7 research outputs found
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 lâĂ©tudeLes lambeaux sont de plus en plus utilisĂ©s lors de la chirurgie reconstructive des cancers de la tĂȘte et du cou pour amĂ©liorer les rĂ©sultats fonctionnels. Il nâexiste pas de recommandations publiĂ©es sur la dĂ©finition du volume cible anatomoclinique en situation de lambeau, et notamment sur lâinclusion du lambeau entier ou de son bord anastomotique seulement dans le volume cible anatomoclinique tumoral de la radiothĂ©rapie postopĂ©ratoire pour prĂ©venir les rechutes locales. Les taux de rechute et de toxicitĂ© peuvent augmenter si lâensemble du lambeau a reçu la dose tumoricide. Notre objectif Ă©tait de dĂ©terminer si les lambeaux Ă©taient inclus dans le volume cible anatomoclinique tumoral et de rapporter les modĂšles de rechute et de toxicitĂ©.MatĂ©riels et mĂ©thodesDes patients consĂ©cutifs entre 2014 et 2016 avec ou sans lambeau ayant reçu une radiothĂ©rapie postopĂ©ratoire ont Ă©tĂ© sĂ©lectionnĂ©s pour une Ă©tude rĂ©trospective de contrĂŽle monocentrique. Les lambeaux ont Ă©tĂ© dĂ©limitĂ©s de maniĂšre homogĂšne, Ă lâinsu des oncologues radiothĂ©rapeutes rĂ©fĂ©rents, Ă lâaide dâun atlas spĂ©cifique aux lambeaux Ă©tabli avec les chirurgiens. Les rĂ©cidives tumorales et la toxicitĂ© aiguĂ« et tardive ont Ă©tĂ© Ă©valuĂ©es Ă lâaide dâanalyses unifactorielles et de scores de propension.RĂ©sultatsCent patients ont Ă©tĂ© inclus ; 54 avec un lambeau. Le volume mĂ©dian du lambeau inclus dans le volume de la tumeur Ă©tait de 80,9 %. Douze patients ont connu des rĂ©cidives locales : six avec un lambeau, dont deux dans leur lambeau (3,7 %). Les patients avec des lambeaux avaient des volumes tumoraux mĂ©dians Ă irradier plus importants (25 cm3 contre 58 cm3, p < 0,001) et des taux de toxicitĂ© aiguĂ« ou tardive plus Ă©levĂ©s (p < 0,001), mĂȘme aprĂšs ajustement sur les biais (stade T plus grand, cavitĂ© buccale, tabagisme actif chez les patients avec des lambeaux). Les taux de rĂ©currence et de survie locorĂ©gionaux Ă©taient similaires entre les patients avec ou sans lambeau.ConclusionLes rĂ©cidives au sein dâun lambeau Ă©taient rares dans cette sĂ©rie dans laquelle le lambeau entier Ă©tait inclus dans le volume cible anatomoclinique 60 Gy, mais lâinclusion du lambeau dans le volume cible anatomoclinique tumoral augmentait la toxicitĂ©. Une Ă©tude 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 (ÎT = 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 Ă 50 Ă 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) reprĂ©sentait en 2020 le deuxiĂšme cancer en termes de frĂ©quence chez lâhomme aprĂšs le cancer bronchopulmonaire, et la 5e cause de dĂ©cĂšs par cancer dans le monde. Quatre-vingt pour cent des patients sont diagnostiquĂ©s Ă un stade localisĂ©. Lâapproche thĂ©rapeutique est dĂ©pendante de la classification de risque. La surveillance active est un des traitements de rĂ©fĂ©rence pour les tumeurs prostatiques de faible risque et peut ĂȘtre proposĂ©e pour certaines tumeurs prostatiques de risque intermĂ©diaire. Les approches radicales sont majoritairement reprĂ©sentĂ©es par la chirurgie ou la radiothĂ©rapie (seule ou associĂ©e Ă une hormonothĂ©rapie). Les thĂ©rapies focales ont pour avantage une meilleure Ă©pargne des tissus sains adjacents, avec des rĂ©sultats prĂ©coces encourageants sur le plan oncologique, mais dont lâinterprĂ©tation reste limitĂ©e par un recul assez faible. Sur le plan systĂ©mique, lâhormonothĂ©rapie (privation androgĂ©nique) est le traitement clef de la prise en charge en association avec la radiothĂ©rapie, pour les tumeurs de risque intermĂ©diaire dĂ©favorable et de haut risque. Les hormonothĂ©rapies de deuxiĂšme gĂ©nĂ©ration ont une place nouvelle et croissante dans la prise en charge des cancers de la prostate localisĂ©s de trĂšs haut risque (ou localement avancĂ©s). Cette revue a pour objectif de dĂ©tailler les diffĂ©rents traitements locaux et systĂ©miques pouvant ĂȘtre proposĂ©s aux patients diagnostiquĂ©s avec un CaP de stade localisĂ©