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Targeted therapy for capillary-venous malformations

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 san.la 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

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Mechanism of diarrhea in microscopic colitis

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World Journal of Gastroenterology 2005年第35期11卷 5535-5539页

作者： Marijana protic Njegica Jojic Daniela Bojic Svetlana Milutinovic Dusanka Necic Bozidar Bojic Petar Svorcan Miodrag Krstic Obren Popovic Center for Gastroenterology and Hepatology Zvezdara University Clinical Center Belgrade Metabolic Department Center for Gastroenterology and Hepatology Zvezdara University Clinical Center Belgrade Institute for Pathology Zvezdara University Clinical Center Belgrade Metabolic laboratory Center for Gastroenterology and Hepatology Zvezdara University Clinical Center Belgrade Endoscopic Unit Center for Gastroenterology and Hepatology Zvezdara University Clinical Center Belgrade Center for Gastroenterology and Hepatology Clinical Center of Serbia Belgrade

AIM: To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes,osmotic gap and ***: Seventy-six patients were included: 51 with microscopic colitis (MC) [40 with lymphocytic colitis (LC);11 with collagenous colitis (CC)]; 7 with MC without diarrhea and 18 as a control group (CG). They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium ***: Fecal fluid sodium concentration was significantly increased in LC 58.11±5.38 mmol/L (P＜0.01)and CC 54.14±8.42 mmol/L (P＜0.05) than in CG 34.28±2.98 mmol/L. Potassium concentration in LC 74.65±5.29 mmol/L (P＜0.01) and CC 75.53±8.78 mmol/L (P＜0.05) was significantly less compared to CG 92.67±2.99 mmol/*** concentration in CC 36.07±7.29 mmol/L was significantly higher than in CG 24.11±2.05 mmol/L (P＜0.05).Forty-four (86.7%) patients had a secretory diarrhea compared to fecal osmotic gap. Seven (13.3%) patients had osmotic ***: Diarrhea in MC mostly belongs to the secretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased Cl/HCO3 exchange rate and increased chloride secretion are coexistent pathways.

关键词：痢疾显微镜大肠炎病理机制

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Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

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World Journal of Gastroenterology 2017年第16期23卷 2995-3002页

作者： Shomron Ben-Horin Jane M Andrews Konstantinos H Katsanos Florian Rieder Flavio Steinwurz Konstantinos Karmiris Jae Hee Cheon Gordon William Moran Monica Cesarini Christian D Stone Doron Schwartz Marijana protic Xavier Roblin Giulia Roda Min-Hu Chen Ofir Har-Noy Charles N Bernstein Department of Gastroenterology Sheba Medical CenterSackler School of MedicineTel-Aviv UniversityRamat-Gan 52621Israel the First Affiliated Hospital of Sun Yat-Sen University Guangzhou 510700Guangdong provinceChina Department of Gastroenterology and Hepatology Inflammatory Bowel Disease ServiceRoyal Adelaide HospitalSchool of MedicineUniversity of AdelaideAdelaideSA 5005Australia Division of Gastroenterology School of Health SciencesUniversity of IoanninaIoannina 45500Greece Department of Gastroenterology Hepatology and NutritionDigestive Disease Diseases and Surgery InstituteCleveland Clinic FoundationClevelandOH 44109United States Unit of Inflammatory Bowel Disease Hospital Israelita Albert EinsteinSao PauloSP 05652-900Brazil Department of Gastroenterology Venizeleio General HospitalHeraklion71409 CreteGreece Department of Internal Medicine Yonsei University College of MedicineSeoul 03722South Korea NIHR Nottingham Digestive Diseases Biomedical Research Unit Nottingham University Hospitals NHS Trust and University of NottinghamNottingham NG7 2UHUnited Kingdom Dipartimento di Medicina Interna e SpecialitàMediche “Sapienza”University of Rome00185 RomaItaly Comprehensive Digestive Institute of Nevada Las VegasNV 89113United States Department of Gastroenterology and Hepatology Soroka University Medical CenterBeer-Sheva 6400111Israel Department of Gastroenterology University Hospital ZvezdaraBelgrade 11000Serbia Department of Gastroenterology University-Hospital of Saint-Etienne42100 Saint EtienneFrance Gastroenterology Unit S.Orsola-Malpighi40138 BolognaItaly IBD Clinical and Research Centre University of ManitobaWinnipegMB R3T2N2Canada

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P larly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

关键词： Inflammatory bowel disease Corticosteroids 5-aminosalicylates Ulcerative colitis

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Polarization Measurements in Radiative Electron Capture into High-Z Ions

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近代物理研究所和兰州重离子加速器实验室年报：英文版 2002年第1期 77-77页

作者： F.Bosch A.Gumberidze S.Hagmann C.Kozhuharov Th.Krings A.OrsicMuthig D.protic D.Sierpowski U.Spillmann Z.Stachura A.Warczak MaXinwen S.Tachenov Th.Stoehlker D.Banas H.F.Beyer GSI-Darmstadt Germany. IKF UniversityofFrankfurtGermany. KansasStateUniversity USA. InstituteofPhysics CracowUniversityPoland. INP CracowPoland. InstituteofPhysicsSwietokrzyakaAcademy KielcePoland. TbilislStateUniversity Georgia. FZ-3urich Germany. 不详

Recently, there has been great interest in the linear polarization of photons produced by radiative electron capture (REC, the time reversed photoionization in ion-atom collisions). No such data are available for the high-Z regime till now. By using high efficiency by by a new generation of segmented germanium detectors that have energy as well as position resolution this field can be investigated experimentally. The

关键词：高电荷态离子俘获电子辐射极化测量散射截面观测角原子物理学能量谱

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Polarization Measurements in Radiative Electron Capture into High-Z Ions

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IMP & HIRFL Annual Report 2002年 77-77页

作者： S.Tachenov,Th.Sthlker,D.Banas,H.F.Beyer,F.Bosch,A.Gumberidze,S.Hagmann,C.Kozhuharov,Th.Krings,A.Orsic Muthig,D.protic,D.Sierpowski,U.Spillmann,Z.Stachura,A.Warczak GSI-Darmstadt Germany.IKF University of Frankfurt Germany. GSI-Darmstadt Germany.IKF University of Frankfurt Germany. GSI-Darmstadt Germany.Institute of Physics Swietokrzyska Academy Kielce Poland. GSI-Darmstadt Germany. GSI-Darmstadt Germany. GSI-Darmstadt Germany.IKF University of Frankfurt Germany.Tbilisi State University Georgia. GSI-Darmstadt Germany. Kansas State University USA. GSI-Darmstadt Germany. FZ-J ulich Germany. GSI-Darmstadt Germany.IKF University of Frankfurt Germany. FZ-J ulich Germany. Institute of Physics Cracow University Poland. GSI-Darmstadt Germany.IKF University of Frankfurt Germany. INP Cracow Poland. Institute of Physics Cracow University Poland.

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