Arnica montana : évaluation des ressources génétiques françaises en vue du développement de la culture en plaine et en montagne

Ce volume regroupe les textes issus du programme Casdar "Innovation et Partenariat" et "Recherche finalisée et innovation" de 2013. Le colloque de restitution s’est déroulé le 6 février 2019 sous l’égide du GIS Relance AgronomiqueArnica montana is a major medicinal specie, which is now mainly produced from wild harvesting,especially in mainland France. As the wild resource is decreasing, and in order to maintain or even Gourlin L. et al. 68 Innovations Agronomiques 71 (2019), 67-80 develop the French production, cultivation is a good option, that is still very limited, because of its difficulty. Finding the right plant material could help to enhance cultivation programs. This project aimed at growing 24 wild populations, which were collected in mainland France, and to compare them with 2 commercial varieties, ‘Arbo’ and ‘Arnimed’. This was set on 4 experimentation spots, chosen for their potential match for Arnica cultivation. The experiment lasted 3 years, and morphological andagronomical subjects were studied on the populations. Sesquiterpene lactones and flavonoidsanalyzed, and a new methodology of evaluation was developed. The results showed extreme variabilityof phenotypic and chemical expression of the different populations. An important death rate has beennoticed on wild populations, but the causes are still unknown. On the set of variables chosen,commercial varieties ‘Arbo’ and ‘Arnimed’ were particularly competitive, and two wild populations standout with promising results. One seems appropriate for starting selection works on a variety that would besuitable for loaw altitude, and the other one could be a local (French) alternative to the cultivation ofselected varieties (‘Arbo’ and ‘Arnimed’ are from Swiss and German selection work).L’arnica des montagnes est une espèce médicinale importante dont la production est principalementissue de la cueillette à l’état sauvage, notamment sur le territoire métropolitain. La ressource étant enrégression, le maintien, voire le développement de la production française passe donc par la mise enculture, actuellement anecdotique car difficile. Certains freins pourraient être levés par la mise enévidence de matériel végétal adapté à la production. L’objectif de ce projet était de mettre en culture 24populations d’origines sauvages (prospectées en France métropolitaine) et de les comparer à deuxvariétés commerciales témoins ‘Arbo’ et ‘Arnimed’, sur 4 sites d’expérimentation aux contextespédoclimatiques variés mais a priori adaptés à la culture de l’espèce. Durant les 3 années d’essai, unsuivi morphologique et agronomique des populations a été réalisé. Des analyses des sesquiterpèneslactones et flavonoïdes ont été effectuées, et une nouvelle méthodologie de dosage de ces composés aété développée. Les résultats mettent en exergue la forte variabilité de l’expression phénotypique etchimique des différentes souches testées. Une forte mortalité globale a pu être constatée surl’ensemble des populations sauvages étudiées sans que les causes aient pu en être identifiées. Surl’ensemble des variables suivies, les variétés commerciales ‘Arbo’ et ‘Arnimed’ sont particulièrementperformantes, et deux populations sauvages se démarquent par leurs résultats intéressants : l’uneparait pertinente pour démarrer des travaux de sélection d’une variété adaptée à la basse altitude,tandis que l’autre, originaire du Massif central, pourrait se proposer comme une alternative d’originelocale (française) à la culture de variétés commerciales sélectionnées (suisse et allemande)

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

New crystal in the pineal gland : characterization and potential role in electromechano-transduction

The pineal gland is a neuroendocrine transducer secreting melatonin, responsible for the physiological circadian rhythm control. A new form of biomineralization has been studied in the human pineal gland. It consists of small crystals that are less than 20 µm in length. These crystals could be responsible for an electromechanical biological transduction mechanism in the pineal gland due to their structure and piezoelectric properties. Using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), we identified crystals morphology and showed that they only contain calcium, carbon and oxygen elements. Furthermore, the selected-area electron diffraction (SAED) and near-infrared Raman spectroscopy established that the crystals are calcite. We will now focus on the physiological effect of microcrystals in pinealocyte cell culture under Radio-Frequency Electromagnetic-Fields (RF-EMF)

Les monocristaux de la glande pinéale (caractérisation physico-chimique et rôle potentiel d'électromécanotransducteur)

GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

International audienceBackground: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults witha dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targetingFZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecularvehicle to specifically deliver radiation to FZD10 expressing SS lesions.Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistributionand lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dosewhen using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy.Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Eventhough 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy foreach patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake toproceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were notrandomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, whichwere more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patientslasting up to 21 weeks for 1 patient.Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least onelesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However,because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a betteroption to wider the therapeutic index.Trial registration: The study was registered on the NCT01469975 website with a registration code NCT01469975 onNovember the third, 2011

Bridging Communities in the field of Nanomedicine

An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the Field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing Horizon 2020 projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarized in the format of a survey.JRC.F.2-Consumer Products Safet

Bridging communities in the field of nanomedicine

An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled “Bridging communities in the field of Nanomedicine” in Ispra/Italy on the 27th −28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a surve

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011