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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique minard-Colin Caroline Chopinet michael Dussiot Denise mAdams Tristan mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERm U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UmR 5220 Villeurbanne 69100France Service de Radiologie mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERm U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UmR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(mRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

Probing the formation of ultrastable metallic glass from structural heterogeneity

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Journal of materials Science & Technology 2022年第9期104卷 214-223页

作者： Qijing Sun Davidm miskovic michael Ferry School of materials Science and Engineering The University of New South WalesSydneyNSW 2052Australia

Ultrastable metallic glasses(SmGs)exhibit enhanced stability comparable to those of conventional glasses aged for thousands of *** ability to understand why certain alloy compositions and processing conditions generate an SmG is an emerging ***,amplitude-modulation dynamic atomic force microscopy was utilized for tracking the structure of Zr_(50)Cu_(50),Zr_(50)Cu_(44.5)Al_(5.5)and Zr_(50)Cu_(41.5)Al_(5.5)mo_(3) thin film metallic glasses(TFmGs)that were produced by direct current magnetron sputtering at room temperature with the rate of deposition being the only *** transition in stability from bulkto SmG-like behavior resides in the change of relaxation mechanism as the deposition rate is *** formation of SmGs is directly linked with the degree of structural heterogeneity,whereby mGs with greater heterogeneity have a higher potential to form SmGs with more significant enhancement in *** deposition rates,however,are required to yield the more homogenous structure and lower energy state underlying the *** is closely linked with the geometric shape and distribution of loosely packed phases,whereby SmGs containing more slender loosely packed phases with a more skewed distribution achieve more significant improvements in *** work not only provides direct evidence of the structure of SmGs,but also opens new horizons for the design of SmGs.

关键词： Ultrastable metallic glass Structural heterogeneity Relaxation dynamics Amplitude-modulation dynamic atomic force microscopy

Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

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World Journal of Gastroenterology 2006年第12期12卷 1937-1940页

作者： Lauren m Aleksunes José Emanautou michael Goedken University of Connecticut Department of Pharmaceutical SciencesUnit 3092StorrsCTUnited States University of Connecticut Department of PathobiologyUnit 3089StorrsCTUnited States

AIm： To investigate the expression and activity of NAD（P）H quinone oxidoreductase 1 （NQO1） in human liver specimens obtained from patients with liver damage due to acetaminophen （APAP） overdose or primary biliary cirrhosis （PBC）. mETHODS： NQOt activity was determined in cytosol from normal, APAP and PBC liver specimens. Western blot and immunohistochemical staining were used to determine patterns of NQO1 expression using a specific antibody against NQO1. RESULTS： NQO1 protein was very low in normal human livers. In both APAP and PBC livers, there was strong induction of NQO1 protein levels on Western blot. Correspondingly, significant up-regulation of enzyme activity （16- and 22-fold, P〈0.05） was also observed in APAP and PBC livers, respectively. Immunohistochemical analysis highlighted injury-specific patterns of NQO1 staining in both APAP and PBC livers. CONCLUSION： These data demonstrate that NQO1 protein and activity are markedly induced in human livers during both APAP overdose and PBC. Up-regulation of this cytoprotective enzyme may represent an adaptive stress response to limit further disease progression by detoxifying reactive species.

关键词： NQO1 Quinone oxidoreductase Acetaminophen, APAP, Primary biliary cirrhosis PBC Nrf2, Diaphorase

At the Intersection： merging Ca2＋ and ROS Signaling Pathways in Pollen

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molecular Plant 2014年第11期7卷 1595-1597页

作者： michael m. Wudick José A. Feijó Department of Cell Biology and molecular Genetics University of Maryland College Park MD 20742–5815 USA Instituto Gulbenkian de Ciencia 2780-156 Oeiras Portugal

THE mIXED BLESSING OF ROS： DON＇T YOU KNOW THAT I＇m TOXIC？Due to plants＇ aerobic metabolism, reactive oxygen species （ROS） continuously accrue in different tissues and organs as a by-product of many metabolic reactions. Despite their toxic activity, plants also rely on ROS as a major form of second messenger to integrate, induce, and/or propagate biotic and abiotic signals and signaling cascades. Being small, short-lived, and rapidly diffusible makes ROS ideal messenger molecules for local biochemi- cal reactions. Hence, a delicate fine-tuning of localized ROS production and signaling events is crucial for many physi- ologic processes.

关键词： PROTEIN-KINASE CIPK26 NADPH OXIDASE SENSORS CBL1 TUBE GROWTH TIP GROWTH CHANNEL

A Posteriori Error Estimates for Finite Element methods for Systems of Nonlinear,Dispersive Equations

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Communications on Applied mathematics and Computation 2022年第3期4卷 823-854页

作者： Ohannes A.Karakashian michael m.Wise Department of mathematics University of TennesseeKnoxvilleTNUSA Advanced Technology Integration Department DyneticsInc.HuntsvilleALUSA

The present study regards the numerical approximation of solutions of systems of Korteweg-de Vries type,coupled through their nonlinear *** our previous work[9],we constructed conservative and dissipative finite element methods for these systems and presented a priori error estimates for the semidiscrete *** this sequel,we present a posteriori error estimates for the semidiscrete and fully discrete approximations introduced in[9].The key tool employed to effect our analysis is the dispersive reconstruction devel-oped by Karakashian and makridakis[20]for related discontinuous Galerkin *** conclude by providing a set of numerical experiments designed to validate the a posteriori theory and explore the effectivity of the resulting error indicators.

关键词： Finite element methods Discontinuous Galerkin methods Korteweg-de Vries equation A posteriori error estimates Conservation laws Nonlinear equations Dispersive equations

Exotic parrots breeding in urban tree cavities: nesting requirements, geographic distribution, and potential impacts on cavity nesting birds in southeast Florida

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Avian Research 2019年第4期10卷 459-468页

作者： Joshua m.Diamond michael S.Ross Florida International University Earth & Environment

Background:Exotic parrots have established breeding populations in southeast Florida,including several species that nest in tree *** aimed to determine the species identity,nest site requirements,relative nest abundance,geographic distribution,and interactions of parrots with native cavity-nesting bird ***:We searched miami-Dade County,Florida,and nearby areas for natural cavities and holes excavated by woodpeckers,recording attributes of potential nest *** inspected all cavities with an elevated video inspection system to determine occupancy by parrots or other *** mapped nearly 4000 citizen science observations of parrots in our study area corresponding to our study period,and used these to construct range maps,comparing them to our nesting ***:Not all parrots reported or observed in our study area were actively *** parrots were observed at tree cavities,which previous studies have suggested is evidence of reproduction,but our inspections with an elevated video inspection system suggest they never initiated nesting *** parrot species did successfully nest in tree cavities,Red-masked Parakeets(Psittacara erythrogenys)and Orange-winged Parrots(Amazona amazonica)being the most common(n=7 and 6 nests,respectively).These two parrots had similar nesting requirements,but Orange-winged Parrots use nests with larger entrance holes,which they often *** analysis of nests combined with citizen science data indicate that parrots are limited to developed *** most common parrots were less abundant cavity nesters than the native birds which persist in miami’s urban areas,and far less abundant than the invasive European Starling(Sturnus vulgaris).Conclusions:Exotic parrots breeding elsewhere in the world have harmed native cavity-nesting birds through interference competition,but competitive interference in southeast Florida is minimized by the urban affinities of parrots in this ***

关键词： Amazona Cavity nest webs Invasive species Parakeets Psittacara Urban ecology

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

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Asian Journal of Andrology 2012年第2期14卷 177-186页

作者： Roisin m Connolly michael A Carducci Emmanuel S Antonarakis Prostate Cancer Research Program Department of Medical Oncology Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD 21231-1000 USA

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

关键词： androgen deprivation therapy androgen synthesis anti-androgen prostate cancer

Exploring the anti-cancer effects of Panax notoginseng through network pharmacology and molecular modeling

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Genes & Diseases 2023年第6期10卷 2229-2232页

作者： Erin m.Thorpe michael Kalafatis Yan Xu Department of Chemistry Science and Research CenterCleveland State University2121 Euclid AvenueClevelandOH 44115USA

The second leading cause of death worldwide is *** is a general term that refers to a highly diverse and complex set of over 200 diseases where abnormal cells grow uncontrollably and avoid death.1 These diseases can start almost anywhere within the body and may develop the ability to invade nearby tissues and *** cancer is the byproduct of a unique combination of various genetic and environmental factors.1 Even within the same individual,different cells may possess distinct cancerous mutations which can mutate further over time.

关键词： diseases cancer Cancer

A new piecewise linear Chen system of fractional-order:Numerical approximation of stable attractors

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Chinese Physics B 2015年第6期24卷 216-224页

作者： marius-F.Danca m.A.Aziz-Alaoui michael Small Department of mathematics and Computer Science Emanuel University of Oradea Romanian Institute of Science and Technology Normandie University ULH LMAHF-76600 Le Havre FR CNRS 3335 ISCN25 rue Philippe Lebon 76600 Le HavreFrance School of mathematics and Statistics University of Western Australia

In this paper we present a new version of Chen＇s system： a piecewise linear （PWL） Chert system of fractional-order. Via a sigmoid-like function, the discontinuous system is transformed into a continuous system. By numerical simulations, we reveal chaotic behaviors and also multistability, i.e., the existence of small pararheter windows where, for some fixed bifurcation parameter and depending on initial conditions, coexistence of stable attractors and chaotic attractors is possible. moreover, we show that by using an algorithm to switch the bifurcation parameter, the stable attractors can be numerically approximated.

关键词： PWL Chen attractor of fractional-order parameter switching Cellina's Theorem Filippov regu-larization Sigmoid function bifurcation diagram