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27 results on '"Elise Kaspi"'

1. Chest ultrasonography to assess the kinetics and efficacy of talc pleurodesis in a model of pneumothorax: an experimental animal study

Author

Rachid Tazi-Mezalek, Diane Frankel, Marc Fortin, Elise Kaspi, Julien Guinde, Alexandra Assolen, Sophie Laroumagne, Andree Robaglia, Herve Dutau, Patrice Roll, and Philippe Astoul

Subjects
Medicine
Abstract

Talc pleurodesis is used to avoid recurrences in malignant pleural effusions or pneumothorax. The lack of lung sliding detected by chest ultrasonography (CUS) after talc application is indicative of the effectiveness of pleurodesis. The objective of our study was to explore, in an animal model, the capacity of CUS to predict the quality of a symphysis induced by talc poudrage (TP) and talc slurry (TS). We induced an artificial pneumothorax in six healthy pigs prior to talc application. TP was performed on one hemithorax, followed by TS on the other side 1 week later. 108 points on the chest were marked and evaluated by ultrasonography during the study. TP showed higher sonographic scores compared to TS starting from 72 h after talc administration. At autopsy, a higher grade of symphysis was observed for TP, and a high correlation rate was registered between CUS and macroscopic findings. Histological analysis also showed a higher grade of pleural symphysis for TP. CUS is a reliable tool to assess talc pleurodesis. The quality and kinetics of the pleural symphysis are also evaluable by ultrasonography. Pleurodesis by TP is more effective than TS in this experimental model of pneumothorax.

Published
2018
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2. Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor Performance status.

Author

Elise Kaspi, Diane Frankel, Julien Guinde, Sophie Perrin, Sophie Laroumagne, Andrée Robaglia-Schlupp, Kevin Ostacolo, Karim Harhouri, Rachid Tazi-Mezalek, Joelle Micallef, Hervé Dutau, Pascale Tomasini, Annachiara De Sandre-Giovannoli, Nicolas Lévy, Pierre Cau, Philippe Astoul, and Patrice Roll

Subjects
Medicine, Science
Abstract

The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunofluorescence, western blotting, and flow cytometry. In a sub-group of lung adenocarcinomas, we found reduced expression of lamin A but not of lamin C. The reduction in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1, an epithelial marker that is involved in the epithelial to mesenchymal transition (EMT). Finally, the lamin A expression was inversely correlated with the number of metastatic sites and the WHO Performance status, and association of pleural, bone and lung metastatic localizations was more frequent when lamin A expression was reduced. In conclusion, low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis, associated with EMT and could account for a pejorative factor correlated with a poor Performance status.

Published
2017
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3. Correction: HIV Protease Inhibitors Do Not Cause the Accumulation of Prelamin A in PBMCs from Patients Receiving First Line Therapy: The ANRS EP45 'Aging' Study.

Author

Sophie Perrin, Jonathan Cremer, Olivia Faucher, Jacques Reynes, Pierre Dellamonica, Joëlle Micallef, Caroline Solas, Bruno Lacarelle, Charlotte Stretti, Elise Kaspi, Andrée Robaglia-Schlupp, Corine Nicolino-Brunet, Catherine Tamalet, Nicolas Lévy, Isabelle Poizot-Martin, Pierre Cau, and Patrice Roll

Subjects
Medicine, Science
Published
2013
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4. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 'Aging' study.

Author

Sophie Perrin, Jonathan Cremer, Patrice Roll, Olivia Faucher, Amélie Ménard, Jacques Reynes, Pierre Dellamonica, Alissa Naqvi, Joëlle Micallef, Elisabeth Jouve, Catherine Tamalet, Caroline Solas, Christel Pissier, Isabelle Arnoux, Corine Nicolino-Brunet, Léon Espinosa, Nicolas Lévy, Elise Kaspi, Andrée Robaglia-Schlupp, Isabelle Poizot-Martin, and Pierre Cau

Subjects
Medicine, Science
Abstract

The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was 500/mm(3). ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting.Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging.

Published
2012
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5. HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 'aging' study.

Author

Sophie Perrin, Jonathan Cremer, Olivia Faucher, Jacques Reynes, Pierre Dellamonica, Joëlle Micallef, Caroline Solas, Bruno Lacarelle, Charlotte Stretti, Elise Kaspi, Andrée Robaglia-Schlupp, Corinne Nicolino-Brunet, Catherine Tamalet, Nicolas Lévy, Isabelle Poizot-Martin, Pierre Cau, and Patrice Roll

Subjects
Medicine, Science
Abstract

The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes.35 HIV-1 infected patients being treated with first line antiretroviral therapy (ART, mean duration at inclusion: 2.7±1.3 years) containing boosted protease inhibitors (PI/r) (comprising lopinavir/ritonavir in 65% of patients) were recruited together with 49 seronegative age- and sex-matched control subjects (http://clinicaltrials.gov/, NCT01038999). In more than 88% of patients, the viral load was 500/mm³. Prelamin A processing in peripheral blood mononuclear cells (PBMCs) from patients and controls was analysed by western blotting at inclusion. PBMCs from patients were also investigated at 12 and 24 months after enrolment in the study. PBMCs from healthy controls were also incubated with boosted lopinavir in culture medium containing various concentrations of proteins (4 to 80 g/L).Lamin A precursor was not observed in cohort patient PBMC regardless of the PI/r used, the dose and the plasma concentration. Prelamin A was detected in PBMC incubated in culture medium containing a low protein concentration (4 g/L) but not in plasma (60-80 g/L) or in medium supplemented with BSA (40 g/L), both of which contain a high protein concentration.Prelamin A processing abnormalities were not observed in PBMCs from patients under the PI/r first line regimen. Therefore, PI/r do not appear to contribute to lamin A-related aging in PBMCs. In cultured PBMCs from healthy donors, prelamin A processing abnormalities were only observed when the protein concentration in the culture medium was low, thus increasing the amount of PI available to enter cells. ClinicalTrials.gov NCT01038999 http://clinicaltrials.gov/ct2/show/NCT01038999.

Published
2012
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6. Pharmacokinetics and pharmacogenetics of liposomal cytarabine in AML patients treated with CPX-351

Author

Yael Berda-Haddad, Laure Farnault, Mourad Hamimed, Joseph Ciccolini, Geoffroy Venton, Régis Costello, L'Houcine Ouafik, Mélanie Donnette, Raphaelle Fanciullino, Elise Kaspi, Bruno Lacarelle, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)

Subjects
Adult, Daunorubicin, [SDV]Life Sciences [q-bio], Pharmaceutical Science, Pharmacology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Cytarabine, Myeloid leukemia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Pharmacogenetics, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030220 oncology & carcinogenesis, Toxicity, Bone marrow, business, Febrile neutropenia, medicine.drug
Abstract

CPX-351 is a liposome encapsulating cytarabine and daunorubicin for treating Acute Myeloid Leukemia (AML) patients. To what extent differences in cytidine deaminase (CDA) activity, the enzyme that catabolizes free cytarabine in the liver, can affect the pharmacokinetics of liposomal cytarabine as well, is unknown. We have studied the pharmacokinetics (PK) of released, liposomal and total cytarabine using a population-modeling approach in 9 adult AML patients treated with liposomal CPX-351. Exposure levels and PK parameters were compared with respect to the patient's CDA status (i.e., Poor Metabolizer (PM) vs. Extensive Metabolizer (EM)). Overall response rate was 75%, and 56% of patients had non-hematological severe toxicities, including one lethal toxicity. All patients had febrile neutropenia. A large (>60%) inter-individual variability was observed on pharmacokinetics parameters and subsequent drug levels. A trend towards severe toxicities was observed in patients with higher exposure of cytarabine. Results showed that liposomal CPX-351 led to sustained exposure with reduced clearance (Cl = 0.16 L/h) and prolonged half-life (T1/2 = 28 h). Liposomal nanoparticles were observed transiently in bone marrow with cytarabine levels 2.3-time higher than in plasma. Seven out of 9 patients were PM with a strong impact on the PK parameters, i.e., PM patients showing higher cytarabine levels as compared with EM patients (AUC: 5536 vs. 1784 ng/mL.h), sustained plasma exposure (T1/2: 33.9 vs. 13.7 h), and reduced clearance (Cl: 0.12 vs. 0.29 L/h). This proof-of-concept study suggests that CDA status has a major impact on cytarabine PK and possibly safety in AML patients even when administered as a liposome.

Published
2021
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7. Pleural effusion in a patient with Ewing sarcoma

Author

Diane Frankel, Patrice Roll, Elise Kaspi, Corinne Bouvier, Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Histology, Pleural effusion, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, Sarcoma, 030209 endocrinology & metabolism, Sarcoma, Ewing, General Medicine, medicine.disease, Pathology and Forensic Medicine, Pleural Effusion, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Humans, Radiology, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022
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8. The Role of the Adhesion Receptor CD146 and Its Soluble Form in Human Embryo Implantation and Pregnancy

Author

Sylvie Bouvier, Elise Kaspi, Ahmad Joshkon, Odile Paulmyer-Lacroix, Marie-Dominique Piercecchi-Marti, Akshita Sharma, Aurélie S. Leroyer, Alexandrine Bertaud, Jean-Christophe Gris, Françoise Dignat-George, Marcel Blot-Chabaud, Nathalie Bardin, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), D.Y. Patil University , Kolhapur, India, Sechenov First Moscow State Medical University, Leroyer, Aurelie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and I.M. Sechenov First Moscow State Medical University [Moscow, Russia] (MSMU)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Angiogenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Mini Review, Immunology, CD146 Antigen, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Biology, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, In vivo, Pregnancy, medicine, Immunology and Allergy, Humans, Embryo Implantation, Receptor, 030304 developmental biology, 0303 health sciences, In vitro fertilisation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Embryo, Biomarker, RC581-607, medicine.disease, Implantation, Cell biology, Fertility, CD146/sCD146, 030220 oncology & carcinogenesis, embryonic structures, CD146, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunologic diseases. Allergy, Biomarkers
Abstract

CD146 is an adhesion molecule essentially located in the vascular system, which has been described to play an important role in angiogenesis. A soluble form of CD146, called sCD146, is detected in the bloodstream and is known as an angiogenic factor. During placental development, CD146 is selectively expressed in extravillous trophoblasts. A growing body of evidence shows that CD146 and, in particular, sCD146, regulate extravillous trophoblasts migration and invasion both in vitro and in vivo. Hereby, we review expression and functions of CD146/sCD146 in the obstetrical field, mainly in pregnancy and in embryo implantation. We emphasized the relevance of quantifying sCD146 in the plasma of pregnant women or in embryo supernatant in the case of in vitro fertilization (IVF) to predict pathological pregnancy such as preeclampsia or implantation defect. This review will also shed light on some major results that led us to define CD146/sCD146 as a biomarker of placental development and paves the way toward identification of new therapeutic targets during implantation and pregnancy.

Published
2021
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9. Mise en évidence du réarrangement d’ALK et ROS1 en immunocytochimie sur liquides de ponction

Author

Donatienne Bourlard, Diane Frankel, Emel Peker, Patrice Roll, Stéphane Garcia, Adèle Groliere, Elise Kaspi, and Andrée Robaglia-Schlupp

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, medicine.diagnostic_test, Immunocytochemistry, In situ hybridization, Biology, medicine.disease, 3. Good health, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Immunochemistry, Biopsy, ROS1, medicine, Immunohistochemistry, Stage (cooking), Lung cancer
Abstract

The identification of ALK and ROS1 rearrangements has become essential for the theranostic management of patients with non-small cell lung cancer, especially in stage IV or inoperable patients. These testings are now performed by immunohistochemistry on histological samples and confirmed by fluorescent in situ hybridization in case of positive or doubtful results. The diagnosis of lung cancer is often performed at an advanced or metastatic stage and cytological sample could be the only material containing malignant cells available at these stages. Therefore, the detection of ALK and ROS1 rearrangement by immunocytochemical analysis on cytological specimens is needed. We performed this test on 27 cytological samples of lung adenocarcinomas, and we compared our results with several other techniques: on the same sample or on biopsy in another laboratory, on the same sample by fluorescent in situ hybridization and/or immunochemistry. We found a very good concordance between all these techniques, thus validating our immunocytochemical method on cytological samples according to the ISO 15189 norm. (C) 2018 Elsevier Masson SAS. All rights reserved.

Published
2019
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10. A rare case of pleural localisation of both metastatic Merkel cell carcinoma and chronic lymphocytic leukaemia

Author

Diane Frankel, Shirley Fritz, Elise Kaspi, Patrice Roll, J Colle, Florent Amatore, Theories and Approaches of Genomic Complexity (TAGC), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0303 health sciences, Pathology, medicine.medical_specialty, Histology, Lymphocytic leukaemia, Pleural effusion, Merkel cell carcinoma, business.industry, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], General Medicine, medicine.disease, 3. Good health, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Rare case, medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Abstract

International audience

Published
2021
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11. Immunocytochemical Detection of ALK and ROS1 Rearrangements in Lung Cancer Cytological Samples

Author

Elise Kaspi, Patrice Roll, Diane Frankel, Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Immunocytochemistry, Adenocarcinoma, Receptor tyrosine kinase, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Cytology, medicine, ROS1, Lung cancer, ComputingMilieux_MISCELLANEOUS, Lung, biology, Chemistry, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, ALK, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Tyrosine kinase
Abstract

International audience; The detection of molecular alterations such as ROS1 and ALK rearrangements is performed as part of the diagnosis of advanced-stage lung adenocarcinoma. These alterations allow the treatments with tyrosine kinase inhibitors. Cytological samples are very useful as up to 40% patients are diagnosed with this type of sample. Here we describe the immunocytochemistry technique usable to reveal the overexpression of ALK or ROS1 tyrosine kinase receptors secondary to ALK and ROS1 rearrangements, respectively.

Published
2021
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12. Lipid inclusions accumulation in macrophages from peritoneal effusion of a newborn

Author

Patrice Roll, Diane Frankel, Elise Kaspi, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Frankel, Diane

Subjects
[SDV] Life Sciences [q-bio], Pathology, medicine.medical_specialty, Chemistry, [SDV]Life Sciences [q-bio], medicine, Peritoneal Effusion, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020
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13. miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma

Author

Diane Frankel, Audrey Benoit, Stéphane Robert, Elise Kaspi, Patrice Roll, Philippe Astoul, Nicolas Lévy, Julien Guinde, Kevin Ostacolo, Læknadeild (HÍ), Faculty of Medicine (UI), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)

Subjects
0301 basic medicine, Lung adenocarcinoma, Lung Neoplasms, Carcinogenesis, [SDV]Life Sciences [q-bio], MicroRNA-9, medicine.disease_cause, lcsh:Chemistry, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, integumentary system, Communication, General Medicine, Cell sorting, Lamin Type A, 3. Good health, Computer Science Applications, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Adenocarcinoma, Epithelial Membrane Antigen, pleural effusions, congenital, hereditary, and neonatal diseases and abnormalities, animal structures, microRNA-9, Adenocarcinoma of Lung, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Cell Line, Tumor, Carcinoma, medicine, Humans, Pleural effusions, Physical and Theoretical Chemistry, Lung cancer, Molecular Biology, lamin A, Lungnasjúkdómar, Lung, Organic Chemistry, Mucin-1, medicine.disease, lung adenocarcinoma, Pleural Effusion, MicroRNAs, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Lamin A, Cancer research, Lamin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Publisher's version (útgefin grein), In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the ‘Low lamin A expression’ group compared to patients from the ‘High lamin A expression’ group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A– carcinoma cells compared to lamin A+ carcinoma cells in patients from the ‘Low lamin A expression’ group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A– carcinoma cells in patients from the ‘High lamin A expression’ group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells., This research was funded by an ARARD (Association Régionale d’Aide Respiratoire à Domicile) grant, Parc d’activités de Napollon, 100 avenue des Templiers, Aubagne Cedex, France.

Published
2020
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14. Chronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis

Author

Marion Lepelley, Michel Mallaret, Diane Frankel, Patrice Roll, Quentin Boucherie, Joëlle Micallef, Elise Kaspi, Farid Kheloufi, Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre régional de pharmacovigilance, and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
Proton pump inhibitors, Context (language use), 030204 cardiovascular system & hematology, Pharmacology, Bioinformatics, Translational Research, Biomedical, Pharmacovigilance, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Dementia, Pharmacology (medical), Endothelial dysfunction, Myocardial infarction, Adverse effect, Stroke, business.industry, Pharmacoepidemiology, medicine.disease, 3. Good health, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Safety, Vascular risk, business, 030217 neurology & neurosurgery, Kidney disease
Abstract

International audience; Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship. Several mechanisms have been suggested through in vitro studies (endothelial dysfunction, endothelial senescence, hypomagnesemia, increase of chromogranin A levels, decrease of nitric oxide in endothelial cells) leading to the impairment of vascular homesostasis, paving the way to these complications. Evidence that PPIs may have off-targets and pleiotropic effects are mounting and may impose a cautious attitude in the prescription of PPI's, especially in elderly and/or in the context of chronic use.

Published
2018
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15. Chest ultrasonography to assess the kinetics and efficacy of talc pleurodesis in a model of pneumothorax: an experimental animal study

Author

Julien Guinde, Hervé Dutau, Andree Robaglia, Patrice Roll, Marc Fortin, Rachid Tazi-Mezalek, Elise Kaspi, Alexandra Assolen, Diane Frankel, Sophie Laroumagne, Philippe Astoul, Hôpital Nord [CHU - APHM], Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), Assistance Publique - Hôpitaux de Marseille (APHM), Division d'oncologie thoracique, Département des maladies pulmonaires, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Gall, Valérie

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Symphysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, Talc, 03 medical and health sciences, 0302 clinical medicine, Lung structure and function, medicine, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Lung, business.industry, lcsh:R, Talc pleurodesis, Pneumothorax, Original Articles, Lung imaging, medicine.disease, respiratory tract diseases, 3. Good health, [SDV] Life Sciences [q-bio], Experimental animal, medicine.anatomical_structure, 030228 respiratory system, Chest ultrasonography, Radiology, business, Pleurodesis, medicine.drug
Abstract

Talc pleurodesis is used to avoid recurrences in malignant pleural effusions or pneumothorax. The lack of lung sliding detected by chest ultrasonography (CUS) after talc application is indicative of the effectiveness of pleurodesis. The objective of our study was to explore, in an animal model, the capacity of CUS to predict the quality of a symphysis induced by talc poudrage (TP) and talc slurry (TS). We induced an artificial pneumothorax in six healthy pigs prior to talc application. TP was performed on one hemithorax, followed by TS on the other side 1 week later. 108 points on the chest were marked and evaluated by ultrasonography during the study. TP showed higher sonographic scores compared to TS starting from 72 h after talc administration. At autopsy, a higher grade of symphysis was observed for TP, and a high correlation rate was registered between CUS and macroscopic findings. Histological analysis also showed a higher grade of pleural symphysis for TP. CUS is a reliable tool to assess talc pleurodesis. The quality and kinetics of the pleural symphysis are also evaluable by ultrasonography. Pleurodesis by TP is more effective than TS in this experimental model of pneumothorax., Quality of talc pleurodesis and kinetics of pleural symphysis can be evaluated by chest ultrasonography http://ow.ly/8Ejt30jVTjn

Published
2018
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16. Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid

Author

Julien Guinde, Isabelle Nanni-Metellus, Diane Frankel, Philippe Astoul, Elise Kaspi, L'Houcine Ouafik, Pascale Tomasini, Florent Amatore, Véronique Secq, Andrée Robaglia-Schlupp, Patrice Roll, Fabrice Barlesi, Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Oncologie multidisciplinaire et innovations thérapeutiques [Hôpital Nord - APHM], Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division d'oncologie thoracique, Département des maladies pulmonaires, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), service hospitalier d'anatomie et cytologie pathologique humaine, APHM, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], and Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Male, Proto-Oncogene Proteins B-raf, Lung Neoplasms, Clinical Biochemistry, Viral Oncogene, Adenocarcinoma of Lung, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, medicine, Humans, Epidermal growth factor receptor, ComputingMilieux_MISCELLANEOUS, Aged, Sanger sequencing, biology, business.industry, Biochemistry (medical), General Medicine, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, 030104 developmental biology, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, Cancer cell, Mutation, Cancer research, Mutation testing, biology.protein, symbols, Adenocarcinoma, Female, KRAS, business
Abstract

Background:In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed.Methods:We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF.Results:Five patients showed mutations in one or two actionable genes, two harboured anEGFRmutation (exons 19 and 21), one only aKRASmutation, one bothEGFRandKRASmutations and one aBRAFmutation. In all cases, the results of mutation testing provided new major information for patient management, leading to therapeutic adaptation. CSF molecular analysis identified mutations not detected in other neoplastic sites for two patients. In one case, the EGFR p.Thr790Met was identified. CSF was also the only sample available for genetic testing for almost all patients at the time of disease progression.Conclusions:When cancer cells are present in the CSF, the molecular profiling from the cell pellets is relevant, as it can detect supplemental or different mutations compared to a previous analysis of the primitive tumour or plasma cell-free DNA and allows the adaptation of the treatment strategy.

Published
2018
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17. Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

Author

Valérie Delecourt, Sophie Perrin, Julien Guinde, Elise Kaspi, Nicolas Lévy, Philippe Astoul, Diane Frankel, Fabrice Barlesi, Patrice Roll, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), ProGeLife [Marseille], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Context (language use), Review, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, Epithelial–mesenchymal transition, Lung cancer, lcsh:QH301-705.5, business.industry, miR-9, Cancer, General Medicine, Cell cycle, medicine.disease, lung adenocarcinoma, 3. Good health, microRNAs, lung cancer, 030104 developmental biology, lcsh:Biology (General), lamins, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Cancer research, Nuclear lamina, business, Lamin
Abstract

International audience; Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear lamina, where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9.

Published
2018
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18. Identification of CD146 as a novel molecular actor involved in systemic sclerosis

Author

Elise Kaspi, Brigitte Granel, Alexandrine Bertaud-Foucault, Benjamin Guillet, Andrée Robaglia-Schlupp, Richard Bachelier, Audrey Benyamine, Aurélie S. Leroyer, Marie Nollet, Marcel Blot-Chabaud, Patrice Roll, Nathalie Bardin, Xavier Heim, Pierre Cau, Jimmy Stalin, Françoise Dignat-George, Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Assistance Publique - Hôpitaux de Marseille (APHM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Systemic blood, [SDV]Life Sciences [q-bio], Immunology, Computational biology, CD146 Antigen, Disease activity, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, Animals, Humans, Skin pathology, Cells, Cultured, Aged, Skin, Mice, Knockout, soluble CD146, Scleroderma, Systemic, business.industry, Biomarker, Fibroblasts, Middle Aged, Fibrosis, 3. Good health, 030104 developmental biology, CD146, 030220 oncology & carcinogenesis, Biomarker (medicine), Systemic sclerosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Identification (biology), Female, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; We highlight for the first time that CD146/sCD146 is involved in fibrotic process during SSc. sCD146 could thus constitute a new biomarker to assess disease activity, and potentially a new target for therapeutic applications.

Published
2017
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19. Morphology quiz: Mediastinal adenopathy cytology from endobronchial ultrasound transbronchial aspiration (EBUS-TBNA)

Author

Andrée Robaglia-Schlupp, Diane Frankel, Patrice Roll, Elise Kaspi, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Ebus tbna, medicine.medical_specialty, Histology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Mediastinal Neoplasms, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Cytology, medicine, Humans, Endobronchial ultrasound, ComputingMilieux_MISCELLANEOUS, business.industry, Biopsy, Needle, Prostatic Neoplasms, General Medicine, Middle Aged, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Radiology, business
Abstract

International audience

Published
2017
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20. Positive pleural cytology is an indicator for visceral pleural invasion in metastatic pleural effusions

Author

Dan Adler, Stavros Anevlavis, Elise Kaspi, Philippe Astoul, Georgia Karpathiou, Elisa Roca, Sophie Laroumagne, Hervé Dutau, Marios Froudarakis, Jérôme Pierre Olivier Plojoux, Democritus University of Thrace (DUTH), Hôpitaux Universitaires de Genève (HUG), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], University Hospital of Ioannina, Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division d'oncologie thoracique, Département des maladies pulmonaires, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre recherche en CardioVasculaire et Nutrition (C2VN)

Subjects
Male, Mesothelioma, Lung Neoplasms, Pleural effusion, medicine.medical_treatment, Thoracentesis, Gastroenterology, Malignant/epidemiology/pathology/surgery, 0302 clinical medicine, Cytology, Immunology and Allergy, Medicine, Malignant pleural effusion, 10. No inequality, Genetics (clinical), ddc:616, Survival Rate/trends, Univariate analysis, medicine.diagnostic_test, Greece, Incidence, Pleural Neoplasms/pathology, Exudates and Transudates, Middle Aged, respiratory system, Pleura/pathology, 3. Good health, Bloody, Survival Rate, Exudates and Transudates/cytology, 030220 oncology & carcinogenesis, Pleura, Female, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pleural Neoplasms, cytology, malignant pleural effusion, thoracoscopy, Greece/epidemiology, Lung Neoplasms/diagnosis/secondary, Mesothelioma/diagnosis/secondary, 03 medical and health sciences, Internal medicine, Thoracoscopy, Humans, Aged, Retrospective Studies, business.industry, Mesothelioma, Malignant, medicine.disease, Thoracentesis/methods, Pleural Effusion, Malignant, respiratory tract diseases, Pleural Effusion, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, business
Abstract

International audience; IntroductionIn case of undiagnosed pleural effusions, it is necessary to conduct thoracentesis with pleural fluid (PF) cytology. Yet, sensitivity of PF cytology is widely variable as a result of sample size, experience, and preparation method. ObjectivesThe aim of this study was to assess whether pleural fluid (PF) cytology is correlated to visceral or parietal pleural invasion as assessed by thoracoscopy in metastatic pleural effusions. MethodsAll records of patients with pleural effusion were reviewed. The inclusion criteria were as follows: PF cytology, reported appearance of macroscopic pleural invasion during thoracoscopy and malignant diagnosis. Patients with mesothelioma were excluded. Finally, 287 patients who met all criteria were selected. According to the thoracoscopy findings, the extent of the disease on the pleura was analyzed in relation to the PF cytology. ResultsIn this study, 160 patients (55.7%) had a positive PF cytology (Group A) while 127 (44.3%) recorded negative PF cytology (Group B). From Group A, patients with visceral pleural invasion were 120 (75%) while only 49 patients (38.5%) were found from Group B and the difference was statistically significant (P

Published
2017
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21. Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

Author

Stéphane Robert, Sophie Laroumagne, Sylvie Cointe, Alain Brisson, Elisa Roca, Patrice Roll, Coralie Judicone, Elise Kaspi, Romaric Lacroix, Philippe Astoul, Françoise Dignat-George, Claudio Tantucci, Alexandre Muller, Università degli Studi di Brescia = University of Brescia (UniBs), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Università degli Studi di Brescia [Brescia], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and DIGNAT-GEORGE, Françoise

Subjects
0301 basic medicine, Male, Pathology, EpCAM, extracellular vesicles, microparticles, pleural effusion, pleural neoplasia, Biomarkers, Tumor, Cell-Derived Microparticles, Cryoelectron Microscopy, Enzyme-Linked Immunosorbent Assay, Epithelial Cell Adhesion Molecule, Female, Flow Cytometry, Humans, Microscopy, Electron, Transmission, Neoplasms, Pleural Effusion, Malignant, Prospective Studies, Pleural effusion, [SDV]Life Sciences [q-bio], chemistry.chemical_compound, 0302 clinical medicine, Cytology, Medicine, Microscopy, Malignant, Tumor, medicine.diagnostic_test, Epithelial cell adhesion molecule, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Biomarker (medicine), Research Paper, medicine.medical_specialty, Electron, Flow cytometry, 03 medical and health sciences, Antigen, Carcinoma, Transmission, business.industry, Mucin, medicine.disease, respiratory tract diseases, 030104 developmental biology, chemistry, business, Biomarkers
Abstract

International audience; Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions.

Published
2016

22. Detection of EpCAM-positive microparticles in pleural fluid: A new approach for the diagnosis of the tumoral origin of pleural effusions

Author

Elisa Roca, Philippe Astoul, Sylvie Cointe, Sophie Laroumagne, Françoise Dignat-George, Alain Brisson, Claudio Tantucci, Elise Kaspi, Coralie Judicone, Patrice Roll, Romaric Lacroix, Stéphane Robert, and Alexandre Muller

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.disease, Highly sensitive, Flow cytometry, Pleurisy, Cytology, Pleural fluid, Medicine, Adenocarcinoma, Malignant pleural effusion, Stage (cooking), business
Abstract

Background: Pleural biomarkers are needed for the diagnosis of malignant pleural effusion at an early stage before true carcinomatosis. Tumor cells produce microparticles, and, therefore, we hypothesized that tumor-derived microparticles could be present in the pleural liquid and could help to identify patients with malignant pleural effusions by a non-invasive method. Methods: Fifty patients with benign (n=11) or malignant (n=39) pleural effusions were included in this study. Among them, 39 consecutive patients with histologically shown primary or metastatic pleural cancer were included. After the optimization of a sample processing protocols, MPs were enumerated by flow cytometry and the Cryo-Transmission Electron Microscopy was performed. Measurement of EpCAM-positive MPs was analyzed by ELISA. Results: Using highly sensitive flow cytometry and cryo-electron microscopy, this study showed the presence of microparticles in pleural effusions. We demonstrated the presence of tumor-derived microparticles expressing EpCAM (epithelial-cell-adhesion-molecule) in the pleural fluids from adenocarcinoma patients. In our cohort, the detection of EpCAM-positive microparticles was shown to be useful as a tool to complement cytology for better diagnoses of malignant pleurisies. Conclusions: To our knowledge, this is the first work to directly identify tumoral microparticles in pleural liquids using EpCAM. The identification of EpCAM+ microparticles could lead to a new diagnostic and monitoring approach. This study establishes the basis for a potential biomarker for diagnosing and monitoring malignant pleurisy.

Published
2015

23. Low lamin A expression in lung adenocarcinoma cells from pleural effusions is a pejorative factor associated with high number of metastatic sites and poor Performance status

Author

Pascale Tomasini, Elise Kaspi, Hervé Dutau, Diane Frankel, Nicolas Lévy, Sophie Laroumagne, Annachiara De Sandre-Giovannoli, Philippe Astoul, Andrée Robaglia-Schlupp, Patrice Roll, Pierre Cau, Kevin Ostacolo, Karim Harhouri, Joëlle Micallef, Sophie Perrin, Rachid Tazi-Mezalek, Julien Guinde, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Division d'oncologie thoracique, Département des maladies pulmonaires, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), ROLL, Patrice, and Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)

Subjects
Male, 0301 basic medicine, Pathology, Lung Neoplasms, Pulmonology, Protein Extraction, lcsh:Medicine, Fluorescent Antibody Technique, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Biochemistry, Lung and Intrathoracic Tumors, Metastasis, LMNA, 0302 clinical medicine, Adenocarcinomas, Basic Cancer Research, Medicine and Health Sciences, Neoplasm Metastasis, lcsh:Science, Adenocarcinoma Cells, Cultured Tumor Cells, Extraction Techniques, Aged, 80 and over, Multidisciplinary, Adenocarcinoma of the Lung, integumentary system, Middle Aged, Flow Cytometry, Lamin Type A, Lamins, Oncology, 030220 oncology & carcinogenesis, embryonic structures, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Nuclear lamina, Adenocarcinoma, Female, Biological Cultures, Research Article, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, animal structures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma of Lung, Biology, Research and Analysis Methods, World Health Organization, Carcinomas, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Adenocarcinoma of the lung, medicine, Humans, Epithelial–mesenchymal transition, Aged, lcsh:R, Mucin-1, Biology and Life Sciences, Proteins, Cancers and Neoplasms, Cancer, Cell Cultures, medicine.disease, Pleural Effusion, Cytoskeletal Proteins, 030104 developmental biology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Q, Lamin
Abstract

International audience; The type V intermediate filament lamins are the principal components of the nuclear matrix, including the nuclear lamina. Lamins are divided into A-type and B-type, which are encoded by three genes, LMNA, LMNB1, and LMNB2. The alternative splicing of LMNA produces two major A-type lamins, lamin A and lamin C. Previous studies have suggested that lamins are involved in cancer development and progression. A-type lamins have been proposed as biomarkers for cancer diagnosis, prognosis, and/or follow-up. The aim of the present study was to investigate lamins in cancer cells from metastatic pleural effusions using immunoflu-orescence, western blotting, and flow cytometry. In a subgroup of lung adenocarcinomas, we found reduced expression of lamin A but not of lamin C. The reduction in lamin A expression was correlated with the loss of epithelial membrane antigen (EMA)/MUC-1, an epithelial marker that is involved in the epithelial to mesenchymal transition (EMT). Finally, the lamin A expression was inversely correlated with the number of metastatic sites and the WHO Performance status, and association of pleural, bone and lung metastatic localizations was more frequent when lamin A expression was reduced. In conclusion, low lamin A but not lamin C expression in pleural metastatic cells could represent a major actor in the development of metastasis, associated with EMT and could account for a pejorative factor correlated with a poor Performance status.

Published
2017
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24. Identification of soluble CD146 as a regulator of trophoblast migration: potential role in placental vascular development

Author

Laka Rambeloson, Marcel Blot-Chabaud, Nadia Alfaidy, Alexandrine Bertaud-Foucault, Florence Bretelle, Marie-Dominique Piercecchi-Marti, Elise Kaspi, Benjamin Guillet, Françoise Dignat-George, Nathalie Bardin, Jimmy Stalin, Odile Lacroix, Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Cancer Research, MESH: Rats, Physiology, Angiogenesis, MESH: Trophoblasts, Placenta, Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, MESH: Flow Cytometry, CD146 Antigen, Biology, Andrology, Vasculogenesis, MESH: Pregnancy, Cell Movement, Pregnancy, medicine, Animals, Humans, MESH: Animals, MESH: Cell Movement, Cells, Cultured, Matrigel, MESH: Humans, Trophoblast, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Fertility, Embryo, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Flow Cytometry, medicine.disease, MESH: Placenta, Rats, Trophoblasts, Fertility, medicine.anatomical_structure, Immunology, CD146, Female, MESH: CD146 Antigen, MESH: Female, MESH: Cells, Cultured
Abstract

International audience; Both vasculogenesis and angiogenesis occur during normal placental vascular development. Additionally, the placenta undergoes a process of vascular mimicry (pseudo-vasculogenesis) where the placental extravillous trophoblast (EVT) that invade the spiral arteries convert from an epithelial to an endothelial phenotype during normal pregnancy. As soluble CD146 (sCD146) constitutes a new physiological factor with angiogenic properties, we hypothesized that it could be involved in the regulation of placental vascular development by acting on EVT. Using placental villous explants, we demonstrated that sCD146 inhibits EVT outgrowth. Consistently, we showed that sCD146 inhibits the ability of EVT cells (HTR8/SVneo) to migrate, invade and form tubes in Matrigel, without affecting their proliferation or apoptosis. The involvement of sCD146 in human pregnancy was investigated by evaluation of sCD146 levels in 50 pregnant women. We observed physiological down-regulation of sCD146 throughout pregnancy. These results prompted us to investigate the effect of prolonged sCD146 administration in a rat model of pregnancy. Repeated systemic sCD146 injections after coupling caused a significant decrease of pregnancy rate and number of embryos. Histological studies performed on placenta evidenced a reduced migration of glycogen cells (analogous to EVT in rat) in sCD146-treated rats. We propose that in human, sCD146 could represent both an attractive biomarker of placental vascular development and a therapeutic target in pregnancy complications associated with pathological angiogenesis.

Published
2014
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25. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective

Author

Pierre Cau, Karim Harhouri, Elise Kaspi, Claire Navarro, Patrice Roll, Sophie Perrin, Annachiara De Sandre-Giovannoli, Sabine Sigaudy, Nicolas Lévy, Perrin, Sophie, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Premature aging, Senescence, Aging, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, DNA Repair, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Bioinformatics, Vieillissement, Progeroid syndromes, Translational Research, Biomedical, Ataxia Telangiectasia, Mice, Progeria, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Humans, Nuclear matrix, Cellular Senescence, Nuclear Lamina, Aging, Premature, Cell Biology, medicine.disease, Lamin Type A, Lamins, 3. Good health, Aging diseases, Disease Models, Animal, Maladie du vieillissement, Physiological Aging, matrice nucléaire, Nuclear lamina, Protein Processing, Post-Translational, Lamin, Developmental Biology
Abstract

International audience; Lamin A-related progeroid syndromes are genetically determined, extremely rare and severe. In the past ten years, our knowledge and perspectives for these diseases has widely progressed, through the progressive dissection of their pathophysiological mechanisms leading to precocious and accelerated aging, from the genes mutations discovery until therapeutic trials in affected children. A-type lamins are major actors in several structural and functional activities at the nuclear periphery, as they are major components of the nuclear lamina. However, while this is usually poorly considered, they also play a key role within the rest of the nucleoplasm, whose defects are related to cell senescence. Although nuclear shape and nuclear envelope deformities are obvious and visible events, nuclear matrix disorganization and abnormal composition certainly represent the most important causes of cell defects with dramatic pathological consequences. Therefore, lamin-associated diseases should be better referred as laminopathies instead of envelopathies, this later being too restrictive, considering neither the key structural and functional roles of soluble lamins in the entire nucleoplasm, nor the nuclear matrix contribution to the pathophysiology of lamin-associated disorders and in particular in defective lamin A processing-associated aging diseases. Based on both our understanding of pathophysiological mechanisms and the biological and clinical consequences of progeria and related diseases, therapeutic trials have been conducted in patients and were terminated less than 10 years after the gene discovery, a quite fast issue for a genetic disease. Pharmacological drugs have been repurposed and used to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA in progeria. To date, none of them may be considered as a cure for progeria and these clinical strategies were essentially designed toward reducing a subset of the most dramatic and morbid features associated to progeria. New therapeutic strategies under study, in particular targeting the protein expression pathway at the mRNA level, have shown a remarkable efficacy both in vitro in cells and in vivo in mice models. Strategies intending to clear the toxic accumulated proteins from the nucleus are also under evaluation. However, although exceedingly rare, improving our knowledge of genetic progeroid syndromes and searching for innovative and efficient therapies in these syndromes is of paramount importance as, even before they can be used to save lives, they may significantly (i) expand the affected childrens' lifespan and preserve their quality of life; (ii) improve our understanding of aging-related disorders and other more common diseases; and (iii) expand our fundamental knowledge of physiological aging and its links with major physiological processes such as those involved in oncogenesis.

Published
2014
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26. HIV-1 Infection and First Line ART Induced Differential Responses in Mitochondria from Blood Lymphocytes and Monocytes: The ANRS EP45 'Aging' Study

Author

Nicolas Lévy, Leon Espinosa, Andrée Robaglia-Schlupp, Catherine Tamalet, Amélie Menard, Christel Pissier, Jonathan Cremer, Isabelle Poizot-Martin, Isabelle Arnoux, Corine Nicolino-Brunet, Jacques Reynes, Alissa Naqvi, Caroline Solas, Patrice Roll, Olivia Faucher, Pierre Cau, Pierre Dellamonica, Elisabeth Jouve, Joëlle Micallef, Sophie Perrin, Elise Kaspi, Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Service de Maladies Infectieuses [Nice], Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Fédération de Microbiologie Clinique, Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacocinétique Toxicocinétique - [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire de Génétique Moléculaire [Hôpital de la Timone - APHM], Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), ANRS EP45 ‘‘Aging’’, Sidaction grant [B/22-2-02032], Sidaction grant [A/19-3-01487], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Perrin, Sophie

Subjects
Male, Aging, Lymphocyte, lcsh:Medicine, Apoptosis, HIV Infections, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mitochondrion, Biochemistry, Monocytes, Cohort Studies, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Cell Biology, Viral load, Lymphocytes, lcsh:Science, Energy-Producing Organelles, Cellular Stress Responses, Membrane Potential, Mitochondrial, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, Flow Cytometry, 3. Good health, Antiretroviral therapy, Mitochondria, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Infectious diseases, HIV clinical manifestations, Female, Cellular Types, Research Article, Senescence, Mitochondrial DNA, Clinical Research Design, Anti-HIV Agents, T cells, Viral diseases, Biology, Bioenergetics, Peripheral blood mononuclear cell, Flow cytometry, 03 medical and health sciences, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, 030304 developmental biology, Blood Cells, Population Biology, lcsh:R, HIV, Case-Control Studies, Immunology, HIV-1, lcsh:Q, Cytometry
Abstract

Background The ANRS EP45 “Aging” study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence. Methods 49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was 500/mm3. ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting. Results Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria. Conclusions In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging. Trial Registration ClinicalTrials.gov NCT01038999 NCT01038999

Published
2012
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27. LETTERS TO THE EDITOR: Comparison of three low-ionic-strength solutions for routine pretransfusion testing: antibody screening/identification, cross-matching, immune anti-ABO detection, and direct antiglobulin tests

Author

Frédéric Mallié, Isabelle Dettori, Julia Gouvitsos, Elise Kaspi, Jacques Chiaroni, and V Ferrera

Subjects
Cross matching, Immune system, business.industry, ABO blood group system, Immunology, Immunology and Allergy, Medicine, Identification (biology), Hematology, business, Antibody screening, Low ionic strength
Published
2009
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