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1. Automatic Segmentation of Metastatic Breast Cancer Lesions on 18F-FDG PET/CT Longitudinal Acquisitions for Treatment Response Assessment

Author: Noémie Moreau, Caroline Rousseau, Constance Fourcade, Gianmarco Santini, Aislinn Brennan, Ludovic Ferrer, Marie Lacombe, Camille Guillerminet, Mathilde Colombié, Pascal Jézéquel, Mario Campone, Nicolas Normand, Mathieu Rubeaux, Keosys, Nantes Université (Nantes Univ), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Image Perception Interaction (LS2N - équipe IPI), Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, and Université d'Angers (UA)
Subjects: Cancer Research, automatic segmentation, Oncology, disease monitoring, deep learning, metastatic breast cancer, imaging biomarkers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, RC254-282, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: Simple Summary In the recent years, several deep learning methods for medical image segmentation have been developed for different purposes such as diagnosis, radiotherapy planning or to correlate images findings with other clinical data. However, few studies focus on longitudinal images and response assessment. To the best of our knowledge, this is the first study to date evaluating the use of automatic segmentation to obtain imaging biomarkers that can be used to assess treatment response in patients with metastatic breast cancer. Moreover, the statistical analysis of the different biomarkers shows that automatic segmentation can be successfully used for their computation, reaching similar performances compared to manual segmentation. Analysis also demonstrated the potential of the different biomarkers including novel/original ones to determine treatment response. Abstract Metastatic breast cancer patients receive lifelong medication and are regularly monitored for disease progression. The aim of this work was to (1) propose networks to segment breast cancer metastatic lesions on longitudinal whole-body PET/CT and (2) extract imaging biomarkers from the segmentations and evaluate their potential to determine treatment response. Baseline and follow-up PET/CT images of 60 patients from the EPICUREseinmeta study were used to train two deep-learning models to segment breast cancer metastatic lesions: One for baseline images and one for follow-up images. From the automatic segmentations, four imaging biomarkers were computed and evaluated: SULpeak, Total Lesion Glycolysis (TLG), PET Bone Index (PBI) and PET Liver Index (PLI). The first network obtained a mean Dice score of 0.66 on baseline acquisitions. The second network obtained a mean Dice score of 0.58 on follow-up acquisitions. SULpeak, with a 32% decrease between baseline and follow-up, was the biomarker best able to assess patients’ response (sensitivity 87%, specificity 87%), followed by TLG (43% decrease, sensitivity 73%, specificity 81%) and PBI (8% decrease, sensitivity 69%, specificity 69%). Our networks constitute promising tools for the automatic segmentation of lesions in patients with metastatic breast cancer allowing treatment response assessment with several biomarkers.
Published: 2022
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2. The Impact of Resampling and Denoising Deep Learning Algorithms on Radiomics in Brain Metastases MRI

Author: Ilyass Moummad, Cyril Jaudet, Alexis Lechervy, Samuel Valable, Charlotte Raboutet, Zamila Soilihi, Juliette Thariat, Nadia Falzone, Joëlle Lacroix, Alain Batalla, Aurélien Corroyer-Dulmont, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Equipe Image - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CLCC Baclesse], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and GenesisCare
Subjects: Cancer Research, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, deep learning, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Oncology, radiomics, MRI, resampling, denoising, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, RC254-282
Abstract: Simple Summary Due to the central role of magnetic resonance Imaging (MRI) in the management of patients with cancer, waiting lists exceed clinically relevant delays. For this reason, many research groups and MRI manufacturers develop algorithms as resampling and denoising models to allow faster acquisition time without deterioration in image quality. Whereas these algorithms are available in all new MRI, it is not clear how they will impact image features as well as the validity of statistical model of radiomics which use deep images characteristics to predict treatment outcome. The aim of this study was to develop resampling and denoising deep learning (DL) models and evaluate their impact on radiomics from post-Gd-T1w-MRI brain images with brain metastases. We show that resampling and denoising DL models reconstruct low resolution and noised MRI images acquired quickly into high quality images. While fast acquisition loses most of the radiomic-features and invalidates predictive radiomic models, DL models restore these parameters. Abstract Background: Magnetic resonance imaging (MRI) is predominant in the therapeutic management of cancer patients, unfortunately, patients have to wait a long time to get an appointment for examination. Therefore, new MRI devices include deep-learning (DL) solutions to save acquisition time. However, the impact of these algorithms on intensity and texture parameters has been poorly studied. The aim of this study was to evaluate the impact of resampling and denoising DL models on radiomics. Methods: Resampling and denoising DL model was developed on 14,243 T1 brain images from 1.5T-MRI. Radiomics were extracted from 40 brain metastases from 11 patients (2049 images). A total of 104 texture features of DL images were compared to original images with paired t-test, Pearson correlation and concordance-correlation-coefficient (CCC). Results: When two times shorter image acquisition shows strong disparities with the originals concerning the radiomics, with significant differences and loss of correlation of 79.81% and 48.08%, respectively. Interestingly, DL models restore textures with 46.15% of unstable parameters and 25.96% of low CCC and without difference for the first-order intensity parameters. Conclusions: Resampling and denoising DL models reconstruct low resolution and noised MRI images acquired quickly into high quality images. While fast MRI acquisition loses most of the radiomic features, DL models restore these parameters.
Published: 2022
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3. Contribution of the IdyllaTM System to Improving the Therapeutic Care of Patients with NSCLC through Early Screening of EGFR Mutations

Author: Emmanuel Bergot, Simon Deshayes, Frédéric Bibeau, Adèle Riot, Marine Dorbeau, Cécile Blanc-Fournier, Radj Gervais, Gwladys Robinet-Zimmermann, Constance Petiteau, Nicolas Richard, Guénaëlle Levallet, 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Département de Pathologie [CHU Caen], Service de Génétique [CHU Caen], Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Oncology, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, EGFR mutations, Article, Idylla (TM), 03 medical and health sciences, 0302 clinical medicine, IdyllaTM, Carcinoma, Non-Small-Cell Lung, Internal medicine, molecular diagnosis, medicine, Humans, Prospective Studies, Epidermal growth factor receptor, Prospective cohort study, Genotyping, Early Detection of Cancer, non-small cell lung cancer, RC254-282, 030304 developmental biology, 0303 health sciences, biology, business.industry, Bone metastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, ErbB Receptors, Egfr mutation, 030220 oncology & carcinogenesis, NGS, Mutation, biology.protein, Treatment decision making, Non small cell, business
Abstract: Epidermal growth factor receptor (EGFR) genotyping, a critical examen for the treatment decisions of patients with non-small cell lung cancer (NSCLC), is commonly assayed by next-generation sequencing (NGS), but this global approach takes time. To determine whether rapid EGFR genotyping tests by the IdyllaTM system guides earlier therapy decisions, EGFR mutations were assayed by both the IdyllaTM system and NGS in 223 patients with NSCLC in a bicentric prospective study. IdyllaTM demonstrated agreement with the NGS method in 187/194 cases (96.4%) and recovered 20 of the 26 (77%) EGFR mutations detected using NGS. Regarding the seven missed EGFR mutations, five were not detected by the IdyllaTM system, one was assayed in a sample with insufficient tumoral cells, and the last was in a sample not validated by the IdyllaTM system (a bone metastasis). IdyllaTM did not detect any false positives. The average time between EGFR genotyping results from IdyllaTM and the NGS method was 9.2 ± 2.2 working days (wd) (12.6 ± 4.0 calendar days (cd)). Subsequently, based on the IdyllaTM method, the timeframe from tumor sampling to the initiation of EGFR-TKI was 7.7 ± 1.2 wd (11.4 ± 3.1 cd), while it was 20.4 ± 6.7 wd (27.5 ± 7.7 cd) with the NGS method (p &lt, 0.001). We thus demonstrated here that the IdyllaTM system contributes to improving the therapeutic care of patients with NSCLC by the early screening of EGFR mutations.
Published: 2021
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4. Inhibiting endothelin receptors with macitentan strengthens the bone protective action of RANKL inhibition and reduces metastatic dissemination in osteosarcoma

Author: Javier Muñoz-Garcia, Jorge William Vargas-Franco, Bénédicte Brounais-Le Royer, Denis Cochonneau, Jérôme Amiaud, Marie-Françoise Heymann, Dominique Heymann, Frédéric Lézot, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Nantes Université (Nantes Univ), Unité de fonctionnalité et ingénierie de protéines (UFIP), Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Sheffield [Sheffield], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Heymann, Dominique
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, musculoskeletal diseases, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cancer Research, RANKL, bone protection, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, osteosarcoma, endothelin, metastases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Abstract: International audience; Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.
Published: 2022
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5. Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

Author: Antoine Gilbert, Mihaela Tudor, Juliette Montanari, Kevin Commenchail, Diana Iulia Savu, Paul Lesueur, François Chevalier, Accueil et Recherche en Radiobiologie des Ions Accélérés (ARIA), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Horia Hulubei National Institute of Physics and Nuclear Engineering (NIPNE), IFIN-HH, University of Bucharest (UniBuc), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), and Region Normandy: RIN CHOXTRACC (2021–2022) 'Recherche de combinaisons thérapeutiques hadronthérapie—thérapies ciblant la radiorésistance biologique liée à l’hypoxie et au stress oxydant tumoral'
Subjects: carbon ions therapy, cancer stem cells, chondrosarcoma, radiation resistance, Cancer Research, Oncology, hypoxia, hadrontherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible in some specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma.
Published: 2023
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6. A Multicenter Study to Assess a Systematic Screening of Occupational Exposures in Lung Cancer Patients

Author: Olivia Pérol, Nadège Lepage, Hugo Noelle, Pierre Lebailly, Benoit de Labrusse, Bénédicte Clin, Mathilde Boulanger, Delphine Praud, Françoise Fournié, Géraud Galvaing, Frédéric Dutheil, Brigitte Le Meur, Daniel Serin, Eric Dansin, Catherine Nisse, Barbara Charbotel, Beatrice Fervers, Centre Léon Bérard [Lyon], Unité Ad Hoc INSERM 000008 'Radiations : Défense, Santé, Environnement' [Lyon] (Inserm U1296), Centre Léon Bérard [Lyon]-Université Lumière - Lyon 2 (UL2)-Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Sainte Catherine [Avignon], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université de Lyon-Université de Lyon-Université Gustave Eiffel, and Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS)
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, [SDV.CAN]Life Sciences [q-bio]/Cancer, LUNG CANCER, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, SYSTEMATIC SCREENING, COMPENSATION, RESPIRATION, occupational exposures, lung cancer, systematic screening, compensation, VISCERES, EXPOSITION AU RISQUE, ENQUETE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, OCCUPATIONAL EXPOSURES, TUMEUR
Abstract: Occupational lung cancer cases remain largely under-reported and under-compensated worldwide. In order to improve the detection and compensation of work-related lung cancers, we implemented a systematic screening of occupational exposures, combining a validated self-administered questionnaire to assess occupational exposures and a specialized occupational cancer consultation. After a pilot study, the present prospective, open-label, scale-up study aimed to assess this systematic screening of occupational exposures in lung cancer patients in five sites in France by associating university hospitals with cancer centers. Patients with lung cancer were sent a self-administered questionnaire to collect their job history and potential exposure to lung carcinogens. The questionnaire was assessed by a physician to determine if a specialized occupational cancer consultation was required. During the consultation, a physician assessed if the lung cancer was occupation-related and, if it was, delivered a medical certificate to claim for compensation. Patients were offered help from a social worker for the administrative procedure. Over 15 months, 1251 patients received the questionnaire and 462 returned it (37%). Among them, 176 patients (38.1%) were convened to the occupational cancer consultation and 150 patients attended the consultation. An exposure to occupational lung carcinogen was identified in 133 patients and a claim for compensation was judged possible for 90 patients. A medical certificate was delivered to 88 patients and 38 patients received compensation. Our national study demonstrated that a systematic screening of occupational exposures is feasible and will bring a significant contribution to improve the detection of occupational exposures in lung cancer patients.
Published: 2023
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7. Deep Hybrid Learning Prediction of Patient-Specific Quality Assurance in Radiotherapy: Implementation in Clinical Routine

Author: Noémie Moreau, Laurine Bonnor, Cyril Jaudet, Laetitia Lechippey, Nadia Falzone, Alain Batalla, Cindy Bertaut, Aurélien Corroyer-Dulmont, Physique médicale (radiophysique) [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), GenesisCare, Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC), GIP Cyceron (Cyceron), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: clinical routine, machine learning, [SDV]Life Sciences [q-bio], deep hybrid learning, Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, VMAT, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, quality assurance, radiotherapy
Abstract: CERVOXY; International audience; Background: Arc therapy allows for better dose deposition conformation, but the radiotherapy plans (RT plans) are more complex, requiring patient-specific pre-treatment quality assurance (QA). In turn, pre-treatment QA adds to the workload. The objective of this study was to develop a predictive model of Delta4-QA results based on RT-plan complexity indices to reduce QA workload. Methods. Six complexity indices were extracted from 1632 RT VMAT plans. A machine learning (ML) model was developed for classification purpose (two classes: compliance with the QA plan or not). For more complex locations (breast, pelvis and head and neck), innovative deep hybrid learning (DHL) was trained to achieve better performance. Results. For not complex RT plans (with brain and thorax tumor locations), the ML model achieved 100% specificity and 98.9% sensitivity. However, for more complex RT plans, specificity falls to 87%. For these complex RT plans, an innovative QA classification method using DHL was developed and achieved a sensitivity of 100% and a specificity of 97.72%. Conclusions. The ML and DHL models predicted QA results with a high degree of accuracy. Our predictive QA online platform is offering substantial time savings in terms of accelerator occupancy and working time.
Published: 2023
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8. Prognostic Value of Metabolic, Volumetric and Textural Parameters of Baseline [18F]FDG PET/CT in Early Triple-Negative Breast Cancer

Author: Clément Bouron, Clara Mathie, Valérie Seegers, Olivier Morel, Pascal Jézéquel, Hamza Lasla, Camille Guillerminet, Sylvie Girault, Marie Lacombe, Avigaelle Sher, Franck Lacoeuille, Anne Patsouris, Aude Testard, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Design and application of innovative loco-regional Treatments in Gliobastoma (CRCI2NA / Eq 5), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and LACOEUILLE, FRANCK
Subjects: [18F]FDG PET/CT, [SDV] Life Sciences [q-bio], Cancer Research, Oncology, [SDV]Life Sciences [q-bio], textural features, TNBC, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: (1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG) is gaining importance for the staging of breast cancers. TNBCs often show high [18F]FDG uptake and some studies have suggested a prognostic value for metabolic and volumetric parameters, but no study to our knowledge has examined textural features in TNBC. The objective of this study was to evaluate the association between metabolic, volumetric and textural parameters measured at the initial [18F]FDG PET/CT and disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic TBNC. (2) Methods: all consecutive nonmetastatic TNBC patients who underwent a [18F]FDG PET/CT examination upon diagnosis between 2012 and 2018 were retrospectively included. The metabolic and volumetric parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG) and the textural features (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) of the primary tumor were collected. (3) Results: 111 patients were enrolled (median follow-up: 53.6 months). In the univariate analysis, high TLG, MTV and entropy values of the primary tumor were associated with lower DFS (p = 0.008, p = 0.006 and p = 0.025, respectively) and lower OS (p = 0.002, p = 0.001 and p = 0.046, respectively). The discriminating thresholds for two-year DFS were calculated as 7.5 for MTV, 55.8 for TLG and 2.6 for entropy. The discriminating thresholds for two-year OS were calculated as 9.3 for MTV, 57.4 for TLG and 2.67 for entropy. In the multivariate analysis, lymph node involvement in PET/CT was associated with lower DFS (p = 0.036), and the high MTV of the primary tumor was correlated with lower OS (p = 0.014). (4) Conclusions: textural features associated with metabolic and volumetric parameters of baseline [18F]FDG PET/CT have a prognostic value for identifying high-relapse-risk groups in early TNBC patients.
Published: 2022
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9. Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study

Author: Eric Leblanc, Fabrice Narducci, Gwenaël Ferron, Audrey Mailliez, Jean-Yves Charvolin, El Houssein, Frédéric Guyon, Virginie Fourchotte, Eric Lambaudie, Agathe Crouzet, Yves Fouche, Sébastien Gouy, Pierre Collinet, Frédéric Caquant, Christophe Pomel, François Golfier, Véronique Vaini-Cowen, Isabelle Fournier, Michel Salzet, Emmanuelle Tresch, Alicia Probst, Anne-Sophie Lemaire, Marie-Cécile Deley, Delphine Hudry, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Claudius Regaud, Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Gustave Roussy (IGR), Hôpital Jeanne de Flandre [Lille], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Hospices Civils de Lyon (HCL), Polyclinique du Parc Rambot, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and Institut National Du Cancer, INCa, (PHRC 2011-06)
Subjects: early menopause, delayed oophorectomy, high risk of breast and ovarian cancer, ovarian cancer prevention, radical fimbriectomy, risk-reducing surgery, Cancer Research, Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20–30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.
Published: 2023
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10. Targeting HGF/c-Met Axis Decreases Circulating Regulatory T Cells Accumulation in Gastric Cancer Patients

Author: Palle, Juliette, Hirsch, Laure, Lapeyre-Prost, Alexandra, Malka, David, Bourhis, Morgane, Pernot, Simon, Marcheteau, Elie, Voron, Thibault, Castan, Florence, Lacotte, Ariane, Benhamouda, Nadine, Tanchot, Corinne, François, Eric, Ghiringhelli, François, de la Fouchardière, Christelle, Zaanan, Aziz, Tartour, Eric, Taieb, Julien, Terme, Magali, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Biostatistics Unit, CTD INCa, ICM-Montpellier Cancer Institute, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Medical Oncology Department, Centre Léon Bérard, Lyon, Department of Gastrointestinal Oncology, AP-HP, HEGP, Université de Paris, and TERME, Magali
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], gastric cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, regulatory T cells, targeted therapies, [SDV] Life Sciences [q-bio], hepatocyte growth factor, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.IMM]Life Sciences [q-bio]/Immunology, pro-angiogenic factor, anti-HGF, RC254-282, c-Met
Abstract: Simple Summary Restoring an effective immune response is the key goal of immunotherapy. One of the major mechanisms of tumor-induced immunosuppression is regulatory T cells (Treg) accumulation. In this study, using in vitro and in vivo analysis, we assessed the impact of the HGF/c-Met pathway, involved notably in tumor angiogenesis, on Treg accumulation in patients with gastric cancer. First, we reported that c-Met is expressed on circulating monocytes of gastric cancer patients and this expression seems to be associated with the worst outcome. Secondly, during in vitro cultures, c-Met+ monocytes differentiate into dendritic cells with tolerogenic properties able to induce the proliferation of Treg. Finally, rilotumumab, an anti-HGF antibody, decreases the percentage of circulating Treg in gastric cancer patients. Using HGF/c-Met inhibitors to partially reverse immunosuppression could lead to the development of new treatment associations, for example with immune checkpoint blockers. Abstract Elucidating mechanisms involved in tumor-induced immunosuppression is of great interest since it could help to improve cancer immunotherapy efficacy. Here we show that Hepatocyte Growth Factor (HGF), a pro-tumoral and proangiogenic factor, and its receptor c-Met are involved in regulatory T cells (Treg) accumulation in the peripheral blood of gastric cancer (GC) patients. We observed that c-Met is expressed on circulating monocytes from GC patients. The elevated expression on monocytes is associated with clinical parameters linked to an aggressive disease phenotype and correlates with a worse prognosis. Monocyte-derived dendritic cells from GC patients differentiated in the presence of HGF adopt a regulatory phenotype with a lower expression of co-stimulatory molecules, impaired maturation capacities, and an increased ability to produce interleukin-10 and to induce Treg differentiation in vitro. In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation. Rilotumumab decreased circulating Treg in GC patients. Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.
Published: 2021
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11. LightSpot®-FL-1 Fluorescent Probe: An Innovative Tool for Cancer Drug Resistance Analysis by Direct Detection and Quantification of the P-glycoprotein (P-gp) on Monolayer Culture and Spheroid Triple Negative Breast Cancer Models

Author: Pierre Daumar, Bernard Vidalinc, Marie Depresle, Frédérique Penault-Llorca, Corinne Aubel, Emmanuelle Mounetou, Mahchid Bamdad, Antoine Goisnard, Clémence Dubois, Jean Gauthier, Manon Roux, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), BIOMARQUEURS Company, BIOPASS Company, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, COLO, Mouniati, and Université Clermont Auvergne (UCA)
Subjects: Cancer Research, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Flow cytometry, Olaparib, multidrug resistance, P-gp staining, LightSpot®-FL-1 cell-permeant fluorescent probe, triple-negative breast cancer, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Triple-negative breast cancer, RC254-282, 030304 developmental biology, P-glycoprotein, 0303 health sciences, biology, medicine.diagnostic_test, Chemistry, Colocalization, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Immunostaining
Abstract: P-gp is the most widely studied MDR protein conferring cellular resistance to many standard or targeted therapeutic agents. For this reason, P-gp chemoresistance evaluation, established before or during chemotherapy, can be very relevant in order to optimize the efficacy of treatments, particularly for aggressive tumoral subtypes such as triple-negative breast cancer (TNBC). In this context, our team developed an innovative cell-permeant fluorescent probe called the LightSpot®-FL-1, which is able to specifically localize and quantify the P-gp in cells or cell masses, as evidenced on different TNBC cell models. First, flow cytometry analysis showed LightSpot®-FL-1 cell penetration and persistence in time, in TNBC cells. Then, LightSpot®-FL-1 staining was compared to anti-P-gp immunostaining by fluorescence microscopy on five TNBC cell lines. Results showed a clear similarity of P-gp localization and expression level, confirmed by Pearson’s and Mander’s colocalization coefficients with 92.1% and 100.0%, and a strong correlation coefficient of R2 = 0.99. In addition, the LightSpot®-FL-1 staining allowed the quantification of a P-gp induction (33% expression increase) following a 6-hour spheroid model exposure to the anti-PARP Olaparib. Thus, the new LightSpot®-FL-1 cell-permeant probe, targeting P-gp, appears to be an effective tool for drug resistance evaluation in preclinical models and shows promising possibilities for future use in clinical diagnosis.
Published: 2021
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12. A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

Author: François Chevalier, Jean Armengaud, Sonia Hem, Mihaela Tudor, Charlotte Lepleux, Diana Savu, Antoine Gilbert, Siamak Haghdoost, Emilie Brotin, Mihaela Temelie, Horia Hulubei National Institute of Physics and Nuclear Engineering (NIPNE), IFIN-HH, University of Bucharest (UniBuc), Accueil et Recherche en Radiobiologie des Ions Accélérés (ARIA), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, 0301 basic medicine, stress granules, DNA damage, QH301-705.5, Bone Neoplasms, Radiation induced, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cytoplasmic Granules, medicine.disease_cause, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Chondrocytes, 0302 clinical medicine, Stress granule, Western blot, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], bystander signaling, Conditioned medium, Bystander effect, medicine, Humans, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, chondrosarcoma, medicine.diagnostic_test, Chemistry, X-Rays, Organic Chemistry, Bystander Effect, General Medicine, proteomic analysis, Microvesicles, Computer Science Applications, Cell biology, secretome, 030104 developmental biology, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Oxidative stress
Abstract: Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area, irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules.
Published: 2021
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13. TUMOSPEC: A Nation-Wide Study of Hereditary Breast and Ovarian Cancer Families with a Predicted Pathogenic Variant Identified through Multigene Panel Testing

Author: Celine Garrec, Monique Mozelle-Nivoix, Jérôme Lemonnier, Etienne Rouleau, Tan Dat Nguyen, Dominique Vaur, Elodie Lacaze, Sarah Bonnet-Boissinot, Sophie Nambot, Jean Chiesa, Sophie Giraud, Dominique Stoppa-Lyonnet, Michel Longy, Alain Lortholary, Jean-Marc Rey, Olivier Caron, Christine Lasset, Claude Houdayer, Christine Maugard, Virginie Bubien, Véronique Mari, Marie-Emmanuelle Morin-Meschin, Nadine Andrieu, Nancy Uhrhammer, Louise Crivelli, Hélène Dreyfus, Vincent Goussot, Stephanie Chieze-Valéro, Nicolas Sevenet, Lisa Golmard, Séverine Eon-Marchais, Mathilde Martinez, Isabelle Coupier, Marie-Gabrielle Dondon, Odile Béra, Paul Vilquin, Capucine Delnatte, Odile Cohen-Haguenauer, Cornel Popovici, Christine Toulas, Laurence Gladieff, Marie-Agnès Collonge-Rame, Chrystelle Colas, Paul Gesta, Catherine Noguès, Fanny Brayotel, Audrey Mailliez, Fabienne Lesueur, Julie Tinat, Marie Bidart, Yves-Jean Bignon, Florence Coulet, Nadia Boutry-Kryza, Fabienne Prieur, Juana Beauvallet, Philippe Denizeau, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôtel-Dieu de Nantes, CHU Rouen, Normandie Université (NU), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], UNICANCER, Centre Eugène Marquis (CRLCC), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Paul Strauss, CRLCC Paul Strauss, Institut Bergonié [Bordeaux], Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Genetic and Immunology Medical Institute (GIMI), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU de Saint-Étienne Hôpital Nord [Saint Etienne], Hôpital Nord (Saint Etienne), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Bordeaux [Bordeaux], Centre Catherine-de-Sienne [Nantes] (CCS), Hôpital privé du Confluent [Nantes], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de Troyes, Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe Hospitalier du Havre, CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CRLCC René Gauducheau, 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), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre médical de Bligny, Onco-génétique, Département de médecine oncologique [Gustave Roussy], COLO, Mouniati, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute) (institut GIMI), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Lille-UNICANCER, 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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-FHU TRANSLAD (CHU de Dijon), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Sequencing data, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030105 genetics & heredity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Care plan, Internal medicine, Epidemiology, medicine, RC254-282, Genetic testing, medicine.diagnostic_test, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, genetic predisposition to breast and ovarian cancer, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Oncology, 030220 oncology & carcinogenesis, multigene panels, Cancer risk, Ovarian cancer, business, cancer risk estimate, penetrance of pathogenic variants
Abstract: Simple Summary TUMOSPEC was designed for estimating the risk of cancer for carriers of a predicted pathogenic variant (PPV) in a gene usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and are tested for the familial PPV. Genetic, clinical, family and epidemiological data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. This showed that the study logistics are well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) is smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene. Abstract Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.
Published: 2021
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14. Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer

Author: Jessica W.T. Leung, Sana Al-Sukhun, Omalkhair Abulkhair, Benjamin O. Anderson, Meteb Foheidi, Nagi S. El Saghir, Hany Abdel Aziz, Joseph Gligorov, Mohamed Sabry, Hamdy A. Azim, Hagar Elghazawy, Edith A. Perez, Frédérique Penault-Llorca, Bahadir M. Gulluoglu, Joaira Bakkach, Khaled Abdel Karim, Banu Arun, Pierfranco Conte, Valentina Guarneri, Hope S. Rugo, Hesham Elghazaly, Mohamed A Shehata, Mona Frolova, Philip Poortmans, Cheng Har Yip, Sandra M. Swain, Manal Mohamed El-mahdy, Nermean Bahie Eldin, Alaa Kandil, Mohamed El-Shinawi, Charles M. Balch, Marwan Ghosn, Wentao Yang, Matti Aapro, Heba M. El-Zawahry, Adel T. Aref, Armando E. Giuliano, Roberto Orecchia, Ruslan M. Paltuev, Ain Shams University (ASU), Department of Medicine, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA 94158, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Giza 12613, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, MedStar Health, Washington, DC 20007, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Breast Center, Clinique de Genolier, 1272 Genolier, Department of Hematology & Oncology, Mayo Clinic, Jacksonville, FL 32224, University of Washington [Seattle], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Department of Surgery, Oncology and Gastroenterology, University of Padova, Istituto Oncologico Veneto IOV IRCCS, 35128 Padova, Department of Internal Medicine, Division of Hematology Oncology, American University of Beirut Medical Center, Beirut 1107 2020, Subang Jaya Medical Centre, Kuala Lumpur 47500, Université Saint-Joseph de Beyrouth (USJ), University of Antwerp (UA), Clinical oncology Department, Menoufia University, Shebin Elkom 51132, Department of Surgery, Surgical Oncology Division, Cedars-Sinai Medical Center, Los Angeles, CA 90048, Department of Breast Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Breast & Endocrine Surgery Unit, Marmara University School of Medicine, University Hospital, Istanbul 34722, Federal State Budgetary Institution 'NN Blokhin National Medical Research Center of Oncology' of the Ministry of Health of the Russian Federation, 127994 Moscow, Surgical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Università degli Studi di Milano = University of Milan (UNIMI), Al Hyatt Oncology Practice, Amman 11183, Department of Clinical Oncology, Alexandria School of Medicine, Alexandria 21131, Russian Association of Oncological Mammology, Department of Breast Tumours of Federal State Budgetary Institution 'Petrov Research Institute of Oncology', 197758 Saint Petersburg, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Adult Medical Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah 22384, Vice President of Galala University, Galala University, Suez 435611, Oncology Department, Alfaisal university, Alhabib Hospital, Riyad 11533, Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, University of Adelaide, Biomedical Genomics & Oncogenetics Research Laboratory, Faculty of Sciences and Techniques of Tangier, Abdel Malek Essaadi University, Tangier 90000, Elghazaly, Hesham, Rugo, Hope S., Azim, Hamdy A., Swain, Sandra M., Arun, Banu, Aapro, Matti, Perez, Edith A., Anderson, Benjamin O., Penault-Llorca, Frederique, Conte, Pierfranco, El Saghir, Nagi S., Yip, Cheng-Har, Ghosn, Marwan, Poortmans, Philip, Shehata, Mohamed A., Giuliano, Armando E., Leung, Jessica W. T., Guarneri, Valentina, Gligorov, Joseph, Gulluoglu, Bahadir M., Abdel Aziz, Hany, Frolova, Mona, Sabry, Mohamed, Balch, Charles M., Orecchia, Roberto, El-Zawahry, Heba M., Al-Sukhun, Sana, Abdel Karim, Khaled, Kandil, Alaa, Paltuev, Ruslan M., Foheidi, Meteb, El-Shinawi, Mohamed, ElMahdy, Manal, Abulkhair, Omalkhair, Yang, Wentao, Aref, Adel T., Bakkach, Joaira, Bahie Eldin, Nermean, Elghazawy, Hagar, Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Breast Health Global Initiative, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98195, Hematology and Oncology Department, Saint Joseph University, Beirut 1104 2020, Iridium Kankernetwerk and Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk-Antwer, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Scientific Directorate, IRCCS European Institute of Oncology (IEO), and University of Milan, 20122 Milan, Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo 11566, Department of Pathology, Ain shams University, Cairo 11566, and The School of Public Health, University of Adelaide, Adelaide 5005
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, POSTMASTECTOMY RADIOTHERAPY, medicine.medical_treatment, [SDV]Life Sciences [q-bio], education, COMPLETE RESPONSE PCR, Disease, MUTATION CARRIERS, Guidelines, 03 medical and health sciences, NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, Breast cancer, ADJUVANT CHEMOTHERAPY, medicine, DISEASE-FREE SURVIVAL, TUMOR-INFILTRATING LYMPHOCYTES, platinum, LOCOREGIONAL RECURRENCE, AMERICAN SOCIETY, Triple-negative breast cancer, RC254-282, business.industry, BRCA mutations, Consensus, Immunotherapy, Platinum, Cancer conference, Consensus conference, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Evidence-based medicine, RANDOMIZED PHASE-III, medicine.disease, 3. Good health, Clinical trial, 030104 developmental biology, Oncology, consensus, 030220 oncology & carcinogenesis, Family medicine, triple-negative breast cancer, Human medicine, immunotherapy, business, Mastectomy
Abstract: Simple Summary Despite the impressive progress in the treatment of triple-negative breast cancer (TNBC), oncologists still face several provocative clinical scenarios in daily practice where clear evidence-based recommendations are lacking, and expert opinion is of utmost importance. In an attempt to seek guidance for these controversial topics in TNBC management, a consensus recommendations session for TNBC was held during the 12th round of the Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020. This special session convened a multidisciplinary committee of 35 panellists who specialize in breast cancer care from 13 countries. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials. Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when >= 75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.
Published: 2021
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15. Adherence to French and ESGO Quality Indicators in Ovarian Cancer Surgery: An Ad-Hoc Analysis from the Prospective Multicentric CURSOC Study

Author: Pierre-Emmanuel Colombo, Denis Querleu, Eric Lambaudie, Nicolas Bourdel, Roman Rouzier, Amélie Lusque, Witold Gertych, Frédéric Guyon, Martina Aida Angeles, Christophe Pomel, François Golfier, Michel Canis, Martinez Alejandra, Naoual Bakrin, Olivier Glehen, Nicolas Pouget, Gwenael Ferron, Jacques Meurette, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], CHU Clermont-Ferrand, Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, CHU Strasbourg, COLO, Mouniati, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inconnu, and Fondazione Policlinico Universitario Agostino Gemelli [Rome]
Subjects: Cancer Research, medicine.medical_specialty, Referral, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Certification, lcsh:RC254-282, Article, surgery, 03 medical and health sciences, 0302 clinical medicine, Health care, Medicine, Quality (business), Stage (cooking), Radical surgery, media_common, 030219 obstetrics & reproductive medicine, business.industry, Cancer, quality indicators, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Family medicine, France, business, Quality assurance
Abstract: Simple Summary French and European Quality Indicators have been developed for the management of ovarian cancer. In this study, we aimed to assess the ovarian cancer care distribution in France according to the volume of patients treated per hospital, and to evaluate the adherence of different centers to the quality indicators. We found that the majority of ovarian cancer patients were treated in hospitals that did not reach recommended cut-off values in terms of volume, and it is known that surgical care in low-volume hospitals is associated with worse outcome. Only 44% of high-volume centers met all the quality indicator criteria. Therefore, access to high-volume ovarian cancer providers accomplishing all the recommended institutional quality indicators is restricted to a minority of patients in France. It is mandatory that national authorities work both to improve the centralization of ovarian cancer management and to incorporate quality assurance programs into certified centers. Abstract Background: Quality Indicators for ovarian cancer (OC) have been developed by the European Society of Gynaecological Oncology (ESGO) and by the French National Cancer Institute (Institut National du Cancer, INCa). The aim of the study was to characterize OC care distribution in France by case-volume and to prospectively evaluate the adherence of high-volume institutions to INCa/ESGO quality indicators. Methods: The cost-utility of radical surgery in ovarian cancer (CURSOC) trial is a prospective, multicenter, comparative and non-randomized study that includes patients with stage IIIC-IV epithelial OC treated in nine French health care tertiary institutions. Adherence to institutional quality indicators were anonymously assessed by an independent committee. OC care distribution in France were provided by the nationwide database of hospital procedures. Results: More than half of patients are treated in low-volume institutions. Among the nine high-volume centers participating in the study, four (44.4%) met all institutional INCa/ESGO quality indicators. The other five (55.6%) did not fulfil one of the quality indicator criteria. Conclusions: Access to high-volume OC providers in France is restricted to a minority of patients, and yet half of the referral institutions included in this study failed to meet all recommended institutional quality indicators. It is mandatory that national authorities work both to improve OC centralization and to incorporate quality assurance programs into certified centers.
Published: 2021
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16. Management of Cancer-Associated Thrombosis in France: A National Survey among Vascular Disease and Supportive Care Specialists

Author: Isabelle Mahé, Céline Chapelle, Ludovic Plaisance, Laurent Bertoletti, Patrick Mismetti, Didier Mayeur, Guillaume Mahé, Francis Couturaud, Université Paris Cité (UPCité), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), F-Crin Innovte [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Mouvement Sport Santé (M2S), Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), BAYER [FR01902036138N], Jonchère, Laurent, Innovations thérapeutiques en hémostase (IThEM - U1140), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Biologie intégrative du tissu osseux
Subjects: [SDV] Life Sciences [q-bio], anticoagulants, Cancer Research, Oncology, [SDV]Life Sciences [q-bio], venous thromboembolism, cancer, treatment guidelines, survey
Abstract: International audience; Low molecular weight heparins (LMWHs) are recommended by international guidelines for at least 6 months in patients with cancer-associated thromboembolism (CAT). Direct oral anticoagulants (DOACs) have been proposed as an alternative to LMWH. In clinical practice, the specialists in charge of CAT have to decide which anticoagulant to prescribe. An electronic survey tool, including vignettes and questions, was sent to members of the French Society of Vascular Medicine, the French-speaking association for supportive care in oncology and the Investigation Network On Venous Thrombo-Embolism. Among the 376 respondents, LMWHs were reported as the first choice by most specialists. The prescription of DOACs within the first 3 weeks of CAT diagnosis was highly dependent on the cancer site: 5.9%, 18.6% and 24.5% in patients with locally advanced colorectal, lung and breast cancer, respectively. The determinants were mostly related to cancer (site and stage or evolution) and to anticancer treatments. For 61% of physicians, some anticancer treatments were contraindications to DOACs. However, almost 90% of physicians considered switching to DOAC after a median 3-month period of LMWHs. In daily practice, LMWHs and DOACs are now considered by specialists of CAT; the decision is mostly driven by the site of cancer. The role of anticancer treatments in the decision remains to be investigated.
Published: 2022
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17. Systematic Review of COVID-19-Related Physical Activity-Based Rehabilitations: Benefits to Be Confirmed by More Robust Methodological Approaches

Author: Mélina Bailly, Léna Pélissier, Emmanuel Coudeyre, Bertrand Evrard, Rea Bingula, Corinne Rochette, Laurent Mériade, Christelle Blavignac, Anne-Cécile Fournier, Yves-Jean Bignon, Fabrice Rannou, Frédéric Dutheil, David Thivel, Martine Duclos, Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, chaire Santé et Territoires (S&T), Institut d'Administration des Entreprises - Clermont-Auvergne (IAE - UCA), Université Clermont Auvergne (UCA), Clermont Recherche Management (CleRMa), École Supérieure de Commerce (ESC) - Clermont-Ferrand (ESC Clermont-Ferrand)-Université Clermont Auvergne (UCA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: SARS-CoV-2, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, physical activity, COVID-19, functional capacity, rehabilitation, [SHS]Humanities and Social Sciences, Quality of Life, Humans, Prospective Studies, Exercise, Aged, Retrospective Studies
Abstract: International audience; The first emergency was to receive and treat COVID-19 patients in their acute phase; today, there is a clear need to propose appropriate post-acute rehabilitation programs. The aim of this research was to systematically review the effects of physical activity programs in the recovery of post-COVID-19 patients. The literature search followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was registered in the PROSPERO database (CRD42022289219), and was conducted between August and December 2021. A total of 35 studies out of the 1528 initially identified were finally included in the analysis. The systematic review clearly showed the health benefits of rehabilitation including physical activity in post-COVID-19 recovery, regardless of exercise modalities. These positive results were even observed using minor muscle re-mobilization for severe cases (i.e., postural changes, few steps—2 times/day) or using low volumes of exercise for mild-to-moderate cases (i.e., 120 min/week). A total of 97% of the 29 studies that performed statistical analyses demonstrated a significant increase in at least one parameter of functional capacity, and 96% of the 26 studies that statistically investigated the effects on the quality of life, mental health, and general state reported improvements. Yet, most of the studies were retrospective, uncontrolled, and enrolled aged people with comorbidities presented in severe forms of COVID-19. Physical activity programs, in addition to their high heterogeneity, remained poorly described in 83% of the studies and were part of a multidisciplinary program for 89% of the studies. Despite promising results, there is today a real need for prospective well-designed studies specifically assessing the effects of physical activity. In addition, it might appear relevant to propose standardized programs further considering the main characteristics of patients such as age, comorbidities, or the severity of COVID-19.
Published: 2022
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18. Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network

Author: Gabriel Ichim, Benjamin Gibert, Sahil Adriouch, Catherine Brenner, Nathalie Davoust, Solange Desagher, David Devos, Svetlana Dokudovskaya, Laurence Dubrez, Jérôme Estaquier, Germain Gillet, Isabelle Guénal, Philippe P. Juin, Guido Kroemer, Patrick Legembre, Romain Levayer, Stéphen Manon, Patrick Mehlen, Olivier Meurette, Olivier Micheau, Bernard Mignotte, Florence Nguyen-Khac, Nikolay Popgeorgiev, Jean-Luc Poyet, Muriel Priault, Jean-Ehrland Ricci, Franck B. Riquet, Santos A. Susin, Magali Suzanne, Pierre Vacher, Ludivine Walter, Bertrand Mollereau, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hospices Civils de Lyon (HCL), Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Universiteit Gent = Ghent University (UGENT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Mignotte, Bernard, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), École Pratique des Hautes Études (EPHE), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: NF-KAPPA-B, ANTICANCER CHEMOTHERAPY, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, necrosis, SIGNALING PATHWAYS, COMPENSATORY PROLIFERATION, NEURONAL APOPTOSIS, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Medicine and Health Sciences, Animals, Humans, cancer, TARGETING AAC-11, IMMUNE-RESPONSE, CANCER-CELLS, Caenorhabditis elegans, Molecular Biology, CHRONIC LYMPHOCYTIC-LEUKEMIA, APOPTOSIS-INDUCING LIGAND, apoptosis, Biology and Life Sciences, cell death
Abstract: International audience; Since the Nobel Prize award more than twenty years ago for discovering the core apoptotic pathway in C. elegans, apoptosis and various other forms of regulated cell death have been thoroughly characterized by researchers around the world. Although many aspects of regulated cell death still remain to be elucidated in specific cell subtypes and disease conditions, many predicted that research into cell death was inexorably reaching a plateau. However, this was not the case since the last decade saw a multitude of cell death modalities being described, while harnessing their therapeutic potential reached clinical use in certain cases. In line with keeping research into cell death alive, francophone researchers from several institutions in France and Belgium established the French Cell Death Research Network (FCDRN). The research conducted by FCDRN is at the leading edge of emerging topics such as non-apoptotic functions of apoptotic effectors, paracrine effects of cell death, novel canonical and non-canonical mechanisms to induce apoptosis in cell death-resistant cancer cells or regulated forms of necrosis and the associated immunogenic response. Collectively, these various lines of research all emerged from the study of apoptosis and in the next few years will increase the mechanistic knowledge into regulated cell death and how to harness it for therapy.
Published: 2022
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19. Marine Exopolysaccharide Complexed with Scandium Aimed as Theranostic Agents

Author: Cyrille Alliot, Sandrine Huclier-Markai, Mattia Mazza, Corinne Sinquin, Sylvia Colliec-Jouault, Pascal E. Reiller, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Ecosystèmes microbiens et Molécules Marines pour les Biotechnologies (EM3B), Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Service d'études analytiques et de réactivité des surfaces (SEARS), Département de Physico-Chimie (DPC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Biotechnologies et Ressources Marines (BRM)
Subjects: Light, Intrinsic viscosity, theranostic, complexation, Dispersity, scandium, Pharmaceutical Science, Ionic bonding, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, 01 natural sciences, Theranostic Nanomedicine, Analytical Chemistry, Coordination Complexes, Drug Discovery, Carbohydrate Conformation, Scattering, Radiation, characterization, Scandium, Molar mass, Viscosity, exopolysaccharides, 021001 nanoscience & nanotechnology, Fractionation, Field Flow, 3. Good health, Chemistry (miscellaneous), visual_art, visual_art.visual_art_medium, Molecular Medicine, 0210 nano-technology, Inorganic chemistry, chemistry.chemical_element, Fractionation, 010402 general chemistry, Article, Metal, lcsh:QD241-441, lcsh:Organic chemistry, Polysaccharides, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, Depolymerization, Osmolar Concentration, Organic Chemistry, 0104 chemical sciences, chemistry, Hydrodynamics, Nuclear Medicine, Alteromonas
Abstract: (1) Background: Exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium, showed anti-metastatic properties. They may represent a new class of ligands to be combined with theranostic radionuclides, such as 47Sc/44Sc. The goal of this work was to investigate the feasibility of such coupling. (2) Methods: EPSs, as well as heparin used as a drug reference, were characterized in terms of molar mass and dispersity using Asymmetrical Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering (AF4-MALS). The intrinsic viscosity of EPSs at different ionic strengths were measured in order to establish the conformation. To determine the stability constants of Sc with EPS and heparin, a Free-ion selective radiotracer extraction (FISRE) method has been used. (3) Results: AF4-MALS showed that radical depolymerization produces monodisperse EPSs, suitable for therapeutic use. EPS conformation exhibited a lower hydrodynamic volume for the highest ionic strengths. The resulting random-coiled conformation could affect the complexation with metal for high concentration. The LogK of Sc-EPS complexes have been determined and showing that they are comparable to the Sc-Hep. (4) Conclusions: EPSs are very promising to be coupled with the theranostic pair of scandium for Nuclear Medicine.
Published: 2021
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20. Evidence of Tri-Exponential Decay for Liver Intravoxel Incoherent Motion MRI: A Review of Published Results and Limitations

Author: Kévin Guillen, Julie Pellegrinelli, Yi-Xiang J. Wang, Jean-Pierre Cercueil, Olivier Chevallier, Romaric Loffroy, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Clinical Biochemistry, Review, computer.software_genre, liver, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Voxel, medicine, diffusion weighted imaging, cardiovascular diseases, Exponential decay, Diffusion (business), Compartment (pharmacokinetics), Intravoxel incoherent motion, intravoxel incoherent motion, Physics, Molecular diffusion, lcsh:R5-920, medicine.diagnostic_test, tri-exponential, Magnetic resonance imaging, 3. Good health, b-value, lcsh:Medicine (General), computer, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Diffusion weighted imaging (DWI) and intravoxel incoherent motion (IVIM) have been explored to assess liver tumors and diffused liver diseases. IVIM reflects the microscopic translational motions that occur in voxels in magnetic resonance (MR) DWI. In biologic tissues, molecular diffusion of water and microcirculation of blood in the capillary network can be assessed using IVIM DWI. The most commonly applied model to describe the DWI signal is a bi-exponential model, with a slow compartment of diffusion linked to pure molecular diffusion (represented by the coefficient Dslow), and a fast compartment of diffusion, related to microperfusion (represented by the coefficient Dfast). However, high variance in Dfast estimates has been consistently shown in literature for liver IVIM, restricting its application in clinical practice. This variation could be explained by the presence of another very fast compartment of diffusion in the liver. Therefore, a tri-exponential model would be more suitable to describe the DWI signal. This article reviews the published evidence of the existence of this additional very fast diffusion compartment and discusses the performance and limitations of the tri-exponential model for liver IVIM in current clinical settings.
Published: 2021
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21. Spatially-Resolved Multiply-Excited Autofluorescence and Diffuse Reflectance Spectroscopy: SpectroLive Medical Device for Skin In Vivo Optical Biopsy

Author: Blondel, Walter, Delconte, Alain, Khairallah, Grégoire, Marchal, Frédéric, Gavoille, Amélie, Amouroux, Marine, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, SD Innovation, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: metrological validation, skin cancer, medical device, [SDV]Life Sciences [q-bio], lcsh:Electronics, lcsh:TK7800-8360, autofluorescence, calibration, diffuse reflectance, optical biopsy, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, fibered spectroscopy, [SDV.IB]Life Sciences [q-bio]/Bioengineering, spatial resolution
Abstract: This contribution presents the development of an optical spectroscopy device, called SpectroLive, that allows spatially-resolved multiply-excited autofluorescence and diffuse reflectance measurements. Besides describing the device, this study aims at presenting the metrological and safety regulation validations performed towards its aimed application to skin carcinoma in vivo diagnosis. This device is made of six light sources and four spectrometers for detection of the back-scattered intensity spectra collected through an optical probe (made of several optical fibers) featuring four source-to-detector separations (from 400 to 1000 &micro, m). In order to be allowed by the French authorities to be evaluated in clinics, the SpectroLive device was successfully checked for electromagnetic compatibility and electrical and photobiological safety. In order to process spectra, spectral correction and metrological calibration were implemented in the post-processing software. Finally, we characterized the device&rsquo, s sensitivity to autofluorescence detection: excitation light irradiance at the optical probe tip in contact with skin surface ranges from 2 to 11 W/m&sup2, depending on the light source. Such irradiances combined to sensitive detectors allow the device to acquire a full spectroscopic sequence within 6 s which is a short enough duration to be compatible with optical-guided surgery. All these results about sensitivity and safety make the SpectroLive device mature enough to be evaluated through a clinical trial that aims at evaluating its diagnostic accuracy for skin carcinoma diagnosis.
Published: 2021
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22. Radiosensitizing Chemotherapy (Irinotecan) with Stereotactic Body Radiation Therapy for the Treatment of Inoperable Liver and/or Lung Metastases of Colorectal Cancer

Author: Xavier Mirabel, Véronique Vendrely, Loig Vaugier, Jean-Luc Raoul, Marc-André Mahé, Christian Carrie, Loïc Campion, Séverine Racadot, Isabelle Martel-Lafay, Hélène Senellart, Emmanuel Rio, Bernardo, Elizabeth, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Léon Bérard [Lyon], Hôpital Saint-André, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, Gastroenterology, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Quality of life, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, irinotecan, Response rate (survey), Chemotherapy, Lung, business.industry, lung metastases, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, oligometastases, 3. Good health, Irinotecan, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Concomitant, Radiosensitizing Agent, stereotactic radiotherapy, business, liver metastases, medicine.drug
Abstract: Background: Stereotactic body radiotherapy (SBRT) is a recognized treatment for colorectal cancer (CRC) metastases. We postulated that local responses could be improved by SBRT with a concomitant radiosensitizing agent (irinotecan). Methods: RADIOSTEREO-CAMPTO was a prospective multi-center phase 2 trial investigating SBRT (40&ndash, 48 Gy in 4 fractions) for liver and/or lung inoperable CRC oligometastases (&le, 3), combined with two weekly intravenous infusions of 40 mg/m2 Irinotecan. Primary outcome was the objective local response rate as per RECIST. Secondary outcomes were early and late toxicities, EORTC QLQ-C30 quality of life, local control and overall survival. Results: Forty-four patients with 51 lesions (liver = 39, lungs = 12) were included. Median age was 69 years (46&ndash, 84), 37 patients (84%) had received at least two prior chemotherapy treatments. Median follow-up was 48.9 months. One patient with two lung lesions was lost during follow-up. Assuming maximum bias hypothesis, the objective local response rate in ITT was 86.3% (44/51&mdash, 95% CI: [76.8&ndash, 95.7]) or 82.4% (42/51&mdash, 95% CI: [71.9&ndash, 92.8]). The observed local response rate was 85.7% (42/49&mdash, 95% CI: [75.9&ndash, 95.5]). The 1 and 2-year local (distant) progression-free survivals were 84.2% (38.4%) and 67.4% (21.3%), respectively. The 1 and 2-year overall survivals were 97.5% and 75.5%. There were no severe acute or late reactions. The EORTC questionnaire scores did not significantly worsen during or after treatment. Conclusions: SBRT with irinotecan was well tolerated with promising results despite heavily pretreated patients.
Published: 2021
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23. Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases

Author: Ludovic Ferrer, Françoise Kraeber-Bodéré, Gregory Delpon, B. Pichon, Stéphane Supiot, Matthieu Le Turnier, David M. Goldenberg, Caroline Rousseau, Vincent Libois, Cédric Lenoble, Caroline Bodet-Milin, Audrey Blanc-Lapierre, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Clinique Pasteur [Toulouse], Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Center for Molecular Medicine and Immunology [Mendham, NJ, USA] (C2MI), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: GTV, PET-CT, vertebral metastases, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, CEA, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Positron emission, stereotactic ablative body radiotherapy (SABR), lcsh:QH301-705.5, targeting, medicine.diagnostic_test, business.industry, Communication, Medullary thyroid cancer, Magnetic resonance imaging, radiation oncology, stereotactic body radiation therapy (SBRT), medicine.disease, Spinal cord, Metastatic breast cancer, 3. Good health, bispecific antibody, medicine.anatomical_structure, lcsh:Biology (General), Positron emission tomography, 030220 oncology & carcinogenesis, immuno-PET, CTV, Tomography, Nuclear medicine, business
Abstract: (1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.
Published: 2020
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24. From 1957 to Nowadays: A Brief History of Epigenetics

Author: Eric Hervouet, Paul Peixoto, Aurélien A. Sérandour, Pierre-François Cartron, 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), EPIgenetics and GENe EXPression Technical Plateform (EPIGENExp), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-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), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Apoptose et progression tumorale (ICO, Saint-Herblain), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire], EpiSAVMEN Network (Région Pays de la Loire) [Saint-Herblain], LabEX IGO Immunothérapie Grand Ouest, École Centrale de Nantes (ECN), DImaCell Platform, Université Bourgogne Franche-Comté [COMUE] (UBFC), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Dispositif Inter-régional d'Imagerie Cellulaire [Dijon] (DImaCell), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Agroécologie [Dijon], and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Epigenomics, History, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, History, 21st Century, Catalysis, Epigenesis, Genetic, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Epitranscriptomics, histones, Animals, Humans, Epigenetics, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, 030304 developmental biology, Cognitive science, 0303 health sciences, DNA methylation, epigenetics, Organic Chemistry, General Medicine, History, 20th Century, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, 030220 oncology & carcinogenesis, Identification (biology), history, epitranscriptomics, Protein Processing, Post-Translational
Abstract: International audience; Due to the spectacular number of studies focusing on epigenetics in the last few decades, and particularly for the last few years, the availability of a chronology of epigenetics appears essential. Indeed, our review places epigenetic events and the identification of the main epigenetic writers, readers and erasers on a historic scale. This review helps to understand the increasing knowledge in molecular and cellular biology, the development of new biochemical techniques and advances in epigenetics and, more importantly, the roles played by epigenetics in many physiological and pathological situations.
Published: 2020
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25. What Are Young Women Living Conditions after Breast Cancer? Health-Related Quality of Life, Sexual and Fertility Issues, Professional Reinsertion

Author: A. Mamguem Kamga, Clémentine Jankowski, H. Costaz, Geneviève Jolimoy, Charles Coutant, Tienhan Sandrine Dabakuyo-Yonli, E.L.F. Assogba, Agnès Dumas, P. Arveux, Patrick Roignot, Registre des Cancers du Sein et autres Cancers Gynécologiques de Côte d'Or - Breast and Gynaecologic Cancer Registry of Côte d’Or, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]-Université de Paris (UP), Centre de pathologie [Dijon], Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Hôpital Paul Brousse, Plateforme Qualité de vie et cancer, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service de chirurgie [Centre Georges-François Leclerc], Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), University of Lausanne (UNIL), 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, and Plateforme Nationale Qualité de vie et Cancer
Subjects: Gerontology, medicine.medical_specialty, Cancer Research, Epidemiology, media_common.quotation_subject, Population, Psychological intervention, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fertility, lcsh:RC254-282, Article, 03 medical and health sciences, Social support, 0302 clinical medicine, Breast cancer, Quality of life, breast neoplasm, Political science, Medicine, 030212 general & internal medicine, education, ComputingMilieux_MISCELLANEOUS, media_common, Gynecology, Health related quality of life, fertility, education.field_of_study, young women, [SHS.SOCIO]Humanities and Social Sciences/Sociology, business.industry, Public Health, Environmental and Occupational Health, return to work, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, humanities, 3. Good health, sexuality, health-related quality of life, Social deprivation, Oncology, 030220 oncology & carcinogenesis, Anxiety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business
Abstract: In recent decades, the living conditions of young breast cancer (BC) survivors have garnered increasing attention. This population-based study aimed to identify the clinical, social and economic determinants of Health-Related Quality of Life (HRQoL), and to describe other living conditions of young long-term BC survivors. Women with non-metastatic BC diagnosed between 2006 and 2015, aged 45 years and younger at the time of diagnosis, were identified through the Breast and Gynecologic Cancer Registry of the C&ocirc, te d&rsquo, Or, France. Participants completed self-report questionnaires including standardized measures of HRQoL, anxiety, depression, social deprivation, social support and sexuality. Fertility and professional reintegration issues were also assessed. The determinants of HRQoL were identified using mixed regression model. In total, 218 BC survivors participated in the survey. The main determinants of poor HRQoL were anxiety, depression, comorbidities, social deprivation and menopausal status. Among 72% of women who did not receive information about fertility preservation, 38% of them would have liked to have been informed. Finally, 39% of survivors reported a negative impact of BC on their professional activity. This study showed that BC stage or treatments did not have an impact on HRQOL of young long-term BC survivors. Fertility, sexuality and professional reintegration remained the main concerns for survivors. Specific interventions in these population should focus on these issues.
Published: 2020
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26. Prevalence of Migraine and Neuropathic Pain in Rheumatic Diseases

Author: Anne Tournadre, Marion Couderc, Jean-Jacques Dubost, Xavier Moisset, Martin Soubrier, Sandrine Malochet-Guinamand, Sylvain Mathieu, Bruno Pereira, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Rhumatologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), and COLO, Mouniati
Subjects: medicine.medical_specialty, Population, lcsh:Medicine, Article, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Internal medicine, medicine, migraine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Risk factor, education, 030203 arthritis & rheumatology, neuropathic pain, education.field_of_study, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, lcsh:R, Chronic pain, General Medicine, medicine.disease, 3. Good health, Migraine, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Neuropathic pain, rheumatic diseases, Anxiety, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13&ndash, 3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease.
Published: 2020
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27. SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma

Author: Andréa Witz, Pauline Gilson, Julie Dardare, Alexandre Harlé, Jean-Louis Merlin, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: 0301 basic medicine, Epithelial-Mesenchymal Transition, endocrine system diseases, pancreatic cancer, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, SMAD, Review, Malignancy, SMAD4, Catalysis, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, TGFβ, 0302 clinical medicine, Transforming Growth Factor beta, Pancreatic cancer, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Smad4 Protein, business.industry, Organic Chemistry, EMT, Cancer, PDAC, General Medicine, medicine.disease, digestive system diseases, 3. Good health, Computer Science Applications, Pancreatic Neoplasms, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Transforming growth factor, Carcinoma, Pancreatic Ductal, Signal Transduction
Abstract: International audience; Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide. PDAC is an aggressive disease with an 11-month median overall survival and a five-year survival of less than 5%. Incidence of PDAC is constantly increasing and is predicted to become the second leading cause of cancer in Western countries within a decade. Despite research and therapeutic development, current knowledge about PDAC molecular mechanisms still needs improvements and it seems crucial to identify novel therapeutic targets. Genomic analyses of PDAC revealed that transforming growth factor β (TGFβ) signaling pathways are modified and the SMAD4 gene is altered in 47% and 60% of cases, respectively, highlighting their major roles in PDAC development. TGFβ can play a dual role in malignancy depending on the context, sometimes as an inhibitor and sometimes as an inducer of tumor progression. TGFβ signaling was identified as a potent inducer of epithelial-to-mesenchymal transition (EMT), a process that confers migratory and invasive properties to epithelial cells during cancer. Therefore, aberrant TGFβ signaling and EMT are linked to promoting PDAC aggressiveness. TGFβ and SMAD pathways were extensively studied but the mechanisms leading to cancer promotion and development still remain unclear. This review aims to describe the complex role of SMAD4 in the TGFβ pathway in patients with PDAC.
Published: 2020
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28. Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe

Author: Denis Horgan, Giuseppe Curigliano, Olaf Rieß, Paul Hofman, Reinhard Büttner, Pierfranco Conte, Tanja Cufer, William M. Gallagher, Nadia Georges, Keith Kerr, Frédérique Penault-Llorca, Ken Mastris, Carla Pinto, Jan Van Meerbeeck, Elisabetta Munzone, Marlene Thomas, Sonia Ujupan, Gilad W. Vainer, Janna-Lisa Velthaus, Fabrice André, Division of Medical Oncology, European Institute of Oncology [Milan] (ESMO), Laboratory of Clinical and Experimental Pathology, Centre Hospitalier Universitaire de Nice (CHU Nice), University Hospital of Cologne [Cologne], Department of Surgery, Oncology and Gastroenterology, University of Padova, Istituto Oncologico Veneto IOV IRCCS, 35128 Padova, University Clinic Golnik, University College Dublin [Dublin] (UCD), Ministère de la santé, Department of Pathology, Aberdeen University Medical School, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, University of Antwerp (UA), Division of Medical Senology [Milan, Italy], Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Milano = University of Milan (UNIMI), University of Tübingen, Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], Università degli Studi di Padova = University of Padua (Unipd), University of Ljubljana, University of Aberdeen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), F. Hoffmann-La Roche [Basel], The Hebrew University of Jerusalem (HUJ), Institut Gustave Roussy (IGR), and Direction de la recherche [Gustave Roussy]
Subjects: Evropski načrt za premagovanje raka, [SDV]Life Sciences [q-bio], testing infrastructure, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, ozaveščanje in izobraževanje deležnikov, pravično povračilo, klinična standardizacija, sekvenciranje naslednje generacije, testiranje infrastrukture, molekularno vodene možnosti zdravljenja, clinical standardization, European Alliance for Personalised Medicine, Europe’s Beating Cancer Plan, stakeholder awareness and education, pridobivanje dokazov, Evropska zveza za personalizirano medicino, evidence generation, governance, Perspective, Medicine, molecularly guided treatment options, next-generation sequencing, Human medicine, equitable reimbursement, upravljanje
Abstract: International audience; Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.
Published: 2022
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29. Analysis of Fluorescence Decay Kinetics of Indocyanine Green Monomers and Aggregates in Brain Tumor Model In Vivo

Author: Lina Bezdetnaya, Yuliya S. Maklygina, Dina Farrakhova, Victor B. Loschenov, I.D. Romanishkin, Prokhorov General Physics Institute of the Russian Academy of Sciences, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, The National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) [Moscow, Russia], and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: indocyanine green, genetic structures, General Chemical Engineering, Kinetics, Brain tumor, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, [SPI.AUTO]Engineering Sciences [physics]/Automatic, chemistry.chemical_compound, In vivo, medicine, General Materials Science, fluorescent lifetime, QD1-999, brain cancer, fluorescent dyes, fluorescent diagnosis, near-infrared range, H-aggregates, glioma C6, Biological tissue, 021001 nanoscience & nanotechnology, medicine.disease, Fluorescence, eye diseases, 0104 chemical sciences, 3. Good health, body regions, Chemistry, Monomer, chemistry, Systemic administration, Biophysics, 0210 nano-technology, Indocyanine green
Abstract: International audience; Spectroscopic approach with fluorescence time resolution allows one to determine the state of a brain tumor and its microenvironment via changes in the fluorescent dye’s fluorescence lifetime. Indocyanine green (ICG) is an acknowledged infra-red fluorescent dye that self-assembles into stable aggregate forms (ICG NPs). ICG NPs aggregates have a tendency to accumulate in the tumor with a maximum accumulation at 24 h after systemic administration, enabling extended intraoperative diagnostic. Fluorescence lifetime analysis of ICG and ICG NPs demonstrates different values for ICG monomers and H-aggregates, indicating promising suitability for fluorescent diagnostics of brain tumors due to their affinity to tumor cells and stability in biological tissue.
Published: 2021
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30. RESVEGA, a Nutraceutical Omega-3/Resveratrol Supplementation, Reduces Angiogenesis in a Preclinical Mouse Model of Choroidal Neovascularization

Author: Ida Chiara Guerrera, Niyazi Acar, Dominique Delmas, Lionel Bretillon, Jean-Paul Pais de Barros, Cerina Chhuon, Virginie Aires, Flavie Courtaut, Céline Olmiere, Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoires Théa, Partenaires INRAE, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Agence Nationale de la Recherche + Association Nationale de la Recherche et de la Technologie (ANRT, 2016/0003) + European Regional Development Fund (ERDF) + Conseil régional de Bourgogne-Franche-Comté., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), Julien, Sabine, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011)
Subjects: Proteomics, genetic structures, Angiogenesis, AMD, resveratrol, Pharmacology, Resveratrol, Macular Degeneration, Mice, angiogenesis, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Biology (General), proteomic, Spectroscopy, 0303 health sciences, omega-3 fatty acids, General Medicine, 3. Good health, Computer Science Applications, Chemistry, medicine.anatomical_structure, Choroidal neovascularization, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Female, medicine.symptom, QH301-705.5, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Nutraceutical, In vivo, Fatty Acids, Omega-3, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, In patient, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, 030304 developmental biology, Retina, business.industry, ocular diseases, Organic Chemistry, Macular degeneration, medicine.disease, Choroidal Neovascularization, eye diseases, Disease Models, Animal, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Dietary Supplements, 030221 ophthalmology & optometry, sense organs, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Age-related macular degeneration (AMD) is an eye disease that is characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. At an advanced stage, a blind spot grows in the center of vision, severely handicapping patients with this degenerative condition. Despite therapeutic advances thanks to the use of anti-VEGF, many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether supplementation with Resvega®, a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, a well-known polyphenol in grapes, was able to counteract laser-induced choroidal neovascularization (CNV) in mice. We highlight that Resvega® significantly reduced CNV in mice compared with supplementations containing omega-3 or resveratrol alone. Moreover, a proteomic approach confirmed that Resvega® could counteract the progression of AMD through a pleiotropic effect targeting key regulators of neoangiogenesis in retina cells in vivo. These events were associated with an accumulation of resveratrol metabolites within the retina. Therefore, a supplementation of omega-3/resveratrol could improve the management or slow the progression of AMD in patients with this condition.
Published: 2021
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31. Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years

Author: Franck Morschhauser, Clément Bailly, Corinne Haioun, Benoit Tessoulin, Hervé Tilly, Vincent Ribrag, Marc André, Steven Le Gouill, Catherine Thieblemont, Bruno Villemagne, Thierry Lamy, Lucie Oberic, René-Olivier Casasnovas, Luc-Matthieu Fornecker, Kamal Bouabdallah, Remy Gressin, Maxime Jullien, Pierre Feugier, Guillaume Cartron, Jean-Marc Schiano de Colella, Olivier Hermine, Hervé Ghesquières, Gandhi Damaj, Christophe Bonnet, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Gustave Roussy (IGR), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Strasbourg, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Necker - Enfants Malades [AP-HP], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, CHU UCL Namur, Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth
Subjects: Cancer Research, medicine.medical_specialty, diffuse large B-cell lymphoma, convolutional neural network, [SDV.CAN]Life Sciences [q-bio]/Cancer, muscle depletion, Gastroenterology, Article, sarcopenia, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Hounsfield scale, medicine, Progression-free survival, Risk factor, RC254-282, Predictive marker, muscle hypodensity, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Skeletal muscle, medicine.disease, U-NET, medicine.anatomical_structure, Oncology, Sarcopenia, Cohort, business, Diffuse large B-cell lymphoma
Abstract: Background. Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin’s lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. Methods. This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). Results. After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58–4.95), p &lt, 0.001, and HR = 2.22 (95% CI 1.43–3.45), p &lt, 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice.
Published: 2021
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32. Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma

Author: Thomas Carlier, Françoise Kraeber-Bodere, Anne-Victoire Michaud, Cyrille Touzeau, Philippe Moreau, Mickaël Bourgeois, Bastien Jamet, Caroline Bodet-Milin, Clément Bailly, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Nucléaire [Nantes] (Centre René Gauducheau), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Cancer Research, medicine.medical_specialty, Osteolysis, Myeloma protein, mgus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, wbct, lcsh:RC254-282, smm, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, medicine, Stage (cooking), Multiple myeloma, mri, fdg-pet/ct, medicine.diagnostic_test, business.industry, imaging, Magnetic resonance imaging, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Biomarker (medicine), Radiology, business, Monoclonal gammopathy of undetermined significance, 030215 immunology
Abstract: International audience; Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.
Published: 2020
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33. Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy

Author: Corinne Aubel, Frédérique Penault-Lorca, F. Magnier, Clémence Dubois, Emmanuelle Mounetou, Mahchid Bamdad, Fanny Martin, Pierre Daumar, Chervin Hassel, Sylvie Guerder, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_treatment, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Olaparib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, the three-dimensional cell culture, sum1315, Medicine, Triple negative, parpi olaparib, Triple-negative breast cancer, transcriptomic analysis, 030304 developmental biology, Mda mb 231, 0303 health sciences, business.industry, mda-mb-231, lcsh:R, Spheroid, General Medicine, fractioned radiotherapy, 3. Good health, Radiation therapy, co-treatment, chemistry, Cell culture, spheroid, 030220 oncology & carcinogenesis, Cancer research, triple-negative breast cancer, business
Abstract: The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 &micro, M), combined with fractioned irradiation (i.e., 5 &times, 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 &micro, M Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 &micro, M and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 &micro, M and 10 Gy and of only 0.9 (both models) after 50 &micro, M and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation.
Published: 2019
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34. Dual Epigenetic Regulation of ERα36 Expression in Breast Cancer Cells

Author: Jean-Louis Merlin, Maelle Chesnel, Charlène Thiébaut, Hélène Dumond, Alexandre Harlé, Agnès Leroux, Amand Chesnel, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
Subjects: Epigenesis, Genetic, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, 3' Untranslated Regions, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, microRNA, General Medicine, Transfection, Middle Aged, Phenotype, 3. Good health, Computer Science Applications, 030220 oncology & carcinogenesis, MCF-7 Cells, Female, medicine.drug, Adult, Decitabine, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Breast cancer, breast cancer, Downregulation and upregulation, medicine, Humans, Epigenetics, Physical and Theoretical Chemistry, Molecular Biology, Aged, 030304 developmental biology, business.industry, Organic Chemistry, endocrine therapy resistance, Estrogen Receptor alpha, Epithelial Cells, DNA Methylation, medicine.disease, Demethylating agent, MicroRNAs, chemistry, ERα36, lcsh:Biology (General), lcsh:QD1-999, Cancer research, methylation, business
Abstract: Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ER&alpha, 36 was reported to play a crucial role in this process. High expression of this ER&alpha, isoform was associated to preneoplastic phenotype in mammary epithelial cells, disease progression, and enhanced resistance to therapeutic agents in breast tumors. In this study, we identified two mechanisms that could together contribute to ER&alpha, 36 expression regulation. We first focused on hsa-miR-136-5p, an ER&alpha, 36 3&rsquo, UTR-targeting microRNA, the expression of which inversely correlated to the ER&alpha, 36 one in breast cancer cells. Transfection of hsa-miR136-5p mimic in MCF-7 cells resulted in downregulation of ER&alpha, 36. Moreover, the demethylating agent decitabine was able to stimulate hsa-miR-136-5p endogenous expression, thus indirectly decreasing ER&alpha, 36 expression and counteracting tamoxifen-dependent stimulation. The methylation status of ER&alpha, 36 promoter also directly modulated its expression level, as demonstrated after decitabine treatment of breast cancer cell and confirmed in a set of tumor samples. Taken together, these results open the way to a direct and an indirect ER&alpha, 36 epigenetic modulation by decitabine as a promising clinical strategy to counteract acquired resistance to treatment and prevent relapse.
Published: 2019
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35. Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age

Author: Aude Lacourt, Bénédicte Clin, Gilbert Ferretti, A. Gislard, Pascal Andujar, Ilyes Benlala, Gaël Dournes, François Laurent, Fleur Delva, Céline Gramond, Jean-Claude Pairon, Isabelle Thaon, Christophe Paris, Patrick Brochard, Justine Gallet, Soizick Chamming's, CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Aliments Bioprocédés Toxicologie Environnements (ABTE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Rouen, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Institut Interuniversitaire de Médecine du Travail de Paris Ile-de-France (IIMTPIF), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), 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 ), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), French National Health Insurance (Occupational Risk Prevention Department), French Ministry of Labour and Social Relations, French Agency for Food, Environmental and Occupational Health and Safety (ANSES) [07-CRD-51, EST 2006/1/43, EST 2009/68], Chard-Hutchinson, Xavier, CHU Henri Mondor [Créteil], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )
Subjects: [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, asbestosis, Asbestosis, Population, Cumulative Exposure, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, Asbestos, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Medicine, 030212 general & internal medicine, education, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, education.field_of_study, Lung, business.industry, General Medicine, respiratory system, medicine.disease, asbestos-exposition, 3. Good health, medicine.anatomical_structure, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, HRCT, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Population study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objective: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. Methods: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema &lt, 25%, moderate: between 25 and 50% and severe: &gt, 50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. Results: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02–1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. Conclusion: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos.
Published: 2021
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36. Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

Author: Igor Yankovsky, Vladimir Zorin, Lina Bezdetnaya, Ilya Yakavets, Tatyana E. Zorina, Mikhail Belevtsev, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Laboratory of Biophysics and Biotechnology [Belarusian], Belarusian State University, and Belarusian State Medical University (BSMU)
Subjects: Biodistribution, white blood cells, medicine.medical_treatment, Pharmaceutical Science, Raji human Burkitt’s lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Photodynamic therapy, 02 engineering and technology, Pharmacology, 010402 general chemistry, 01 natural sciences, Article, Flow cytometry, Temoporfin, chemistry.chemical_compound, Pharmacy and materia medica, temoporfin, medicine, Distribution (pharmacology), cyclodextrins, medicine.diagnostic_test, flow cytometry, 021001 nanoscience & nanotechnology, medicine.disease, Blood proteins, 0104 chemical sciences, 3. Good health, Lymphoma, Raji cell, RS1-441, chemistry, 0210 nano-technology, red blood cells
Abstract: International audience; Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.
Published: 2021
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37. Use of Super Paramagnetic Iron Oxide Nanoparticles as Drug Carriers in Brain and Ear: State of the Art and Challenges

Author: Guigou, Caroline, Millot, Nadine, Belharet, Karim, Bozorg Grayeli, Alexis, Girum, Kibrom Berihu, Crehange, Gilles, Lalande, Alain, Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire pluridisciplinaire de recherche en ingénierie des systèmes, mécanique et énergétique (PRISME), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Laboratoire Interdisciplinaire Carnot de Bourgogne [Dijon] (LICB), and Université de Bourgogne (UB)-Université de Technologie de Belfort-Montbeliard (UTBM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: blood–perilymph barrier, inner ear, Drug, Materials science, Biocompatibility, Superparamagnetic iron oxide nanoparticles, media_common.quotation_subject, Nanotechnology, Review, blo-od–brain barrier, 02 engineering and technology, lcsh:RC321-571, 03 medical and health sciences, chemistry.chemical_compound, blood–perilymph barrier, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Distribution (pharmacology), lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, media_common, 0303 health sciences, General Neuroscience, iron oxide nanoparticles, central nervous system, 021001 nanoscience & nanotechnology, 3. Good health, chemistry, drug delivery, Drug delivery, blood–brain barrier, sense organs, Nanocarriers, 0210 nano-technology, Drug carrier, Iron oxide nanoparticles
Abstract: International audience; Drug delivery and distribution in the central nervous system (CNS) and the inner ear represent a challenge for the medical and scientific world, especially because of the blood–brain and the blood–perilymph barriers. Solutions are being studied to circumvent or to facilitate drug diffusion across these structures. Using superparamagnetic iron oxide nanoparticles (SPIONs), which can be coated to change their properties and ensure biocompatibility, represents a promising tool as a drug carrier. They can act as nanocarriers and can be driven with precision by magnetic forces. The aim of this study was to systematically review the use of SPIONs in the CNS and the inner ear. A systematic PubMed search between 1999 and 2019 yielded 97 studies. In this review, we describe the applications of the SPIONS, their design, their administration, their pharmacokinetic, their toxicity and the methods used for targeted delivery of drugs into the ear and the CNS.
Published: 2021
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38. iPSC-Derived Hereditary Breast Cancer Model Reveals the BRCA1-Deleted Tumor Niche as a New Culprit in Disease Progression

Author: Noufissa Oudrhiri, Christophe Desterke, Fatima Dkhissi, Lucie Portier, Ali G. Turhan, Frank Griscelli, Annelise Bennaceur-Griscelli, Diana Chaker, Afag Asgarova, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, Service de Santé des Armées-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hématologie Moléculaire et Cytogénétique Paul Brousse CHU Paris Sud, Université Paris Sud, Inserm UMRS935, 94800 Villejuif, 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), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP. Université Paris Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service d'Hématologie biologique [AP-HP Hôpital Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris Sud-Paris Saclay, Institut Gustave Roussy (IGR), National Infrastructure INGESTEM, Université Paris Sud, Université Paris Cité (UPCité), and Département de biologie et pathologie médicales [Gustave Roussy]
Subjects: Lung Neoplasms, endocrine system diseases, Angiogenesis, [SDV]Life Sciences [q-bio], Haploinsufficiency, Mice, SCID, Metastasis, lcsh:Chemistry, angiogenesis, Mice, Cell Movement, Mice, Inbred NOD, Basic Helix-Loop-Helix Transcription Factors, Tumor Microenvironment, RNA, Small Interfering, skin and connective tissue diseases, lcsh:QH301-705.5, Spectroscopy, periostin, iPSC, Neovascularization, Pathologic, BRCA1 Protein, General Medicine, Computer Science Applications, KLF4, Disease Progression, Female, Stromal cell, Induced Pluripotent Stem Cells, Breast Neoplasms, Biology, Article, Catalysis, Inorganic Chemistry, Kruppel-Like Factor 4, breast cancer, SOX2, Cell Line, Tumor, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, mesenchymal stem cells, Wound Healing, Gene Expression Profiling, Organic Chemistry, Cancer, BRCA1, medicine.disease, Xenograft Model Antitumor Assays, Gene Ontology, lcsh:Biology (General), lcsh:QD1-999, Tumor progression, Cancer cell, Cancer research, Transcriptome, Cell Adhesion Molecules
Abstract: Tumor progression begins when cancer cells recruit tumor-associated stromal cells to produce a vascular niche, ultimately resulting in uncontrolled growth, invasion, and metastasis. It is poorly understood, though, how this process might be affected by deletions or mutations in the breast cancer type 1 susceptibility (BRCA1) gene in patients with a lifetime risk of developing breast and/or ovarian cancer. To model the BRCA1-deleted stroma, we first generated induced pluripotent stem cells (iPSCs) from patients carrying a germline deletion of exon 17 of the BRCA1 gene (BRCA1+/&minus, who, based on their family histories, were at a high risk for cancer. Using peripheral blood mononuclear cells (PBMCs) of these two affected family members and two normal (BRCA1+/+) individuals, we established a number of iPSC clones via non-integrating Sendai virus-based delivery of the four OCT4, SOX2, KLF4, and c-MYC factors. Induced mesenchymal stem cells (iMSCs) were generated and used as normal and pathological stromal cells. In transcriptome analyses, BRCA1+/&minus, iMSCs exhibited a unique pro-angiogenic signature: compared to non-mutated iMSCs, they expressed high levels of HIF-1&alpha, angiogenic factors belonging to the VEGF, PDGF, and ANGPT subfamilies showing high angiogenic potential. This was confirmed in vitro through the increased capacity to generate tube-like structures compared to BRCA1+/+ iMSCs and in vivo by a matrigel plug angiogenesis assay where the BRCA1+/&minus, iMSCs promoted the development of an extended and organized vessel network. We also reported a highly increased migration capacity of BRCA1+/&minus, iMSCs through an in vitro wound healing assay that correlated with the upregulation of the periostin (POSTN). Finally, we assessed the ability of both iMSCs to facilitate the engraftment of murine breast cancer cells using a xenogenic 4T1 transplant model. The co-injection of BRCA1+/&minus, iMSCs and 4T1 breast cancer cells into mouse mammary fat pads gave rise to highly aggressive tumor growth (2-fold increase in tumor volume compared to 4T1 alone, p = 0.01283) and a higher prevalence of spontaneous metastatic spread to the lungs. Here, we report for the first time a major effect of BRCA1 haploinsufficiency on tumor-associated stroma in the context of BRCA1-associated cancers. The unique iMSC model used here was generated using patient-specific iPSCs, which opens new therapeutic avenues for the prevention and personalized treatment of BRCA1-associated hereditary breast cancer.
Published: 2021
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39. Packing Technique with or without Remodeling for Endovascular Coil Embolization of Renal Artery Aneurysms: Safety, Efficacy and Mid-Term Outcomes

Author: Olivier Chevallier, Pierre-Olivier Comby, Nabil Majbri, Marco Midulla, Kévin Guillen, Nicolas Falvo, Christiane Mousson, Grégory Secco, Romaric Loffroy, Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
Subjects: endovascular treatment, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, lcsh:Medicine, embolization, 030204 cardiovascular system & hematology, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, medicine.artery, Medicine, cardiovascular diseases, Embolization, Endovascular treatment, Renal artery, ComputingMilieux_MISCELLANEOUS, Renal artery aneurysms, Coil embolization, Surgical repair, renal artery, business.industry, lcsh:R, General Medicine, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, aneurysm, cardiovascular system, business, Artery
Abstract: The endovascular treatment of renal artery aneurysms (RAAs) has lower morbidity and shorter stay lengths compared to surgical repair. Here, we describe coil packing with or without remodeling and assess outcomes and complications. We retrospectively identified the 19 consecutive preventive endovascular RAA coil embolizations done in 18 patients at our center in 2010&ndash, 2020. Patient and aneurysm characteristics, technical success rate, complications, and recurrences were recorded. Mean patient age was 63 &plusmn, 13 years. The RAA was &gt, 1.5 cm in 11 cases, and in four cases, the aneurysm-to-parent artery size ratio was &gt, 2. Simple coiling was performed for 11 (57.9%) aneurysms, stent-assisted coiling for seven (36.8%) aneurysms, and balloon-assisted coiling for one (5.3%) aneurysm. Technical success rate was 100%. Complete definitive RAA exclusion was achieved with a single procedure for 17 (89.5%) aneurysms, whereas two (10.5%) aneurysms required a repeat procedure. Four minor complications occurred but resolved with no long-term consequences. No major complications occurred during the mean follow-up of 41.1 &plusmn, 29.7 months. Coil embolization by sac packing or remodeling proved very safe and effective. Together with the known lower morbidity and shorter stay length compared to open surgery, these data indicate that this endovascular procedure should become the preventive treatment of choice for RAAs.
Published: 2021
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40. Public Health Impact of Using Biosimilars, Is Automated Follow up Relevant?

Author: Gaël Grimandi, Jean-François Simonet, Anne Chiffoleau, Stéphane Birklé, Antoine Perpoil, François Bocquet, Amgen SAS [Paris], Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes (UN), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, PHU 11 Pharmacie [CHU Nantes] (Pharmacie Centrale), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Droit et changement social (DCS), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Droit et Sciences Politiques (UFR DSP), Jehan, Frederic, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes - UFR Droit et Sciences Politiques (UFR DSP), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: safety, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, Computer science, Health, Toxicology and Mutagenesis, Population, lcsh:Medicine, Review, immunogenicity, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Health care, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, Relevance (law), biosimilars, 030212 general & internal medicine, Product (category theory), education, Biosimilar Pharmaceuticals, economic incentives, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, education.field_of_study, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public health, lcsh:R, Public Health, Environmental and Occupational Health, Biosimilar, 3. Good health, Clinical trial, machine learning, Incentive, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Risk analysis (engineering), Neural Networks, Computer, Public Health, business, Follow-Up Studies
Abstract: International audience; Biologic reference drugs and their copies, biosimilars, have a complex structure. Biosimilars need to demonstrate their biosimilarity during development but unpredictable variations can remain, such as micro-heterogeneity. The healthcare community may raise questions regarding the clinical outcomes induced by this micro-heterogeneity. Indeed, unwanted immune reactions may be induced for numerous reasons, including product variations. However, it is challenging to assess these unwanted immune reactions because of the multiplicity of causes and potential delays before any reaction. Moreover, safety assessments as part of preclinical studies and clinical trials may be of limited value with respect to immunogenicity assessments because they are performed on a standardised population during a limited period. Real-life data could therefore supplement the assessments of clinical trials by including data on the real-life use of biosimilars, such as switches. Furthermore, real-life data also include any economic incentives to prescribe or use biosimilars. This article raises the question of relevance of automating real life data processing regarding Biosimilars. The objective is to initiate a discussion about different approaches involving Machine Learning. So, the discussion is established regarding implementation of Neural Network model to ensure safety of biosimilars subject to economic incentives. Nevertheless, the application of Machine Learning in the healthcare field raises ethical, legal and technical issues that require further discussion.
Published: 2020
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41. Glucose Metabolism Quantified by SUVmax on Baseline FDG-PET/CT Predicts Survival in Newly Diagnosed Multiple Myeloma Patients: Combined Harmonized Analysis of Two Prospective Phase III Trials

Author: Caroline Bodet-Milin, Thomas Carlier, Bastien Jamet, Françoise Kraeber-Bodere, Elena Zamagni, Cyrille Touzeau, Anne-Victoire Michaud-Robert, Clément Bailly, Philippe Moreau, Cristina Nanni, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), University of Bologna, Nuclear Oncology (CRCINA-ÉQUIPE 13), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Sant'Orsola-Malpighi Polyclinic [Bologna, Italy], Michaud-Robert A.-V., Zamagni E., Carlier T., Bailly C., Jamet B., Touzeau C., Moreau P., Kraeber-Bodere F., Nanni C., Bodet-Milin C., Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of Bologna/Università di Bologna, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: prognostic value, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Multivariate analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Standardized uptake value, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Prospective cohort study, Multiple myeloma, medicine.diagnostic_test, business.industry, Communication, SUVmax, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, FDG-PET/CT, 3. Good health, multiple myeloma, 030104 developmental biology, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Biomarker (medicine), Hematological neoplasm, Bone marrow, Radiology, business
Abstract: Simple Summary Multiple myeloma (MM) is associated with high morbidity and mortality and variable survival that requires early identification of high-risk patients in order to quickly adapt treatment. FDG-PET/CT is a promising technique for initial staging of symptomatic MM. The aim of our retrospective study was to asses the prognostic value of this technique at baseline in symptomatic MM patients included in two large European prospective studies. After harmonization of data by and ad-hoc approach called M-Combat, we confirmed the prognostic value of FDG-PET/CT in a population of 227 MM patients, by integrating a new prognostic biomarker named “bone SUVmax” (including the maximum intensity of fixation of focal lesions and bone marrow) which is strongly correlated with a poorer prognosis of MM patients. Prognostic patient stratification is currently based on laboratory tests and genomic abnormalities, but FDG-PET/CT is likely to be an important method of defining high-risk patients, and thus, to potentially better adapt future therapeutic management. Abstract Background: Multiple myeloma is a hematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow, and is associated with high morbidity and mortality and variable survival. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a promising technique for initial staging of symptomatic multiple myeloma patients. The objective of this study was to assess the prognostic value of this technique at baseline in symptomatic multiple myeloma patients included in two large European prospective studies (French and Italian). Methods: We retrospectively performed a combined harmonized analysis of 227 newly diagnosed transplant eligible multiple myeloma patients from two separate phase III trials. All images were centrally reviewed and analyzed using visual criteria and maximal standardized uptake value. An ad-hoc approach (called modified Combat) was applied to harmonize the data and then remove the “country effect” in order to strengthen the reliability of the final conclusions. Results: Using a multivariate analysis including treatment arm, R-ISS score, presence of extra-medullary disease and bone SUVmax, only bone SUVmax (p = 0.016) was an independent prognosis factor with an OS threshold of 7.1. For PFS, treatment arm and presence of extra-medullary disease were both independent prognosis biomarkers (p = 0.022 and 0.006 respectively). Conclusions: Our results show that bone SUVmax is a simple and reliable biomarker to analyze FDG-PET/CT at baseline that strongly correlates with a poorer prognosis for MM patients.
Published: 2020
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42. Non-Small-Cell Lung Cancer-Sensitive Detection of the p.Thr790Met EGFR Alteration by Preamplification before PNA-Mediated PCR Clamping and Pyrosequencing

Author: Amandine Billaud, Alain Morel, Jonathan Dauvé, Louise-Marie Chevalier, Véronique Verriele, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, detection sensitivity, EGFR, Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, NSCLC, medicine.disease_cause, T790M, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, preamplification, Lung cancer, lcsh:R5-920, Mutation, Peptide nucleic acid, business.industry, p.Thr790Met, biomarkers, medicine.disease, Resistance mutation, respiratory tract diseases, 3. Good health, 030104 developmental biology, non-small-cell lung cancer, chemistry, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, peptide nucleic acid, Pyrosequencing, lcsh:Medicine (General), business, PNA, DNA
Abstract: Targeted therapies and, more precisely, EGFR tyrosine kinase inhibitors (TKIs) have been a major improvement in the therapeutic management of EGFR-mutated non-small-cell lung cancers (NSCLCs). Earlier administration of these TKIs throughout tumor progression is imperative to improve patient outcomes. Consequently, studies have focused on refining the characterization of biomarkers, especially concerning the resistance mutation p.Thr790Met of EGFR. Herein, we developed peptide nucleic acid (PNA)-mediated PCR clamping followed by pyrosequencing, favoring enrichment of the mutated fraction. A preamplification step was first added to increase the amplifiable DNA fraction. Throughout the application of our method on DNA extracted from FFPE samples of 46 patients with NSCLC who had relapsed under first-generation EGFR TKI, we evaluated a sensitivity of 93.3% and a specificity of 100%. All 19 patients who were positive for the p.Thr790Met mutation with NGS were also found to be positive with our protocol. The only discordant case was a sample with no mutation detected with NGS, but which was positive with PNA. This protocol allows for the detection of the p.Thr790Met mutation with a sensitivity of 0.5% which will permit earlier detection and an improvement of therapeutic management.
Published: 2020
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43. Targeting of BCL-2 Family Members during Anticancer Treatment: A Necessary Compromise between Individual Cell and Ecosystemic Responses?

Author: Sophie Barillé-Nion, Philippe Juin, Steven Lohard, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, SIRIC ILIAD program supported by theFrench National Cancer Institute national (INCa), Barillé-Nion, Sophie, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: BH3 mimetics, 0301 basic medicine, Programmed cell death, [SDV]Life Sciences [q-bio], Cell, lcsh:QR1-502, Antineoplastic Agents, Apoptosis, Review, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neoplasms, Drug Discovery, medicine, Animals, Humans, cancer, Molecular Targeted Therapy, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Caspase, biology, Bcl-2 family, Mitochondria, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, tumor ecosystem, 030220 oncology & carcinogenesis, Cancer cell, biology.protein, MOMP, Intracellular
Abstract: International audience; The imbalance between BCL-2 homologues and pro-death counterparts frequently noted in cancer cells endows them with a cell autonomous survival advantage. To eradicate ectopic cells, inhibitors of these homologues (BH3 mimetics) were developed to trigger, during anticancer treatment, full activation of the canonical mitochondrial apoptotic pathway and related caspases. Despite efficiency in some clinical settings, these compounds do not completely fulfill their initial promise. We herein put forth that a growing body of evidence indicates that mitochondrial integrity, controlled by BCL-2 family proteins, and downstream caspases regulate other cell death modes and influence extracellular signaling by committed cells. Moreover, intercellular communications play a key role in spreading therapeutic response across cancer cell populations and in engaging an immune response. We thus advocate that BH3 mimetics administration would be more efficient in the long term if it did not induce apoptosis in all sensitive cells at the same time, but if it could instead allow (or trigger) death signal production by non-terminally committed dying cell populations. The development of such a trade-off strategy requires to unravel the effects of BH3 mimetics not only on each individual cancer cell but also on homotypic and heterotypic cell interactions in dynamic tumor ecosystems.
Published: 2020
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44. Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer

Author: Sylvie Girault, Aude Testard, Ludovic Ferrer, Sandrine Hiret, Olivier Morel, Maelle Le Thiec, Françoise Kraeber-Bodéré, Bruno Maucherat, Loïc Campion, D. Rusu, Camille Guillerminet, Emmanuel Rio, Hadji Hamidou, Véronique Guérin Meyer, Marie Lacombe, Caroline Rousseau, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Département de Médecine Nucléaire [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Physique Médicale [Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Département de Physique Médicale [Angers], Service de la Radio-Oncologie [Angers], Service Oncologie Médicale [Angers], Service de la Radio-Oncologie [Saint-Herblain], Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Cancer Research, medicine.medical_specialty, Multivariate statistics, anal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Standardized uptake value, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, parasitic diseases, medicine, Clinical endpoint, Anal cancer, FDG-PET, metabolic tumour volume, 10. No inequality, Lymph node, Fluorodeoxyglucose, medicine.diagnostic_test, business.industry, Anal Squamous Cell Carcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, prognosis, Radiology, business, medicine.drug
Abstract: International audience; Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient's sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cutoff for discrimination between a low and high risk of event occurrence was 40 cm 3. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.
Published: 2020
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45. Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma

Author: Magali Humbert, Mario P. Tschan, Sylvie Giuriato, Mojgan Djavaheri-Mergny, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurology, Children's Hospital [Boston], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University of Bern, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Myeloid, Lymphoma, media_common.quotation_subject, [SDV.CAN]Life Sciences [q-bio]/Cancer, 610 Medicine & health, Review, lymphomas, Blood cell, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Autophagy, Animals, Humans, Progenitor cell, lcsh:QH301-705.5, media_common, Clinical Trials as Topic, Leukemia, business.industry, therapy response, Longevity, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, haematopoiesis, medicine.disease, 3. Good health, Hematopoiesis, Haematopoiesis, macroautophagy, 030104 developmental biology, medicine.anatomical_structure, Tumour development, lcsh:Biology (General), ageing, 030220 oncology & carcinogenesis, leukaemia, Cancer research, business
Abstract: International audience; Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly people. Unfortunately, elderly patients with leukaemia or lymphoma still have an unsatisfactory prognosis compared to younger ones highlighting the need to develop more efficient therapies for this group of patients. Growing evidence indicates that macroautophagy (hereafter referred to as autophagy) is essential for health and longevity. This review is focusing on the role of autophagy in normal haematopoiesis as well as in leukaemia and lymphoma development. Attenuated autophagy may support early hematopoietic neoplasia whereas activation of autophagy in later stages of tumour development and in response to a variety of therapies rather triggers a pro-tumoral response. Novel insights into the role of autophagy in haematopoiesis will be discussed in light of designing new autophagy modulating therapies in hematopoietic cancers.
Published: 2019
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46. Tumor Immunotargeting Using Innovative Radionuclides

Author: Jean-François Chatal, Eric Frampas, Nicolas Chouin, Caroline Bodet-Milin, Jacques Barbet, Cédric Mathieu, Thomas Carlier, François Guérard, Caroline Rousseau, Alain Faivre-Chauvet, Michel Chérel, Françoise Kraeber-Bodéré, Ferid Haddad, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Médecine Nucléaire [ICO-Site Gauducheau, Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département de Radiologie [CHU Nantes], Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Département de Physique [Nantes] (GIP Arronax), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), This work has been supported in part by a grant from the French National Agency for Research, called 'Investissements d’Avenir' no. ANR-11-LABX-0018-01., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Diagnostic Imaging, medicine.medical_specialty, alpha particle-emitting radionuclides, medicine.medical_treatment, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Catalysis, Radiolabeled Antibodies, Inorganic Chemistry, lcsh:Chemistry, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Medical imaging, Humans, Medicine, Medical physics, Physical and Theoretical Chemistry, Radionuclide Imaging, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, innovative radionuclides, Pretargeting, Radioisotopes, Tumor imaging, business.industry, Organic Chemistry, Antibodies, Monoclonal, General Medicine, Pet imaging, 3. Good health, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, Radioimmunotherapy, immuno-PET, radioimmunotherapy, Personalized medicine, business, alpha-immunotherapy
Abstract: International audience; This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.
Published: 2015
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47. Mini-P-gp and P-gp Co-Expression in Brown Trout Erythrocytes: A Prospective Blood Biomarker of Aquatic Pollution

Author: François Desmolles, Bruno Combourieu, Mahchid Bamdad, Christian Amblard, Frédérique Penault-Llorca, Emeline Valton, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Synthèse et étude de systèmes à intêret biologique (SEESIB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Laboratoire Biochimie Médicale (UMR 384), Institut National de la Santé et de la Recherche Médicale (INSERM), BRICHEUX, Genevieve, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Clinical Biochemistry, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 010501 environmental sciences, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 01 natural sciences, Article, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Brown trout, brown trout, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Pollutant, lcsh:R5-920, 0303 health sciences, biology, river pollution, Pesticide, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Multiple drug resistance, Biomarker, Trout, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental chemistry, erythrocytes, mini-P-gp, P-gp, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, blood biomarker, lcsh:Medicine (General), Xenobiotic
Abstract: In aquatic organisms, such as fish, blood is continually exposed to aquatic contaminants. Multidrug Resistance (MDR) proteins are ubiquitous detoxification membrane pumps, which recognize various xenobiotics. Moreover, their expression is induced by a large class of drugs and pollutants. We have highlighted the co-expression of a mini P-gp of 75 kDa and a P-gp of 140 kDa in the primary culture of brown trout erythrocytes and in the erythrocytes of wild brown trout collected from three rivers in the Auvergne region of France. In vitro experiments showed that benzo[a]pyrene, a highly toxic pollutant model, induced the co-expression of mini-P-gp and P-gp in trout erythrocytes in a dose-dependent manner and relay type response. Similarly, in the erythrocytes of wild brown trout collected from rivers contaminated by a mixture of PAH and other multi-residues of pesticides, mini-P-gp and P-gp were able to modulate their expression, according to the nature of the pollutants. The differential and complementary responses of mini-P-gp and P-gp in trout erythrocytes suggest the existence in blood cells of a real protective network against xenobiotics/drugs. This property could be exploited to develop a blood biomarker of river pollution.
Published: 2015
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48. From Targeting Somatic Mutations to Finding Inherited Cancer Predispositions: The Other Side of the Coin

Author: Pascal Pujol, Thibault De La Motte Rouge, Frédérique Penault-Llorca, 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), Centre Eugène Marquis (CRLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, and Salvy-Córdoba, Nathalie
Subjects: 0301 basic medicine, Cancer-Predisposing Gene, Referral, Clinical Biochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bioinformatics, Genome, Germline, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Informed consent, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Genetic testing, lcsh:R5-920, somatic analysis, medicine.diagnostic_test, business.industry, Brief Report, Cancer, Geneticist, medicine.disease, 3. Good health, cancer predisposing genes, 030104 developmental biology, 030220 oncology & carcinogenesis, secondary findings, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Medicine (General), business
Abstract: International audience; The expanding use of tumor genome analysis by next generation sequencing to drive target therapies has led to increased germline findings in genes predisposing to hereditary cancer. These putative germline findings obtained from theranostic analyses, such as BRCA1/2 gene testing, large panels, whole-exome, or whole-genome sequencing, need to be managed carefully and in an anticipated way with the patient. Before the genetic analysis of a tumor, specific information should be given to patients, who should be aware that the results may have extra-therapeutic medical issues for themselves and relatives. We previously published a list of 36 actionable genes predisposing to cancer for which informing the patient is recommended prior to pangenomic germline analysis because of available screening or preventive strategies. Here, we report clinical practice considerations and schemes for managing germline findings in tumor analyses, including written informed consent and a multidisciplinary approach involving an oncologist, molecular biologist/pathologist, and geneticist in case of germline findings. A somatic result showing a deleterious mutation in a known predisposing gene in a patient who has consented to this purpose should result in referral to a geneticist who is part of the multidisciplinary team. At any time of the somatic analysis process, the patient may have access to a geneticist consultation if additional information is required. This framework will optimally manage both personalized theranostic issues and specific preventive strategies for individuals and relatives; it will also simplify and accelerate the process of genetic testing.
Published: 2019
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49. The New Synthetic Serum-Free Medium OptiPASS Promotes High Proliferation and Drug Efficacy Prediction on Spheroids from MDA-MB-231 and SUM1315 Triple-Negative Breast Cancer Cell Lines

Author: Pierre Daumar, Jean Gauthier, Clémence Dubois, Bernard Vidalinc, Frédérique Penault-Llorca, Mahchid Bamdad, Corinne Aubel, Emmanuelle Mounetou, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Technologie - Clermont-Ferrand (IUT Clermont-Ferrand), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), and UNICANCER
Subjects: Drug, MDA-MB-231, media_common.quotation_subject, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Efficacy, synthetic medium OptiPASS, triple negative breast cancer, SUM1315, spheroid development, drug screening, 03 medical and health sciences, 3D cell culture, 0302 clinical medicine, Breast cancer, medicine, ComputingMilieux_MISCELLANEOUS, Triple-negative breast cancer, 030304 developmental biology, media_common, 0303 health sciences, business.industry, lcsh:R, Spheroid, General Medicine, medicine.disease, In vitro, Cell culture, 030220 oncology & carcinogenesis, Cancer research, business
Abstract: Triple-negative breast cancers are particularly aggressive. In vitro cultures are one of the major pathways for developing anticancer strategies. The effectiveness and reproducibility of the drug screenings depend largely on the homogeneity of culture media. In order to optimize the predictive responses of triple-negative breast cancer 3D cell culture models, these works were focused on the development of SUM1315 and MDA-MB-231 cell lines in OptiPASS medium, a new serum-free formulation (BIOPASS). In monolayer cell culture, OptiPASS medium was more suitable for MDA-MB-231 than SUM1315 cell line but maintained cell phenotype and allowed sufficient proliferation. For spheroids produced in OptiPASS, the size monitoring showed a 1.3 and 1.5-fold increase for MDA-MB-231 and SUM1315 cell lines, respectively and viability/mortality profiles were maintained. Spheroids drug sensitivity thresholds were also improved allowing quicker high throughput drug screenings. These results showed the suitability of OptiPASS for 2D and 3D cell cultures of these two triple-negative breast cancer cell lines, with reproducibility of spheroid formation superior to 98%. This opens the way to the common use of this synthetic medium in future preclinical breast cancer research studies.
Published: 2019
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50. Role of Calcium Signaling in GA101-Induced Cell Death in Malignant Human B Cells

Author: Marion Zanese, Laurence Bresson-Bepoldin, Pierre Soubeyran, Françoise Durrieu, Valérie Le Morvan, Fontanet Bijou, Simon Latour, Ariel Savina, Anne-Marie Vacher, Nelly Menard, Pierre Vacher, Université de Bordeaux (UB), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER, Division Physico-chimie des Matériaux (LCPC/PCM), Laboratoire Central des Ponts et Chaussées (LCPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Plateforme de génétique moléculaire des cancers d'Aquitaine, UNICANCER-UNICANCER, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département des Sciences de la Santé, Université de Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, and Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Cancer Research, Programmed cell death, Cell type, Chronic lymphocytic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, calcium signaling, lcsh:RC254-282, malignant B cells, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, GA101, Calcium signaling, Chemistry, Endoplasmic reticulum, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Cell biology, cell death, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Unfolded protein response, anti-CD20, Intracellular
Abstract: GA101/obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb), which is more effective than rituximab (RTX) in preclinical and clinical studies when used in combination with chemotherapy. Ca2+ signaling was shown to play a role in RTX-induced cell death. This report concerns the effect of GA101 on Ca2+ signaling and its involvement in the direct cell death induced by GA101. We reveal that GA101 triggered an intracellular Ca2+ increase by mobilizing intracellular Ca2+ stores and activating Orai1-dependent Ca2+ influx in non-Hodgkin lymphoma cell lines and primary B-Cell Chronic Lymphocytic Leukemia (B-CLL) cells. According to the cell type, Ca2+ was mobilized from two distinct intracellular compartments. In Raji, BL2, and B-CLL cells, GA101 induced a Ca2+ release from lysosomes, leading to the subsequent lysosomal membrane permeabilization and cell death. Inhibition of this calcium signaling reduced GA101-induced cell death in these cells. In SU-DHL-4 cells, GA101 mobilized Ca2+ from the endoplasmic reticulum (ER). Inhibition of ER replenishment, by blocking Orai1-dependent Ca2+ influx, led to an ER stress and unfolded protein response (UPR) which sensitized these cells to GA101-induced cell death. These results revealed the central role of Ca2+ signaling in GA101&rsquo, s action mechanism, which may contribute to designing new rational drug combinations improving its clinical efficacy.
Published: 2019
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