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Your search keyword '"Gharzeddine, Khaldoun"' showing total 15 results
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15 results on '"Gharzeddine, Khaldoun"'

1. Metabolic reprogramming of hypoxic tumour-associated macrophages through CSF-1R targeting favours treatment efficiency in colorectal cancers

Author

Gharzeddine, Khaldoun, primary, Gonzales Pietro, Cristina, additional, Malier, Marie, additional, Hennot, Clara, additional, Grespan, Renata, additional, Yamaryo, Yoshiki, additional, Botte, Cyrille, additional, Thomas, Fabienne, additional, Laverriere, Marie Helene, additional, Girard, Edouard, additional, Roth, Gael, additional, and MILLET, Arnaud, additional

Published
2024
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7. Coupled mechanical mapping and interference contrast microscopy reveal viscoelastic and adhesion hallmarks of monocytes differentiation into macrophages

Author

Eroles, Mar, primary, Lopez-Alonso, Javier, additional, Ortega, Alexandre, additional, Boudier, Thomas, additional, Gharzeddine, Khaldoun, additional, Lafont, Frank, additional, Franz, Clemens M., additional, Millet, Arnaud, additional, Valoteau, Claire, additional, and Rico, Felix, additional

Published
2022
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8. Les macrophages associés à la tumeur

Author

Malier, Marie, Gharzeddine, Khaldoun, Laverriere, Marie-Hélène, Decaens, Thomas, Roth, Gael, Millet, Arnaud, 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), Centre Hospitalier Universitaire [Grenoble] (CHU), and Sciences, EDP

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Le fluorouracile (5-FU) est un analogue de base pyrimidique utilisé dans de nombreuses combinaisons de chimiothérapie, notamment contre les cancers colorectaux. Malgré les progrès dans le traitement de ces cancers, le pronostic des formes avancées reste sombre, notamment en raison de la forte prévalence de la chimiorésistance au 5-FU. Les mécanismes impliqués dans cette chimiorésistance sont multiples : modulation du transport du 5-FU dans la cellule (ainsi que son exportation), métabolisme de la molécule, modification de sa cible, modification de l’équilibre entre facteurs apoptotiques et anti-apoptotiques, adaptation au microenvironnement tumoral, et transition épithélio-mésenchymateuse [1]. La plupart des études portant sur la chimiorésistance se sont focalisées sur la cellule cancéreuse elle-même, et l’importance du microenvironnement tumoral a été longtemps minimisée. Des travaux récents, dont ceux de notre laboratoire, montrent cependant que le microenvironnement joue en réalité un rôle beaucoup plus important dans la chimiorésistance des tumeurs.

Published
2022

11. DEN-Induced Rat Model Reproduces Key Features of Human Hepatocellular Carcinoma

Author

Kurma, Keerthi, primary, Manches, Olivier, additional, Chuffart, Florent, additional, Sturm, Nathalie, additional, Gharzeddine, Khaldoun, additional, Zhang, Jianhui, additional, Mercey-Ressejac, Marion, additional, Rousseaux, Sophie, additional, Millet, Arnaud, additional, Lerat, Herve, additional, Marche, Patrice N., additional, Macek Jilkova, Zuzana, additional, and Decaens, Thomas, additional

Published
2021
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14. Metabolic reprogramming of hypoxic tumor-associated macrophages through CSF-1R targeting favors treatment efficiency in colorectal cancers.

Author

Gharzeddine K, Gonzalez Prieto C, Malier M, Hennot C, Grespan R, Yamaryo-Botté Y, Botté CY, Thomas F, Laverriere MH, Girard E, Roth G, and Millet A

Subjects
Humans, Receptor, Macrophage Colony-Stimulating Factor metabolism, Fluorouracil pharmacology, Fluorouracil therapeutic use, Metabolic Reprogramming, Colorectal Neoplasms drug therapy, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Tumor-Associated Macrophages metabolism
Abstract

Background: Tumor-associated macrophages participate in the complex network of support that favors tumor growth. Among the various strategies that have been developed to target these cells, the blockade of the colony-stimulating factor 1 receptor (CSF-1R) receptor is one of the most promising ones. Here, we characterize the resulting state of human macrophages exposed to a CSF-1R kinase inhibitor., Methods: Using RNA sequencing and metabolomics approach, we characterize the reprogramming of human monocyte-derived macrophages under CSF-1R targeting., Results: We find that CSF-1R receptor inhibition in human macrophages is able to impair cholesterol synthesis, fatty acid metabolism and hypoxia-driven expression of dihydropyrimidine dehydrogenase, an enzyme responsible for the 5-fluorouracil macrophage-mediated chemoresistance. We show that this inhibition of the CSF-1R receptor leads to a downregulation of the expression of sterol regulatory element-binding protein 2, a transcription factor that controls cholesterol and fatty acid synthesis. We also show that the inhibition of extracellular signal-regulated kinase 1/2 phosphorylation resulting from targeting the CSF-1R receptor destabilizes the expression of hypoxic induced factor 2 alpha in hypoxia resulting in the downregulation of dihydropyrimidine dehydrogenase expression restoring the sensitivity to 5-fluorouracil in colorectal cancer., Conclusions: These results reveal the unexpected metabolic rewiring resulting from the CSF-1R receptor targeting of human macrophages and its potential to reverse macrophage-mediated chemoresistance in colorectal tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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15. [Tumor-associated macrophages: New targets to thwart 5-FU chemoresistance in colorectal cancers?]

Author

Malier M, Gharzeddine K, Laverriere MH, Decaens T, Roth G, and Millet A

Subjects
Apoptosis, Cell Line, Tumor, Cell Proliferation, Fluorouracil pharmacology, Fluorouracil therapeutic use, Gene Expression Regulation, Neoplastic, Humans, Tumor-Associated Macrophages, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Drug Resistance, Neoplasm
Published
2022
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