12 research outputs found
Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer
Background: Treatment of patients with residual disease after neoadjuvant chemotherapy for breast cancer is an unmet clinical need. We hypothesised that tumour subclones showing expansion in residual disease after chemotherapy would contain mutations conferring drug resistance. Methods: We studied oestrogen receptor and/or progesterone receptor-positive, HER2-negative tumours from 42 patients in the EORTC 10994/BIG 00-01 trial who failed to achieve a pathological complete response. Genes commonly mutated in breast cancer were sequenced in pre and post-treatment samples. Results: Oncogenic driver mutations were commonest in PIK3CA (38% of tumours), GATA3 (29%), CDH1 (17%), TP53 (17%) and CBFB (12%); and amplification was commonest for CCND1 (26% of tumours) and FGFR1 (26%). The variant allele fraction frequently changed after treatment, indicating that subclones had expanded and contracted, but there were changes in both directions for all of the commonly mutated genes. Conclusions: We found no evidence that expansion of clones containing recurrent oncogenic driver mutations is responsible for resistance to neoadjuvant chemotherapy. The persistence of classic oncogenic mutations in pathways for which targeted therapies are now available highlights their importance as drug targets in patients who have failed chemotherapy but provides no support for a direct role of driver oncogenes in resistance to chemotherapy. ClinicalTrials.gov: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe
Apprendre les métiers du care en France et en Allemagne au-delà des assignations de genre. Une approche ethnographique par les capabilities
International audienc
Inwiefern erweitert die Ausbildung zu Care-Berufen die Freiheit der Berufswahl in der Ăle de France und in Nordrhein-Westfalen?
La thĂ©orie des effets sociĂ©taux des politiques dâĂ©ducation sur lâorganisation industrielle a prĂ©valu dans la recherche française des annĂ©es 1970 Ă nos jours sous lâimpulsion de lâĂ©cole dâAix menĂ©e par les chercheurs du Lest François Sellier, Marc Maurice et Jean-Jacques Silvestre (1982). Les mĂ©tiers du soin et de lâaide Ă lâenfant et Ă la personne ĂągĂ©e dĂ©pendante appris sous statut scolaire en Allemagne et en apprentissage en France tĂ©moignent de lâeffet nĂ©gatif de lâapprentissage sur le parcours des jeunes apprentis.The theory of societal effects of the education policies on the industrial organisation prevails in the french research from the seventieth to today at the instigation oft he researcher oft he labor Lest Franços Sellier, Marc Maurice and Jean-Jacques Silvestre (1982). The profession of the care to children and old people wich is as pupills in Germany and apprentice in France learns gives evidence to an negative effect on the educational path of the young apprentice.Die Theorie der gesellschaftlichen Effekten der Bildungspolitiken auf die Industrieorganisation vorherrschte in der französische Forschung von den siebziger Jahren bis heute unter der Schwung der von Forschern des Lestlaboratorium geleiteten Schule von Aix François Sellier, Marc Maurice und Jean-Jacques Silvestre (1982). Die Pflege- und Hilfsberufe zur Kinder und Alten, die in Deutschland in Berufskollegs und in Frankreich als Lehrling ausgebildet sind beweisen einen negativen Effekt auf der Bildungslaufbahn der jungen Lehrlingen
Wilfried Nippel, LibertĂ© antique, libertĂ© moderne. Les fondements de la dĂ©mocratie, de lâAntiquitĂ© Ă nos jours
La dĂ©mocratie athĂ©nienne, sans thĂ©orie ni intention missionnaire, tient lieu de cas particulier dans le monde grec. Or ce systĂšme politique, mis au point dans le cadre dâĂ©tats de petite taille â selon les critĂšres modernes â a fascinĂ© la postĂ©ritĂ© jusquâĂ nos jours, tantĂŽt comme un repoussoir (lâochlocratie, tyrannie de la majoritĂ© tant redoutĂ©e) tantĂŽt comme un modĂšle exemplaire dâautodĂ©termination collective dĂ©passant nettement toutes les formes de dĂ©mocraties indirectes et reprĂ©sentatives...
Wilfried Nippel, LibertĂ© antique, libertĂ© moderne. Les fondements de la dĂ©mocratie, de lâAntiquitĂ© Ă nos jours
La dĂ©mocratie athĂ©nienne, sans thĂ©orie ni intention missionnaire, tient lieu de cas particulier dans le monde grec. Or ce systĂšme politique, mis au point dans le cadre dâĂ©tats de petite taille â selon les critĂšres modernes â a fascinĂ© la postĂ©ritĂ© jusquâĂ nos jours, tantĂŽt comme un repoussoir (lâochlocratie, tyrannie de la majoritĂ© tant redoutĂ©e) tantĂŽt comme un modĂšle exemplaire dâautodĂ©termination collective dĂ©passant nettement toutes les formes de dĂ©mocraties indirectes et reprĂ©sentatives...
Data from Sentis et al. (2015) for main publication
Functional response data provided by Arnaud Sentis and colleagues (https://doi.org/10.1111/gcb.12931).
âDaphnia_densityâ is the initial prey number; âDaphnia_eatenâ is the number of eaten prey individuals after the experiment. Please see the original publication by Sentis et al. (2015, https://doi.org/10.1111/gcb.12931) for details and also cite their paper if using these data! These data appear only in the main publication (D1) published in MEE
Multigenerational exposure to temperature influences mitochondrial oxygen fluxes in the Medaka fish ( Oryzias latipes )
International audienceThermal sensitivity of cellular metabolism is crucial for animal physiology and survival under climate change. Despite recent efforts, effects of multigenerational exposure to temperature on the metabolic functioning remain poorly understood. We aimed at determining whether multigenerational exposure to temperature modulate the mitochondrial respiratory response of Medaka fish. Methods We conducted a multigenerational exposure with Medaka fish reared multiple generations at 20 and 30°C (COLD and WARM fish, respectively). We then measured the oxygen consumption of tail muscle at two assay temperatures (20 and 30°C). Mitochondrial function was determined as the respiration supporting ATP synthesis (OXPHOS) and the respiration required to offset proton leak (LEAK(Omy)) in a full factorial design (COLDâ20°C; COLDâ30°C; WARMâ20°C; WARMâ30°C). Results We found that higher OXPHOS and LEAK fluxes at 30°C compared to 20°C assay temperature. At each assay temperature, WARM fish had lower tissue oxygen fluxes than COLD fish. Interestingly, we did not find significant differences in respiratory flux when mitochondria were assessed at the rearing temperature of the fish (i.e., COLDâ20°C vs. WARM â30°C). Conclusion The lower OXPHOS and LEAK capacities in warm fish are likely the result of the multigenerational exposure to warm temperature. This is consistent with a modulatory response of mitochondrial capacity to compensate for potential detrimental effects of warming on metabolism. Finally, the absence of significant differences in respiratory fluxes between COLDâ20°C and WARMâ30°C fish likely reflects an optimal respiration flux when organisms adapt to their thermal conditions
Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRASG12D-driven Pancreatic TumorigenesisSummary
Background & Aims: Transforming growth factor beta (TGFĂÂČ) acts either as a tumor suppressor or as an oncogene, depending on the cellular context and time of activation. TGFĂÂČ activates the canonical SMAD pathway through itsĂÂ interaction with the serine/threonine kinase type I and II heterotetrameric receptors. Previous studies investigating TGFĂÂČ-mediated signaling in the pancreas relied eitherĂÂ onĂÂ loss-of-function approaches or on ligand overexpression, and its effects on acinar cells have so far remained elusive. Methods: We developed a transgenic mouse model allowing tamoxifen-inducible and Cre-mediated conditional activation of a constitutively active type I TGFĂÂČ receptor (TĂÂČRICA) in the pancreatic acinar compartment. Results: We observed that TĂÂČRICA expression induced acinar-to-ductal metaplasia (ADM) reprogramming, eventually facilitating the onset of KRASG12D-induced pre-cancerous pancreatic intraepithelial neoplasia. This phenotype was characterized by the cellular activation of apoptosis and dedifferentiation, two hallmarks of ADM, whereas at the molecular level, we evidenced a modulation in the expression of transcription factors such as Hnf1ĂÂČ, Sox9, and Hes1. Conclusions: We demonstrate that TGFĂÂČ pathway activation plays a crucial role in pancreatic tumor initiation through its capacity to induce ADM, providing a favorable environment for KRASG12D-dependent carcinogenesis. Such findings are highly relevant for the development of early detection markers and of potentially novel treatments for pancreatic cancer patients. Keywords: Pancreas, Cancer, TGFĂÂČ, Acinar-to-Ductal Metaplasia, KRASG12