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3. Radiobiology of Combining Radiotherapy with Other Cancer Treatment Modalities

Author

Ahire, Vidhula, Ahmadi Bidakhvidi, Niloefar, Boterberg, Tom, Chaudhary, Pankaj, Chevalier, Francois, Daems, Noami, Delbart, Wendy, Baatout, Sarah, Deroose, Christophe M., Fernandez-Palomo, Cristian, Franken, Nicolaas A. P., Gaipl, Udo S., Geenen, Lorain, Heynickx, Nathalie, Koniarová, Irena, Selvaraj, Vinodh Kumar, Levillain, Hugo, Michaelidesová, Anna Jelínek, Montoro, Alegría, Oei, Arlene L., Penninckx, Sébastien, Reindl, Judith, Rödel, Franz, Sminia, Peter, Tabury, Kevin, Vermeulen, Koen, Viktorsson, Kristina, Waked, Anthony, and Baatout, Sarah, editor

Published
2023
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4. Basic Concepts of Radiation Biology

Author

Baeyens, Ans, Abrantes, Ana Margarida, Ahire, Vidhula, Ainsbury, Elizabeth A., Baatout, Sarah, Baselet, Bjorn, Botelho, Maria Filomena, Boterberg, Tom, Chevalier, Francois, Da Pieve, Fabiana, Delbart, Wendy, Edin, Nina Frederike Jeppesen, Fernandez-Palomo, Cristian, Geenen, Lorain, Georgakilas, Alexandros G., Heynickx, Nathalie, Meade, Aidan D., Michaelidesova, Anna Jelinek, Mistry, Dhruti, Montoro, Alegría, Mothersill, Carmel, Pires, Ana Salomé, Reindl, Judith, Schettino, Giuseppe, Socol, Yehoshua, Selvaraj, Vinodh Kumar, Sminia, Peter, Vermeulen, Koen, Vogin, Guillaume, Waked, Anthony, Wozny, Anne-Sophie, and Baatout, Sarah, editor

Published
2023
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5. Radar, without tears

Author

Chevalier, Francois Le

Subjects
Physics - Popular Physics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

A brief introduction to radar: principles, Doppler effect, antennas, waveforms, power budget - and future radars. [13 pages]

Published
2017

6. Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET.

Author

Gilbert, Antoine, Tudor, Mihaela, Delaunay, Amandine, Leman, Raphaël, Levilly, Julien, Atkinson, Alexandre, Castéra, Laurent, Dinischiotu, Anca, Savu, Diana Iulia, Valable, Samuel, and Chevalier, François

Subjects
LINEAR energy transfer, CELL survival, CHONDROSARCOMA, DNA damage, POLY(ADP-ribose) polymerase
Abstract

Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.

Author

Rødland, Gro Elise, Temelie, Mihaela, Eek Mariampillai, Adrian, Hauge, Sissel, Gilbert, Antoine, Chevalier, François, Savu, Diana I., and Syljuåsen, Randi G.

Subjects
HEAVY ion radiotherapy, DNA repair, DNA damage, PROTONS, CLUSTERING of particles
Abstract

The use of charged particle radiotherapy is currently increasing, but combination therapy with DNA repair inhibitors remains to be exploited in the clinic. The high-linear energy transfer (LET) radiation delivered by charged particles causes clustered DNA damage, which is particularly effective in destroying cancer cells. Whether the DNA damage response to this type of damage is different from that elicited in response to low-LET radiation, and if and how it can be targeted to increase treatment efficacy, is not fully understood. Although several preclinical studies have reported radiosensitizing effects when proton or carbon ion irradiation is combined with inhibitors of, e.g., PARP, ATR, ATM, or DNA-PKcs, further exploration is required to determine the most effective treatments. Here, we examine what is known about repair pathway choice in response to high- versus low-LET irradiation, and we discuss the effects of inhibitors of these pathways when combined with protons and carbon ions. Additionally, we explore the potential effects of DNA repair inhibitors on antitumor immune signaling upon proton and carbon ion irradiation. Due to the reduced effect on healthy tissue and better immune preservation, particle therapy may be particularly well suited for combination with DNA repair inhibitors. [ABSTRACT FROM AUTHOR]

Published
2024
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13. NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.

Author

Nisar, Hasan, Sanchidrián González, Paulina Mercedes, Labonté, Frederik M., Schmitz, Claudia, Roggan, Marie Denise, Kronenberg, Jessica, Konda, Bikash, Chevalier, François, and Hellweg, Christine E.

Subjects
NON-small-cell lung carcinoma, LINEAR energy transfer, CANCER cells, RADIOBIOLOGY, HYPOXEMIA, IRRADIATION, X-rays
Abstract

Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate nuclear factor κB (NF-κB), which can modulate radioresistance by influencing cancer cell survival. The effect of high-LET radiation on NF-κB activation in hypoxic NSCLC cells is unclear. Therefore, we compared the effect of low (X-rays)- and high (12C)-LET radiation on NF-κB responsive genes' upregulation, as well as its target cytokines' synthesis in normoxic and hypoxic A549 NSCLC cells. The cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h, followed by irradiation with 8 Gy X-rays or 12C ions, maintaining the oxygen conditions until fixation or lysis. Regulation of NF-κB responsive genes was evaluated by mRNA sequencing. Secretion of NF-κB target cytokines, IL-6 and IL-8, was quantified by ELISA. A greater fold change increase in expression of NF-κB target genes in A549 cells following exposure to 12C ions compared to X-rays was observed, regardless of oxygenation status. These genes regulate cell migration, cell cycle, and cell survival. A greater number of NF-κB target genes was activated under hypoxia, regardless of irradiation status. These genes regulate cell migration, survival, proliferation, and inflammation. X-ray exposure under hypoxia additionally upregulated NF-κB target genes modulating immunosurveillance and epithelial-mesenchymal transition (EMT). Increased IL-6 and IL-8 secretion under hypoxia confirmed NF-κB-mediated expression of pro-inflammatory genes. Therefore, radiotherapy, particularly with X-rays, may increase tumor invasiveness in surviving hypoxic A549 cells. [ABSTRACT FROM AUTHOR]

Published
2024
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17. A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology: Rationale and Research Protocol of the HARMONIC Project

Author

Andreassi, Maria Grazia, primary, Haddy, Nadia, additional, Harms-Ringdahl, Mats, additional, Campolo, Jonica, additional, Borghini, Andrea, additional, Chevalier, François, additional, Schwenk, Jochen M., additional, Fresneau, Brice, additional, Bolle, Stephanie, additional, Fuentes, Manuel, additional, and Haghdoost, Siamak, additional

Published
2023
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27. A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology : Rationale and Research Protocol of the HARMONIC Project

Author

Andreassi, Maria Grazia, Haddy, Nadia, Harms-Ringdahl, Mats, Campolo, Jonica, Borghini, Andrea, Chevalier, François, Schwenk, Jochen M., Fresneau, Brice, Bolle, Stephanie, Fuentes, Manuel, Haghdoost, Siamak, Andreassi, Maria Grazia, Haddy, Nadia, Harms-Ringdahl, Mats, Campolo, Jonica, Borghini, Andrea, Chevalier, François, Schwenk, Jochen M., Fresneau, Brice, Bolle, Stephanie, Fuentes, Manuel, and Haghdoost, Siamak

Abstract

The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.

Published
2023
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28. A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology: Rationale and Research Protocol of the HARMONIC Project

Author

European Commission, Grazia Andreassi, María, Haddy, Nadia, Harms-Ringdahl, Mats, Campolo, Jonica, Borghini, Andrea, Chevalier, François, Schwenk, Jochen M., Fresneau, Brice, Bolle, Stephanie, Fuentes, Manuel, Haghdoost, Siamak, European Commission, Grazia Andreassi, María, Haddy, Nadia, Harms-Ringdahl, Mats, Campolo, Jonica, Borghini, Andrea, Chevalier, François, Schwenk, Jochen M., Fresneau, Brice, Bolle, Stephanie, Fuentes, Manuel, and Haghdoost, Siamak

Abstract

The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.

Published
2023

30. Dosimetry for radiobiology experiments at GANIL

Author

Durantel, Florent, Balanzat, Emmanuel, Cassimi, Amine, Chevalier, François, Ngono-Ravache, Yvette, Madi, Toiammou, Poully, Jean-Christophe, Ramillon, Jean-Marc, Rothard, Hermann, Ropars, Frédéric, Schwob, Lucas, Testard, Isabelle, and Saintigny, Yannick

Published
2016
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31. CYCLHAD: A French Facility Dedicated for Research and Treatment in Hadrontherapy

Author

Chevalier, François, Lesueur, P., Gaubert, G., 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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de radiothérapie Guillaume le Conquérant (CGLC), 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 Pantechnik

Subjects
Nuclear and High Energy Physics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience

Published
2022

35. Role of KRAS mutation on NSCLC resistance to X-rays and protons

Author

Montanari, Juliette, Césaire, Mathieu, Gilbert, Antoine, Chevalier, François, 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), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience; Unresectable locally advanced non-small cell lung cancer (NSCLC) is a frequent cancer with a prognosis that remains poor despite several treatments for radiotherapy, chemotherapy and immunotherapy. Mechanisms of resistance to treatments have been highlighted such as KRAS mutations. A new therapy type tyrosine kinase inhibitor targeting the KRAS G12C mutation has enabled efficacy in metastatic NSCLC and could have an interest in the treatment by radiotherapy locally advanced forms. However, the radiosensitizing effect of such molecules targeting KRAS remains unknown. KRAS resistance mechanisms could be related to hypoxia and the proliferation of tumor stem cells and irradiation by carbon ions and protons compared to photon irradiation might also have future interest in the treatment of these patients. In this study, we propose to use in vitro models of KRAS G12C mutated cell lines (vs. non-mutated). These cells are treated with a combination of KRAS G12C inhibitors and irradiations (X-rays, carbon ions and protons). Following a complete characterization of the cell lines and drug toxicity tests, the clonogenic survival of the cells is then analysed.Our preliminary results show a differential response of the cells, depending on the cell lines, irradiation doses and quality and drug combinations.

Published
2022

38. Analysis of ionizing radiation induced effects in radioresistant tumours and bystander normal cells

Author

Tudor, M, Gilbert, A, Temelie, M, Dinischiotu, A, Chevalier, François, Savu, D, 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), 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), and This work was supported by Romanian Ministry of Research and Innovation: PN-III-P3-3.1-PM-RO-FR-2019-0300 24BM,543PED/2017, PN 19060203/2019.

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience; Chondrosarcoma is a chemo and radioresistant tumour for which the main treatment remains surgery. Hadron therapy has shown better specificity and lower toxicity for the surrounding normal tissue when compared to conventional photon therapy. This study focuses on analysing cellular mechanisms involved in stress and response to DNA damage induced by ionizing radiation in radioresistant tumour cells and bystander normal cells. Two different chondrosarcoma cell lines (SW1353 and L835) were irradiated with X-ray and low energy protons at doses in the range 0.1-2 Gy. To study the bystander phenomena we used a medium transfer protocol. The bystander supernatant containing signals emitted by irradiated chondrosarcoma cells, was transferred to non-irradiated normal chondrocyte (T/C-28a2) and endothelial (EA.hy926) cells. In order to investigate the oxidative stress induced by irradiation we used flow cytometry to quantify the mitochondrial and cellular reactive oxygen species at 3h and 24h following exposure to X-ray. Similar, for the bystander cells, we investigated the oxidative stress induced by the irradiated cells at 3 and 24h after media transfer. Chondrosarcoma cells present an increase in mitochondrial stress 3h after irradiation in contrast with the bystander cells that present modifications 24h after media transfer. To understand the mechanisms behind the cellular response in bystander cells we used a proteomic assay for the chondrocyte cells receiving medium from the irradiated chondrosarcoma SW1353 cells at the dose of 0.1 Gy. The proteomic assay of the bystander chondrocytes receiving media from either X-ray and proton irradiated cells highlighted a series of modified proteins involved in several cellular mechanisms such as oxidative stress responses, cellular motility, cell death, cancer pathways and exosomes pathways. Our results showed the potential for these proteins to be good biomarker-candidates involved in cellular response in bystander cells.

Published
2022

40. Impact de l'hadronthérapie par ions carbone et protons sur les cellules souches cancéreuses de chondrosarcome en hypoxie

Author

Gilbert, Antoine, Montanari, Juliette, Commenchail, Kévin, Guillamin, Marilyne, Valable, Samuel, Chevalier, François, 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), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-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), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), 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)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and soutien de la région Normandie au sein du projet RIN CHOXTRACC

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience

Published
2022

41. Impact of Hypoxia and Hadrontherapy on Radioresistant Chondrosarcoma Cancer Stem Cells

Author

Gilbert, Antoine, Laurence, Julie, Guillamin, Marilyne, Haghdoost, Siamak, Valable, Samuel, Chevalier, François, 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), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU), 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
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience

Published
2021

42. Préface

Author

Chevalier, François

Abstract

En Nouvelle-Espagne – au Mexique – les mines d’argent ont été la plus grande source de liquidités tant pour le Roi que, directement ou indirectement, pour les habitants espagnols. L’un des deux principaux centres miniers, Zacatecas, n’y avait été étudié – par Peter Bakewell –, que de 1546 à 1700, avant que la production d’argent n’eût atteint ses plus hauts et constants sommets au 18e siècle. C’est pourtant dans le sillage de ce « boom » des mines que se développe un grand commerce d’abord pr...

Published
2021

48. Sensitization of chondrosarcoma cells with PARP inhibitor and impact on cancer stem cells

Author

Césaire, Mathieu, Gilbert, Antoine, Laurence, Julie, Elie, Nicolas, Giffard, Florence, Haghdoost, Siamak, Weiswald, Louis-Bastien, Chevalier, François, Chevalier, Francois, 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), Centre de Microscopie Appliquée à la Biologie [Caen] (CMABio3), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Axe BioTICLA, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), and support of the Normandy region within the CHOXTRACC project

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract

International audience; Chondrosarcoma is a primary tumour of bone and cartilage. One of the gold standard treatments is conventional X-ray therapy but chondrosarcomas of high malignancy are resistant. One of the mechanisms of radioresistance concerns the compartment of cancer stem cells (CSC) via their self-renewal and tumorogenesis capabilities. Radiosensitizing molecules, such as PARP inhibitors (PARPi) and carbon ions irradiation (C-ions), could overcome radioresistance and act on the CSC [1–3]. We investigated the cell survival and the impact on CSC of a chondrosarcoma line L835 in 2D and 3D culture models after X-ray compared to C-ray, in combination or not with PARPi.For the study of cell survival, we carried out clonogenic tests. For the study of the CSC, we wanted to determine the ability of cells to form tumospheres in wells containing a depleted culture medium. We also performed a kinetic analysis on 3D models of spheroids, using DNA damage tests (g-H2AX foci) and immunohistochemistry of ALDH, an enzyme more expressed in CSC.PARPi increased irradiation sensitivity with X-ray and in a lesser extent with C-ions, in 2D cultures. While X-ray alone did not appear to affect the number of tumospheres, we observed a decrease with exposure to PARPi alone and an increase in both X-ray and C-ions associated with PARPi. In 3D spheroids, the DNA damages increased immediately after irradiation, decreased 24 hours after irradiation in case of X-rays, and stayed constant in case of C-ions. Association of PARPi with irradiations did not modify this response. ALDH labeling of spheroids was very diffuse and did not reveal any modification in CSC proportions. This study highlights the complexity of the antitumor response to irradiations and the combination of treatment with PARPi, which can induce radiosensitization. Encouraging results are obtained with spheroids models, which appear relevant for studying the response of chondrosarcoma cells to irradiation with PARP inhibitor and the corresponding impact on cancer stem cells.

Published
2021

49. Pass'Concours - QCM d'entrée dans la fonction publique : Révision et entrainement Ed. 7

Author

Chevalier, François, Marquetty, Thierry, Philbert, Michel, Chevalier, François, Chevalier, François, Marquetty, Thierry, Philbert, Michel, and Chevalier, François

Abstract

730 QCM pour faire le point sur ses acquis dans les 4 disciplines que l'on rencontre aux épreuves des concours de catégories A, B et C de la fonction publique. Connaissances générales Aptitude verbale Aptitude logique Aptitude numérique L'ouvrage idéal pour s’entraîner et réviser ! > Un ouvrage d'entrainement pour toutes les catégories de concours de la fonction publique (A, B et C)> Un très large public : + de 200 000 candidats > 750 QCMpour faire le point sur ses acquis dans les 4 disciplines des concours Aptitude verbale Culture générale Aptitude logique Aptitude numérique > Un ouvrage revu idéal pour s’entraîner et en même temps réviser !Un ouvrage d'entrainement ultra riche en QCM pour faire le point avant de passer les concours de la Fonction publique

Published
2018

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