64 research outputs found
Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma
Correction: Volume: 119 Pages: 200-201 DOI: 10.1016/j.ejca.2019.04.012 Published: SEP 2019Background: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naive patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. Methods: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. Results: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (>= 6 months) with 8 versus 5 months for short responder (= 3. Conclusion: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence. (C) 2018 Published by Elsevier Ltd.Peer reviewe
Design et synthÚse de sondes fluorogéniques excitables à deux photons pour la chimie bioorthogonale
The emergence of bioorthogonal chemistry, that is the development of reactions which do not interfere with biological processes, enables to better understand living organisms. In fact, thanks to biocompatible reactions, protein modification allows to probe and modulate their activity. In this context, fluorescent probes are widely used to label and track biomolecules in their native environment. A smart process consists in using a fluorogenic probe, that becomes fluorescent only once it has reacted with its biological target. In addition, studies in living organisms requires probes which absorb and emit in the NIR window where the absorption and diffusion of light by biological samples are minimized. To achieve this goal, it is possible to design probes that can absorb simultaneously two photons. As consequence, they can be excited with about half the energy of single-photon excitation. The first part of this thesis is thus devoted to the development of probes with optimised photophysical and physicochemical properties for biphoton microscopy in living cells. The most promising fluorophore was then used in the second part to design a two-photon excitable fluorogenic probe for bioorthogonal chemistry.Pour mieux comprendre le vivant, la modification des protĂ©ines est devenue un outil prĂ©cieux, notamment afin de sonder leur activitĂ© et de la moduler. Dans cette dĂ©marche, la chimie bioorthogonale, câest-Ă -dire le dĂ©veloppement de rĂ©actions compatibles avec les milieux biologiques, est actuellement en plein essor. Par ailleurs, les sondes fluorescentes constituent un outil prĂ©cieux pour sonder le vivant. Un processus Ă©lĂ©gant consiste ainsi Ă utiliser une sonde fluorescente qui sâallume uniquement lorsque la rĂ©action a eu lieu, elle est alors qualifiĂ©e de fluorogĂ©nique. Dans le but de limiter la dĂ©gradation des tissus et dâavoir une meilleure pĂ©nĂ©tration du rayonnement dans ces derniers, il est primordial dâutiliser des fluorophores excitables et qui Ă©mettent dans le proche IR. Pour atteindre un tel objectif, il est possible de concevoir des sondes qui peuvent absorber simultanĂ©ment deux photons. Elles peuvent ainsi ĂȘtre excitĂ©es avec un rayonnement dâĂ©nergie environ deux fois moindre que lors dâune excitation Ă un photon. La premiĂšre partie de cette thĂšse est ainsi consacrĂ©e au dĂ©veloppement de sondes aux propriĂ©tĂ©s photophysiques et physico-chimiques optimisĂ©es pour la microscopie biphotonique en cellules vivantes. Le fluorophore le plus prometteur a ensuite Ă©tĂ© utilisĂ© dans la seconde partie afin de concevoir une sonde fluorogĂ©nique excitable Ă deux photons pour la chimie bioorthogonale
Design and synthesis of two-photon excitable fluorogenic probes for bioorthogonal chemistry
Pour mieux comprendre le vivant, la modification des protĂ©ines est devenue un outil prĂ©cieux, notamment afin de sonder leur activitĂ© et de la moduler. Dans cette dĂ©marche, la chimie bioorthogonale, câest-Ă -dire le dĂ©veloppement de rĂ©actions compatibles avec les milieux biologiques, est actuellement en plein essor. Par ailleurs, les sondes fluorescentes constituent un outil prĂ©cieux pour sonder le vivant. Un processus Ă©lĂ©gant consiste ainsi Ă utiliser une sonde fluorescente qui sâallume uniquement lorsque la rĂ©action a eu lieu, elle est alors qualifiĂ©e de fluorogĂ©nique. Dans le but de limiter la dĂ©gradation des tissus et dâavoir une meilleure pĂ©nĂ©tration du rayonnement dans ces derniers, il est primordial dâutiliser des fluorophores excitables et qui Ă©mettent dans le proche IR. Pour atteindre un tel objectif, il est possible de concevoir des sondes qui peuvent absorber simultanĂ©ment deux photons. Elles peuvent ainsi ĂȘtre excitĂ©es avec un rayonnement dâĂ©nergie environ deux fois moindre que lors dâune excitation Ă un photon. La premiĂšre partie de cette thĂšse est ainsi consacrĂ©e au dĂ©veloppement de sondes aux propriĂ©tĂ©s photophysiques et physico-chimiques optimisĂ©es pour la microscopie biphotonique en cellules vivantes. Le fluorophore le plus prometteur a ensuite Ă©tĂ© utilisĂ© dans la seconde partie afin de concevoir une sonde fluorogĂ©nique excitable Ă deux photons pour la chimie bioorthogonale.The emergence of bioorthogonal chemistry, that is the development of reactions which do not interfere with biological processes, enables to better understand living organisms. In fact, thanks to biocompatible reactions, protein modification allows to probe and modulate their activity. In this context, fluorescent probes are widely used to label and track biomolecules in their native environment. A smart process consists in using a fluorogenic probe, that becomes fluorescent only once it has reacted with its biological target. In addition, studies in living organisms requires probes which absorb and emit in the NIR window where the absorption and diffusion of light by biological samples are minimized. To achieve this goal, it is possible to design probes that can absorb simultaneously two photons. As consequence, they can be excited with about half the energy of single-photon excitation. The first part of this thesis is thus devoted to the development of probes with optimised photophysical and physicochemical properties for biphoton microscopy in living cells. The most promising fluorophore was then used in the second part to design a two-photon excitable fluorogenic probe for bioorthogonal chemistry
Les « contre-espaces » dans La TournĂ©e dâautomne et Les Yeux bleus de Mistassini de Jacques Poulin : des refuges pour rĂ©sister au vieillissement
Chez Poulin, lâindividu est crĂ©ateur de son propre espace de vie, oscillant entre espaces utopiques â « des pays sans lieu et des histoires sans chronologie » â, hĂ©tĂ©rotopiques â « des utopies qui ont un lieu prĂ©cis et rĂ©el » (Foucault 23) â, et non utopiques. Les espaces utopiques et hĂ©tĂ©rotopiques, autrement nommĂ©s « contre-espaces » sont rĂ©sistance : « des lieux qui sâopposent Ă tous les autres, qui sont destinĂ©s en quelque sorte Ă les effacer, Ă les neutraliser ou Ă les purifier » (Foucault 24). In fine, le rapport Ă la rĂ©alitĂ© est propre Ă soi, mais, selon Poulin, lâĂ©quilibre est essentiel.Cet article tend Ă montrer comment les personnages du Chauffeur dans La tournĂ©e dâautomne et de Jack dans Les Yeux bleus de Mistassini trouvent leur propre Ă©quilibre grĂące Ă des « contre-espaces », et Ă©chappent par lĂ mĂȘme au drame du corps vieillissant. Ainsi, en incarnant pour les personnages un refuge au service dâune rĂ©flexion sur eux-mĂȘmes, leur rapport Ă lâautre et sur la vie, ces « contre-espaces » pouliniens participent-ils de leur quĂȘte identitaire et de leur rĂ©sistance Ă la peur de lâeffacement de soi.In Poulin's work, the individual remains the creator of his own space of life, oscillating between utopian spaces â « countries without a place and histories without a chronology » â, heterotopian spaces â « utopias that have a precise and real place » (Foucault 23) â and not utopian. Utopian and heterotopic spaces, otherwise referred to as « counter-spaces » are perceived here as spaces of resistance: « places that oppose all others, that are intended in some way to erase, neutralize or purify them » (Foucault 24). In the end, the relationship to reality is different for everyone, but, according to Poulin, balance is essential.This paper seeks to show how the characters of the Driver in La tournĂ©e dâautomne and Jack in Les yeux bleus de Mistassini find their own equilibrium thanks to « counter-spaces », thereby escaping the drama of the ageing body. By providing a refuge for the characters to reflect on themselves and their relationship to others and to life, these âcounter-spacesâ contribute to their search for identity and to their resilience against the fear of erasure
Récits de voyage au féminin : des Parisiennes autour du monde au XIXe siÚcle
L'auteure s'intĂ©resse Ă trois rĂ©cits de voyages Ă©crits par des femmes, Ă la fin du XIXe siĂšcle, et dont la particularitĂ© est de comprendre le mot « parisienne » dans le titre. Les Ćuvres sont : Louise Bourbonnaud, Les Indes et lâExtrĂȘme-Orient, Impressions de voyage dâune Parisienne, Paris, chez lâauteur, 1888 ; Laure Durand-Fardel, De Marseille Ă Shanghai et Yedo, RĂ©cits dâune Parisienne, Paris, Hachette, 2e Ă©dition, 1881 ; AdĂšle Toussaint-Samson, Une Parisienne au BrĂ©sil, Paris, P. Ollendorff, 1883. Ce travail veut dĂ©terminer si le rĂ©cit de voyage fĂ©minin, rĂ©digĂ© dans un contexte d'apparition de mouvements de libĂ©ration des femmes, favorise cette Ă©mancipation ou renforce l'ordre social Ă©tabli et les stĂ©rĂ©otypes. Le mĂ©moire propose une analyse critique et comparĂ©e des Ćuvres. La premiĂšre partie prĂ©cise le contexte historique de la fin du XIXe siĂšcle et prĂ©sente les Ćuvres retenues ainsi que le genre de la littĂ©rature de voyage. Ensuite, l'auteure prĂ©sente la littĂ©rature de voyage fĂ©minine et s'interroge sur le caractĂšre fĂ©ministe ou non des rĂ©cits rĂ©digĂ©s par des femmes. La troisiĂšme partie est consacrĂ©e Ă la rĂ©ception de ces Ćuvres et Ă leur portĂ©e
Abus de droits contractuels dans l'exécution du contrat: critÚres et sanctions
info:eu-repo/semantics/publishe
L'INSULINOTHERAPIE CHEZ LE PATIENT DIABETIQUE AGE DE PLUS DE 70 ANS ET PRISE EN CHARGE EN VILLE
PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
ĂTUDE DE L'INFLUENCE DE LA D-L THYROXINE SUR LE POIDS DE L'OEUF, SUR LE POIDS DU JAUNE ET SA COMPOSITION
International audienc
Silafluorene as a promising core for cell-permeant, highly bright and two-photon excitable fluorescent probes for live-cell imaging
International audienceIn this study, we report the synthesis, linear and non-linear photophysical studies and live cell imaging of two two-photon activatable probes based on a silafluorene core: SiFluo-V and SiFluo-L. Thanks to their quadrupolar (A-Ï-D-Ï-A) design, these probes exhibit respectively good to impressive two-photon cross sections (from 210 GM to 2150 GM). TD-DFT calculations support the experimental evidence that SiFluo-L displays far better two-photon absorption properties than SiFluo-V. Moreover, SiFluo-L possesses all requirements for bioimaging as it is water soluble, cell-permeant and and presents a low cytotoxicity (IC80â„10 ”M). It labels mitochondria in live-cell imaging at low laser power with high brightness, contrast and photostability. This study demonstrates that silafluorene is a promising core to develop new two-photon fluorophores for live cell imaging
Covalent hybrids based on Re( i ) tricarbonyl complexes and polypyridine-functionalized polyoxometalate: synthesis, characterization and electronic properties
International audienceA series of [Re(CO)3Br(N^N)] (N^N = substituted 2,2'-Ââbipyridine ligand) complexes based on polypyridine-Ââfunctionalized Dawson polyoxometalate (1-Ââ3) has been synthesized. The new hybrids (4-Ââ6) were characterized by various analytical techniques, including absorption, vibrational and luminescence spectroscopies as well as electrochemistry. Both units, the polyoxometalate and the transition metal complex, retain their intrinsic properties. Their combination in the newly prepared hybrids results in improved photosensitization in the high-Ââenergy visible region. However, a complete quenching of the emission for the [Re(CO)3Br(N^N)] complexes is observed due to formation of a charge separated state, Re(II) â POM-Ââ , as shown by quenching experiments as well as theoretical modelization via DFT
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