Preclinical Evaluation of panobinostat and ONC201 for the treatment of diffuse intrinsic pontine glioma (DIPG)

Diffuse intrinsic pontine glioma (DIPG) also referred as paediatric high-grade glioma (pHGG) is a fast-growing and aggressive type of childhood brain cancer. Recent studies investigating the molecular pathogenesis of DIPG have identified new therapeutic targets, paving the way for a new line of drugs mainly HDAC inhibitors. However, despite long years of trials, no significant results have been generated yet. Panobinostat is a HDAC inhibitor that has shown promising preclinical cytotoxicity in DIPG but failed so far in clinical trials. This study aims to re-evaluate the efficacy of Panobinostat in DIPG in vitro using patient-derived DIPG cell cultures obtained directly from patients. ONC201 is another potentially effective drug in DIPG. This apoptotic agent has been considered in a few clinical trials in diffuse glioma including DIPG. Our results reveal a dose-dependent response to Panobinostat and ONC201 in DIPG cells. However, Panobinostat caused a significant reduction in the mean percentage cell viability at a lower concentration compared to ONC201. Panobinostat caused significant decreases in DIPG cell viability at concentrations greater than or equal to 0.002 μM (p<0.05), the response reached a plateau after 0.1 μM, which reduced cell viability to 32.81 % ± 0.25 % (p = 6.74E−06) when compared to control cells. ONC201 only significantly induced apoptosis at concentrations equal or higher than 0.01 μM (p<0.05), with its effect plateauing after 0.2 μM. This pre-clinical study supports the effectiveness of Panobinostat as a potential therapeutic agent for DIPG compared to ONC201, with no apparent synergistic effect observed in combination

Two-dimensional fluctuations and competing phases in the stripe-like antiferromagnet BaCoS2_{2}

10 pages, 6 figuresInternational audienceBy means of a combined x-ray diffraction, magnetic susceptibility and specific heat study, we investigate the interplay between orthorhombic distortion and stripe-like antiferromagnetic (AFM) order in the Mott insulator BaCoS$_{2}$ at $T_N=290$ K. The data give evidence of a purely electronic AFM transition with no participation of the lattice. The observation of large thermal fluctuations in the vicinity of $T_N$ and a Schottky anomaly unveils competing ground states within a minute $\sim$1 meV energy range that differ in the orbital and spin configurations of the Co ions. This interpretation suggests that the stripe-like order results from a spontaneous symmetry breaking of the geometrically frustrated pristine tetragonal phase, which offers an ideal playground to study the driving force of multi-orbital Mott transitions without the participation of the lattice

Manipulating Dirac states in BaNiS2_2 by surface charge doping

International audienceIn the Dirac semimetal BaNiS$_2$ , the Dirac nodes are located along the Γ − M symmetry line of the Brillouin zone, instead of being pinned at fixed high-symmetry points. We take advantage of this peculiar feature to demonstrate the possibility of moving the Dirac bands along the Γ − M symmetry line in reciprocal space by varying the concentration of K atoms adsorbed onto the surface of cleaved BaNiS$_2$ single crystals. By means of first-principles calculations, we give full account for this observation by considering the effect of the electrons donated by the K atom on the charge transfer gap, which establishes a promising tool for engineering Dirac states at surfaces, interfaces and heterostructures