Search results for "MICE"

p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53

2010

10 p.-5 fig.

Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity

2021

Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

2018

Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but it…

SMOOTHLY SHIFTING FLUORESCENT WINDOW: TUNABLE “OFF-ON-OFF”MICELLAR BIOSENSORS FOR pH

2009

A revision of the structure and stratigraphy of pre-Green Tuff ignimbrites at Pantelleria (Strait of Sicily)

2013

International audience; At Pantelleria, peralkaline silicic magmas were erupted across a range of eruptive typologies and magnitudes: pyroclastic flows, Plinian to strombolian pumice fallout and lava flows. In this paper we focus on the intermediate cycle of eruptive activity which is bracketed by ignimbrite units slightly older than the two caldera collapses which marked the volcanological activity of the island. This age interval (180-85 ka) was punctuated by six ignimbrite-forming eruptions (silicic and variably peralkaline) for a cumulative erupted magma volume of approximately 6 km3 dense rock equivalent. Based on new 40Ar/39Ar (Na,K)-feldspar ages and petrographic data, we propose an …

Inulin-Based Polymeric Micelles Functionalized with Ocular Permeation Enhancers: Improvement of Dexamethasone Permeation/Penetration through Bovine C…

2021

Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG2000, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted abl…

Amphoteric, prevailingly cationic L-arginine polymers of poly(amidoamino acid) structure: Synthesis, acid/base properties and preliminary cytocompati…

2013

A linear amphoteric poly(amidoamino acid), L-ARGO7, is prepared by Michael-type polyaddition of L-arginine with N,N′-methylenebisacrylamide. Chain-extension of acrylamide end-capped L-ARGO7 oligomers with piperazine leads to high-molecular-weight copolymers in which L-arginine maintains its absolute configuration. Acid/base properties of L-ARGO7 polymers show isolectric points of ≈10 and positive net average charges per repeating unit at pH = 7.4 from 0.25 to 0.40. These arginine-rich synthetic polymers possibly share some of the unique biological properties of polyarginine cell-permeating peptides. In vitro tests with mouse embryo fibroblasts balb/3T3 clone A31 show that L-ARGO7 polymers a…

Acid-Labile Surfactants Based on Poly(ethylene glycol), Carbon Dioxide and Propylene Oxide: Miniemulsion Polymerization and Degradation Studies

2017

Partially degradable, nonionic AB and ABA type di- and triblock copolymers based on poly(propylene carbonate) and poly(ethylene glycol) blocks were synthesized via immortal copolymerization of carbon dioxide and propylene oxide, using mPEG or PEG as a macroinitiator, and (R,R)-(salcy)-CoOBzF5 as a catalyst in a solvent-free one-pot procedure. The amphiphilic surfactants were prepared with molecular weights (Mn) between 2800 and 10,000 g·mol−1 with narrow molecular weight distributions (1.03–1.09). The copolymers were characterized using 1H-, 13C- and DOSY-NMR spectroscopy and size exclusion chromatography (SEC). Surface-active properties were determined by surface tension measurements (crit…

NOVEL PAHY-GRAFT COPOLYMERS AS MICELLAR DRUG CARRIER FOR ANTICANCER DRUGS

2009

HYALURONIC ACID BASED-MICELLES FOR OFF-LABEL USE OF IMATINIB IN RETINOPATHIES TREATMENT

2018

The aim of this work was to obtain polymeric micelles able to cross corneal barrier and to improve the permeation of imatinib free base. Micelles were prepared by using hyaluronic acid (HA) derivatives containing ethylenediamine (EDA), chains of hexadecyl (C16), polyethylene glycol (PEG) and/or L-carnitine (CRN). The resulting samples, named as HA-EDA-C16, HA-EDA-C16-PEG and HA-EDA-C16-CRN micelles, were designed to allow a non-invasive way of administration, i.e. topical ocular instillation. These nanocarriers showed an optimal particle size in aqueous media and mucoadhesive properties. Imatinib-loaded micelles were able to interact with corneal barrier and to promote imatinib transcorneal…