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Your search keyword '"Massimiliano Bardotti"' showing total 3 results
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3 results on '"Massimiliano Bardotti"'

1. Extracellular ATP and CD39 Activate cAMP-Mediated Mitochondrial Stress Response to Promote Cytarabine Resistance in Acute Myeloid Leukemia

Author

Margherita Ghisi, Jerome Tamburini, Marie Sabatier, Massimiliano Bardotti, Francisco Azuaje, Jean-Charles Portais, Christian Récher, Carine Joffre, Lucille Stuani, Pierre-Luc Mouchel, Camille Laurent, Marie-Laure Nicolau-Travers, Fetta Mazed, Claudie Bosc, Nathalie Nicot, Nesrine Aroua, Mathilde Gotanègre, Jean-Emmanuel Sarry, Estelle Saland, Clément Larrue, Floriant Bellvert, Fabienne De Toni, Latifa Jarrou, Mohsen Hosseini, Charlotte Syrykh, Ryan Gwilliam, François Vergez, Tony Kaoma, Sarah Gandarillas, Muriel Picard, Thomas Farge, Emeline Boet, Nathalie Bonnefoy, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Genève = University of Geneva (UNIGE), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Anesthésie Réanimation [CHU de Toulouse], Service d'anatomopathologie, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Luxembourg Institute of Health (LIH), Canceropole GSO 2014-E07, Région Auvergne-Rhone-AlpesRégion Bourgogne-Franche-ComteRégion Hauts-de-FranceRégion Nouvelle-Aquitaine, Fondation Toulouse Cancer Santé, Plan Cancer 2014-BioSys, Fondation ARC, Fondation de France, ANR-11-LABX-0068,TOUCAN,Analyse intégrée de la résistance dans les cancers hématologiques(2011), ANR-11-PHUC-0001,CAPTOR,Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région(2011), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Genève (UNIGE), Intensive Care Unit, Department of Anesthesiology and Critical Care, Rangueil Hospital, Centre Hospitalier Universitaire, Toulouse, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, Male, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, In vivo, Antigens, CD, hemic and lymphatic diseases, medicine, Humans, Ectonucleotidase, Cytotoxicity, business.industry, Apyrase, Cytarabine, Myeloid leukemia, Middle Aged, 3. Good health, Mitochondria, Leukemia, Myeloid, Acute, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cell culture, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, Female, business, medicine.drug
Abstract

Relapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that the ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine-resistant leukemic cells from both AML cell lines and patient samples in vivo and in vitro. CD39 cell-surface expression and activity is increased in patients with AML upon chemotherapy compared with diagnosis, and enrichment in CD39-expressing blasts is a marker of adverse prognosis in the clinics. High CD39 activity promotes cytarabine resistance by enhancing mitochondrial activity and biogenesis through activation of a cAMP-mediated adaptive mitochondrial stress response. Finally, genetic and pharmacologic inhibition of CD39 ecto-ATPase activity blocks the mitochondrial reprogramming triggered by cytarabine treatment and markedly enhances its cytotoxicity in AML cells in vitro and in vivo. Together, these results reveal CD39 as a new residual disease marker and a promising therapeutic target to improve chemotherapy response in AML. Significance: Extracellular ATP and CD39–P2RY13–cAMP–OxPHOS axis are key regulators of cytarabine resistance, offering a new promising therapeutic strategy in AML. This article is highlighted in the In This Issue feature, p. 1426

Published
2020

2. Extracellular ATP and CD39 activate cAMP-mediated mitochondrial stress response to promote cytarabine resistance in acute myeloid leukemia

Author

Francisco Azuale, Margherita Ghisi, Fetta Mazed, Claudie Bosc, Marie-Laure Nicolau-Travers, François Vergez, Thomas Farge, Mathilde Gotanègre, Jean-Emmanuel Sarry, Jerome Tamburini, Nesrine Aroua, Clément Larrue, Jean-Charles Portais, Floriant Bellvert, Pierre-Luc Mouchel, Christian Récher, Massimiliano Bardotti, Fabienne De Toni, Camille Laurent, Emeline Boet, Marie Sabatier, Lucille Stuani, Nathalie Bonnefoy, Charlotte Syrykh, Ryan Gwilliam, Tony Kaoma, Latifa Jarrou, Sarah Gandarillas, Estelle Saland, Nathalie Nicot, and Mohsen Hosseini

Subjects
Chemotherapy, business.industry, medicine.medical_treatment, Cell, Myeloid leukemia, medicine.anatomical_structure, Downregulation and upregulation, Cell culture, In vivo, hemic and lymphatic diseases, Cancer research, medicine, Cytarabine, business, Cytotoxicity, medicine.drug
Abstract

Relapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that the ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine (AraC)-resistant leukemic cells from both AML cell lines and patient samplesin vivoandin vitro. CD39 cell surface expression and activity is increased in AML patients upon chemotherapy compared to diagnosis and enrichment in CD39-expressing blasts is a marker of adverse prognosis in the clinics. High CD39 activity promotes AraC resistance by enhancing mitochondrial activity and biogenesis through activation of a cAMP-mediated response. Finally, genetic and pharmacological inhibition of CD39 eATPase activity blocks the mitochondrial reprogramming triggered by AraC treatment and markedly enhances its cytotoxicity in AML cellsin vitroandin vivo. Together, these results reveal CD39 as a new prognostic marker and a promising therapeutic target to improve chemotherapy response in AML.SIGNIFICANCEExtracellular ATP and CD39-cAMP-OxPHOS axis are key regulators of cytarabine resistance, offering a new promising therapeutic strategy in AML.

Published
2019

3. Immune function alterations in mice tolerant to Δ9- tetrahydrocannabinol: Functional and biochemical parameters

Author

Massimiliano Bardotti, Wilma Ponti, Tiziana Rubino, Daniela Viganò, Daniela Parolaro, Paola Sacerdote, Barbara Manfredi, Domenica Fuzio, and Paola Massi

Subjects
Drug, Male, medicine.medical_specialty, Natural killer, media_common.quotation_subject, T-Lymphocytes, Cytotoxicity, Splenocyte composition, Immunology, Biology, Flow cytometry, Interferon-gamma, Leukocyte Count, Mice, Immune system, In vivo, Reference Values, Internal medicine, medicine, Splenocyte, Concanavalin A, Immune Tolerance, Chronic Δ, Immunology and Allergy, Animals, Dronabinol, Tetrahydrocannabinol, Cells, Cultured, media_common, B-Lymphocytes, medicine.diagnostic_test, Cytokine levels, THC treatment, 9, Splenocyte proliferation, Killer Cells, Natural, Endocrinology, Neurology, Immune System, Antibody Formation, Interleukin-2, Neurology (clinical), Δ9-tetrahydrocannabinol, Cell Division, Spleen, medicine.drug
Abstract

We studied the effect of acute (1 h) or chronic exposure (7 and 14 days) to delta9-tetrahydrocannabinol (delta9-THC) on immune parameters in male Swiss mice. One hour after a dose of 10 mg/kg s.c., the splenocyte proliferative response to ConA and NK activity were not inhibited, but there was a significant decrease in the production of IL-2. After 7 days of treatment, when mice were tolerant to delta9-THC-induced analgesia, these functional parameters were strongly inhibited and there was a persistent reduction in IL-2 and IFNgamma. With 14 days exposure to the drug, splenocyte proliferation was significantly reduced only with 5 microg/ml ConA, and NK activity was still significantly depressed (about 37%). IL-2 had returned to the control value, whereas IFNgamma was still 40% down. Flow cytometry analysis of spleen cell composition indicated no changes after the acute and 7 day treatments, but at 14 days there was a 20% decrease in the number of T lymphocytes, mirrored by a 26% increase of B lymphocytes. In conclusion, in vivo exposure to psychoactive doses of delta9-THC has profound effects on immune function. This implies some important questions in relation to the liberalization of marijuana and its therapeutic uses.

Published
1998

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