Rôle de la signalisation du TGF-beta et du facteur de transcription GLI2 dans la régulation de MITF et de TRP2 (mécanismes et implications dans la progression du mélanome)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

L'échantillonnage

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienc

In Vitro and In Vivo Activity of Lucitanib in FGFR1/2 Amplified or Mutated Cancer Models

The fibroblast growth factor receptor (FGFR) pathway has been implicated both as an escape mechanism from anti-angiogenic therapy and as a driver oncogene in different tumor types. Lucitanib is a small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors 1 to 3 (VEGFR1 to 3), platelet derived growth factor α/β (PDGFRα/β) and FGFR1–3 tyrosine kinases and has demonstrated activity in a phase I/II clinical study, with objective RECIST responses in breast cancer patients with FGFR1 or FGF3/4/19 gene amplification, as well as in patients anticipated to benefit from anti-angiogenic agents. We report here the in vitro and in vivo antitumor activity of lucitanib in experimental models with or without FGFR1/2 amplification or mutations. In cell assays, lucitanib potently inhibited the growth of tumor cell lines with amplified FGFR1 or mutated/amplified FGFR2. In all xenograft models studied, lucitanib demonstrated marked tumor growth inhibition due to potent inhibition of angiogenesis. Notably, in two lung cancer models with FGFR1 amplification, the antitumor efficacy was higher, suggesting that the simultaneous inhibition of VEGF and FGF receptors in FGFR1 dependent tumors can be therapeutically advantageous. Similar antitumor activity was observed in FGFR2 wild-type and amplified or mutated xenograft models. Pharmacokinetic studies showed lucitanib plasma concentrations in the micro/sub-micromolar range demonstrated drug accumulation following repeated lucitanib administration

Introduction à la décision statistique

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienc

Maternal employment and socio‐economic status of families raising children born very preterm with motor or cognitive impairments: the EPIPAGE cohort study

International audienceAim To describe maternal employment and the socio-economic status of the household up to 8 years after the very preterm birth of a child, according to the presence and type of motor or cognitive impairment. Method A total of 1885 families from the French EPIPAGE cohort of children who were born very preterm between 1997 and 1998 were included. Motor and cognitive impairments were identified in children between the ages of 2 and 8 years in 770 families and were classified according to type. The 1115 families with children born very preterm without these impairments were considered the reference group. Results Mothers of children with severe motor or cognitive impairments were less often working at 5 years after the birth than the reference mothers (21% and 30% vs 57%;p<0.001). Those working before birth returned to work less often and those not working started to work less often after the birth than did reference mothers. At 8 years, mothers of children with severe impairments reported financial difficulties more often than mothers of children without impairments. Interpretation Despite a fairly protective regulatory framework in France, families of infants born very preterm with severe motor or cognitive impairments are socially underprivileged. Measures to maintain an acceptable standard of living for these families and their children are needed

Introduction à la décision statistique

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienc

Introduction à la décision statistique

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienc

Lucitanib for the treatment of HR+/ HER2- metastatic breast cancer: results from the multicohort phase II FINESSE study

reserved23siFGFR1 gene is amplified in 14% of HR+/ HER2- breast cancer patients. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3 and PDGFRα/β, were assessed.mixedHui, Rina; Pearson, Alex; Cortés, Javier; Campbell, Christine; Poirot, Camille; Azim, Hatem A; Fumagalli, Debora; Lambertini, Matteo; Daly, Fergus; Arahmani, Amal; Pérez-Garcia, José; Aftimos, Philippe; Bedard, Phillipe L; Xuereb, Laura; Scheepers, Elsemieke D; Vicente, Malou; Goulioti, Theodora; Loibl, Sibylle; Loi, Sherene; Pierrat, Marie-Jeanne; Turner, Nicholas C; Andre, Fabrice; Curigliano, GiuseppeHui, Rina; Pearson, Alex; Cortés, Javier; Campbell, Christine; Poirot, Camille; Azim, Hatem A; Fumagalli, Debora; Lambertini, Matteo; Daly, Fergus; Arahmani, Amal; Pérez-Garcia, José; Aftimos, Philippe; Bedard, Phillipe L; Xuereb, Laura; Scheepers, Elsemieke D; Vicente, Malou; Goulioti, Theodora; Loibl, Sibylle; Loi, Sherene; Pierrat, Marie-Jeanne; Turner, Nicholas C; Andre, Fabrice; Curigliano, Giusepp