca Gianotti, Luca Azzolin, Giulia Moreni, Ivan Ferrari, Oriana Romano, N. Mariani, Tanya Fabbris, Alberto Bardelli, Claudio Tripodo, Claudia D'Oria, Lorenzo Drufuca, Chiara Godano, Salvatore Siena, Massimiliano Pagani, Ramona Bason, Maria Lucia Sarnicola, Andrea Sartore-Bianchi, Enrico Opocher, Michelangelo Cordenonsi, Jimmy Caroli, Francesco Panariello, Federica Pisati, Marco De Simone, Stefano Piccolo, Silvio Bicciato, Nicola Zucchini, Giuseppe Testa, Mattia Forcato, Raoul J. P. Bonnal, Giuseppe Macino, Federica Gervasoni, Graduate School, Medical Microbiology and Infection Prevention, Della Chiara, G, Gervasoni, F, Fakiola, M, Godano, C, D'Oria, C, Azzolin, L, Bonnal, R, Moreni, G, Drufuca, L, Rossetti, G, Ranzani, V, Bason, R, De Simone, M, Panariello, F, Ferrari, I, Fabbris, T, Zanconato, F, Forcato, M, Romano, O, Caroli, J, Gruarin, P, Sarnicola, M, Cordenonsi, M, Bardelli, A, Zucchini, N, Ceretti, A, Mariani, N, Cassingena, A, Sartore-Bianchi, A, Testa, G, Gianotti, L, Opocher, E, Pisati, F, Tripodo, C, Macino, G, Siena, S, Bicciato, S, Piccolo, S, Pagani, M, Della Chiara G., Gervasoni F., Fakiola M., Godano C., D'Oria C., Azzolin L., Bonnal R.J.P., Moreni G., Drufuca L., Rossetti G., Ranzani V., Bason R., De Simone M., Panariello F., Ferrari I., Fabbris T., Zanconato F., Forcato M., Romano O., Caroli J., Gruarin P., Sarnicola M.L., Cordenonsi M., Bardelli A., Zucchini N., Ceretti A.P., Mariani N.M., Cassingena A., Sartore-Bianchi A., Testa G., Gianotti L., Opocher E., Pisati F., Tripodo C., Macino G., Siena S., Bicciato S., Piccolo S., and Pagani M.
- Subjects
0301 basic medicine ,Organoid ,Epigenomics ,Transcription Factor ,General Physics and Astronomy ,Colorectal Neoplasm ,Adaptor Proteins, Signal Transducing ,Colorectal Neoplasms ,Gene Expression Regulation, Neoplastic ,Histone Code ,Humans ,Models, Genetic ,Organoids ,RNA-Seq ,Single-Cell Analysis ,Trans-Activators ,Transcription Factors ,Tumor Cells, Cultured ,Enhancer Elements, Genetic ,Epigenesis, Genetic ,0302 clinical medicine ,Models ,Adaptor Proteins, Signal Transducing, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic,Histone Code, Humans, Models, Genetic, Organoids, RNA-Seq, Single-Cell Analysis, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, Enhancer Elements, Genetic, Epigenesis, Genetic ,Cancer genomics ,Histone code ,Transcriptional Coactivator with PDZ-Binding Motif Proteins ,YAP-Signaling Proteins ,Multidisciplinary ,Cultured ,Adaptor Proteins ,3. Good health ,Chromatin ,Tumor Cells ,Single-Cell Analysi ,Trans-Activator ,030220 oncology & carcinogenesis ,Human ,Enhancer Elements ,Science ,Tumour heterogeneity ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Genetic ,medicine ,Epigenetics ,Enhancer ,Transcription factor ,Neoplastic ,Signal Transducing ,Cancer ,General Chemistry ,medicine.disease ,Colorectal cancer ,digestive system diseases ,030104 developmental biology ,Gene Expression Regulation ,Cancer cell ,Cancer research ,Epigenesis - Abstract
Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues., The role of epigenetic deregulation in colorectal cancer (CRC) is not fully understood yet. Here the authors use patient-derived organoids, epigenomics and single-cell RNA-seq to reveal that YAP/TAZ are key regulators that bind to active enhancers in CRC and promote tumour survival.
- Published
- 2021
32. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence
- Author
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Ubaldo Gioia, Sara Tavella, Pamela Martínez-Orellana, Giada Cicio, Andrea Colliva, Marta Ceccon, Matteo Cabrini, Ana C. Henriques, Valeria Fumagalli, Alessia Paldino, Ettore Presot, Sreejith Rajasekharan, Nicola Iacomino, Federica Pisati, Valentina Matti, Sara Sepe, Matilde I. Conte, Sara Barozzi, Zeno Lavagnino, Tea Carletti, Maria Concetta Volpe, Paola Cavalcante, Matteo Iannacone, Chiara Rampazzo, Rossana Bussani, Claudio Tripodo, Serena Zacchigna, Alessandro Marcello, Fabrizio d’Adda di Fagagna, Gioia U., Tavella S., Martinez-Orellana P., Cicio G., Colliva A., Ceccon M., Cabrini M., Henriques A.C., Fumagalli V., Paldino A., Presot E., Rajasekharan S., Iacomino N., Pisati F., Matti V., Sepe S., Conte M.I., Barozzi S., Lavagnino Z., Carletti T., Volpe M.C., Cavalcante P., Iannacone M., Rampazzo C., Bussani R., Tripodo C., Zacchigna S., Marcello A., and d'Adda di Fagagna F.
- Subjects
SARS-COV-2 infection ,Cell Biology ,Settore MED/08 - Anatomia Patologica - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs’ biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence.
- Published
- 2023
33. PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State
- Author
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Brenda J. Green, Margherita Marazzini, Ben Hershey, Amir Fardin, Qingsen Li, Zongjie Wang, Giovanni Giangreco, Federica Pisati, Stefano Marchesi, Andrea Disanza, Emanuela Frittoli, Emanuele Martini, Serena Magni, Galina V. Beznoussenko, Claudio Vernieri, Riccardo Lobefaro, Dario Parazzoli, Paolo Maiuri, Kristina Havas, Mahmoud Labib, Sara Sigismund, Pier Paolo Di Fiore, Rosalind H. Gunby, Shana O. Kelley, Giorgio Scita, Green, Bj, Marazzini, M, Hershey, B, Fardin, A, Li, Q, Wang, Z, Giangreco, G, Pisati, F, Marchesi, S, Disanza, A, Frittoli, E, Martini, E, Magni, S, Beznoussenko, Gv, Vernieri, C, Lobefaro, R, Parazzoli, D, Maiuri, P, Havas, K, Labib, M, Sigismund, S, Fiore, Ppd, Gunby, Rh, Kelley, So, and Scita, G.
- Subjects
Breast Neoplasms ,Cell Separation ,General Chemistry ,Neoplastic Cells, Circulating ,Prognosis ,Biomaterials ,Mice ,Cell Line, Tumor ,Lab-On-A-Chip Devices ,Animals ,Humans ,Female ,General Materials Science ,Biotechnology - Abstract
Circulating tumor cell (CTC) clusters are associated with increased metastatic potential and worse patient prognosis, but are rare, difficult to count, and poorly characterized biophysically. The PillarX device described here is a bimodular microfluidic device (Pillar-device and an X-magnetic device) to profile single CTCs and clusters from whole blood based on their size, deformability, and epithelial marker expression. Larger, less deformable clusters and large single cells are captured in the Pillar-device and sorted according to pillar gap sizes. Smaller, deformable clusters and single cells are subsequently captured in the X-device and separated based on epithelial marker expression using functionalized magnetic nanoparticles. Clusters of established and primary breast cancer cells with variable degrees of cohesion driven by different cell-cell adhesion protein expression are profiled in the device. Cohesive clusters exhibit a lower deformability as they travel through the pillar array, relative to less cohesive clusters, and have greater collective invasive behavior. The ability of the PillarX device to capture clusters is validated in mouse models and patients of metastatic breast cancer. Thus, this device effectively enumerates and profiles CTC clusters based on their unique geometrical, physical, and biochemical properties, and could form the basis of a novel prognostic clinical tool.
- Published
- 2022
34. Intra-tumour heterogeneity of diffuse large B-cell lymphoma involves the induction of diversified stroma-tumour interfaces
- Author
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Maurilio Ponzoni, Cesare Valenti, Claudia Chiodoni, Sabina Sangaletti, Maria Carmela Vegliante, Laura Botti, Claudio Tripodo, Celeste Rizzello, Mario P. Colombo, Arianna Di Napoli, Paola Portararo, Davide Vacca, Federica Pisati, Alessandro Gulino, Federica Zanardi, Valeria Cancila, Fabio Iannelli, Sangaletti S., Iannelli F., Zanardi F., Cancila V., Portararo P., Botti L., Vacca D., Chiodoni C., Di Napoli A., Valenti C., Rizzello C., Vegliante M.C., Pisati F., Gulino A., Ponzoni M., Colombo M.P., and Tripodo C.
- Subjects
0301 basic medicine ,diffuse large B-cell lymphoma ,digital spatial profiling ,intra-tumour heterogeneity ,microenvironment ,SPARC ,lcsh:Medicine ,Mice ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Tumor Microenvironment ,In Situ Hybridization ,lcsh:R5-920 ,Matricellular protein ,General Medicine ,Diffuse large B-cell lymphoma ,Prognosis ,Gene Expression Regulation, Neoplastic ,Phenotype ,030220 oncology & carcinogenesis ,Lymphoma, Large B-Cell, Diffuse ,lcsh:Medicine (General) ,Research Paper ,Stromal cell ,Microenvironment ,Tumour heterogeneity ,Biology ,Settore MED/08 - Anatomia Patologica ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Immunophenotyping ,Genetic Heterogeneity ,03 medical and health sciences ,Immune system ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Epigenetics ,Sequence Analysis, RNA ,Gene Expression Profiling ,lcsh:R ,Mesenchymal stem cell ,Computational Biology ,Digital spatial profiling ,medicine.disease ,Intra-tumour heterogeneity ,Disease Models, Animal ,030104 developmental biology ,Cancer research ,Neoplastic cell ,Stromal Cells ,Transcriptome - Abstract
Background Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown. Methods Combining in situ quantitative immunophenotypical analyses and RNA sequencing we investigated the intra-tumour heterogeneity and the specific mesenchymal modifications that are associated with A20 diffuse large B-cell lymphoma (DLBCL) cells seeding of different tissue microenvironments. Furthermore, we characterized features of lymphoma-associated stromatogenesis in human DLBCL samples using Digital Spatial Profiling, and established their relationship with prognostically relevant variables, such as MYC. Findings We found that the tissue microenvironment casts a relevant influence over A20 transcriptional landscape also impacting on Myc and DNA damage response programs. Extending the investigation to mice deficient for the matricellular protein SPARC, a stromal prognostic factor in human DLBCL, we demonstrated a different immune imprint on A20 cells according to stromal Sparc proficiency. Through Digital Spatial Profiling of 87 immune and stromal genes on human nodal DLBCL regions characterized by different mesenchymal composition, we demonstrate intra-lesional heterogeneity arising from diversified mesenchymal contextures and impacting on the stromal and immune milieu. Interpretation Our study provides experimental evidence that stromal microenvironment generates topological determinants of intra-tumour heterogeneity in DLBCL involving key transcriptional pathways such as Myc expression, damage response programs and immune checkpoints. Funding This study has been supported by the Italian Foundation for Cancer Research (AIRC) (grants 15999 and 22145 to C. Tripodo) and by the University of Palermo.
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- 2020
35. Altered function of the glutamate–aspartate transporter GLAST, a potential therapeutic target in glioblastoma
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Monica Patanè, Federica Pisati, Bianca Pollo, Pietro Luigi Poliani, Manuela Cominelli, Ileana Zucca, Gaetano Finocchiaro, Cristina Corbetta, Serena Pellegatta, Gabriele Cantini, Maria Grazia Bruzzone, Natalia Di Ianni, Corbetta, C, Di Ianni, N, Bruzzone, M, Patanè, M, Pollo, B, Cantini, G, Cominelli, M, Zucca, I, Pisati, F, Poliani, P, Finocchiaro, G, and Pellegatta, S
- Subjects
Cancer Research ,Amino Acid Transport System X-AG ,Glutamic Acid ,Apoptosis ,glutamate ,STAT3 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Glioma ,medicine ,Glutamate aspartate transporter ,Animals ,Humans ,Benzopyrans ,GLAST/EAAT1 ,Aspartic Acid ,biology ,Chemistry ,Cell Membrane ,glioblastoma ,UCPH-101 ,Glutamate receptor ,Transporter ,medicine.disease ,nervous system diseases ,Excitatory Amino Acid Transporter 1 ,Mice, Inbred C57BL ,Protein Transport ,Oncology ,Astrocytes ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,Sodium-Potassium-Exchanging ATPase ,Function (biology) ,Glioblastoma - Abstract
In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate-aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration compared to GLAST-depleted glioma. Despite their GLAST expression, GBM stem-like cells (GSCs) released rather than taking up glutamate due to their lack of Na+/K+-ATPase. Overexpression of Na+/K+-ATPase in these cells restored glutamate uptake and induced apoptosis. The therapeutic relevance of targeting GLAST in gliomas was assessed using the inhibitor UCPH-101. In glioma-bearing mice, a single intratumoral injection of UCPH-101 significantly increased survival by decreasing GLAST expression and inducing apoptosis. Thus, GLAST has a novel role in GBM that appears to have crucial relevance in glutamate trafficking and may thus be a new therapeutic target.
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- 2019
36. Rai is a New Regulator of Neural Progenitor Migration and Glioblastoma Invasion
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Daniel Levi, Giuliana Pelicci, Serena Pellegatta, Daniela Osti, Lorenzo Fornasari, Paolo Gaetani, Barbara Ortensi, Silvia K. Nicolis, Anna Ferri, Gaetano Finocchiaro, Piergiuseppe Colombo, Paola Brescia, Federica Pisati, Ortensi, B, Osti, D, Pellegatta, S, Pisati, F, Brescia, P, Fornasari, L, Levi, D, Gaetani, P, Colombo, P, Ferri, A, Nicolis, S, Finocchiaro, G, and Pelicci, G
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Cell Survival ,Src Homology 2 Domain-Containing, Transforming Protein 3 ,Nerve Tissue Proteins ,Biology ,Mice ,Neural Stem Cells ,Cell Movement ,Cancer stem cell ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,Animals ,Humans ,Neoplasm Invasiveness ,Progenitor cell ,glioblastoma, cancer stem cells, glioma stem cells, invasiveness ,Interleukin 3 ,Progenitor ,Mice, Knockout ,Cell migration ,Cell Biology ,Olfactory Bulb ,Neural stem cell ,Neoplasm Proteins ,Cell biology ,Gene Expression Regulation, Neoplastic ,Endothelial stem cell ,Shc Signaling Adaptor Proteins ,Neoplastic Stem Cells ,Molecular Medicine ,Glioblastoma ,Developmental Biology ,Adult stem cell - Abstract
The invasive nature of glioblastoma is one important reason of treatment failure. Glioblastoma stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knock-down impairs progenitor migration to the olfactory bulb. Its expression is retained in glioblastoma stem/progenitor cells where it exerts the same promigratory activity. Rai-silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple signaling pathways, yet it always leads to reduced expression of proinvasive genes.
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- 2012
37. Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models
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Sergio M. Gaini, Carlo Giussani, Lorenzo Bello, Giorgio Carrabba, Yvan Torrente, Valeria Lucini, Francesco Acerbi, Marzia Belicchi, Andreas Bikfalvi, Federica Pisati, Nereo Bresolin, C. Marchesi, Martin Hagedorn, Sophie Javerzat, M. Gavina, Pisati, F, Belicchi, M, Acerbi, F, Marchesi, C, Giussani, C, Gavina, M, Javerzat, S, Hagedorn, M, Carrabba, G, Lucini, V, Gaini, S, Bresolin, N, Bello, L, Bikfalvi, A, and Torrente, Y
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Cancer Research ,Pathology ,medicine.medical_specialty ,Human Skin-Derived Stem Cell ,Brain tumor ,Mice, Nude ,Mice, Transgenic ,Cell Growth Processes ,Chick Embryo ,Biology ,Chorioallantoic Membrane ,Transforming Growth Factor beta1 ,Mice ,chemistry.chemical_compound ,Cell Line, Tumor ,Brain Tumor ,Glioma ,medicine ,Animals ,Humans ,Autologous transplantation ,Neoplasm Invasiveness ,Skin ,Neovascularization, Pathologic ,Brain Neoplasms ,Stem Cells ,Mesenchymal stem cell ,medicine.disease ,Xenograft Model Antitumor Assays ,Neural stem cell ,Vascular endothelial growth factor ,medicine.anatomical_structure ,Oncology ,chemistry ,Pericyte ,Stem cell ,Glioblastoma ,Stem Cell Transplantation - Abstract
Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-β1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation. [Cancer Res 2007;67(7):3054–63]
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- 2007
38. Fate of autologous dermal stem cells transplanted into the spinal cord after traumatic injury (TSCI)
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C. Marchesi, A.B. Di Stefano, A.M. Di Giulio, Alfredo Gorio, Federica Pisati, Yvan Torrente, Nereo Bresolin, Marzia Belicchi, L. Madaschi, GORIO A, TORRENTE Y, MADASCHI L, DI STEFANO AB, PISATI F, MARCHESI C, BELICCHI M, DI GIULIO AM, and BRESOLIN N
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Male ,Pathology ,medicine.medical_specialty ,Time Factors ,timing of transplantation ,Neurofilament ,Cellular differentiation ,Blotting, Western ,stem cell migration ,Polymerase Chain Reaction ,Rats, Sprague-Dawley ,Cell Movement ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,stem cell differentiation ,Spinal Cord Injuries ,Neurons ,recovery from disability ,Glial fibrillary acidic protein ,biology ,Stem Cells ,General Neuroscience ,Cell Differentiation ,Dermis ,Recovery of Function ,Nestin ,Rats ,Transplantation ,medicine.anatomical_structure ,Immunology ,Settore BIO/14 - Farmacologia ,biology.protein ,Settore MED/26 - Neurologia ,Neuron ,Antibody ,Stem cell ,Stem Cell Transplantation - Abstract
Rat dermis is a source of cells capable of growing in vitro and, in appropriate conditions, forming floating spheres constituted by nestin-positive cells. We have clonally grown these spheres up to the 15th generation. These spheres can be dissociated into cells that differentiate in vitro under appropriate conditions, these cells are labeled by antibodies to immature neuron markers such as nestin and beta-tubulin III and, later, to mature neuron markers such as microtubule-associated protein 2 and neurofilaments. However, most cells are positive to the astroglial marker glia fibrillary acidic protein (GFAP). When sphere-derived cells are transplanted into the spinal cord after traumatic injury, their migration into the lesion cavity is optimal but their differentiation is dependent upon the time interval between lesioning and cell transplantation. Injection of skin-derived stem cell within 30 min from injury yields mainly membrane activated complex-1 (MAC-1), cluster of differentiation-4 (CD-4) and CD-8 positive cells, that 60-90 days later undergo apoptosis. However, when transplantation is performed 7 days after injury, most cells (65% of total) are positive to staining with antibodies to GFAP, others (16%) to neurofilaments, and a smaller amount (2%) to the endothelial marker, platelet endothelial cell adhesion molecule. Thus our study shows that delayed transplantations of dermis-derived stem cells yield healthy cells that do not die, migrate to the lesion site, and there differentiate mainly in cells expressing glia and neuronal markers. On the other hand there is the possibility of dye transfer from labeled cells to endogenous cells, and this might influence the data. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. Keywords
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- 2004
39. Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma
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Gaetano Finocchiaro, Federica Pisati, Irene Appolloni, Sergio Ottolenghi, Serena Pellegatta, Eleonora Gambini, Alexandra Badiola Sanga, Pierfrancesco Pagella, Silvia K. Nicolis, Paolo Malatesta, Maria Foti, Rebecca Favaro, Favaro, R, Appolloni, I, Pellegatta, S, Sanga, A, Pagella, P, Gambini, E, Pisati, F, Ottolenghi, S, Foti, M, Finocchiaro, G, Malatesta, P, and Nicolis, S
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Cancer Research ,medicine.medical_treatment ,Oligodendroglioma ,Mice, Transgenic ,SOXB1 Transcription Factor ,Tumor initiation ,Biology ,Cancer Vaccines ,Brain Neoplasm ,Mice ,Peptide Fragment ,stomatognathic system ,SOX2 ,Cancer stem cell ,Cell Line, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Cell Proliferation ,Animal ,Brain Neoplasms ,SOXB1 Transcription Factors ,fungi ,Immunotherapy ,medicine.disease ,Molecular biology ,Peptide Fragments ,Neural stem cell ,Mice, Inbred C57BL ,Oncology ,Cell culture ,embryonic structures ,Neoplastic Stem Cells ,Cancer research ,Female ,Neoplastic Stem Cell ,sense organs ,biological phenomena, cell phenomena, and immunity ,Stem cell ,Transcriptome ,Cancer Vaccine - Abstract
The stem cell–determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor–induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells. Cancer Res; 74(6); 1833–44. ©2014 AACR.
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- 2014
40. A murine model of cerebral cavernous malformations with acute hemorrhage
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Claudio Maderna, Federica Pisati, Claudio Tripodo, Elisabetta Dejana, Matteo Malinverno, Maderna C., Pisati F., Tripodo C., Dejana E., and Malinverno M.
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Multidisciplinary ,Neurology ,Neurologi ,Developmental neuroscience, Model organism, Vascular remodeling ,Settore MED/08 - Anatomia Patologica - Abstract
Cavernomas are multi-lumen and blood-filled vascular malformations which form in the brain and the spinal cord. They lead to hemorrhage, epileptic seizures, neurological deficits, and paresthesia. An effective medical treatment is still lacking, and the available murine models for cavernomas have several limitations for preclinical studies. These include disease phenotypes that differ from human diseases, such as restriction of the lesions to the cerebellum, and absence of acute hemorrhage. Additional limitations of current murine models include rapid development of lesions, which are lethal before the first month of age. Here, we have characterized a murine model that recapitulates features of the human disease: lesions develop after weaning throughout the entire CNS, including the spinal cord, and undergo acute hemorrhage. This provides a preclinical model to develop new drugs for treatment of acute hemorrhage in the brain and spinal cord, as an unmet medical emergency for patients with cavernomas.
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41. A combinatorial culture strategy to develop pseudomyxoma peritonei organoid models.
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Varinelli L, Di Bella M, Guaglio M, Battistessa D, Pisati F, Cavalleri T, Milione M, Martínez-Quintanilla J, Caswell PT, Baratti D, Kusamura S, Deraco M, and Gariboldi M
- Abstract
Background and Objectives: Few preclinical models of pseudomyxoma peritonei (PMP) have been developed, probably due to the tumor's low incidence and its peculiar characteristics of slow growth. Therefore, there is a need to develop more refined PMP models that better reflect its characteristics. The aim of the study is to develop a culture strategy to generate organoid models derived from PMP patient samples., Methods: We followed a strategy based on combinatorial culture conditions that include the different factors essential for PMP growth and that mimic the microenvironment present in the patients., Results: We cultured PMP samples in the presence of the various factors produced by the niche environment of PMP. We obtained 12 PMP organoid models, each of which grows under specific culture conditions. PMP-derived organoids show long-term expansion capacity and reproduce the genetic landscape and histological phenotype of the tumor of origin., Conclusion: The organoids we developed faithfully reproduce the key features of PMP disease and will allow us to understand the biology of PMP. With them, we will be able to identify key regulatory networks that support PMP progression, providing a platform for multilevel preclinical testing, identify novel diagnostic biomarkers, and generate novel targets for patient treatments., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)
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- 2024
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42. Correction: Colorectal carcinoma peritoneal metastases‑derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench‑to‑bedside.
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Varinelli L, Battistessa D, Guaglio M, Zanutto S, Illescas O, Lorenc EJ, Pisati F, Kusamura S, Cattaneo L, Sabella G, Milione M, Perbellini A, Noci S, Paolino C, Kuhn E, Galassi M, Cavalleri T, Deraco M, Gariboldi M, and Baratti D
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- 2024
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43. Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside.
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Varinelli L, Battistessa D, Guaglio M, Zanutto S, Illescas O, Lorenc EJ, Pisati F, Kusamura S, Cattaneo L, Sabella G, Milione M, Perbellini A, Noci S, Paolino C, Kuhn E, Galassi M, Cavalleri T, Deraco M, Gariboldi M, and Baratti D
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- Humans, Colorectal Neoplasms pathology, Colorectal Neoplasms therapy, Colorectal Neoplasms drug therapy, Peritoneal Neoplasms secondary, Peritoneal Neoplasms therapy, Peritoneal Neoplasms drug therapy, Hyperthermic Intraperitoneal Chemotherapy methods, Organoids drug effects
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Background: Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy., Methods: Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose-response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage., Results: Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity., Conclusions: Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM., (© 2024. The Author(s).)
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- 2024
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44. Unveiling the mechanistic link between extracellular amyloid fibrils, mechano-signaling and YAP activation in cancer.
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Farris F, Elhagh A, Vigorito I, Alongi N, Pisati F, Giannattasio M, Casagrande F, Veghini L, Corbo V, Tripodo C, Di Napoli A, Matafora V, and Bachi A
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- Humans, Amyloid, Ecosystem, Signal Transduction, Tumor Microenvironment, Melanoma, Pancreatic Neoplasms genetics
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The tumor microenvironment is a complex ecosystem that plays a critical role in cancer progression and treatment response. Recently, extracellular amyloid fibrils have emerged as novel components of the tumor microenvironment; however, their function remains elusive. In this study, we establish a direct connection between the presence of amyloid fibrils in the secretome and the activation of YAP, a transcriptional co-activator involved in cancer proliferation and drug resistance. Furthermore, we uncover a shared mechano-signaling mechanism triggered by amyloid fibrils in both melanoma and pancreatic ductal adenocarcinoma cells. Our findings highlight the crucial role of the glycocalyx protein Agrin which binds to extracellular amyloid fibrils and acts as a necessary factor in driving amyloid-dependent YAP activation. Additionally, we reveal the involvement of the HIPPO pathway core kinase LATS1 in this signaling cascade. Finally, we demonstrate that extracellular amyloid fibrils enhance cancer cell migration and invasion. In conclusion, our research expands our knowledge of the tumor microenvironment by uncovering the role of extracellular amyloid fibrils in driving mechano-signaling and YAP activation. This knowledge opens up new avenues for developing innovative strategies to modulate YAP activation and mitigate its detrimental effects during cancer progression., (© 2024. The Author(s).)
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- 2024
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45. A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer.
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Villani A, Fontana A, Panebianco C, Ferro C, Copetti M, Pavlovic R, Drago D, Fiorentini C, Terracciano F, Bazzocchi F, Canistro G, Pisati F, Maiello E, Latiano TP, Perri F, and Pazienza V
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- Humans, Male, Female, RNA, Ribosomal, 16S genetics, Middle Aged, Feces microbiology, Aged, Metagenomics, Pancreatic Neoplasms microbiology, Pancreatic Neoplasms pathology, Gastrointestinal Microbiome, Machine Learning, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Neoplasm Metastasis
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Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: Anaerostipes hadrus , Coprobacter secundus , Clostridium sp. 619, Roseburia inulinivorans , Porphyromonas and Odoribacter at the genus level, and Rhodospirillaceae , Clostridiaceae and Peptococcaceae at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.
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- 2024
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46. Correction to "An Unexpected Deuterium-Induced Metabolic Switch in Doxophylline".
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Aprile S, Colombo G, Serafini M, Di Paola R, Pisati F, Bhela IP, Cuzzocrea S, Grosa G, and Pirali T
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[This corrects the article DOI: 10.1021/acsmedchemlett.2c00166.]., (© 2023 The Authors. Published by American Chemical Society.)
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- 2023
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47. Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect.
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Hershey BJ, Barozzi S, Orsenigo F, Pompei S, Iannelli F, Kamrad S, Matafora V, Pisati F, Calabrese L, Fragale G, Salvadori G, Martini E, Totaro MG, Magni S, Guan R, Parazzoli D, Maiuri P, Bachi A, Patil KR, Cosentino Lagomarsino M, and Havas KM
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- Humans, Animals, Disease Models, Animal, Population Density, Coloring Agents, Triple Negative Breast Neoplasms
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Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent and nature of these interactions remain largely unknown. We postulated that tumors develop ecological interactions that sustain diversity and facilitate metastasis. Using a combination of fluorescent barcoding, mathematical modeling, metabolic analysis, and in vivo models, we show that the Allee effect, i.e., growth dependency on population size, is a feature of tumor lineages and that cooperative ecological interactions between lineages alleviate the Allee barriers to growth in a model of triple-negative breast cancer. Soluble metabolite exchange formed the basis for these cooperative interactions and catalyzed the establishment of a polyclonal community that displayed enhanced metastatic dissemination and outgrowth in xenograft models. Our results highlight interclonal metabolite exchange as a key modulator of tumor ecology and a contributing factor to overcoming Allee effect-associated growth barriers to metastasis.
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- 2023
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48. Correlation between biological and mechanical properties of extracellular matrix from colorectal peritoneal metastases in human tissues.
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Lorenc E, Varinelli L, Chighizola M, Brich S, Pisati F, Guaglio M, Baratti D, Deraco M, Gariboldi M, and Podestà A
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- Humans, Extracellular Matrix metabolism, Peritoneal Neoplasms pathology, Colorectal Neoplasms pathology
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Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the extracellular matrix (ECM) are important in cancer development; studying their changes is crucial to understand CRC-PM development. We studied the elastic properties of ECMs derived from human samples of normal and neoplastic PM by atomic force microscopy (AFM); results were correlated with patient clinical data and expression of ECM components related to metastatic spread. We show that PM progression is accompanied by stiffening of the ECM, increased cancer associated fibroblasts (CAF) activity and increased deposition and crosslinking in neoplastic matrices; on the other hand, softer regions are also found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells. We have found correlations between the mechanical properties (relative stiffening between normal and neoplastic ECM) of the ECM and patients' clinical data, like age, sex, presence of protein activating mutations in BRAF and KRAS genes and tumour grade. Our findings suggest that the mechanical phenotyping of PM-ECM has the potential to predict tumour development., (© 2023. The Author(s).)
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- 2023
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49. Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.
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Frittoli E, Palamidessi A, Iannelli F, Zanardi F, Villa S, Barzaghi L, Abdo H, Cancila V, Beznoussenko GV, Della Chiara G, Pagani M, Malinverno C, Bhattacharya D, Pisati F, Yu W, Galimberti V, Bonizzi G, Martini E, Mironov AA, Gioia U, Ascione F, Li Q, Havas K, Magni S, Lavagnino Z, Pennacchio FA, Maiuri P, Caponi S, Mattarelli M, Martino S, d'Adda di Fagagna F, Rossi C, Lucioni M, Tancredi R, Pedrazzoli P, Vecchione A, Petrini C, Ferrari F, Lanzuolo C, Bertalot G, Nader G, Foiani M, Piel M, Cerbino R, Giavazzi F, Tripodo C, and Scita G
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- DNA, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Cytosol metabolism, Signal Transduction, Actins, Neoplasms
- Abstract
The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma., (© 2022. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
50. Decellularized extracellular matrix as scaffold for cancer organoid cultures of colorectal peritoneal metastases.
- Author
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Varinelli L, Guaglio M, Brich S, Zanutto S, Belfiore A, Zanardi F, Iannelli F, Oldani A, Costa E, Chighizola M, Lorenc E, Minardi SP, Fortuzzi S, Filugelli M, Garzone G, Pisati F, Vecchi M, Pruneri G, Kusamura S, Baratti D, Cattaneo L, Parazzoli D, Podestà A, Milione M, Deraco M, Pierotti MA, and Gariboldi M
- Subjects
- Humans, Decellularized Extracellular Matrix, Peritoneum, Organoids, Peritoneal Neoplasms metabolism, Peritoneal Neoplasms secondary, Peritoneal Neoplasms therapy, Colorectal Neoplasms metabolism
- Abstract
Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments., (© The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)
- Published
- 2023
- Full Text
- View/download PDF
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