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5. Supplementary Figure 2 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author

Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam

Abstract

PDF file - 283K, Wound healing assay for TAC-V and TAC-Pea3-V cells transfected with ctrl or pea3 siRNAs and treated or not with TGF-β1. Western blot analysis of p27kip1 protein expression.

Published
2023

6. Data from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author

Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam

Abstract

The Ets family transcription factor Pea3 (ETV4) is involved in tumorigenesis especially during the metastatic process. Pea3 is known to induce migration and invasion in mammary epithelial cell model systems. However, the molecular pathways regulated by Pea3 are still misunderstood. In the current study, using in vivo and in vitro assays, Pea3 increased the morphogenetic and tumorigenic capacity of mammary epithelial cells by modulating their cell morphology, proliferation, and migration potential. In addition, Pea3 overexpression favored an epithelial–mesenchymal transition (EMT) triggered by TGF-β1. During investigation for molecular events downstream of Pea3, Cyclin D2 (CCND2) was identified as a new Pea3 target gene involved in the control of cellular proliferation and migration, a finding that highlights a new negative regulatory loop between Pea3 and Cyclin D2. Furthermore, Cyclin D2 expression was lost during TGF-β1–induced EMT and Pea3-induced tumorigenesis. Finally, restored Cyclin D2 expression in Pea3-dependent mammary tumorigenic cells decreased cell migration in an opposite manner to Pea3. As such, these data demonstrate that loss of the negative feedback loop between Cyclin D2 and Pea3 contributes to Pea3-induced tumorigenesis.Implications: This study reveals molecular insight into how the Ets family transcription factor Pea3 favors EMT and contributes to tumorigenesis via a negative regulatory loop with Cyclin D2, a new Pea3 target gene. Mol Cancer Res; 11(11); 1412–24. ©2013 AACR.

Published
2023

9. Supplementary Figure 1 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author

Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam

Abstract

PDF file - 270K, Relative pea3 mRNA and protein expression in TAC-V vs TAC-Pea3-V. Wound healing assay for TAC-V and TAC-Pea3-V cells treated or not with TGF-β1 and with or without Mitomycin C. Apoptosis measurement.

Published
2023

11. Supplementary Table 1 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

PDF file - 55K, Table S1. Expression of cell surface stem cell markers in parental HT29 cells, its 5FUresistant 5F7 and 5F31 clonal derivatives, 5FU- and oxaliplatin-resistant HT29FU and HT29OXA subpopulations.

Published
2023

12. Supplementary Figure 1 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

PDF file - 309K, Figure S1. Expression of cancer stem cell phenotypes in 5FU-resistant 5F7 and 5F31 clones.

Published
2023

13. Data from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

Purpose: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.Results: We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell–like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively).Conclusions: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. Clin Cancer Res; 20(4); 837–46. ©2013 AACR.

Published
2023

14. Supplementary Table 2 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

PDF file - 54K, Table S2. Effect of 5FU on the cell cycle progression in parental HT29 cells and 5FUresistant HT29 clonal derivatives 5F7 and 5F31.

Published
2023

15. Supplementary Figure 2 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

PDF file - 202K, Figure S2. Western blot analysis of c-Yes and YAP in human colon cancer cells HT29 and RKO cells treated by oxaliplatin and 5FU.

Published
2023

16. Supplementary Figure Legend from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil

Abstract

PDF file - 50K

Published
2023

17. Data from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author

Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein

Abstract

Metastasis and drug resistance are major problems in cancer chemotherapy. The purpose of this work was to analyze the molecular mechanisms underlying the invasive potential of drug-resistant colon carcinoma cells. Cellular models included the parental HT-29 cell line and its drug-resistant derivatives selected after chronic treatment with either 5-fluorouracil, methotrexate, doxorubicin, or oxaliplatin. Drug-resistant invasive cells were compared with noninvasive cells using cDNA microarray, quantitative reverse transcription-PCR, flow cytometry, immunoblots, and ELISA. Functional and cellular signaling analyses were undertaken using pharmacologic inhibitors, function-blocking antibodies, and silencing by retrovirus-mediated RNA interference. 5-Fluorouracil– and methotrexate-resistant HT-29 cells expressing an invasive phenotype in collagen type I and a metastatic behavior in immunodeficient mice exhibited high expression of the chemokine receptor CXCR4. Macrophage migration-inhibitory factor (MIF) was identified as the critical autocrine CXCR4 ligand promoting invasion in drug-resistant colon carcinoma HT-29 cells. Silencing of CXCR4 and impairing the MIF-CXCR4 signaling pathways by ISO-1, pAb FL-115, AMD-3100, monoclonal antibody 12G5, and BIM-46187 abolished this aggressive phenotype. Induction of CXCR4 was associated with the upregulation of two genes encoding transcription factors previously shown to control CXCR4 expression (HIF-2α and ASCL2) and maintenance of intestinal stem cells (ASCL2). Enhanced CXCR4 expression was detected in liver metastases resected from patients with colon cancer treated by the standard FOLFOX regimen. Combination therapies targeting the CXCR4-MIF axis could potentially counteract the emergence of the invasive metastatic behavior in clonal derivatives of drug-resistant colon cancer cells. Cancer Res; 70(11); 4644–54. ©2010 AACR.

Published
2023

18. Supplementary Methods, Figure Legends 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author

Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein

Abstract

Supplementary Methods, Figure Legends 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Published
2023

19. Supplementary Table 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author

Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein

Abstract

Supplementary Table 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Published
2023

20. Supplementary Figure 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author

Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein

Abstract

Supplementary Figure 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Published
2023

21. Tailoring maintenance chemotherapy upon response to induction chemotherapy as compared with pemetrexed continuation maintenance in advanced non-squamous NSCLC patients: Results of the IFCT-GFPC-1101 multicenter randomized phase III trial

Author

Alexis B. Cortot, Didier Debieuvre, L. Moreau, Radj Gervais, Jacques Margery, Julien Mazieres, Olivier Molinier, Michel Poudenx, Alexandra Langlais, Nicolas Girard, Patrick Dumont, Gérard Zalcman, Franck Morin, Virginie Westeel, Pierre-Jean Souquet, Eric Pichon, Fabrice Barlesi, Maurice Pérol, Jérôme Dauba, Jacques Cadranel, Clarisse Audigier-Valette, and Denis Moro-Sibilot

Subjects
Adult, Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Adolescent, Pemetrexed, Maintenance Chemotherapy, Young Adult, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Maintenance chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, Treatment Outcome, Non squamous, Cisplatin, business, medicine.drug
Abstract

Benefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen.Eligibility criteria: age 18-70 years, ECOG PS 0-1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival.Between 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected.Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome.NCT01631136.

Published
2022

22. A comparison of two views on the European Commission: engine of integration and conduit of national interests

Author

Patrick Dumont and Robert Thomson

Subjects
Politics, Public Administration, Sociology and Political Science, Political science, Law, European integration, Nationality, European commission, Allegiance, Commission
Abstract

The conventional view of the Commission is that it is above the fray of national politics, and that Commissioners have allegiance to pan-European interests. However, research indicates that the Com...

Published
2021

27. Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trial

Author

Virginie Westeel, Pascal Foucher, Arnaud Scherpereel, Jean Domas, Philippe Girard, Jean Trédaniel, Marie Wislez, Patrick Dumont, Elisabeth Quoix, Olivier Raffy, Denis Braun, Marc Derollez, François Goupil, Jacques Hermann, Etienne Devin, Hubert Barbieux, Eric Pichon, Didier Debieuvre, Gervais Ozenne, Jean-François Muir, Stéphanie Dehette, Jérôme Virally, Michel Grivaux, François Lebargy, Pierre-Jean Souquet, Faraj Al Freijat, Nicolas Girard, Emmanuel Courau, Reza Azarian, Michel Farny, Jean-Paul Duhamel, Alexandra Langlais, Franck Morin, Bernard Milleron, Gérard Zalcman, and Fabrice Barlesi

Subjects
Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, X-Rays, Antineoplastic Combined Chemotherapy Protocols, Humans, Tomography, X-Ray Computed, Early Detection of Cancer, Follow-Up Studies
Abstract

Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC.In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling.Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported.The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures.French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology.For the French translation of the abstract see Supplementary Materials section.

Published
2022

28. Switch maintenance chemotherapy versus observation after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non–small cell lung cancer: IFCT-1201 MODEL trial

Author

Didier Debieuvre, Pierre-Jean Souquet, Jean-Louis Pujol, Jérôme Dauba, Jeannick Madelaine, Olivier Molinier, J. Otto, Jacques Le Treut, Fabrice Barlesi, Elisabeth Quoix, Patrick Aldo Renault, Eric Pichon, Alexandra Langlais, Virginie Westeel, L. Moreau, Franck Morin, Jacques Margery, Clarisse Audigier-Valette, Armelle Lavolé, Patrick Dumont, Denis Moro-Sibilot, CHU Strasbourg, Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Centre Hospitalier du Pays d'Aix, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Layné, Université Côte d'Azur (UCA), Hôpital pasteur [Colmar], Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Chauny, Partenaires INRAE, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, Time Factors, medicine.medical_treatment, NSCLC, Deoxycytidine, Carboplatin, chemistry.chemical_compound, Elderly, MESH: Aged, 80 and over, 0302 clinical medicine, Maintenance therapy, MESH: Progression-Free Survival, MESH: Carboplatin, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, MESH: Aged, MESH: Antimetabolites, Antineoplastic, Drug Substitution, Age Factors, MESH: Neoplasm Staging, Progression-Free Survival, 3. Good health, MESH: Maintenance Chemotherapy, MESH: Antineoplastic Combined Chemotherapy Protocols, Pemetrexed, 030220 oncology & carcinogenesis, Disease Progression, Female, MESH: Disease Progression, France, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Paclitaxel, Maintenance, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Chemotherapy, MESH: Paclitaxel, MESH: Pemetrexed, Lung cancer, Aged, Neoplasm Staging, MESH: Age Factors, MESH: Humans, Performance status, business.industry, MESH: Time Factors, MESH: Deoxycytidine, medicine.disease, Gemcitabine, MESH: Drug Substitution, MESH: Male, MESH: Lung Neoplasms, MESH: France, 030104 developmental biology, chemistry, business, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung
Abstract

International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.

Published
2020

30. Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study

Author

Bruno Coudert, Bénédicte Mastroianni, P. Foucher, Séverine Fraboulet, Adrien Dixmier, Julien Mazieres, Michel Vincent, Eric Dansin, Eric Pichon, M. Locatelli-Sanchez, Jacques Cadranel, Sébastien Couraud, N. Baize, Isabelle Monnet, Franck Morin, Catherine Dubos-Arvis, P. Missy, C. Fontaine-Delaruelle, Patrick Dumont, Denis Moro-Sibilot, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service de pneumologie, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Férération d'oncologie thoracique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université d'Angers (UA), INSAVALOR, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité pneumologie et oncologie thoracique [CHU Tenon], CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Multivariate analysis, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Cohort Studies, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Risk Factors, Internal medicine, Humans, Medicine, Anaplastic Lymphoma Kinase, Lung cancer, Reproductive History, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Smokers, Lung, business.industry, Oncogenes, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, Menarche, Biomarker (medicine), Female, Observational study, France, business, Hormone
Abstract

Background Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. Methods All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. Results Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age > 14 vs. 40% and 41% for 12–14 and ≤ 12 years, respectively; P = 0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P = 0.048), and by 9% for each year at age at first birth (P = 0.035). ALK alteration frequency was greater in women with high parity (50% in ≥ 5 vs. 12% and 7% for 1–4 and nulliparity, respectively; P = 0.021). Conclusion In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Published
2020

31. Luxembourg

Author

Dan Schmit, Raphaël Kies, and Patrick Dumont

Published
2022

33. Lung cancer trends and tumor characteristic changes over 20 years (2000–2020): Results of three French consecutive nationwide prospective cohorts’ studies

Author

Didier Debieuvre, Olivier Molinier, Lionel Falchero, Chrystèle Locher, Dorine Templement-Grangerat, Nicolas Meyer, Hugues Morel, Yannick Duval, Bernard Asselain, Alexia Letierce, Jean Trédaniel, Jean-Bernard Auliac, Olivier Bylicki, Lionel Moreau, Mathieu Fore, Romain Corre, Sébastien Couraud, Alexis Cortot, Faraj Al Freijat, Waad Al Sheikh, Claire Alizon, Karim Amrane, Etienne Auvray, Nicolae Banciu, Alexandra Bedossa, Issam Belhaj, Antoine Belle, Laure Belmont, Kheir Eddine Benmammar, Marie Bernardi, Pascal Beynel, Fréderic Bigot, Acya Bizieux-Thaminy, Anne-Sophie Blanchet-Legens, Philippe Bonnefoy, Soraya Bordier, Anne-Sophie Bravard, Éric Briens, Philippe Brun, Anne-Sophie Bugnet, Laetitia Chablais, Anne-Marie Chiappa, Reda Chikouche, François Christiann, Caroline Clarot, Joelle Courdeau-Labourie, Jacky Crequit, Charles Dayen, Gonzague De chabot, Chantal Decroisette, Stéphanie Dehette, Christian Delafosse, Bertrand Delclaux, Christina Delmas, Pierre Demontrond, Jean-Marc Dot, Cécile Dujon, Patrick Dumont, Christine Dussopt, Fatima Duval, Fethi El Khanjari, Kevin Fouet, Hugues Francois, Yannick Ghalloussi-Tebai, Éric Goarant, Benoît Godbert, François Goupil, Rym Haouachi, Pierre-Alexandre Hauss, Mohamad Jaafar, Baihas Jarjour, Serge Jeandeau, Sylvie Julien, Jean Philippe Kraemer, Pierre Kuntz, Florence Lamotte, Sébastien Larive, Thomas Laurent, Hervé Le Floch, Gwenaëlle Le Garff, Jacques Le Treut, Emmanuelle Lecuyer, Christine Lefoll, Olivier Leleu, Marguerite Lepoulain Doubliez, Virginie Levrat, Sandrine Loutski-Vettese, Edith Maetz, Fanny Magne, Cécile Maincent, Alexa Mairovitz, Catherine Marichy, Nancy Marion, David Marquette, Bénédicte Martignac, Stéphanie Martinez, Clothilde Marty, Philippe Masson, Cyril Maurer, Vincent Meniai, Geoffroy Milliet De Faverges, Isabelle Monnet, Laurent Mosser, Anne-Catherine Neidhardt, David Nunes, Julie Obert, Vanessa Pante, Magalie Paysse, Herve Pegliasco, Jean-Michel Peloni, Christophe Perrin, Lidia Petit, Marjorie Picaud, Julian Pinsolle, Mihai Popa, Laurent Portel, Jean Quieffin, Hong Rabut, Élise Redureau, David Renault, Patrick Aldo Renault, Claudia Rizzo, Maud Russier, Marielle Sabatini, Thierry Saelens, Sophie Schneider, Philippe Slaouti, Luc Stoven, Vincent Tack, Jean-Yves Tavernier, Laurence Thirard, Séverine Thomassin, Marie Tiercin, Jean Tredaniel, Andreea Tudor, Amélie Turlotte, Colette Vincent, and Jérôme Virally

Subjects
Oncology, Health Policy, Internal Medicine
Abstract

Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort.KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010.In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (To our knowledge KBP cohorts have been the largest, prospective, real-world cohort studies involving LC patients conducted in worldwide. The trend found in our study shows an increase in LC in women and still a large proportion of patients diagnosed at metastatic or disseminated stage.The study was promoted by the French College of General Hospital Pulmonologists with financial support of industrials laboratories.

Published
2022

34. Belgium: From Highly Constrained and Complex Bargaining Settings to Paralysis?

Author

Patrick Dumont and Lieven De Winter

Subjects
medicine.medical_specialty, Physical medicine and rehabilitation, medicine, Paralysis, Economics, medicine.symptom
Abstract

While Belgium undoubtedly had the most complex coalition bargaining system in Western Europe during the period 1946–1999, it has become much more difficult for parties to form federal governments ever since. Contrary to a number of European countries, government formation complexity did not peak due the emergence of brand-new parties, nor of any new cleavage. Rather, in Belgium the main ingredients pre-existed: party system fragmentation—which was already high since unitary parties had split along linguistic lines—skyrocketed as the mainstream parties around which post-war coalitions were formed further declined in size, confronting some (in)formateurs with up to ten coalitionable parties. Their task has been further complicated by the growing saliency and Flemish radicalization of the community cleavage which led to the rise of the independentist N-VA, whose positions remain unacceptable for any French-speaking party. As a result, Belgium has often been left without a fully empowered government, the partisan composition of coalitions broke away from previous patterns, and the coalition compromise model, which was already solidly entrenched in the consociational norms and practices since the 1960s, was further elaborated. Coalition partners keep tabs on each other through compromise mechanisms and policy-monitoring devices such as long and detailed coalition agreements, the enhanced role of the inner cabinet composed of the PM and the vice-PMs of each coalition party, and strictly enforced coalition discipline in legislative matters. But, given the increasingly unbridgeable divides between Flemish- and French-speaking parties, the deadlock observed could well lead to the demise of Belgium.

Published
2021

36. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author

Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], 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), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Published
2020

38. Weekly paclitaxel plus bevacizumab versus docetaxel as second- or third-line treatment in advanced non-squamous non-small-cell lung cancer: Results of the IFCT-1103 ULTIMATE study

Author

Olivier Raffy, Adrien Dixmier, Gérard Zalcman, Clara Fontaine-Delaruelle, Damien Pouessel, Olivier Molinier, Sandrine Hiret, Franck Morin, Patrick-Aldo Renault, Julien Mazieres, Charles Dayen, Patrick Dumont, Catherine Becht, Sylvestre Le Moulec, Eric Pichon, Benjamin Besse, Clarisse Audigier-Valette, Claire Poulet, Fabrice Barlesi, Alexis B. Cortot, Denis Moro-Sibilot, and Alexandra Langlais

Subjects
0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Bevacizumab, Adolescent, Paclitaxel, medicine.medical_treatment, Population, Docetaxel, Kaplan-Meier Estimate, Neutropenia, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Lung cancer, education, Aged, Neoplasm Staging, Aged, 80 and over, Chemotherapy, education.field_of_study, Cross-Over Studies, business.industry, Hazard ratio, Middle Aged, medicine.disease, Progression-Free Survival, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, Disease Progression, Female, business, medicine.drug
Abstract

Purpose Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non–small-cell lung cancer (nsNSCLC). Methods In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671 . Results One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44–0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8–30·3) and 5·5% (95% CI: 0·0–11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group). Conclusion Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. Clinical trials registration number ClinicalTrials.gov Identifier: NCT01763671 .

Published
2020

39. Luxembourg: Political development and data for 2017

Author

Raphaël Kies and Patrick Dumont

Subjects
Politics, Political economy, Political science, 0502 economics and business, 05 social sciences, 050602 political science & public administration, 050207 economics, 0506 political science
Published
2018

40. Serine 392 phosphorylation modulates p53 mitochondrial translocation and transcription-independent apoptosis

Author

Patrick Dumont, Cédric Castrogiovanni, Béranger Waterschoot, and Olivier De Backer

Subjects
0301 basic medicine, Transcription, Genetic, Mutant, Apoptosis Regulatory Proteins/metabolism, Apoptosis, Mitochondria/chemistry, Mitochondrion, Serine, 03 medical and health sciences, Genetic, Humans, Phosphorylation, Molecular Biology, Transcription factor, Protein Processing, Serine/metabolism, Original Paper, biology, Chemistry, Cytochrome c, Post-Translational, Cell Biology, Mitochondria, Cell biology, Camptothecin/toxicity, Protein Transport, 030104 developmental biology, HtrA serine peptidase 2, Tumor Suppressor Protein p53/chemistry, Mutation, biology.protein, Camptothecin, Tumor Suppressor Protein p53, CRISPR-Cas Systems, Apoptosis Regulatory Proteins, Protein Processing, Post-Translational, Transcription
Abstract

The tumor suppressor p53 is a key regulator of apoptosis induced by various cellular stresses. p53 can induce apoptosis by two mechanisms. First, p53 acts as a transcription factor inducing and repressing pro-apoptotic and anti-apoptotic targets genes, respectively. Second, p53 is able to translocate to the mitochondria, where it interacts with BCL-2 family members to induce membrane permeabilization and cytochrome c release. p53 transcriptional activity is regulated by a set of post-translational modifications that have been well documented. However, how these modifications impact the direct mitochondrial pathway of death remain poorly understood. In this study, we focused on the role of serine 392 phosphorylation in the control of p53-dependent apoptosis. We used CRISPR/Cas9 genome editing to substitute serine 392 by a non-phosphorylatable alanine in HCT-116 colon carcinoma cells. The S392A mutant displayed normal transcriptional activity following genotoxic stress, but markedly impaired ability to localize to mitochondria. The decreased mitochondrial localization of the S392A mutant correlated with a lower ability to induce apoptosis. Confirmatory observations were made following enforced expression of the S392A p53 mutant or a phospho-mimetic S392E mutant in H1299 lung carcinoma cells. Our observations support the premise that serine 392 phosphorylation of p53 influences its mitochondrial translocation and transcription-independent apoptotic function.

Published
2018

41. Luxembourg

Author

Patrick Dumont and Raphaël Kies

Subjects
0502 economics and business, 05 social sciences, 050602 political science & public administration, 050207 economics, 0506 political science
Published
2017

42. Weekly Paclitaxel Plus Bevacizumab versus Docetaxel As Second- or Third-Line Treatment in Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC): Results of the IFCT-1103 ULTIMATE Study

Author

Alexandra Langlais, Sylvestre Le Moulec, Julien Mazieres, Benjamin Besse, Charles Dayen, Adrien Dixmier, Gérard Zalcman, Olivier Molinier, Sandrine Hiret, Eric Pichon, Fabrice Barlesi, Catherine Becht, Olivier Raffy, Patrick Dumont, Alexis B. Cortot, Denis Moro-Sibilot, Claire Poulet, Patrick-Aldo Renault, Franck Morin, Clarisse Audigier-Valette, and Damien Pouessel

Subjects
education.field_of_study, medicine.medical_specialty, Chemotherapy, Bevacizumab, business.industry, medicine.medical_treatment, Population, non-small cell lung cancer (NSCLC), Neutropenia, medicine.disease, chemistry.chemical_compound, Docetaxel, Paclitaxel, chemistry, Internal medicine, medicine, Clinical endpoint, education, business, medicine.drug
Abstract

Purpose: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell-lung cancer (nsNSCLC). Methods: In this multicentre, open-label phase 3 trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive paclitaxel 90 mg/m² (D1, D8, D15) plus bevacizumab 10 mg/kg (D1, D15) every 28 days or docetaxel (75 mg/m²) every 21 days; crossover was allowed after disease progression. Primary endpoint was progression-free survival (PFS). Results: Between May 2013 and August 2014, 166 patients were randomized (paclitaxel plus bevacizumab: 111, docetaxel: 55). Median PFS was longer in paclitaxel plus bevacizumab patients than in docetaxel patients [5·4 months vs 3·9 months, adjusted hazard ratio (HR) 0·61 (95% CI 0·44-0·86); p=0·005]. Objective response rates (ORR) were respectively 22·5% (95% CI 14·8-30·3) and 5·5% (95% CI 0·0-11·5) (p=0·006). Median overall survivals were similar (adjusted HR 1·17; p=0·50). Crossover occurred in 21/55 (38·2%) docetaxel-treated patients. Grade 3-4 adverse events were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p=NS), including neutropenia (19·3% vs 45·4%), neuropathy (8·3% vs 0·0%), and hypertension (7·3% vs 0·0%). Three patients died due to treatment-related adverse events (1·8% in each group). Conclusion: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared to docetaxel in nsNSCLC patients, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT01763671. Funding Statement: The study was sponsored by IFCT. Roche (Boulogne Billancourt, France) supplied bevacizumab, and a complementary grant but had no role in the study design, conduct of the study, and data analysis and had no other involvement in the study. The study was also supported by the French National Cancer Institute (INCa) and French League Against Cancer. Declaration of Interests: ABC has received honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Pfizer, and travel grants from Roche, AstraZeneca, Boehringer Ingelheim, Novartis and Pfizer. CAV has declared grants, personal fees and non-financial support from Roche. OM has declared personal fees from BMS, Boehringer Ingelheim, Astra Zeneca, Novartis, ans Hoffman-Roche. FB has declared personal fees from Astra Zeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. GZ has declared grant from Roche and BMS, personal fees from Roche, BMS, Astra Zeneca, and MSD, and non-financial support from BMS, Astra Zeneca and Pfizer. DP has declared has declared personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. CFD has declared other from MSD (CPLF 2017), Laidet Medical (ERS 2016), and Boehringer Ingelheim (CPLF 2016). EP has declared personal fees and non-financial support from Astra Zeneca, BMS and personal fees from Pfizer. DMS has declared personal fees from Roche, BMS, MSD and Eli Lilly. BB has received institutional grants for clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, OncoMed, Inivata, OSE Pharma. Ethics Approval Statement: This study was approved by a local Ethic Committee (CPP Nord-Ouest III, France), and complied with French legislation, Good Clinical Practices, and the principles outlined in the latest version of Declaration of Helsinki. After approvals, the study was implemented in 36 hospitals and cancer centres in France.

Published
2019

43. Increasing the complexity of respiratory syncytial virus infection: Reactive oxygen species, DNA damage, and premature senescence

Author

Patrick Dumont

Subjects
0301 basic medicine, Microbiology (medical), DNA damage, Immunology, Cellular senescence, Respiratory Mucosa, Respiratory Syncytial Virus Infections, Biology, Microbiology, Virus, Cell Line, Histones, Mice, 03 medical and health sciences, medicine, Animals, Cyclin-Dependent Kinase Inhibitor p18, Humans, DNA Breaks, Double-Stranded, Respiratory system, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, chemistry.chemical_classification, Reactive oxygen species, Premature senescence, Glutathione, Virology, Acetylcysteine, Oxidative Stress, Editorial, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, chemistry, A549 Cells, Respiratory Syncytial Virus, Human, Host-Pathogen Interactions, Parasitology, Reactive Oxygen Species, DNA Damage, Respiratory tract
Abstract

Human respiratory syncytial virus (HRSV) accounts for the majority of lower respiratory tract infections during infancy and childhood and is associated with significant morbidity and mortality. HRSV provokes a proliferation arrest and characteristic syncytia in cellular systems such as immortalized epithelial cells. We show here that HRSV induces the expression of DNA damage markers and proliferation arrest such as P-TP53, P-ATM, CDKN1A and γH2AFX in cultured cells secondary to the production of mitochondrial reactive oxygen species (ROS). The DNA damage foci contained γH2AFX and TP53BP1, indicative of double-strand breaks (DSBs) and could be reversed by antioxidant treatments such as N-Acetylcysteine (NAC) or reduced glutathione ethyl ester (GSHee). The damage observed is associated with the accumulation of senescent cells, displaying a canonical senescent phenotype in both mononuclear cells and syncytia. In addition, we show signs of DNA damage and aging such as γH2AFX and CDKN2A expression in the respiratory epithelia of infected mice long after viral clearance. Altogether, these results show that HRSV triggers a DNA damage-mediated cellular senescence program probably mediated by oxidative stress. The results also suggest that this program might contribute to the physiopathology of the infection, tissue remodeling and aging, and might be associated to long-term consequences of HRSV infections.

Published
2016

44. Phase II study assessing the benefit of cisplatin re-introduction (stop-and-go strategy) in patients with advanced non-squamous non-small cell lung cancer: the IFCT-1102 BUCiL study (a Better Use of Cisplatin in Lung cancer)

Author

Alexandra Langlais, Franck Morin, Pascal Do, Judith Raimbourg, Olivier Molinier, Jaafar Bennouna, Elisabeth Quoix, Didier Debieuvre, Pierre-Jean Souquet, Fabrice Barlesi, Patrick Dumont, Werner Hilgers, and Jacques Cadranel

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, Phases of clinical research, cisplatin, bevacizumab, Internal medicine, medicine, Clinical endpoint, Lung cancer, pemetrexed, Original Research, Cisplatin, Chemotherapy, Performance status, business.industry, medicine.disease, metastatic, Pemetrexed, business, nsclc, medicine.drug
Abstract

Introduction This single-arm phase II trial aimed to evaluate a stop-and-go strategy with cisplatin-based chemotherapy and bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC). Methods Patients were initially treated with three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 1) followed by bevacizumab maintenance and after progression, re-introduction of three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 2) and pemetrexed plus bevacizumab maintenance. The primary endpoint was the proportion of patients with advanced non-squamous NSCLC receiving the complete sequence 2 without platinum dose reduction (hypothesis ≥75%). Results 120 patients with performance status ≤1 were included. Of 113 patients evaluable for efficacy, 65 (57.5%) entered in sequence 2 and 56 (86%) received the three planned cycles including 37 (56.9%, 95% CI 45.1 to 73.6) without platinum dose reduction. The median progression-free survival 1 (PFS1; inclusion to progression 1) was 5.6 months (95% CI 5.0 to 6.3) and median PFS2 (progression 1 to progression 2) was 6.8 months (95% CI 5.8 to 8.8). The median disease control duration (PFS1+PFS2; n=65) was 12.4 months (95% CI 11.2 to 14.9). The median overall survival was 17.7 months (95% CI 13.1 to 21.6) and 20.5 months (95% CI 16.9 to 26.9) for patients reaching the sequence 2 (n=65). Conclusion Although the stringent primary endpoint was not met, this stop-and-go strategy with platinum-based chemotherapy plus bevacizumab continuation beyond progression compares favourably with standard schedule, deserving to be further studied in advanced non-squamous NSCLC.

Published
2018

45. Association between lung cancer somatic mutations and occupational exposure in never-smokers

Author

Christophe, Paris, Pascal, Do, Bénédicte, Mastroianni, Adrien, Dixmier, Patrick, Dumont, Eric, Pichon, Christos, Chouaid, Bruno, Coudert, Pascal, Foucher, Séverine, Fraboulet, Myriam, Locatelli-Sanchez, Nathalie, Baize, Eric, Dansin, Lionel, Moreau, Michel, Vincent, Pascale, Missy, Franck, Morin, Denis, Moro-Sibilot, Sébastien, Couraud, Etienne, Suc, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional d'Orléans (CHRO), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pneumologie (CRETEIL - Pneumologie), CHI Créteil, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Foch [Suresnes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CH Colmar, INSAVALOR, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité d'Oncologie Thoracique-Pneumologie, CHU de Grenoble, INSERM U823, Grenoble, France., Centre Hospitalier Universitaire [Grenoble] (CHU), Boehringer Ingelheim, Pfizer, AstraZeneca, Roche, Eli Lilly and Company, Pierre Fabre, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, Proto-Oncogene Proteins B-raf, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Pathology, Lung Neoplasms, Receptor, ErbB-2, Adenocarcinoma, medicine.disease_cause, Asbestos, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Occupational Exposure, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Prospective Studies, Risk factor, Lung cancer, Prospective cohort study, Carcinogen, Aged, Aged, 80 and over, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, Smoking, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, Logistic Models, 030228 respiratory system, 030220 oncology & carcinogenesis, Mutation, Female, France, KRAS, business, Gasoline, Cohort study
Abstract

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

Published
2017

46. Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author

Georges Grard, Fan Fan, Lee M. Ellis, Laurence Stechly, Pierre Formstecher, Jerome Vandomme, Nicolas Skrypek, Carole Langlois, Matthieu Corvaisier, François-René Pruvot, Guillaume Millet, Renata Polakowska, Anne-Frédérique Dessein, Christian Gespach, Patrick Dumont, Stéphanie Truant, Mohamed Hebbar, Isabelle Van Seuningen, Guillemette Huet, Emmanuelle Leteurtre, Yasmine Touil, Didier Monté, Wassila Igoudjil, Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cancer Research, Pathology, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Cell, Gene Expression, Cell Cycle Proteins, Kaplan-Meier Estimate, Metastasis, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, Neoadjuvant therapy, Proto-Oncogene Proteins c-yes, 0303 health sciences, education.field_of_study, Liver Neoplasms, Nuclear Proteins, Neoadjuvant Therapy, 3. Good health, Protein Transport, medicine.anatomical_structure, Oncology, Chemotherapy, Adjuvant, Neoplasm Micrometastasis, 030220 oncology & carcinogenesis, Colonic Neoplasms, Neoplastic Stem Cells, Fluorouracil, HT29 Cells, Antimetabolites, Antineoplastic, medicine.medical_specialty, Population, Biology, Disease-Free Survival, Article, 03 medical and health sciences, Biomarkers, Tumor, medicine, Humans, education, Cell Proliferation, Proportional Hazards Models, 030304 developmental biology, Cell Nucleus, Chemotherapy, Cell growth, Cell Cycle Checkpoints, medicine.disease, Checkpoint Kinase 2, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Transcription Factors
Abstract

Purpose: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery. Results: We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell–like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively). Conclusions: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. Clin Cancer Res; 20(4); 837–46. ©2013 AACR.

Published
2014

47. Luxembourg

Author

PATRICK DUMONT, RAPHAËL KIES, and PHILIPPE POIRIER

Subjects
Sociology and Political Science
Published
2012

48. Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

Author

Denis Larsimont, Gabriel Leprivier, Agnès Begue, Martine Duterque-Coquillaud, Didier Monté, Clélia Laitem, Souhaila Choul-Li, Patrick Dumont, and Marc Aumercier

Subjects
Transcriptional Activation, Gene isoform, Cancer Research, Transcription, Genetic, Blotting, Western, Bone Neoplasms, Breast Neoplasms, Electrophoretic Mobility Shift Assay, Adenocarcinoma, Biology, Proto-Oncogene Protein c-ets-1, Transactivation, Transcription (biology), Tumor Cells, Cultured, Genetics, Transcriptional regulation, Animals, Humans, Protein Isoforms, Molecular Biology, Transcription factor, Gene, Genes, Dominant, Cell Nucleus, Osteosarcoma, Alternative splicing, DNA, Exons, Subcellular localization, Molecular biology, Alternative Splicing, Retroviridae, Female, Rabbits, Subcellular Fractions
Abstract

The transcription factor Ets-1 is implicated in various physiological processes and invasive pathologies. We identified a novel variant of ets-1, ets-1Delta(III-VI), resulting from the alternative splicing of exons III to VI. This variant encodes a 27 kDa isoform, named Ets-1 p27. Ets-1 p27 lacks the threonine-38 residue, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes. Both inhibitory domains surrounding the DNA-binding domain are conserved, suggesting that Ets-1 p27, like the full-length Ets-1 p51 isoform, is autoinhibited for DNA binding. We showed that Ets-1 p27 binds DNA in the same way as Ets-1 p51 does and that it acts both at a transcriptional and a subcellular localization level, thereby constituting a dual-acting dominant negative of Ets-1 p51. Ets-1 p27 blocks Ets-1 p51-mediated transactivation of target genes and induces the translocation of Ets-1 p51 from the nucleus to the cytoplasm. Furthermore, Ets-1 p27 overexpression represses the tumor properties of MDA-MB-231 mammary carcinoma cells in correlation with the known implication of Ets-1 in various cellular mechanisms. Thus the dual-acting dominant-negative function of Ets-1 p27 gives to the Ets-1 p27/Ets-1 p51 ratio a determining effect on cell fate.

Published
2016

49. The duration and durability of cabinet ministers

Author

Joern Fischer, Keith Dowding, and Patrick Dumont

Subjects
Sociology and Political Science, business.industry, Comparative politics, computer.file_format, Public relations, Public administration, Affect (psychology), Durability, Political Science and International Relations, Cabinet (file format), Sociology, Duration (project management), business, computer
Abstract

This article surveys the growing research programme on the duration of cabinet ministers. It examines some of the conceptual and methodological issues confronting research, including the nature and measurement of durability, ministerial terms and techniques. It considers some of the theories and hypotheses that have been generated by researchers. Using evidence from studies from around the world, it argues that institutional factors, including regime type, constitutional and parliamentary rules, and party systems, affect ministerial durability. Personal ministerial characteristics, such as gender, education and age, also affect durability. It examines future avenues of research in this field.

Published
2012

50. OA11.01 Prolonged OS of Patients Exposed to Weekly Paclitaxel and Bevacizumab: Impact of the Cross-Over in the IFCT-1103 ULTIMATE Study

Author

Alexis B. Cortot, Franck Morin, Clarisse Audigier Valette, Olivier Molinier, Alexandra Langlais, Patrick Dumont, Claire Poulet, Gérard Zalcman, Denis Moro-Sibilot, Adrien Dixmier, Fabrice Barlesi, Damien Pouessel, Patrick-Aldo Renault, Sylvestre Le Moulec, Benjamin Besse, Sandrine Hiret, Marie-Paule Lebitasy, and Pierre Jean Souquet

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Cross over, medicine.medical_specialty, Bevacizumab, business.industry, Weekly paclitaxel, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, medicine.drug
Published
2017

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