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1. Guidance framework to apply good practices in ecological data analysis: Lessons learned from building Galaxy-Ecology

Author

ROYAUX, Coline, primary, Mihoub, Jean-Baptiste, additional, Jossé, Marie, additional, Pelletier, Dominique, additional, Norvez, Olivier, additional, Reecht, Yves, additional, Fouilloux, Anne, additional, Rasche, Helena, additional, Hiltemann, Saskia, additional, Batut, Bérénice, additional, Eléaume, Marc, additional, Seguineau, Pauline, additional, Massé, Guillaume, additional, Amossé, Alan, additional, Bissery, Claire, additional, Lorrilliere, Romain, additional, Martin, Alexis, additional, Bas, Yves, additional, Virgoulay, Thimothée, additional, Chambon, Valentin, additional, Arnaud, Elie, additional, Michon, Elisa, additional, Urfer, Clara, additional, Trigodet, Eloïse, additional, Delannoy, Marie, additional, Loïs, Gregoire, additional, Julliard, Romain, additional, Grüning, Björn, additional, and Le Bras, Yvan, additional

Published
2024
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2. Guidance framework to apply good practices in ecological data analysis: Lessons learned from building Galaxy-Ecology

Author

Royaux, Coline, Mihoub, Jean-baptiste, Jossé, Marie, Pelletier, Dominique, Norvez, Olivier, Reecht, Yves, Fouilloux, Anne, Rasche, Helena, Hiltemann, Saskia, Batut, Bérénice, Eléaume, Marc, Seguineau, Pauline, Massé, Guillaume, Amossé, Alan, Bissery, Claire, Lorrilliere, Romain, Martin, Alexis, Bas, Yves, Virgoulay, Thimothée, Chambon, Valentin, Arnaud, Elie, Michon, Elisa, Urfer, Clara, Trigodet, Eloïse, Delannoy, Marie, Loïs, Gregoire, Julliard, Romain, Grüning, Björn, Le Bras, Yvan, The 17 Galaxy-e Community, Royaux, Coline, Mihoub, Jean-baptiste, Jossé, Marie, Pelletier, Dominique, Norvez, Olivier, Reecht, Yves, Fouilloux, Anne, Rasche, Helena, Hiltemann, Saskia, Batut, Bérénice, Eléaume, Marc, Seguineau, Pauline, Massé, Guillaume, Amossé, Alan, Bissery, Claire, Lorrilliere, Romain, Martin, Alexis, Bas, Yves, Virgoulay, Thimothée, Chambon, Valentin, Arnaud, Elie, Michon, Elisa, Urfer, Clara, Trigodet, Eloïse, Delannoy, Marie, Loïs, Gregoire, Julliard, Romain, Grüning, Björn, Le Bras, Yvan, and The 17 Galaxy-e Community

Abstract

Numerous conceptual frameworks exist for good practices in research data and analysis (e.g. Open Science and FAIR principles). In practice, there is a need for further progress to improve transparency, reproducibility, and confidence in ecology. Here, we propose a practical and operational framework to achieve good practices for building analytical procedures based on atomisation and generalisation. We introduce the concept of atomisation to identify analytical steps which support generalisation by allowing us to go beyond single analyses. These guidelines were established during the development of the Galaxy-Ecology initiative, a web platform dedicated to data analysis in ecology. Galaxy-Ecology allows us to demonstrate a way to reach higher levels of reproducibility in ecological sciences by increasing the accessibility and reusability of analytical workflows once atomised and generalised.

Published
2024
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3. Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial

Author

Welter, M.L., Cuny, E., Derkinderen, P., Fontaine, D., Houeto, J.L., Jalenques, I., Mallet, L., Pollak, P., Thobois, S., Bissery, A., Oya, H., Bardinet, E., Yelnik, J., Buot, A., Czernecki, V., du Montcel, S. Tezenas, Tanguy, A., Hajji, M., Karachi, C., Hartmann, A., Agid, Y., Worbe, Y., Dormont, D., Vidailhet, M., Cornu, P., Aouizerate, B., Burbaud, P., Durif, F., Fauchon, C., Rondepierre, F., Derost, P., Aya Kombo, M., Polosan, M., Chabardès, S., Krainik, A., Krack, P., Piallat, B., Guenot, M., Poulet, E., Klinger, H., Serra, G., Broussolle, E., Rouaud, T., Sauvaget, A., Damier, P., Raoul, S, Borg, M., Giordana, B., Magnie-Mauro, M.-N., Jaafari, N., Bataille, B., Ansquer, S., Benatru, I., Fradet, A., Dugast, E., Ouerdani, A., Rabois, E., Quintin, M., Palfi, S., Welter, Marie-Laure, Houeto, Jean-Luc, Thobois, Stéphane, Bataille, Benoit, Guenot, Marc, Worbe, Yulia, Hartmann, Andreas, Czernecki, Virginie, Bardinet, Eric, Yelnik, Jerome, du Montcel, Sophie Tezenas, Agid, Yves, Vidailhet, Marie, Cornu, Philippe, Tanguy, Audrey, Ansquer, Solène, Jaafari, Nematollah, Poulet, Emmanuel, Serra, Giulia, Burbaud, Pierre, Cuny, Emmanuel, Aouizerate, Bruno, Pollak, Pierre, Chabardes, Stephan, Polosan, Mircea, Borg, Michel, Fontaine, Denys, Giordana, Bruno, Raoul, Sylvie, Rouaud, Tiphaine, Sauvaget, Anne, Jalenques, Isabelle, Karachi, Carine, and Mallet, Luc

Published
2017
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6. Positron emission tomography with [18 F]‐ DPA ‐714 unveils a smoldering component in most multiple sclerosis lesions which drives disease progression

Author

Hamzaoui, Mariem, primary, Garcia, Jeanne, additional, Boffa, Giacomo, additional, Lazzarotto, Andrea, additional, Absinta, Martina, additional, Ricigliano, Vito A.G., additional, Soulier, Theodore, additional, Tonietto, Matteo, additional, Gervais, Philippe, additional, Bissery, Anne, additional, Louapre, Céline, additional, Bottlaender, Michel, additional, Bodini, Benedetta, additional, and Stankoff, Bruno, additional

Published
2023
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7. Positron Emission Tomography with [ <scp> 18 F </scp> ]‐ <scp>DPA</scp> ‐714 Unveils a Smoldering Component in Most Multiple Sclerosis Lesions which Drives Disease Progression

Author

Mariem Hamzaoui, Jeanne Garcia, Giacomo Boffa, Andrea Lazzarotto, Martina Absinta, Vito A.G. Ricigliano, Theodore Soulier, Matteo Tonietto, Philippe Gervais, Anne Bissery, Céline Louapre, Michel Bottlaender, Benedetta Bodini, and Bruno Stankoff

Subjects
Neurology, Neurology (clinical)
Published
2023
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8. Supplemental Table S2 from GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Author

Van Damme, Pierre, primary, Bouillette-Marussig, Myriam, primary, Hens, Annick, primary, De Coster, Ilse, primary, Depuydt, Christophe, primary, Goubier, Anne, primary, Van Tendeloo, Viggo, primary, Cools, Nathalie, primary, Goossens, Herman, primary, Hercend, Thierry, primary, Timmerman, Benedikt, primary, and Bissery, Marie-Christine, primary

Published
2023
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9. Supplementary Table 1 from Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

Author

Galmarini, Carlos M., primary, Treilleux, Isabelle, primary, Cardoso, Fatima, primary, Bernard-Marty, Chantal, primary, Durbecq, Virginie, primary, Gancberg, David, primary, Bissery, Marie-Christine, primary, Paesmans, Marianne, primary, Larsimont, Denis, primary, Piccart, Martine J., primary, Di Leo, Angelo, primary, and Dumontet, Charles, primary

Published
2023
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11. Supplementary Tables from Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Author

Idbaih, Ahmed, primary, Canney, Michael, primary, Belin, Lisa, primary, Desseaux, Carole, primary, Vignot, Alexandre, primary, Bouchoux, Guillaume, primary, Asquier, Nicolas, primary, Law-Ye, Bruno, primary, Leclercq, Delphine, primary, Bissery, Anne, primary, De Rycke, Yann, primary, Trosch, Clementine, primary, Capelle, Laurent, primary, Sanson, Marc, primary, Hoang-Xuan, Khe, primary, Dehais, Caroline, primary, Houillier, Caroline, primary, Laigle-Donadey, Florence, primary, Mathon, Bertrand, primary, André, Arthur, primary, Lafon, Cyril, primary, Chapelon, Jean-Yves, primary, Delattre, Jean-Yves, primary, and Carpentier, Alexandre, primary

Published
2023
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12. Supplemental Figures S1-S6 from GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Author

Van Damme, Pierre, primary, Bouillette-Marussig, Myriam, primary, Hens, Annick, primary, De Coster, Ilse, primary, Depuydt, Christophe, primary, Goubier, Anne, primary, Van Tendeloo, Viggo, primary, Cools, Nathalie, primary, Goossens, Herman, primary, Hercend, Thierry, primary, Timmerman, Benedikt, primary, and Bissery, Marie-Christine, primary

Published
2023
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13. Supplemental Methods from GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Author

Van Damme, Pierre, primary, Bouillette-Marussig, Myriam, primary, Hens, Annick, primary, De Coster, Ilse, primary, Depuydt, Christophe, primary, Goubier, Anne, primary, Van Tendeloo, Viggo, primary, Cools, Nathalie, primary, Goossens, Herman, primary, Hercend, Thierry, primary, Timmerman, Benedikt, primary, and Bissery, Marie-Christine, primary

Published
2023
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15. Supplementary Table 1 from Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

Author

Charles Dumontet, Angelo Di Leo, Martine J. Piccart, Denis Larsimont, Marianne Paesmans, Marie-Christine Bissery, David Gancberg, Virginie Durbecq, Chantal Bernard-Marty, Fatima Cardoso, Isabelle Treilleux, and Carlos M. Galmarini

Abstract

Supplementary Table 1 from Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

Published
2023
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17. Supplementary Table S5 from Preclinical Antitumor Activity of Cabazitaxel, a Semisynthetic Taxane Active in Taxane-Resistant Tumors

Author

Marie-Christine Bissery, François Lavelle, Alain Commerçon, Jean-François Riou, Cecile Combeau, Loreley Calvet, Hervé Bouchard, Pascale Lejeune, Dorothée Sémiond, and Patricia Vrignaud

Abstract

Supplementary Table S5 - PDF file 68K, In vitro antiproliferative effects of cabazitaxel against cell lines resistant to standard clinical agents not expressing P-glycoprotein

Published
2023
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18. Data from Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Author

Alexandre Carpentier, Jean-Yves Delattre, Jean-Yves Chapelon, Cyril Lafon, Arthur André, Bertrand Mathon, Florence Laigle-Donadey, Caroline Houillier, Caroline Dehais, Khe Hoang-Xuan, Marc Sanson, Laurent Capelle, Clementine Trosch, Yann De Rycke, Anne Bissery, Delphine Leclercq, Bruno Law-Ye, Nicolas Asquier, Guillaume Bouchoux, Alexandre Vignot, Carole Desseaux, Lisa Belin, Michael Canney, and Ahmed Idbaih

Abstract

Purpose:The blood–brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations.Patients and Methods:A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy.Results:Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption (n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months.Conclusions:SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity.See related commentary by Sonabend and Stupp, p. 3750

Published
2023
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19. Data from GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Author

Marie-Christine Bissery, Benedikt Timmerman, Thierry Hercend, Herman Goossens, Nathalie Cools, Viggo Van Tendeloo, Anne Goubier, Christophe Depuydt, Ilse De Coster, Annick Hens, Myriam Bouillette-Marussig, and Pierre Van Damme

Abstract

Purpose: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if high-grade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology.Experimental Design: This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 μg GTL001 + topical 5% imiquimod cream at the injection site. In a double-blind part, subjects were randomized 2:1:1 to two vaccinations 6 weeks apart of 600 μg GTL001 + imiquimod, 600 μg GTL001 + placebo cream, or placebo + imiquimod.Results: Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 μg GTL001 + imiquimod group. In post hoc analyses, the 600 μg GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigen-specific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA.Conclusions: For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. Clin Cancer Res; 22(13); 3238–48. ©2016 AACR.

Published
2023
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20. Data from Preclinical Antitumor Activity of Cabazitaxel, a Semisynthetic Taxane Active in Taxane-Resistant Tumors

Author

Marie-Christine Bissery, François Lavelle, Alain Commerçon, Jean-François Riou, Cecile Combeau, Loreley Calvet, Hervé Bouchard, Pascale Lejeune, Dorothée Sémiond, and Patricia Vrignaud

Abstract

Purpose: Taxanes are important chemotherapeutic agents with proven efficacy in human cancers, but their use is limited by resistance development. We report here the preclinical characteristics of cabazitaxel (XRP6258), a semisynthetic taxane developed to overcome taxane resistance.Experimental Design: Cabazitaxel effects on purified tubulin and on taxane-sensitive or chemotherapy-resistant tumor cells were evaluated in vitro. Antitumor activity and pharmacokinetics of intravenously administered cabazitaxel were assessed in tumor-bearing mice.Results:In vitro, cabazitaxel stabilized microtubules as effectively as docetaxel but was 10-fold more potent than docetaxel in chemotherapy-resistant tumor cells (IC50 ranges: cabazitaxel, 0.013–0.414 μmol/L; docetaxel, 0.17–4.01 μmol/L). The active concentrations of cabazitaxel in these cell lines were achieved easily and maintained for up to 96 hours in the tumors of mice bearing MA16/C tumors treated with cabazitaxel at 40 mg/kg. Cabazitaxel exhibited antitumor efficacy in a broad spectrum of murine and human tumors (melanoma B16, colon C51, C38, HCT 116, and HT-29, mammary MA17/A and MA16/C, pancreas P03 and MIA PaCa-2, prostate DU 145, lung A549 and NCI-H460, gastric N87, head and neck SR475, and kidney Caki-1). Of particular note, cabazitaxel was active in tumors poorly sensitive or innately resistant to docetaxel (Lewis lung, pancreas P02, colon HCT-8, gastric GXF-209, mammary UISO BCA-1) or with acquired docetaxel resistance (melanoma B16/TXT).Conclusions: Cabazitaxel is as active as docetaxel in docetaxel-sensitive tumor models but is more potent than docetaxel in tumor models with innate or acquired resistance to taxanes and other chemotherapies. These studies were the basis for subsequent clinical evaluation. Clin Cancer Res; 19(11); 2973–83. ©2013 AACR.

Published
2023
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22. Supplementary Tables from Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Author

Alexandre Carpentier, Jean-Yves Delattre, Jean-Yves Chapelon, Cyril Lafon, Arthur André, Bertrand Mathon, Florence Laigle-Donadey, Caroline Houillier, Caroline Dehais, Khe Hoang-Xuan, Marc Sanson, Laurent Capelle, Clementine Trosch, Yann De Rycke, Anne Bissery, Delphine Leclercq, Bruno Law-Ye, Nicolas Asquier, Guillaume Bouchoux, Alexandre Vignot, Carole Desseaux, Lisa Belin, Michael Canney, and Ahmed Idbaih

Abstract

Supplementary Table 1. The acoustic pressure levels are determined by a calibration of the implants in water prior to implantation in patients. The 95% confidence interval given in the table denotes the measurement uncertainty inherent to this process. Acoustic pressure levels reported previously (19) were re-evaluated using enhanced acoustic calibration methods with reduced uncertainty. The former values are given in the pold column to ease comparison with our previous publication. Supplementary Table 2. BBB disruption grade and acoustic pressure. Data are n (%). Supplementary Table 3. The secondary outcomes of the trial were calculated based on the grading assigned to post-contrast MR images evaluating the level of BBB disruption. Greater amounts of post-sonication BBB disruption resulted in a trend towards longer PFS and OS.

Published
2023
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24. Supplemental Figures S1-S6 from GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Author

Marie-Christine Bissery, Benedikt Timmerman, Thierry Hercend, Herman Goossens, Nathalie Cools, Viggo Van Tendeloo, Anne Goubier, Christophe Depuydt, Ilse De Coster, Annick Hens, Myriam Bouillette-Marussig, and Pierre Van Damme

Abstract

Mean background corrected ELISpot magnitudes

Published
2023
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25. Primary progressive aphasias associated with C9orf72 expansions: Another side of the story

Author

idier Hannequin, Eino Solje, Sabrina Sayah, Emmanuel Gerardin, Marie Sarazin, Florence Pasquier, Marion Houot, Assi-Hervé Oya, Martine Vercelletto, Julien Lagarde, Marie Noguès-Lassiaille, Marie Chupin, Vincent Deramecourt, Sophie Auriacombe, Agnès Camuzat, Marc Teichmann, Jérémie Pariente, Sophie Ferrieux, Lucette Lacomblez, Mathieu Chastan, Jacques Monteil, Yaohua Chen, Marie-Paule Boncoeur, Lorenzo Cipriano, Anne Bissery, Simona Bottani, David Wallon, Christine Delmaire, Carole Roué-Jagot, Benjamin Le Toullec, Bernard-François Michel, Grégory Petyt, Olivier Martinaud, Philippe Couratier, Dario Saracino, Adeline Rollin-Sillaire, Daisy Rinaldi, Mira Didic, Serge Belliard, Amandine Géraudie, Géraldine Lautrette, Frédérique Etcharry-Bouyx, Xavier Delbeuck, Richard Levy, Frédéric Blanc, Mathieu Ceccaldi, Christel Thauvin-Robinet, Marie-Odile Habert, Eve Benchetrit, Maïté Formaglio, Alexis Brice, Isabelle Le Ber, Charles Duyckaerts, Véronique Golfier, Raffaella Migliaccio, Marie-Anne Mackowiak, Catherine Thomas-Antérion, Anne Bertrand, Olivier Colliot, François Sellal, Claire Boutoleau-Bretonnière, Anne M. Remes, Hugo Bertin, Aurélie Funkiewiez, and Stéphanie Bombois

Subjects
medicine.medical_specialty, C9orf72 Protein, Apraxias, Cognitive Neuroscience, Inferior frontal gyrus, Experimental and Cognitive Psychology, Frontotemporal lobar degeneration, respiratory system, Audiology, medicine.disease, Magnetic Resonance Imaging, Apraxia, Primary progressive aphasia, Aphasia, Primary Progressive, Neuropsychology and Physiological Psychology, Atrophy, C9orf72, medicine, Humans, Speech, Orbitofrontal cortex, Psychology, Language, Frontotemporal dementia
Abstract

C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them. This study depicts the spectrum of C9orf72–related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant. Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.

Published
2021
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27. Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers

Author

Brice, Alexis, Auriacombe, Sophie, Belliard, Serge, Blanc, Frédéric, Bouteleau-Bretonnière, Claire, Ceccaldi, Mathieu, Couratier, Philippe, Didic, Mira, Dubois, Bruno, Duyckaerts, Charles, Etcharry-Bouix, Frédérique, Golfier, Véronique, Hannequin, Didier, Lacomblez, Lucette, Le Ber, Isabelle, Levy, Richard, Michel, Bernard-François, Pasquier, Florence, Thomas-Anterion, Catherine, Pariente, Jérémie, Sellal, François, Vercelletto, Martine, Benchetrit, Eve, Bertin, Hugo, Bertrand, Anne, Bissery, Anne, Bombois, Stéphanie, Boncoeur, Marie-Paule, Cassagnaud, Pascaline, Chastan, Mathieu, Chen, Yaohua, Chupin, Marie, Colliot, Olivier, Delbeucq, Xavier, Deramecourt, Vincent, Delmaire, Christine, Gerardin, Emmanuel, Hossein-Foucher, Claude, Habert, Marie-Odile, Lautrette, Géraldine, Lebouvier, Thibaud, Lehéricy, Stéphane, Le Toullec, Benjamin, Martineau, Kelly, Mackowiak, Marie-Anne, Monteil, Jacques, Petyt, Grégory, Pradat, Pierre-François, Oya, Assi-Hervé, Rinaldi, Daisy, Rollin-Sillaire, Adeline, Salachas, François, Sayah, Sabrina, Wallon, David, Fournier, Clémence, Barbier, Mathieu, Camuzat, Agnès, Anquetil, Vincent, Lattante, Serena, Clot, Fabienne, Cazeneuve, Cécile, Sabatelli, Mario, Forlani, Sylvie, Jornea, Ludmila, and Leguern, Eric

Published
2019
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28. Positron Emission Tomography with [18F]‐DPA‐714 Unveils a Smoldering Component in Most Multiple Sclerosis Lesions which Drives Disease Progression.

Author

Hamzaoui, Mariem, Garcia, Jeanne, Boffa, Giacomo, Lazzarotto, Andrea, Absinta, Martina, Ricigliano, Vito A.G., Soulier, Theodore, Tonietto, Matteo, Gervais, Philippe, Bissery, Anne, Louapre, Céline, Bottlaender, Michel, Bodini, Benedetta, and Stankoff, Bruno

Subjects
POSITRON emission tomography, DISEASE progression, MULTIPLE sclerosis, CEREBRAL atrophy, MAGNETIC resonance imaging
Abstract

Objective: To determine the prognostic value of persisting neuroinflammation in multiple sclerosis (MS) lesions, we developed a 18 kDa‐translocator‐protein‐positron emission tomography (PET) ‐based classification of each lesion according to innate immune cell content and localization. We assessed the respective predictive value of lesion phenotype and diffuse inflammation on atrophy and disability progression over 2 years. Methods: Thirty‐six people with MS (disease duration 9 ± 6 years; 12 with relapsing–remitting, 13 with secondary‐progressive, and 11 with primary‐progressive) and 19 healthy controls (HCs) underwent a dynamic [18F]‐DPA‐714‐PET. At baseline and after 2 years, the patients also underwent a magnetic resonance imaging (MRI) and neurological examination. Based on a threshold of significant inflammation defined by a comparison of [18F]‐DPA‐714 binding between patients with MS and HCs, white matter lesions were classified as homogeneously active (active center), rim‐active (inactive center and active periphery), or nonactive. Longitudinal cortical atrophy was measured using Jacobian integration. Results: Patients with MS had higher innate inflammation in normal‐appearing white matter (NAWM) and cortex than HCs (respective standardized effect size = 1.15, 0.89, p = 0.003 and < 0.001). Out of 1,335 non‐gadolinium‐enhancing lesions, 53% were classified as homogeneously‐active (median = 17 per patient with MS), 6% rim‐active (median = 1 per patient with MS), and 41% non‐active (median = 14 per patient with MS). The number of homogenously‐active lesions was the strongest predictor of longitudinal changes, associating with cortical atrophy (β = 0.49, p = 0.023) and Expanded Disability Status Scale (EDSS) changes (β = 0.35, p = 0.023) over 2 years. NAWM and cortical binding were not associated to volumetric and clinical changes. Interpretation: The [18F]‐DPA‐714‐PET revealed that an unexpectedly high proportion of MS lesions have a smoldering component, which predicts atrophy and clinical progression. This suggests that following the acute phase, most lesions develop a chronic inflammatory component, promoting neurodegeneration and clinical progression. ANN NEUROL 2023;94:366–383 [ABSTRACT FROM AUTHOR]

Published
2023
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29. GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression.

Author

Michaël Esquerré, Myriam Bouillette-Marussig, Anne Goubier, Marie Momot, Christophe Gonindard, Hélène Keller, Astrid Navarro, and Marie-Christine Bissery

Subjects
Medicine, Science
Abstract

BACKGROUND:Prophylactic vaccines are available for women and girls not yet infected with HPV, but women already infected with HPV need a treatment to prevent progression to high-grade cervical lesions and cancer. GTL001 is a bivalent therapeutic vaccine for eradicating HPV-infected cells that contains HPV16 E7 and HPV18 E7 both fused to detoxified adenylate cyclase from Bordetella pertussis, which binds specifically to CD11b+ antigen-presenting cells. This study examined the ability of therapeutic vaccination with GTL001 adjuvanted with topical imiquimod cream to induce functional HPV16 E7- and HPV18 E7-specific CD8+ T cell responses. METHODS:Binding of GTL001 to human CD11b was assessed by a cell-based competition binding assay. Cellular immunogenicity of intradermal vaccination with GTL001 was assessed in C57BL/6 mice by enzyme-linked immunospot assay and in vivo killing assays. In vivo efficacy of GTL001 vaccination was investigated in the TC-1 murine HPV16 E7-expressing tumor model. RESULTS:GTL001 bound specifically to the human CD11b/CD18 receptor. GTL001 adjuvanted with topical 5% imiquimod cream induced HPV16 E7 and HPV18 E7-specific CD8+ T cell responses. This CD8+ T-cell response mediated in vivo killing of HPV E7-expressing cells. In the HPV16 E7-expressing tumor model, GTL001 adjuvanted with imiquimod but not imiquimod alone or a combination of unconjugated HPV16 E7 and HPV18 E7 caused complete tumor regression. CONCLUSIONS:GTL001 adjuvanted with topical 5% imiquimod is immunogenic and induces HPV16 E7 and HPV18 E7-specific CD8+ T cell responses that can kill HPV E7-expressing cells and eliminate HPV E7-expressing tumors.

Published
2017
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30. From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase

Author

Mailliet, Patrick, Laoui, Abdel, Bourzat, Jean-Dominique, Capet, Marc, Chevé, Michel, Commerçon, Alain, Dereu, Norbert, LeBrun, Alain, Martin, Jean-Paul, Peyronel, Jean-François, Salagnad, Christophe, Thompson, Fabienne, Zucco, Martine, Guitton, Jean-Dominique, Pantel, Guy, Bissery, Marie-Christine, Brealey, Clive, Lavayre, Jacques, Lelièvre, Yves, Riou, Jean-François, Vrignaud, Patricia, Duchesne, Marc, Lavelle, François, Teicher, Beverly A., editor, Sebti, Saïd M., editor, and Hamilton, Andrew D., editor

Published
2001
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31. The Taxoids

Author

Bissery, Marie-Christine, Lavelle, François, and Teicher, Beverly A., editor

Published
1997
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32. Colectomia eletiva laparoscópica esquerda para a doença diverticular: estudo monocêntrico sobre 205 pacientes consecutivos Elective laparoscopic left colectomy for diverticular disease: a monocentric study on 205 consecutive patients

Author

João Odilo Gonçalves Pinto, Basmah Fallatah, Phillipe Espalieu, Gilles Poncet, Alvine Bissery, Fernando Antonio Siqueira Pinheiro, and Jean-Claude Boulez

Subjects
Colectomia laparoscópica, Diverticulite, Colectomy, laparoscopic Diverticulitis, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

RACIONAL: O aumento da prevalência de doença diverticular tornou o seu manuseio mais adequado uma questão de debate constante. Especialmente para os casos de diverticulite, progresso considerável tem sido feito em termos de diagnóstico e tratamento. A ressecção cirúrgica do cólon envolvido é a única maneira de erradicar definitivamente essa condição e, portanto, a colectomia laparoscópica eletiva surgiu como uma opção segura e interessante entre as várias formas de tratamento. OBJETIVO: Analisar os resultados das colectomias laparoscópicas esquerdas para a doença diverticular realizadas durante um período de 17 anos em uma única instituição. MÉTODOS: Entre abril de 1990 e maio de 2007, um total de 205 colectomias consecutivas esquerdas laparoscópicas foram revistas retrospectivamente. Os dados obtidos incluíram o pré-operatório, indicações para a operação, os dados cirúrgicos, complicações e seguimento. Análises estatísticas univariada e multivariada foram realizadas em um esforço para identificar os fatores de risco e efeitos adversos na série. RESULTADOS: As indicações foram diverticulite aguda (80%) não-complicada, diverticulite aguda ou crônica complicada (18,05%) e sangramento na doença diverticular (1,95%). A taxa de conversão foi de 5,85% (12 casos). A mediana do tempo operatório foi de 180 minutos (100-420), com internação hospitalar de 7 (5-44) dias. O comprimento médio do espécime ressecado foi 29,12 centímetros. A maioria dos casos (88,3%) teve curso pós-operatório normal, mas complicações ocorreram em 24 (11,7%) pacientes. Em ordem de frequência foram: íleo paralítico (n = 6), coleções pélvica (n = 4), obstruções intestinais (n = 4) e fístulas (n = 2), entre outros. Re-operação foi necessária em oito casos e houve um óbito (0,48%). O seguimento mediano foi de 26,5 (1-156) meses, com resultado satisfatório em 179 (87,32%) dos pacientes. Em 18 (8,78%) casos, os sintomas persistentes de distúrbios funcionais do cólon foram anotados. Houve sete (3,41%), estenoses da anastomose e em dois precisou de re-operação. A taxa de recidiva foi de 1,95% (4 casos). Idade e complicações intra-operatórias foram identificadas como fatores de risco para a conversão. A presença de lesões associadas foi significativamente correlacionada com a persistência de sintomas funcionais do cólon durante o seguimento. CONCLUSÕES: A colectomia laparoscópica esquerda é segura e eficaz em comparação com todas as outras modalidades de tratamento da doença diverticular. Diagnóstico preciso e cuidado nas indicações são essenciais para atingir bons resultados.BACKGROUND: The increased prevalence of diverticular disease has made its most appropriate management a matter of constant debate. Especially for the cases of diverticulitis, considerable progress has been made in terms of diagnosis and management. The surgical resection of the involved colon is the only means of definitely eradicate this condition and so, the elective laparoscopic colectomy has emerged as a safe and interesting choice among the options of treatment. AIM: To analyze the outcomes of the laparoscopic left colectomy for diverticular disease performed over a 17-year period at a single institution. METHODS: Between April 1990 and May 2007, a total of 205 consecutive left laparoscopic colectomies were retrospectively reviewed. Data obtained included the pre-operative work-up, indications for surgery, operative results, complications and follow-up. Univariate and multivariate statistical analyzes were performed in an effort to identity risk factors for adverse outcomes in the series. RESULTS: Indications were for non-complicated acute diverticulitis (80%), acute or chronic complicated diverticulitis (18.05%) and bleeding diverticular disease (1.95%). The conversion rate was 5.85% (12 cases). The median operative time was 180 (100-420) min with a hospital stay of 7 (5-44) days. The mean length of the resected specimen was 29.12 (+8.2) cm. Most cases (88.3%) had an unremarkable postoperative course but complications occurred in 24 (11.7%) patients. In order of frequency, these were: paralytic ileus (n=6), pelvic collections (n=4), bowel obstructions (n=4) and fistulas (n=2), among others. A re-operation was necessary in eight cases and there was one death (0.48%). Median follow-up was 26.5 (1-156) months with a satisfying result seen in 179 (87.32%) of the patients. In 18 (8.78%) cases, persistent symptoms of functional colonic disorders were noted. There were 7 (3.41%) anastomotic stenosis in witch two needed a re-operation. The recurrence rate was 1.95% (4 cases). Age and intraoperative complications were identified as risk factors for conversion. The presence of associated lesions was significantly correlated with the persistence of functional colonic symptoms during the follow-up. CONCLUSIONS: The laparoscopic left colectomy is safe and effective in comparison to all other modalities of management for diverticular disease. Precise diagnosis and respect of the current indications are essential to achieve such results.

Published
2010
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34. Anemia normalization in patients with type 2 diabetes and chronic kidney disease: results of the NEPHRODIAB2 randomized trial

Author

Villar, Emmanuel, Lièvre, Michel, Kessler, Michèle, Lemaître, Vincent, Alamartine, Eric, Rodier, Michel, François, Maud, Zaoui, Philippe, Moranne, Olivier, Choukroun, Gabriel, Guerraoui, Abdallah, Jolivot, Anne, Janin, Gérard, Branger, Bernard, Heng, Anne-Elisabeth, Boudray, Catherine, Bissery, Alvine, Rabilloud, Muriel, and Pouteil-Noble, Claire

Published
2011
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37. Discovery of Solid Tumor Active Agents Using a Soft-Agar-Colony-Formation Disk-Diffusion-Assay

Author

Corbett, Thomas H., Valeriote, Frederick A., Polin, Lisa, Panchapor, Chiab, Pugh, Susan, White, Kathryn, Lowichik, Nancy, Knight, Juiwanna, Bissery, Marie-Christine, Wozniak, Antoinette, LoRusso, Patricia, Biernat, Laura, Polin, Daniel, Knight, Lentawn, Biggar, Sandra, Looney, Darrell, Demchik, Lisa, Jones, Julie, Jones, Lynne, Blair, Scott, Palmer, Kerry, Essenmacher, Sandra, Lisow, Loretta, Mattes, Ken C., Cavanaugh, Paul F., Rake, James B., Baker, Laurence, Valeriote, Frederick A., editor, Corbett, Thomas H., editor, and Baker, Laurence H., editor

Published
1992
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40. SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration

Author

Barbier, Mathieu, Camuzat, Agnès, Hachimi, Khalid El, Guegan, Justine, Rinaldi, Daisy, Lattante, Serena, Houot, Marion, Sánchez-Valle, Raquel, Sabatelli, Mario, Antonell, Anna, Molina-Porcel, Laura, Clot, Fabienne, Couratier, Philippe, van der Ende, Emma, van der Zee, Julie, Manzoni, Claudia, Camu, William, Cazeneuve, Cécile, Sellal, François, Didic, Mira, Golfier, Véronique, Pasquier, Florence, Duyckaerts, Charles, Rossi, Giacomina, Bruni, Amalia C, Alvarez, Victoria, Gómez-Tortosa, Estrella, de Mendonça, Alexandre, Graff, Caroline, Masellis, Mario, Nacmias, Benedetta, Oumoussa, Badreddine Mohand, Jornea, Ludmila, Forlani, Sylvie, Van Deerlin, Viviana, Rohrer, Jonathan D, Gelpi, Ellen, Rademakers, Rosa, Van Swieten, John, Le Guern, Eric, Van Broeckhoven, Christine, Ferrari, Raffaele, Génin, Emmanuelle, Brice, Alexis, Ber, Le, Isabelle Alexis Brice, Sophie, Auriacombe, Serge, Belliard, Anne, Bertrand, Anne, Bissery, Fre ́ de, ́ ric Blanc, Marie-Paule, Boncoeur, Ste, ́ phanie Bombois, Claire Boutoleau-Bretonnie` re, Agne`, s Camuzat, Mathieu, Ceccaldi, Marie, Chupin, Philippe, Couratier, Olivier, Colliot, Vincent, Deramecourt, Mira, Didic, Bruno, Dubois, Charles, Duyckaerts, Fre ́ de, ́ rique Etcharry-Bouyx, Aure, ́ lie Guignebert-Funkiewiez, Maı ̈te, ́ Formaglio, ́ ronique Golfier, Ve, Marie-Odile, Habert, Didier, Hannequin, Lucette, Lacomblez, Julien, Lagarde, ́ raldine Lautrette, Ge, Isabelle Le Ber, Benjamin Le Toullec, Richard, Levy, Marie-Anne, Mackowiak, Bernard-Franc ̧ois Michel, Florence, Pasquier, Thibaud, Lebouvier, Carole Roue, ́ -Jagot, Christel Thauvin- Robinet, Catherine, Thomas-Anterion, Je ́ re, ́ mie Pariente, Franc ̧ois Salachas, Sabrina, Sayah, Franc ̧ois Sellal, Assi-Herve, ́ Oya, Daisy, Rinaldi, Adeline, Rollin-Sillaire, Martine, Vercelletto, David, Wallon, Armelle, Rametti-Lacroux, Raffaele, Ferrari, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Adaikalavan, Ramasamy, Kwok, John B. J., Carol Dobson- Stone, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Olivier, Piguet, Lauren, Bartley, Elizabeth, Thompson, Isabel Herna, ́ ndez, Agustı ́n Ruiz, Merce`, Boada, Barbara, Borroni, Alessandro, Padovani, Carlos, Cruchaga, Cairns, Nigel J., Luisa, Benussi, Giuliano, Binetti, Roberta, Ghidoni, Gianluigi, Forloni, Diego, Albani, Daniela, Galimberti, Chiara, Fenoglio, Maria, Serpente, Elio, Scarpini, ́ n, Jordi Clarimo, Alberto Lleo, ́, Rafael, Blesa, Maria Landqvist Waldo, ̈, Karin, Nilsson, Christer, Nilsson, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Jordan, Grafman, Morris, Christopher M., Johannes, Attems, Griffiths, Timothy D., Mckeith, Ian G., Thomas, Alan J., Pietro, Pietrini, Edward, Uey, Wassermann, Eric M., Atik, Baborie, Evelyn, Jaros, Tierney, Michael C., Pau, Pastor, Cristina, Razquin, Sara, Ortega-Cubero, Elena, Alonso, Robert, Perneczky, Janine, Diehl-Schmid, Panagiotis, Alexopoulos, Alexander, Kurz, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Ekaterina, Rogaeva, Peter St George-Hyslop, Giacomina, Rossi, Fabrizio, Tagliavini, Giorgio, Giaccone, Rowe, James B., Schlachetzki, Johannes C. M., James, Uphill, John, Collinge, Simon, Mead, Adrian, Danek, Van Deerlin, Vivianna M., Murray, Grossman, Trojanowski, John Q., Julie van der Zee, Christine Van Broeckhoven, Cappa, Stefano F., Isabelle, Leber, Alexis, Brice, Benedetta, Nacmias, Sandro, Sorbi, Silvia, Bagnoli, Irene, Piaceri, Nielsen, Jørgen E., Hjermind, Lena E., Matthias, Riemenschneider, Manuel, Mayhaus, Bernd, Ibach, Gilles, Gasparoni, Sabrina, Pichler, Wei, Gu, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Maria Grazia Spillantini, Morris, Huw R., Patrizia, Rizzu, Peter, Heutink, Snowden, Julie S., Sara, Rollinson, Anna, Richardson, Alexander, Gerhard, Bruni, Amalia C., Raffaele, Maletta, Francesca, Frangipane, Chiara, Cupidi, Livia, Bernardi, Maria, Anfossi, Maura, Gallo, Maria Elena Conidi, Nicoletta, Smirne, Rosa, Rademakers, Matt, Baker, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., David, Knopman, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Howard, Rosen, van Swieten, John C., Dopper, Elise G. P., Harro, Seelaar, Pijnenburg, Yolande A. L., Philip, Scheltens, Giancarlo, Logroscino, Rosa, Capozzo, Valeria, Novelli, Puca, Annibale A., Massimo, Franceschi, Alfredo, Postiglione, Graziella, Milan, Paolo, Sorrentino, Mark, Kristiansen, Huei-Hsin, Chiang, Caroline, Graff, Adeline, Rollin, Dimitrios, Kapogiannis, Luigi, Ferrucci, Stuart, Pickering-Brown, Singleton, Andrew B., John, Hardy, Parastoo, Momeni., Neurology, Amsterdam Neuroscience - Neurodegeneration, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Dupuytren [CHU Limoges], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Molecular Neurology (VIB-UAntwerp), University of Antwerp (UA), University College of London [London] (UCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Yves le Foll, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Hospital Central de Asturias, Institute of Health Research of Principado de Asturias (ISPA), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Karolinska University Hospital [Stockholm], Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione Don Carlo Gnocchi, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), The French clinical and genetic Research network on FTLD/FTLD-ALS and PREVDEMALS, The International Frontotemporal Dementia Genomics Consortium, The European Early Onset Dementia (EU -EOD) Consortium, Brainbank Neuro-CEB Neuropathology Network, and Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS

Subjects
Adult, Male, TDP-43, C9orf72, SLITRK2, amyotrophic lateral sclerosis, frontotemporal dementia, Nerve Tissue Proteins, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Cohort Studies, Genes, X-Linked, 80 and over, Medicine, Dementia, Humans, Allele, Age of Onset, Polymorphism, Aged, Aged, 80 and over, biology, C9orf72 Protein, business.industry, Membrane Proteins, MESH: Frontotemporal Lobar Degeneration / epidemiology, Frontotemporal Lobar, Degeneration / genetics, Genes, X-Linked / genetics, Genome-Wide Association Study / methods, Frontotemporal lobar degeneration, Single Nucleotide, Middle Aged, X-Linked, medicine.disease, Amyotrophic lateral sclerosis, Minor allele frequency, Genes, Immunology, Synaptophysin, biology.protein, Female, MESH: Adult, C9orf72 Protein / genetics, Frontotemporal Lobar Degeneration / diagnosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Human medicine, Neurology (clinical), MESH: Humans, Membrane Proteins / genetics, Nerve Tissue Proteins / genetics, Polymorphism, Single Nucleotide / genetics, Age of onset, Frontotemporal Lobar Degeneration, business, Frontotemporal dementia, Genome-Wide Association Study
Abstract

The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.

Published
2021
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48. Radiotherapy for glioblastoma in the elderly

Author

Keime-Guibert, Florence, Chinot, Olivier, Taillandier, Luc, Cartalat-Carel, Stephanie, Frenay, Marc, Kantor, Guy, Guillamo, Jean-Sebastien, Jadaud, Eric, Colin, Philippe, Bondiau, Pierre-Yves, Menei, Philippe, Loiseau, Hugues, Bernier, Valerie, Honnorat, Jerome, Barrie, Maryline, Mokhtari, Karima, Mazeron, Jean-Jacques, Bissery, Anne, and Delattre, Jean-Yves

Subjects
Glioblastoma multiforme -- Drug therapy, Radiotherapy -- Usage, Aged patients -- Drug therapy
Abstract

Trials conducted reveal that in elderly glioblasotma radiotherapy treatment with supportive cared had mild improvement in survival compared to supportive care alone. Radiotherapy did not have damaging effect on quality of life or cognitive function in the patients.

Published
2007

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