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2. In vivo mitochondria‐targeted protection against uterine artery vascular dysfunction and remodelling in rodent hypoxic pregnancy

Author

Wang, Zhongchao, primary, Camm, Emily J., additional, Nuzzo, Anna Maria, additional, Spiroski, Ana‐Mishel, additional, Skeffington, Katie L., additional, Ashmore, Thomas J., additional, Rolfo, Alessandro, additional, Todros, Tullia, additional, Logan, Angela, additional, Ma, Jin, additional, Murphy, Michael P., additional, Niu, Youguo, additional, and Giussani, Dino A., additional

Published
2024
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3. MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer

Author

Petrelli, Annalisa, Bellomo, Sara Erika, Sarotto, Ivana, Kubatzki, Franziska, Sgandurra, Paola, Maggiorotto, Furio, Di Virgilio, Maria Rosaria, Ponzone, Riccardo, Geuna, Elena, Galizia, Danilo, Nuzzo, Anna Maria, Medico, Enzo, Miglio, Umberto, Berrino, Enrico, Venesio, Tiziana, Ribisi, Salvatore, Provero, Paolo, Sapino, Anna, Giordano, Silvia, and Montemurro, Filippo

Published
2020
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11. Neoadjuvant chemotherapy in high‐risk soft tissue sarcomas: A Sarculator‐based risk stratification analysis of the ISG‐STS 1001 randomized trial

Author

Pasquali, Sandro, primary, Palmerini, Emanuela, additional, Quagliuolo, Vittorio, additional, Martin‐Broto, Javier, additional, Lopez‐Pousa, Antonio, additional, Grignani, Giovanni, additional, Brunello, Antonella, additional, Blay, Jean‐Yves, additional, Tendero, Oscar, additional, Diaz‐Beveridge, Robert, additional, Ferraresi, Virginia, additional, Lugowska, Iwona, additional, Infante, Gabriele, additional, Braglia, Luca, additional, Merlo, Domenico Franco, additional, Fontana, Valeria, additional, Marchesi, Emanuela, additional, Donati, Davide Maria, additional, Palassini, Elena, additional, Bianchi, Giuseppe, additional, Marrari, Andrea, additional, Morosi, Carlo, additional, Stacchiotti, Silvia, additional, Bagué, Silvia, additional, Coindre, Jean Michel, additional, Dei Tos, Angelo Paolo, additional, Picci, Piero, additional, Bruzzi, Paolo, additional, Miceli, Rosalba, additional, Casali, Paolo Giovanni, additional, Gronchi, Alessandro, additional, Dani, Carla, additional, Villa, Chiara, additional, Messina, Antonella, additional, Rusi, Lorella, additional, Nuzzo, Anna Maria, additional, Nuzzo, Carmen, additional, De Paoli, Antonino, additional, Buonadonna, Angela, additional, Comandone, Alessandro, additional, Boglione, Antonella, additional, Livi, Lorenzo, additional, Greto, Daniela, additional, Riva, Nada, additional, Monti, Manuela, additional, Pennacchioli, Elisabetta, additional, De Pas, Tommaso, additional, Ippolito, Vincenzo, additional, Ledesma, Patrico, additional, Redondo, Andres, additional, Valverde, Claudia, additional, Bratos, Raquel, additional, Cruz, Josefina, additional, Martinez Trufero, Javier, additional, Cubedo, Ricardo, additional, Sevilla, Isabel, additional, Luna, Pablo, additional, Lopez, Rafael, additional, Sancho, Pilar, additional, Bally, Olivia, additional, Brahmi, Mehdi, additional, Ray‐Coquard, Isabelle, additional, Cassier, Philippe, additional, Marques, Nathalie, additional, Tassy, Luis, additional, Boudou‐Rouquette, Pascaline, additional, Tlemsani, Camille, additional, Alexandre, Jerome, additional, Goldwasser, Francois, additional, Bompas, Emmanuelle, additional, Rolland, Frederic, additional, Perrin, Christophe, additional, Talarmin, Marie, additional, Italiano, Antoine, additional, Toulmonde, Maud, additional, Laramas, Mathieu, additional, Bay, Jacques‐Olivier, additional, Dubray‐Longeras, Pascale, additional, and Rutkowski, Piotr, additional

Published
2021
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14. Altered Expression of G1/S Phase Cell Cycle Regulators in Placental Mesenchymal Stromal Cells Derived from Preeclamptic Pregnancies with Fetal-Placental Compromise

Author

Nuzzo, Anna Maria, Giuffrida, Domenica, Masturzo, Bianca, Mele, Paolo, Piccoli, Ettore, Eva, Carola, Todros, Tullia, and Rolfo, Alessandro

Subjects
endocrine system
Abstract

Herein, we evaluated whether Placental Mesenchymal Stromal Cells (PDMSCs) derived from normal and Preeclamptic (PE) placentae presented differences in the expression of G1/S-phase regulators p16INK4A, p18INK4C, CDK4 and CDK6. Finally, we investigated normal and PE-PDMSCs paracrine effects on JunB, Cyclin D1, p16INK4A, p18INK4C, CDK4 and CDK6 expressions in physiological term villous explants. PDMSCs were isolated from physiological (n = 20) and PE (n = 24) placentae. Passage three normal and PE-PDMSC and conditioned media (CM) were collected after 48 h. Physiological villous explants (n = 60) were treated for 72 h with normal or PE-PDMSCs CM. Explants viability was assessed by Lactate Dehydrogenase Cytotoxicity assay. Cyclin D1 localization was evaluated by Immuofluorescence (IF) while JunB, Cyclin-D1 p16INK4A, p18INK4C, CDK4 and CDK6 levels were assessed by Real Time PCR and Western Blot assay. We reported significantly increased p16INK4A and p18INK4C expression in PE- relative to normal PDMSCs while no differences in CDK4 and CDK6 levels were detected. Explants viability was not affected by normal or PE-PDMSCs CM. Normal PDMSCs CM increased JunB, p16INK4 and p18INK4C and decreased Cyclin-D1 in placental tissues. In contrast, PE-PDMSCs CM induced JunB down-regulation and Cyclin D1 increase in placental explants. Cyclin D1 IF staining showed that CM treatment targeted mainly the syncytiotrophoblast. We showed Cyclin D1-p16INK4A/p18INK4C altered pathway in PE-PDMSCs demonstrating an aberrant G1/S phase transition in these pathological cells. The abnormal Cyclin D1-p16INK4A/p18INK4C expression in explants conditioned by PE-PDMSCs media suggest a key contribution of mesenchymal cells to the altered trophoblast cell cycle regulation typical of PE pregnancies with fetal-placental compromise.

Published
2016
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25. The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin.

Author

Zenerino, Cristian, Nuzzo, Anna Maria, Giuffrida, Domenica, Biolcati, Marilisa, Zicari, Alessandra, Todros, Tullia, and Rolfo, Alessandro

Subjects
*PLACENTA, *PREECLAMPSIA, *CARRIER proteins, *BIOLOGICAL transport, *HEPARIN
Abstract

We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response. [ABSTRACT FROM AUTHOR]

Published
2017
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30. Amniotic mesenchymal cells from pre‐eclamptic placentae maintain immunomodulatory features as healthy controls

Author

Pianta, Stefano, primary, Magatti, Marta, additional, Vertua, Elsa, additional, Bonassi Signoroni, Patrizia, additional, Muradore, Ivan, additional, Nuzzo, Anna Maria, additional, Rolfo, Alessandro, additional, Silini, Antonietta, additional, Quaglia, Federico, additional, Todros, Tullia, additional, and Parolini, Ornella, additional

Published
2015
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34. Is It Possible to Differentiate Chronic Kidney Disease and Preeclampsia by means of New and Old Biomarkers? A Prospective Study

Author

Rolfo, Alessandro, primary, Attini, Rossella, additional, Tavassoli, Elisabetta, additional, Vigotti Neve, Federica, additional, Nigra, Marco, additional, Cicilano, Matteo, additional, Nuzzo, Anna Maria, additional, Giuffrida, Domenica, additional, Biolcati, Marilisa, additional, Nichelatti, Michele, additional, Gaglioti, Pietro, additional, Todros, Tullia, additional, and Piccoli, Giorgina Barbara, additional

Published
2015
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38. Characterization of DUFFY Decoy Receptor in Placentae from Pregnancies Complicated by both Preeclampsia and Gestational Diabetes

Author

Giuffrida Domenica, Todros Tullia, Zenerino Cristian, Rolfo Alessandro, and Nuzzo Anna Maria

Subjects
medicine.medical_specialty, business.industry, Obstetrics, Placenta, Obstetrics and Gynecology, gestational diabetes mellitus, Preeclampsia, Decoy Receptors, DUFFY, medicine.disease, Gestational diabetes, medicine.anatomical_structure, Endocrinology, Reproductive Medicine, Internal medicine, medicine, Decoy receptors, Receptor, business, Decoy, Developmental Biology
Published
2013

46. Amniotic mesenchymal cells from pre-eclamptic placentae maintain immunomodulatory features as healthy controls.

Author

Pianta, Stefano, Magatti, Marta, Vertua, Elsa, Bonassi Signoroni, Patrizia, Muradore, Ivan, Nuzzo, Anna Maria, Rolfo, Alessandro, Silini, Antonietta, Quaglia, Federico, Todros, Tullia, and Parolini, Ornella

Subjects
PREECLAMPSIA diagnosis, AMNIOTIC liquid, MESENCHYMAL stem cells, ABRUPTIO placentae, IMMUNOREGULATION, CYTOKINES
Abstract

Pre-eclampsia (PE) is one of the most severe syndromes in human pregnancy, and the underlying mechanisms of PE have yet to be determined. Pre-eclampsia is characterized by the alteration of the immune system's activation status, an increase in inflammatory Th1/Th17/APC cells, and a decrease in Th2/Treg subsets/cytokines. Moreover, inflammatory infiltrates have been detected in the amniotic membranes of pre-eclamptic placentae, and to this date limited data are available regarding the role of amniotic membrane cells in PE. Interestingly, we and others have previously shown that human amniotic mesenchymal stromal cells (hAMSC) possess anti-inflammatory properties towards almost all immune cells described to be altered in PE. In this study we investigated whether the immunomodulatory properties of hAMSC were altered in PE. We performed a comprehensive study of cell phenotype and investigated the in vitro immunomodulatory properties of hAMSC isolated from preeclamptic pregnancies (PE-hAMSC), comparing them to hAMSC from normal pregnancies (N-hAMSC). We demonstrate that PE-hAMSC inhibit CD4/CD8 T-cell proliferation, suppress Th1/Th2/Th17 polarization, induce Treg and block dendritic cells and M1 differentiation switching them to M2 cells. Notably, PE-hAMSC generated a more prominent induction of Treg and higher suppression of interferon-γ when compared to NhAMSC, and this was associated with higher transforming growth factor-β1 secretion and PD-L2/PD-L1 expression in PE-hAMSC. In conclusion, for the first time we demonstrate that there is no intrinsic impairment of the immunomodulatory features of PE-hAMSC. Our results suggest that amniotic mesenchymal stromal cells do not contribute to the disease, but conversely, could participate in offsetting the inflammatory environment which characterizes PE. [ABSTRACT FROM AUTHOR]

Published
2016
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48. Prolonged disease stability with trabectedin in a heavily pretreated elderly patient with metastatic leiomyosarcoma of the thigh and renal failure: a case report and review of the literature.

Author

Galizia D, Palesandro E, Nuzzo AM, Pignochino Y, Aliberti S, Aglietta M, and Grignani G

Subjects
Aged, Antineoplastic Agents, Alkylating therapeutic use, Disease Progression, Humans, Leiomyosarcoma complications, Leiomyosarcoma secondary, Lung Neoplasms complications, Lung Neoplasms secondary, Male, Renal Insufficiency diagnosis, Salvage Therapy, Time Factors, Tomography, X-Ray Computed, Trabectedin, Treatment Outcome, Dioxoles therapeutic use, Leiomyosarcoma drug therapy, Lung Neoplasms drug therapy, Renal Insufficiency complications, Tetrahydroisoquinolines therapeutic use
Abstract

Leiomyosarcoma represents about 24% of all soft tissue sarcomas and can originate from retroperitoneum, uterus, or extremities. Adequate local control may be achieved with surgery and radiotherapy. In the presence of unresectable metastases either doxorubicin- or gemcitabine-based chemotherapy is the standard of treatment. Nevertheless, prognosis remains poor regardless of the selected chemotherapy regimen, and new effective therapeutic agents for patients with advanced leiomyosarcoma are needed. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that is different from that of traditional alkylating agents, is approved in Europe for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. We present a case of a 76-year-old patient with progressive metastatic lung lesions from a previously resected primary leiomyosarcoma of the thigh and moderate renal failure, who achieved 17 months of disease stability during third-line treatment with trabectedin. Trabectedin was not associated with any cumulative toxicity and was consistently well tolerated for a total of 22 treatment cycles. Current evidence on trabectedin is also presented.

Published
2013
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