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c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

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World Journal of Gastroenterology 2008年第41期14卷 6339-6346页

作者： Meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence Michel Alain Mauviel Dominique Bernuau fanny daniel Institut National de laSanté et de la Recherche Médicale U697 Hpital Saint-Louis Institut National de la Santé et de la RechercheMédicale U591 Faculté de Médecine Necker Institut National de la Santé et de la RechercheMédicale U773 Centre de Recherche Bichat Beaujon CRB3and Université Paris 7 Denis Diderot site Bichat

AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. METHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate

关键词： c-Fos Cyclin DI GSK-3 Cell growth, Cell cycle Hepatoma Epidermal growth factor

Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors

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Journal of Geriatric Cardiology 2019年第11期16卷 806-811页

作者： Marjorie Bernier Sarah-Line Lancrerot fanny Rocher Elise K Van-Obberghen Pierre Olivier Thibaud Lavrut Nadège Parassol-Girard Milou-daniel Drici Department of Pharmacology and Toxicology PharmacoVigilance CenterUniversity of Nice Côte d'Azur Medical CenterHôpital de Cimiez4 Avenue Reine VictoriaBP 117906003NiceFrance Emergency Department Short Stay Unit University of Nice Côte d'Azur Medical CenterHôpital Pasteur 230Voie Romaine 06001NiceFrance

Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug ***,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised *** aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very *** Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective *** were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).Conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.

关键词： Dabigatran Drug interaction Hemorrhage P-gp inhibitors,The elderly

Effect of Ambient Temperature and Humidity Conditions on the Efficacy of Organic Treatments against Varroa destructor in Different Climatic Zones of Chile

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Journal of Agricultural Science and Technology(A) 2013年第6期3卷 I0003-I0003,475-483页

作者： Aldea Patricia Rodriguez Rafael Olivares Alejandra Farffin Macarena Riveros daniel Nfifiez fanny Trivelli Luz Center for Apicultural Entrepreneurship of Universidad Mayor CEAP1MA YOR-Camino La Pirc~mide Huechuraba Santiago 5 750Chile

Varroasis is a disease caused by the mite Varroa destructor, which affects honeybees worldwide. It is estimated that it entered Chile in 1992, and it must be controlled through different types of treatments such as thymol, formic and oxalic acid in different formulations and presentations. This kind of organic products has shown a variable acaricidal capacity, since different factors affect their efficacy such as ambient temperature and humidity, product presentation and location inside the hive, etc.. In Chile, beekeeping takes place in four different climatic zones, in which ambient temperature and humidity as well as the duration of the apicultural season are different. Therefore, the aim of this study was to determine how ambient temperature and humidity influence the efficacy of the organic treatments used in the beekeeping season. Different apiaries were installed in those climatic zones in three seasons between the years 2009 and 2012. All beehives received the same management in each apiary and it was evaluated the same organic treatments in different formulations and presentations. All the beehives were positive to Varroa, which was obtained using samples of adult bees and the soapy water test before and after each treatment. A thermo-hygrometer was installed in each apiary in order to monitor the ambient temperature （T°） and humidity （H°） conditions, which were registered daily for a period of 30 days since the beginning. It was obtained that the treatments＇ efficacy increases as the minimum T° and average T° rose, whereas on the contrary, the efficacy decreases when maximum H° was higher.

关键词： Varroa organics treatments effectiveness acaricidal effects.

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王雅

汽车之友 2018年第10期 14-25页

作者：雷鸣 daniel Zhai

王雅fanny出生：1986年身高：166cm职业：服装设计师创建品牌：Aprés-file 性感狮王没错,我也认为7座SUV是时下最媚俗的车型,当Jeep、Subaru都不顾一切要打造出这样一台带着二胎时代鲜明印记的家用车时,你就知道市场的力量有多么强大... 详细信息

王雅fanny出生：1986年身高：166cm职业：服装设计师创建品牌：Aprés-file 性感狮王没错,我也认为7座SUV是时下最媚俗的车型,当Jeep、Subaru都不顾一切要打造出这样一台带着二胎时代鲜明印记的家用车时,你就知道市场的力量有多么强大了。当然法国人也没能抵住诱惑,大概谁也没想到。

关键词：家用车车型一台印记标致带着小巧别致进气格栅王错下界

EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”

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Open Journal of Internal Medicine 2016年第2期6卷 56-67页

作者： Jean-Philippe Metges Erick Gamelin Alain Volant Olivier Capitain Jean-François Ramée Jean-Luc Raoul Jean-Yves Douillard Pierre-Luc Etienne Isabelle Cumin Olivier Dupuis Roger Faroux Marie-Aude Coulon Philippe Deguiral Karine Bideau Nacr Eddine Achour Alain Gourlaouen Corinne Alleaume Annie Wdowik Laurent Miglianico Yann Touchefeu Vincent Klein Alain Penchet Ludovic Rosenfeld daniel Martin Claire Stampfli Jean-Jacques Auger Alain Bargain Murielle Broyer-Petit Jérome Chettrit Louis-Rémi De Ybarlucea Serge Eloit Pierre Marie Girardot Nathalie Heresbach Christian Laboisse Eric Lavoine Gilles Lemasson Claire Magois Sophie Michalak Norbert Padilla Joseph Politis Frédéric Staroz Bruno Turlin Arnaud Uguen Viorel Vasiliu Véronique Verriele fanny Marhuenda Delphine Déniel Lagadec Christian Riché Françoise Grudé Observatoire dédié au Cancer des régions Bretagne et Pays de la Loire France Centre Hospitalier Régional Universitaire (CHRU) Brest France Institut de Cancérologie de l’Ouest (ICO) Paul Papin Angers France Centre Catherine de Sienne Nantes France CRLCC Eugène Marquis Rennes France ICO René Gauducheau Nantes France Centre CARIO-HCPA Plérin France Centre Hospitalier Bretagne Sud (CHBS) Lorient France Clinique Victor Hugo Le Mans France Centre Hospitalier Départemental (CHD) La Roche-sur-Yon France CH Le Mans France Clinique Mutualiste de l’Estuaire Saint-Nazaire France CHIC Quimper France Clinique Pasteur Lanroze Brest France CH MORLAIX France CH Saint-Brieuc France CHBA Vannes France CHP Saint-Grégoire France CHU Nantes France Hopital Privé Océane Vannes France Clinique Saint-Michel et Sainte-Anne Quimper France Pole Santé Sarthe et Loire La Flèche France Polyclinique du Maine Laval France Polyclinique Sud Quimper France CH Laval France Polyclinique Cesson Sévigné France Laboratoire d’anatomie et de cytologie pathologiques Cholet France Cabinet d’anatomie et de cytologie pathologiques Saint-Malo France Laboratoire d’anatomie et de cytologie pathologiques Lorient France Institut d’histopathologie Nantes France Laboratoire de Pathologie Médicale Laval France ARMOR Pathologie Plérin France Laboratoire d’anatomie et de cytologie pathologiques Rennes France Laboratoire d’anatomie et de cytologie pathologiques Angers France Laboratoire Analyses Biologie Glasgow Brest France CHU Angers France Centre d’anatomie et de cytologie pathologiques Le Mans France Cabinet d’anatomie et de cytologie pathologiques Vannes France Laboratoire d’anatomie et de cytologie pathologiques Quimper France CHU Rennes France

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

关键词： Metastatic Colorectal Cancer Cetuximab EGFR Expression