Sex-Specific Regulation of AMP-Activated Protein Kinase (AMPK) in the Pacific Oyster Crassostrea gigas

The hermaphrodite Pacific oyster Crassostrea gigas displays a high energy allocation to reproduction. We studied the expression of AMP-activated protein kinase (AMPK) during gametogenesis in the gonad and characterized the mRNA sequences of the AMPK subunits: the AMPK alpha mRNA sequence was previously characterized; we identified AMPK beta, AMPK gamma, and mRNAs of putative AMPK-related targets following bioinformatics mining on existing genomic resources. We analyzed the mRNA expression of the AMPK alpha, beta, and gamma subunits in the gonads of male and female oysters through a reproductive cycle, and we quantified the mRNA expression of genes belonging to fatty acid and glucose metabolism. AMPK alpha mRNA levels were more abundant in males at the first stage of gametogenesis, when mitotic activity and the differentiation of germinal cells occur, and were always more abundant in males than in females. Some targets of fatty acid and glucose metabolism appeared to be correlated with the expression of AMPK subunits at the mRNA level. We then analyzed the sex-specific AMPK activity by measuring the phosphorylation of the catalytic AMPK alpha protein and its expression at the protein level. Both the amount of AMPK alpha protein and threonine 172 phosphorylation appeared to be almost totally inhibited in mature female gonads at stage 3, at the time when accumulation of reserves in oocytes was promoted, while it remained at a high level in mature spermatozoa. Its activation might play a sex-dependent role in the management of energy during gametogenesis in oyster

Sex-Specific Regulation of AMP-Activated Protein Kinase (AMPK) in the Pacific Oyster Crassostrea gigas

The hermaphrodite Pacific oyster Crassostrea gigas displays a high energy allocation to reproduction. We studied the expression of AMP-activated protein kinase (AMPK) during gametogenesis in the gonad and characterized the mRNA sequences of the AMPK subunits: the AMPK alpha mRNA sequence was previously characterized; we identified AMPK beta, AMPK gamma, and mRNAs of putative AMPK-related targets following bioinformatics mining on existing genomic resources. We analyzed the mRNA expression of the AMPK alpha, beta, and gamma subunits in the gonads of male and female oysters through a reproductive cycle, and we quantified the mRNA expression of genes belonging to fatty acid and glucose metabolism. AMPK alpha mRNA levels were more abundant in males at the first stage of gametogenesis, when mitotic activity and the differentiation of germinal cells occur, and were always more abundant in males than in females. Some targets of fatty acid and glucose metabolism appeared to be correlated with the expression of AMPK subunits at the mRNA level. We then analyzed the sex-specific AMPK activity by measuring the phosphorylation of the catalytic AMPK alpha protein and its expression at the protein level. Both the amount of AMPK alpha protein and threonine 172 phosphorylation appeared to be almost totally inhibited in mature female gonads at stage 3, at the time when accumulation of reserves in oocytes was promoted, while it remained at a high level in mature spermatozoa. Its activation might play a sex-dependent role in the management of energy during gametogenesis in oyster

Radiothérapie postopératoire en situation de lambeau : série monocentrique avec délinéation de tous les lambeaux pour évaluer les profils de toxicité et de rechute

CERVOXY CLINInternational audiencePurposeFlaps are increasingly used during reconstructive surgery of head and neck cancers to improve functional outcomes. There are no guidelines as to whether the whole flap or its anastomotic border should be included in the primary tumour target volume of postoperative radiotherapy to prevent local relapses. Relapse and toxicity rates can increase substantially if the whole flap received full dose. Our aim was to determine whether flaps were included in the primary tumour target volume and to report the patterns of relapse and toxicity.Materials and methodsConsecutive patients in 2014 through 2016, with or without a flap, receiving postoperative radiotherapy were selected in a retrospective monocentric control study. Flaps were homogenously delineated blind to treating radiation oncologists using a flap-specific atlas. Tumour recurrence, acute and late toxicity were evaluated using univariate and propensity score analyses.ResultsA hundred patients were included; 54 with a flap. Median flap volume included in the tumour volume was 80.9%. Twelve patients experienced local recurrences: six with a flap, among whom two within their flap (3.7%). Patients with flaps had larger median tumour volumes to be irradiated (25 cm3 versus 58 cm3, p < 0.001) and higher acute/late toxicity rates (p < 0.001) even after adjustment on biases (more advanced T stage, oral cavity, active smoking in patients with flaps). Locoregional recurrence and survival rates were similar between patients with/without a flap.ConclusionRecurrences within a flap were rare in this series when including the whole flap body in the 60Gy-clinical target volume but inclusion of the flap in the primary tumour target volume increased toxicity. Multicentric studies are warranted.Objectif de l’étudeLes lambeaux sont de plus en plus utilisés lors de la chirurgie reconstructive des cancers de la tête et du cou pour améliorer les résultats fonctionnels. Il n’existe pas de recommandations publiées sur la définition du volume cible anatomoclinique en situation de lambeau, et notamment sur l’inclusion du lambeau entier ou de son bord anastomotique seulement dans le volume cible anatomoclinique tumoral de la radiothérapie postopératoire pour prévenir les rechutes locales. Les taux de rechute et de toxicité peuvent augmenter si l’ensemble du lambeau a reçu la dose tumoricide. Notre objectif était de déterminer si les lambeaux étaient inclus dans le volume cible anatomoclinique tumoral et de rapporter les modèles de rechute et de toxicité.Matériels et méthodesDes patients consécutifs entre 2014 et 2016 avec ou sans lambeau ayant reçu une radiothérapie postopératoire ont été sélectionnés pour une étude rétrospective de contrôle monocentrique. Les lambeaux ont été délimités de manière homogène, à l’insu des oncologues radiothérapeutes référents, à l’aide d’un atlas spécifique aux lambeaux établi avec les chirurgiens. Les récidives tumorales et la toxicité aiguë et tardive ont été évaluées à l’aide d’analyses unifactorielles et de scores de propension.RésultatsCent patients ont été inclus ; 54 avec un lambeau. Le volume médian du lambeau inclus dans le volume de la tumeur était de 80,9 %. Douze patients ont connu des récidives locales : six avec un lambeau, dont deux dans leur lambeau (3,7 %). Les patients avec des lambeaux avaient des volumes tumoraux médians à irradier plus importants (25 cm3 contre 58 cm3, p < 0,001) et des taux de toxicité aiguë ou tardive plus élevés (p < 0,001), même après ajustement sur les biais (stade T plus grand, cavité buccale, tabagisme actif chez les patients avec des lambeaux). Les taux de récurrence et de survie locorégionaux étaient similaires entre les patients avec ou sans lambeau.ConclusionLes récidives au sein d’un lambeau étaient rares dans cette série dans laquelle le lambeau entier était inclus dans le volume cible anatomoclinique 60 Gy, mais l’inclusion du lambeau dans le volume cible anatomoclinique tumoral augmentait la toxicité. Une étude multicentrique est en cours

A Novel Concept of Transperineal Focused Ultrasound Transducer for Prostate Cancer Local Deep Hyperthermia Treatments

Design, embodiment, and experimental study of a novel concept of extracorporeal phased array ultrasound transducer for prostate cancer regional deep hyperthermia treatments using a transperineal acoustic window is presented. An optimized design of hyperthermia applicator was derived from a modelling software where acoustic and thermal fields were computed based on anatomical data. Performance tests have been experimentally conducted on gel phantoms and tissues, under 3T MRI guidance using PRFS thermometry. Feedback controlled hyperthermia (ΔT = 5 °C during 20min) was performed on two ex vivo lamb carcasses with prostate mimicking pelvic tissue, to demonstrate capability of spatio-temporal temperature control and to assess potential risks and side effects. Our optimization approach yielded a therapeutic ultrasound transducer consisting of 192 elements of variable shape and surface, pseudo randomly distributed on 6 columns, using a frequency of 700 kHz. Radius of curvature was 140 mm and active water circulation was included for cooling. The measured focusing capabilities covered a volume of 24 × 50 × 60 mm3. Acoustic coupling of excellent quality was achieved. No interference was detected between sonication and MR acquisitions. On ex vivo experiments the target temperature elevation of 5 °C was reached after 5 min and maintained during another 15 min with the predictive temperature controller showing 0.2 °C accuracy. No significant temperature rise was observed on skin and bonny structures. Reported results represent a promising step toward the implementation of transperineal ultrasound hyperthermia in a pilot study of reirradiation in prostate cancer patients

Les grands principes des traitements du cancer de prostate localisé

National audienceLe cancer de la prostate (CaP) représentait en 2020 le deuxième cancer en termes de fréquence chez l’homme après le cancer bronchopulmonaire, et la 5e cause de décès par cancer dans le monde. Quatre-vingt pour cent des patients sont diagnostiqués à un stade localisé. L’approche thérapeutique est dépendante de la classification de risque. La surveillance active est un des traitements de référence pour les tumeurs prostatiques de faible risque et peut être proposée pour certaines tumeurs prostatiques de risque intermédiaire. Les approches radicales sont majoritairement représentées par la chirurgie ou la radiothérapie (seule ou associée à une hormonothérapie). Les thérapies focales ont pour avantage une meilleure épargne des tissus sains adjacents, avec des résultats précoces encourageants sur le plan oncologique, mais dont l’interprétation reste limitée par un recul assez faible. Sur le plan systémique, l’hormonothérapie (privation androgénique) est le traitement clef de la prise en charge en association avec la radiothérapie, pour les tumeurs de risque intermédiaire défavorable et de haut risque. Les hormonothérapies de deuxième génération ont une place nouvelle et croissante dans la prise en charge des cancers de la prostate localisés de très haut risque (ou localement avancés). Cette revue a pour objectif de détailler les différents traitements locaux et systémiques pouvant être proposés aux patients diagnostiqués avec un CaP de stade localisé