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132 results on '"Petrachi, Tiziana"'

1. Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma

Author

Grisendi, Giulia, Dall’Ora, Massimiliano, Casari, Giulia, Spattini, Giliola, Farshchian, Moein, Melandri, Aurora, Masciale, Valentina, Lepore, Fabio, Banchelli, Federico, Costantini, Riccardo Cuoghi, D’Esposito, Angela, Chiavelli, Chiara, Spano, Carlotta, Spallanzani, Andrea, Petrachi, Tiziana, Veronesi, Elena, Ferracin, Manuela, Roncarati, Roberta, Vinet, Jonathan, Magistri, Paolo, Catellani, Barbara, Candini, Olivia, Marra, Caterina, Eccher, Albino, Bonetti, Luca Reggiani, Horwitz, Edwin M., Di Benedetto, Fabrizio, and Dominici, Massimo

Published
2024
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2. GD2 CAR T cells against human glioblastoma

Author

Prapa, Malvina, Chiavelli, Chiara, Golinelli, Giulia, Grisendi, Giulia, Bestagno, Marco, Di Tinco, Rosanna, Dall’Ora, Massimiliano, Neri, Giovanni, Candini, Olivia, Spano, Carlotta, Petrachi, Tiziana, Bertoni, Laura, Carnevale, Gianluca, Pugliese, Giuseppe, Depenni, Roberta, Feletti, Alberto, Iaccarino, Corrado, Pavesi, Giacomo, and Dominici, Massimo

Published
2021
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4. Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study.

Author

Samarelli, Anna Valeria, Tonelli, Roberto, Raineri, Giulia, Mastrolia, Ilenia, Costantini, Matteo, Fabbiani, Luca, Catani, Virginia, Petrachi, Tiziana, Bruzzi, Giulia, Andrisani, Dario, Gozzi, Filippo, Marchioni, Alessandro, Masciale, Valentina, Aramini, Beatrice, Ruggieri, Valentina, Grisendi, Giulia, Dominici, Massimo, Cerri, Stefania, and Clini, Enrico

Subjects
LUNGS, PULMONARY fibrosis, IDIOPATHIC pulmonary fibrosis, PROOF of concept, GENE families, LUNG cancer, INTERSTITIAL lung diseases
Abstract

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Novel bioprinted 3D model to human fibrosis investigation

Author

Petrachi, Tiziana, primary, Portone, Alberto, additional, Arnaud, Gaëlle Françoise, additional, Ganzerli, Francesco, additional, Bergamini, Valentina, additional, Resca, Elisa, additional, Accorsi, Luca, additional, Ferrari, Alberto, additional, Delnevo, Annalisa, additional, Rovati, Luigi, additional, Marra, Caterina, additional, Chiavelli, Chiara, additional, Dominici, Massimo, additional, and Veronesi, Elena, additional

Published
2023
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9. Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer

Author

Spano, Carlotta, Grisendi, Giulia, Golinelli, Giulia, Rossignoli, Filippo, Prapa, Malvina, Bestagno, Marco, Candini, Olivia, Petrachi, Tiziana, Recchia, Alessandra, Miselli, Francesca, Rovesti, Giulia, Orsi, Giulia, Maiorana, Antonino, Manni, Paola, Veronesi, Elena, Piccinno, Maria Serena, Murgia, Alba, Pinelli, Massimo, Horwitz, Edwin M., Cascinu, Stefano, Conte, Pierfranco, and Dominici, Massimo

Published
2019
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10. A new strategy to prevent biofilm and clot formation in medical devices: The use of atmospheric non-thermal plasma assisted deposition of silver-based nanostructured coatings

Author

Gallingani, Tommaso, primary, Resca, Elisa, additional, Dominici, Massimo, additional, Gavioli, Giuliana, additional, Laurita, Romolo, additional, Liguori, Anna, additional, Mari, Giorgio, additional, Ortolani, Luca, additional, Pericolini, Eva, additional, Sala, Arianna, additional, Laghi, Giulia, additional, Petrachi, Tiziana, additional, Arnauld, Gaëlle Francoise, additional, Accorsi, Luca, additional, Rizzoli, Rita, additional, Colombo, Vittorio, additional, Gherardi, Matteo, additional, and Veronesi, Elena, additional

Published
2023
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12. Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis

Author

Mastrolia, Ilenia, primary, Giorgini, Andrea, additional, Murgia, Alba, additional, Loschi, Pietro, additional, Petrachi, Tiziana, additional, Rasini, Valeria, additional, Pinelli, Massimo, additional, Pinto, Valentina, additional, Lolli, Francesca, additional, Chiavelli, Chiara, additional, Grisendi, Giulia, additional, Baschieri, Maria Cristina, additional, Santis, Giorgio De, additional, Catani, Fabio, additional, Dominici, Massimo, additional, and Veronesi, Elena, additional

Published
2022
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13. Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance

Author

Piccinno, Maria Serena, primary, Petrachi, Tiziana, additional, Pignatti, Marco, additional, Murgia, Alba, additional, Grisendi, Giulia, additional, Candini, Olivia, additional, Resca, Elisa, additional, Bergamini, Valentina, additional, Ganzerli, Francesco, additional, Portone, Alberto, additional, Mastrolia, Ilenia, additional, Chiavelli, Chiara, additional, Castelli, Ilaria, additional, Bernabei, Daniela, additional, Tagliazucchi, Mara, additional, Bonetti, Elisa, additional, Lolli, Francesca, additional, De Santis, Giorgio, additional, Dominici, Massimo, additional, and Veronesi, Elena, additional

Published
2022
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15. TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma

Author

Dall Ora, Massimiliano, Giulia Rovesti, Luca Reggiani Bonetti, Casari, Giulia, Banchelli, Federico, Fabbiani, Luca, Veronesi, Elena, Petrachi, Tiziana, Paolo Magistri, Fabrizio Di Benedetto, Andrea Spallanzani, Chiavelli, Chiara, Spano, Maria Carlotta, Antonino Maiorana, Massimo Dominici, and Giulia Grisendi

Subjects
endocrine system diseases, stroma characterization, pancreatic adenocarcinoma, TRAIL receptors, Original Article, digestive system diseases
Abstract

This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory’s trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients.

Published
2021

16. Additional file 1 of Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression

Author

Casari, Giulia, Resca, Elisa, Giorgini, Andrea, Candini, Olivia, Petrachi, Tiziana, Piccinno, Maria Serena, Foppiani, Elisabetta Manuela, Pacchioni, Lucrezia, Starnoni, Marta, Pinelli, Massimo, De Santis, Giorgio, Selleri, Filippo, Catani, Fabio, Dominici, Massimo, and Veronesi, Elena

Abstract

Additional file 1. Supplementary Material and Method.

Published
2021
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17. Additional file 2 of Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression

Author

Casari, Giulia, Resca, Elisa, Giorgini, Andrea, Candini, Olivia, Petrachi, Tiziana, Piccinno, Maria Serena, Foppiani, Elisabetta Manuela, Pacchioni, Lucrezia, Starnoni, Marta, Pinelli, Massimo, De Santis, Giorgio, Selleri, Filippo, Catani, Fabio, Dominici, Massimo, and Veronesi, Elena

Abstract

Additional file 2. Fig. S1: BrdU staining of Lipogems derived MSC after SF stimulation for 24 hours. SF stimulation showed approximately twofold increased fluorescence compared to untreated cells, resulting in 63,3% of positive cells when SF is added to cell culture versus 27.0% obtained in untreated cells. Fig. S2: In-Cell Western quantification of the relative intracellular level of HOXB7 (Fig S2A) and bFGF (Fig S2B) protein in Lipogems derived MSC after 1 and 5 days of stimulation with SF. At 1 day of SF stimulation, the level protein of HOXB7 decreases in a statistically significant manner. Indeed, at 5 days no significant effect on HOXB7 protein expression were observed when SF was added. Moreover, untreated cells decreased the levels of HOXB7 at 5 days of culture (p-value

Published
2021
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18. Assessing Biocompatibility of Face Mask Materials during COVID-19 Pandemic by a Rapid Multi-Assays Strategy

Author

Petrachi, Tiziana, primary, Ganzerli, Francesco, additional, Cuoghi, Aurora, additional, Ferrari, Alberto, additional, Resca, Elisa, additional, Bergamini, Valentina, additional, Accorsi, Luca, additional, Burini, Francesco, additional, Pasini, Davide, additional, Arnaud, Gaelle Françoise, additional, Piccini, Mattia, additional, Aldrovandi, Laura, additional, Mari, Giorgio, additional, Tomasi, Aldo, additional, Rovati, Luigi, additional, Dominici, Massimo, additional, and Veronesi, Elena, additional

Published
2021
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23. MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma

Author

Rossignoli, Filippo, primary, Spano, Carlotta, additional, Grisendi, Giulia, additional, Foppiani, Elisabetta Manuela, additional, Golinelli, Giulia, additional, Mastrolia, Ilenia, additional, Bestagno, Marco, additional, Candini, Olivia, additional, Petrachi, Tiziana, additional, Recchia, Alessandra, additional, Miselli, Francesca, additional, Rovesti, Giulia, additional, Orsi, Giulia, additional, Veronesi, Elena, additional, Medici, Gregorio, additional, Petocchi, Benedetta, additional, Pinelli, Massimo, additional, Horwitz, Edwin M., additional, Conte, Pierfranco, additional, and Dominici, Massimo, additional

Published
2019
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28. GD2 expression in breast cancer

Author

Orsi, Giulia, primary, Barbolini, Monica, additional, Ficarra, Guido, additional, Tazzioli, Giovanni, additional, Manni, Paola, additional, Petrachi, Tiziana, additional, Mastrolia, Ilenia, additional, Orvieto, Enrico, additional, Spano, Carlotta, additional, Prapa, Malvina, additional, Kaleci, Shaniko, additional, D’Amico, Roberto, additional, Guarneri, Valentina, additional, Dieci, Maria Vittoria, additional, Cascinu, Stefano, additional, Conte, Pierfranco, additional, Piacentini, Federico, additional, and Dominici, Massimo, additional

Published
2017
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30. Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

Author

Lotti, Roberta, primary, Palazzo, Elisabetta, additional, Petrachi, Tiziana, additional, Dallaglio, Katiuscia, additional, Saltari, Annalisa, additional, Truzzi, Francesca, additional, Quadri, Marika, additional, Puviani, Mario, additional, Maiorana, Antonino, additional, Marconi, Alessandra, additional, and Pincelli, Carlo, additional

Published
2016
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40. Mesenchymal Progenitors Expressing TRAIL Induce Apoptosis in Sarcomas

Author

Grisendi, Giulia, primary, Spano, Carlotta, additional, D'souza, Naomi, additional, Rasini, Valeria, additional, Veronesi, Elena, additional, Prapa, Malvina, additional, Petrachi, Tiziana, additional, Piccinno, Serena, additional, Rossignoli, Filippo, additional, Burns, Jorge S., additional, Fiorcari, Stefania, additional, Granchi, Donatella, additional, Baldini, Nicola, additional, Horwitz, Edwin M., additional, Guarneri, Valentina, additional, Conte, Pierfranco, additional, Paolucci, Paolo, additional, and Dominici, Massimo, additional

Published
2015
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44. Proteomic Analysis ofPTCH1+/− Fibroblast Lysate and Conditioned Culture Media Isolated from the Skin of Healthy Subjects and Nevoid Basal Cell Carcinoma Syndrome Patients

Author

Ponti, Giovanni, primary, Bertazzoni, Giorgia, additional, Pastorino, Lorenza, additional, Monari, Emanuela, additional, Cuoghi, Aurora, additional, Bergamini, Stefania, additional, Bellei, Elisa, additional, Benassi, Luisa, additional, Azzoni, Paola, additional, Petrachi, Tiziana, additional, Magnoni, Cristina, additional, Pellacani, Giovanni, additional, Loschi, Pietro, additional, Pollio, Annamaria, additional, Witkowski, Alexander Michael, additional, and Tomasi, Aldo, additional

Published
2013
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46. Mesenchymal Progenitors Expressing TRAILInduce Apoptosis in Sarcomas

Author

Grisendi, Giulia, Spano, Carlotta, D'souza, Naomi, Rasini, Valeria, Veronesi, Elena, Prapa, Malvina, Petrachi, Tiziana, Piccinno, Serena, Rossignoli, Filippo, Burns, Jorge S., Fiorcari, Stefania, Granchi, Donatella, Baldini, Nicola, Horwitz, Edwin M., Guarneri, Valentina, Conte, Pierfranco, Paolucci, Paolo, and Dominici, Massimo

Abstract

Sarcomas are frequent tumors in children and young adults that, despite a relative chemo‐sensitivity, show high relapse rates with up to 80% of metastatic patients dying in 5 years from diagnosis. The real ontogeny of sarcomas is still debated and evidences suggest they may derive from precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part in generation of a supportive stroma. Based on this knowledge, we conceived to use modified MSC to deliver tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) targeting different sarcoma histotypes. Gene modified MSC expressing TRAIL were cocultured with different osteosarcoma, rhabdomyosarcoma, and Ewing's Sarcoma (ES) cell lines assessing viability and caspase‐8 activation. An in vivo model focused on ES was then implemented considering the impact of MSC‐TRAIL on tumor size, apoptosis, and angiogenesis. MSC expressing TRAIL induced significantly high apoptosis in all tested lines. Sarcoma death was specifically associated with caspase‐8 activation starting from 8 hours of coculture with MSC‐TRAIL. When injected into pre‐established ES xenotransplants, MSC‐TRAIL persisted within its stroma, causing significant tumor apoptosis versus control groups. Additional histological and in vitro studies reveal that MSC‐TRAIL could also exert potent antiangiogenic functions. Our results suggest that MSC as TRAIL vehicles could open novel therapeutic opportunities for sarcoma by multiple mechanisms. StemCells2015;33:859–869

Published
2015
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47. Proteomic Analysis of PTCH1+/-Fibroblast Lysate and Conditioned Culture Media Isolated from the Skin of Healthy Subjects and Nevoid Basal Cell Carcinoma Syndrome Patients.

Author

Ponti, Giovanni, Bertazzoni, Giorgia, Pastorino, Lorenza, Monari, Emanuela, Cuoghi, Aurora, Bergamini, Stefania, Bellei, Elisa, Benassi, Luisa, Azzoni, Paola, Petrachi, Tiziana, Magnoni, Cristina, Pellacani, Giovanni, Loschi, Pietro, Pollio, Annamaria, Witkowski, Alexander Michael, and Tomasi, Aldo

Abstract

Background. The pathogenesis underlying the increased predisposition to the development of basal cell carcinomas (BCCs) in the context of Gorlin-Goltz syndrome is linked to molecular mechanisms that differ from sporadic BCCs. Patients with Gorlin syndrome tend to develop multiple BCCs at an early age and present with tumors of non-sun-exposed skin. The aim of this study was to compare the proteomic profile of cultured fibroblast and fibroblast conditioned culture media of PTCH1+ and nonmutated fibroblasts. Results. Proteomic analysis was performed using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry in PTCH1+ fibroblast conditioned media isolated from not affected sun-protected skin areas of Gorlin patients and from healthy subjects. 12 protein cluster peaks, >5 kDa, had significant differences in their peak intensities between PTCH1+ and PTCH1- subject groups. We detected a strongly MMP1 overexpression in PTCH1+ fibroblasts obtained from NBCCS patients with respect to healthy donors. Conclusion. Protein profiles in the fibroblast conditioned media revealed statistically significant differences between two different types (missense versus nonsense) of PTCH1 mutations. These differences could be useful as signatures to identify PTCH1 gene carriers at high risk for the development of NBCCS-associated malignancies and to develop novel experimental molecular tailored therapies based on these druggable targets. [ABSTRACT FROM AUTHOR]

Published
2013
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48. Role of neurotrophins on dermal fibroblast survival and differentiation.

Author

Palazzo, Elisabetta, Marconi, Alessandra, Truzzi, Francesca, Dallaglio, Katiuscia, Petrachi, Tiziana, Humbert, Philippe, Schnebert, Sylvianne, Perrier, Eric, Dumas, Marc, and Pincelli, Carlo

Subjects
SKIN physiology, NEUROTROPHINS, FIBROBLASTS, CELL differentiation, HOMEOSTASIS, PROTEIN receptors, CELL proliferation, TISSUE remodeling, WOUND healing
Abstract

Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re-modeling and wound healing. J. Cell. Physiol. 227: 1017-1025, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2012
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49. Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance

Author

Maria Serena Piccinno, Tiziana Petrachi, Marco Pignatti, Alba Murgia, Giulia Grisendi, Olivia Candini, Elisa Resca, Valentina Bergamini, Francesco Ganzerli, Alberto Portone, Ilenia Mastrolia, Chiara Chiavelli, Ilaria Castelli, Daniela Bernabei, Mara Tagliazucchi, Elisa Bonetti, Francesca Lolli, Giorgio De Santis, Massimo Dominici, Elena Veronesi, Piccinno, Maria Serena, Petrachi, Tiziana, Pignatti, Marco, Murgia, Alba, Grisendi, Giulia, Candini, Olivia, Resca, Elisa, Bergamini, Valentina, Ganzerli, Francesco, Portone, Alberto, Mastrolia, Ilenia, Chiavelli, Chiara, Castelli, Ilaria, Bernabei, Daniela, Tagliazucchi, Mara, Bonetti, Elisa, Lolli, Francesca, De Santis, Giorgio, Dominici, Massimo, and Veronesi, Elena

Subjects
mesenchymal stem cells (MSCs), Animal, Green Fluorescent Proteins, adipogenesis, adipose stem cells, tissue engineering, adipose stem cell, Mesenchymal Stem Cells, Rabbit, General Medicine, Mice, SCID, Green Fluorescent Protein, Mice, Adipose Tissue, Mice, Inbred NOD, Animals, Humans, adipogenesi, Rabbits, Human
Abstract

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption.

Published
2022

50. Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer

Author

Tiziana Petrachi, Malvina Prapa, Giulia Orsi, Olivia Candini, Marco Bestagno, Antonino Maiorana, Edwin M. Horwitz, Giulia Grisendi, Giulia Golinelli, Massimo Pinelli, Alba Murgia, Massimo Dominici, Pierfranco Conte, Giulia Rovesti, Elena Veronesi, Stefano Cascinu, Maria Serena Piccinno, Francesca Miselli, Paola Manni, Filippo Rossignoli, Alessandra Recchia, Carlotta Spano, Spano, Carlotta, Grisendi, Giulia, Golinelli, Giulia, Rossignoli, Filippo, Prapa, Malvina, Bestagno, Marco, Candini, Olivia, Petrachi, Tiziana, Recchia, Alessandra, Miselli, Francesca, Rovesti, Giulia, Orsi, Giulia, Maiorana, Antonino, Manni, Paola, Veronesi, Elena, Piccinno, Maria Serena, Murgia, Alba, Pinelli, Massimo, Horwitz, Edwin M., Cascinu, Stefano, Conte, Pierfranco, and Dominici, Massimo

Subjects
0301 basic medicine, Stromal cell, endocrine system diseases, Genetic enhancement, pancreatic cancer, lcsh:Medicine, Adipose tissue, Apoptosis, TRAIL, Adenocarcinoma, Article, TNF-Related Apoptosis-Inducing Ligand, MSC, Mice, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Carcinoma, medicine, Animals, Humans, lcsh:Science, TRAIL, pancreatic cancer, gene therapy, MSC, Multidisciplinary, business.industry, lcsh:R, Mesenchymal stem cell, Mesenchymal Stem Cells, Genetic Therapy, medicine.disease, Xenograft Model Antitumor Assays, gene therapy, digestive system diseases, Pancreatic Neoplasms, Receptors, TNF-Related Apoptosis-Inducing Ligand, 030104 developmental biology, Cancer research, lcsh:Q, Stem cell, business, 030217 neurology & neurosurgery, Carcinoma, Pancreatic Ductal
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.

Published
2019

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