Multiprong control of glioblastoma multiforme invasiveness: blockade of pro-inflammatory signaling, anti-angiogenesis, and homeostasis restoration

Glioblastoma multiforme (GBM) is the most invasive type of glial tumor with poor overall survival, despite advances in surgical resection, chemotherapy, and radiation. One of the main challenges in treating GBM is related to the tumor’s location, complex and heterogeneous biology, and high invasiveness. To meet the demand for oxygen and nutrients, growing tumors induce new blood vessels growth. Antibodies directed against vascular endothelial growth factor (VEGF), which promotes angiogenesis, have been developed to limit tumor growth. Bevacizumab (Avastin), an anti-VEGF monoclonal antibody, is the first approved angiogenesis inhibitor with therapeutic promise. However, it has limited efficacy, likely due to adaptive mutations in GBM, leading to overall survival compared to the standard of care in GBM patients. Molecular connections between angiogenesis, inflammation, oxidative stress pathways, and the development of gliomas have been recognized. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the converging dysregulation of signaling pathways. While most GBM clinical trials focus on “anti-angiogenic” modalities, stimulating inflammation resolution is a novel host-centric therapeutic avenue. The selective therapeutic possibilities for targeting the tumor microenvironment, specifically angiogenic and inflammatory pathways expand. So, a combination of agents aiming to interfere with several mechanisms might be beneficial to improve outcomes. Our approach might also be combined with other therapies to enhance sustained effectiveness. Here, we discuss Suramab (anti-angiogenic), LAU-0901 (a platelet-activating factor receptor antagonist), Elovanoid (ELV; a novel lipid mediator), and their combination as potential alternatives to contain GBM growth and invasiveness.Fil: Bazan, Nicolas G.. State University of Louisiana; Estados UnidosFil: Reid, Madigan M.. State University of Louisiana; Estados UnidosFil: Cruz Flores, Valerie A.. State University of Louisiana; Estados UnidosFil: Gallo, Juan Eduardo Maria. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Lewis, William. State University of Louisiana; Estados UnidosFil: Belayev, Ludmila. State University of Louisiana; Estados Unido

The impact of realistic models of mass segregation on the event rate of extreme-mass ratio inspirals and cusp re-growth

One of the most interesting sources of gravitational waves (GWs) for LISA is the inspiral of compact objects on to a massive black hole (MBH), commonly referred to as an "extreme-mass ratio inspiral" (EMRI). The small object, typically a stellar black hole (bh), emits significant amounts of GW along each orbit in the detector bandwidth. The slowly, adiabatic inspiral of these sources will allow us to map space-time around MBHs in detail, as well as to test our current conception of gravitation in the strong regime. The event rate of this kind of source has been addressed many times in the literature and the numbers reported fluctuate by orders of magnitude. On the other hand, recent observations of the Galactic center revealed a dearth of giant stars inside the inner parsec relative to the numbers theoretically expected for a fully relaxed stellar cusp. The possibility of unrelaxed nuclei (or, equivalently, with no or only a very shallow cusp) adds substantial uncertainty to the estimates. Having this timely question in mind, we run a significant number of direct-summation $N-$body simulations with up to half a million particles to calibrate a much faster orbit-averaged Fokker-Planck code. We then investigate the regime of strong mass segregation (SMS) for models with two different stellar mass components. We show that, under quite generic initial conditions, the time required for the growth of a relaxed, mass segregated stellar cusp is shorter than a Hubble time for MBHs with $M_\bullet \lesssim 5 \times 10^6 M_\odot$ (i.e. nuclei in the range of LISA). SMS has a significant impact boosting the EMRI rates by a factor of $\sim 10$ for our fiducial models of Milky Way type galactic nuclei.Comment: Accepted by CQG, minor changes, a bit expande

HST Observations of the Stellar Distribution Near Sgr A*

We present HST/NICMOS data to study the surface brightness distribution of stellar light within the inner 10" of Sgr A* at 1.4, 1.7 and 1.9 microns. We use these data to independently examine the surface brightness distribution that had been measured previously with NICMOS and to determine whether there is a drop in the surface density of stars very near Sgr A*. Our analysis confirms that a previously reported drop in the surface brightness within 0.8" of Sgr A* is an artifact of bright and massive stars near that radius. We also show that the surface brightness profile within 5" or ~0.2 pc of Sgr A* can be fitted with broken power laws. The power laws are consistent with previous measurements, in that the profile becomes shallower at small radii. For radii > 0.7" the slope is beta=-0.34\pm0.04 where Sigma is proportional to r^beta and becomes flatter at smaller radii with beta=-0.13\pm0.04. Modeling of the surface brightness profile gives a stellar density that increases roughly as r^-1 within the inner 1" of Sgr A*. This slope confirms earlier measurements in that it is not consistent with that expected from an old, dynamically-relaxed stellar cluster with a central supermassive black hole. Assuming that the diffuse emission is not contaminated by a faint population of young stars down to the 17.1 magnitude limit of our imaging data at 1.70$\mu$, the shallow cusp profile is not consistent with a decline in stellar density in the inner arcsecond. In addition, converting our measured diffuse light profile to a stellar mass profile, with the assumption that the light is dominated by K0 dwarfs, the enclosed stellar mass within radius r < 0.1 pc of Sgr A* is ~ 3.2x10^4 M_solar (r/0.1 {pc})^2.1.Comment: 16 pages, 7 figures, ApJ, in pres

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum