Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes):

BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population

Do pea nodulated roots have a memory like a sieve or like an elephant when faced with recurrent water deficits ?

National audienceIn the current context of climate change, periods of water deficit occur more frequentlyalong the crop cycle, leading to high yield losses. To limit the negative impact of recurrentwater deficits, plants can adapt, via the mobilization of “stress memory”, allowing them torespond to a subsequent stress in a faster and/or more intensive manner. After a first stressevent, plants can keep an imprint of this stress via the induction of epigenetic (e.g. memorygene regulation), physiological (e.g. stomatal closure) and molecular (e.g. compoundaccumulation) changes. When maintained between two stress periods, these changes mayprepare plants for a subsequent water deficit.This work addresses the potential role of stress memory in plant adaptation to recurrent waterdeficits with a special focus on plant hydro-mineral uptake by roots. For this purpose, anexperiment was conducted on the high throughput phenotyping platform (4PMI, Dijon, France),where several frequencies of water deficits were applied to pea plants. An integrativeapproach, including a structure-function ecophysiological framework characterizing planthydromineral nutrition (nutrients and beneficial elements), enriched with root and noduletranscriptomic analyses (RNA-seq), revealed the mechanisms underlying the “memory effect”throughout the plant cycle. We will discuss the role of memory genes during recurrent stressesand plant strategies to acquire water as well as macro- and micro-nutrients more efficientlyduring recurrent stresses. This work offers the new perspective of considering plant memoryin the design of ideotypes better adapted to multiple stress events in a context of climatechange.Study conducted in the framework of the EAUPTIC project, supported by the “Fond UniqueInterministériel" (n° 3870401/1), BPIFrance (n° DOS0097244/00), the Regional Council ofBurgundy (n° DOS0133465/00), Dijon Metropole (n° CONV-DM2018-118-20180820), and theFonds Européen de Développement Régional (n° 2018-6200FEO003S01889)

Does the memory of a first water deficit enable a more efficient response to a subsequent water deficit?

National audienc

Does the memory of a first water deficit enable a more efficient response to a subsequent water deficit?

National audienceIn the current context of climate change, periods of water deficit occur more frequently along the crop cycle, leading to high yield losses. To limit the negative impact of recurrent water deficits, plants can adapt, via the mobilization of “stress memory”, allowing them to respond to a subsequent stress in a faster and/or more intensive manner. After a first stress event, plants can keep an imprint of this stress via the induction of epigenetic (e.g. memory gene regulation), physiological (e.g. stomatal closure) and molecular (e.g. compound accumulation) changes. When maintained between two stress periods, these changes may prepare plants for a subsequent water deficit. This work addresses the potential role of stress memory in plant adaptation to recurrent water deficits with a special focus on plant hydro-mineral uptake by roots. For this purpose, an experiment was conducted on the high throughput phenotyping platform (4PMI, Dijon, France), where several frequencies of water deficits were applied to pea plants. An integrative approach, including a structure-function ecophysiological framework characterizing plant hydromineral nutrition (nutrients and beneficial elements), enriched with root and nodule transcriptomic analyses (RNA-seq), and metabolomic analyses revealed the mechanisms underlying the “memory effect” throughout the plant cycle. We will discuss the role of memory genes during recurrent stresses and plant strategies to acquire water as well as macro- and micro-nutrients more efficiently during recurrent stresses. This work offers the new perspective of considering plant memory in the design of ideotypes better adapted to multiple stress events in a context of climat

Le pois lors de stress hydriques répétés : mémoire d’éléphant ou de poisson rouge ?

International audienceDans le contexte actuel du changement climatique où les épisodes de déficits hydriques deviennent de plus fréquents et surviennent àdifférents stades au cours du cycle, les légumineuses à graines telles que le pois voient leur rendement fortement impacté. Afin de limiter lesimpacts négatifs de stress répétés, les plantes peuvent mettre en place une « mémoire » du stress, qui induit une modification de leur réponseà des stress ultérieurs. Cette mémoire dépend de plusieurs paramètres qui vont moduler l’ampleur et la rapidité de la réponse à un secondstress. Le premier stress peut induire des modifications épigénétiques, physiologiques (e.g. fermeture des stomates) et moléculaires (e.g.accumulation de certains composés avec différentes activités) permettant à la plante de se préparer à un stress futur, la plante gardant une «empreinte du stress passé ». Ces modifications peuvent aussi se poursuivre à la fin du stress en l’attente d’un suivant. Cette préparation de laplante aux stress répétés peut ainsi reposer sur la régulation de l’expression de gènes mémoire. Dans ce contexte, nous faisons l’hypothèseque la valorisation de cet effet mémoire pourrait être une nouvelle cible d’amélioration des variétés de pois, confrontées à des déficitshydriques multiples impactant leur nutrition minérale.Pour tester cette hypothèse, une expérimentation en conditions contrôlées a été mise en place sur la plateforme 4PMI de phénotypage haut-débit de Dijon. Au cours de cette expérimentation, en prenant pour modèle d’étude le génotype Kayanne, quatre modalités de stress hydriquesont été appliquées : un stress hydrique avant floraison (WS1), un stress hydrique après floraison (WS2), une combinaison de deux stresshydriques répétés (WS1+WS2) espacés d’une période de réarrosage, et un stress hydrique continu (WSc). Des analyses écophysiologiquesont été intégrées dans un cadre d’analyse de type structure/fonction et complétées par des analyses moléculaires afin de mettre en évidencel’effet mémoire mis en jeu lors d’un stress répété sur la croissance, le développement et la nutrition hydrominérale de la plante (incluant macro-et micro-nutriments). Afin de mettre en avant les principaux gènes impliqués dans l’effet mémoire de la réponse à un stress hydrique répété,des analyses transcriptomiques ont été réalisées par RNAseq. Nous discuterons de leur rôle dans les grandes voies métaboliques impliquéeset tenterons de les corréler aux variables écophysiologiques étudiées par des approches de modélisation de réseau de gènes. Les processuspermettant d’améliorer la réponse à un stress hydrique répété par la valorisation de la mémoire des plantes ainsi que des gènes candidatssous-jacents seront l’occasion de porter un nouveau regard pour l’amélioration du pois sous conditions hydriques fluctuantes

Memory or acclimation of water stress in pea rely on root system's plasticity and plant's ionome modulation

International audienceIntroduction: Peas, as legume crops, could play a major role in the future of food security in the context of worldwide human nutrient deficiencies coupled with the growing need to reduce consumption of animal products. However, pea yields, in terms of quantity and quality (i.e. grain content), are both susceptible to climate change, and more specifically to water deficits, which nowadays occur more frequently during crop growth cycles and tend to last longer. The impact of soil water stress on plant development and plant growth is complex, as its impact varies depending on soil water availability (through the modulation of elements available in the soil), and by the plant's ability to acclimate to continuous stress or to memorize previous stress events. Method: To identify the strategies underlying these plant responses to water stress events, pea plants were grown in controlled conditions under optimal water treatment and different types of water stress; transient (during vegetative or reproductive periods), recurrent, and continuous (throughout the plant growth cycle). Traits related to water, carbon, and ionome uptake and uses were measured and allowed the identification typical plant strategies to cope with water stress. Conclusion: Our results highlighted (i) the common responses to the three types of water stress in shoots, involving manganese (Mn) in particular, (ii) the potential implications of boron (B) for root architecture modification under continuous stress, and (iii) the establishment of an "ecophysiological imprint" in the root system via an increase in nodule numbers during the recovery period

Pea resilience to water deficits: tolerance, acclimation, and stress memory of the nodulated root system

Book of abstracts p 163International audiencePeas have the potential to play a significant role in ensuring future food security. However, the yields of peas, both in terms of quantity and quality (such as grain content), are vulnerable to the impacts of climate change, specifically water deficits.Nowadays, water deficits occur more frequently during crop growth cycles and persist for longer durations. The effects of soil water stress on plant development and growth are complex, as they depend on soil water availability, the modulation of available soil elements, and the plant’s ability to acclimate to continuous stress or remember previous stress events. To understand the strategies underlying plant responses to water stress events, we conducted controlled experiments with pea plants subjected to optimal water conditions, and different types of water stresses: transient stress during vegetative or reproductive periods, recurrent stress, and continuous stress throughout the entire growth cycle. An integrative approach, including a structure-function ecophysiological framework characterizing plant hydromineral nutrition, enriched with root and nodule transcriptomic analyses (RNA-seq), revealed the mechanisms underlying specific and common responses to the different types of water stress. In addition, a complementary field experiment was carried out in order to validate theobservations made under controlled conditions and to assess the level of expression of the candidate genes identified. This study introduces a fresh perspective by highlighting the importance of plant memory and acclimation in designing ideotypes that are more resilient to longer stresses, or multiple stress events in the context of climate change. This innovative approach has the potential to enhance crop productivity and ensure food security. This work was supported by Plant2Pro as part as the ARECOVER project, by FUI, BPIFrance, the Regional Council of Burgundy, Dijon Metropole, and FEDER, as part as the EAUPTIC project and by ANR-PIA as part as the PHENOME-EMPHASIS project

Pea resilience to water deficits: tolerance, acclimation, and stress memory of the nodulated root system

Peas have the potential to play a significant role in ensuring future food security. However, the yields of peas, both in terms of quantity and quality (such as grain content), are vulnerable to the impacts of climate change, specifically water deficits.Nowadays, water deficits occur more frequently during crop growth cycles and persist for longer durations. The effects of soil water stress on plant development and growth are complex, as they depend on soil water availability, the modulation of available soil elements, and the plant’s ability to acclimate to continuous stress or remember previous stress events. To understand the strategies underlying plant responses to water stress events, we conducted controlled experiments with pea plants subjected to optimal water conditions, and different types of water stresses: transient stress during vegetative or reproductive periods, recurrent stress, and continuous stress throughout the entire growth cycle. An integrative approach, including a structure-function ecophysiological framework characterizing plant hydromineral nutrition, enriched with root and nodule transcriptomic analyses (RNA-seq), revealed the mechanisms underlying specific and common responses to the different types of water stress. In addition, a complementary field experiment was carried out in order to validate theobservations made under controlled conditions and to assess the level of expression of the candidate genes identified. This study introduces a fresh perspective by highlighting the importance of plant memory and acclimation in designing ideotypes that are more resilient to longer stresses, or multiple stress events in the context of climate change. This innovative approach has the potential to enhance crop productivity and ensure food security. This work was supported by Plant2Pro as part as the ARECOVER project, by FUI, BPIFrance, the Regional Council of Burgundy, Dijon Metropole, and FEDER, as part as the EAUPTIC project and by ANR-PIA as part as the PHENOME-EMPHASIS project

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[Virgile, assis sous un arbre, est couronné par trois Muses, qui tiennent, chacune, un de ses ouvrages]Référence bibliographique : IFF18 COPIA (Jacques-Louis), 62Illustratio