P-glycoprotein Mediated Efflux Limits Substrate and Drug Uptake in a Preclinical Brain Metastases of Breast Cancer Model

The blood-brain barrier (BBB) is a specialized vascular interface that restricts the entry of many compounds into brain. This is accomplished through the sealing of vascular endothelial cells together with tight junction proteins to prevent paracellular diffusion. In addition, the BBB has a high degree of expression of numerous efflux transporters which actively extrude compounds back into blood. However, when a metastatic lesion develops in brain the vasculature is typically compromised with increases in passive permeability (blood-tumor barrier; BTB). What is not well documented is to what degree active efflux retains function at the BTB despite the changes observed in passive permeability. In addition, there have been previous reports documenting both increased and decreased expression of P-gp in lesion vasculature. Herein, we simultaneously administer a passive diffusion marker (14C-AIB) and a tracer subject to P-gp efflux (rhodamine 123) into a murine preclinical model of brain metastases of breast cancer. We observed that the metastatic lesions had similar expression (p>0.05; n=756-1214 vessels evaluated) at the BBB and the BTB. Moreover, tissue distribution of R123 was not significantly (p>0.05) different between normal brain and the metastatic lesion. It is possible that the similar expression of P-gp on the BBB and the BTB contribute to this phenomenon. Additionally we observed P-gp expression at the metastatic cancer cells adjacent to the vasculature which may also contribute to reduced R123 uptake into the lesion. The data suggest that despite the disrupted integrity of the BTB, efflux mechanisms appear to be intact, and may be functionally comparable to the normal BBB. The BTB is a significant hurdle to delivering drugs to brain metastasis

Measurement of the W±ZW^{\pm}Z boson pair-production cross section in pppp collisions at s=13\sqrt{s}=13 TeV with the ATLAS Detector

The production of $W^{\pm}Z$ events in proton--proton collisions at a centre-of-mass energy of 13 TeV is measured with the ATLAS detector at the LHC. The collected data correspond to an integrated luminosity of 3.2 fb$^{-1}$. The $W^{\pm}Z$ candidates are reconstructed using leptonic decays of the gauge bosons into electrons or muons. The measured inclusive cross section in the detector fiducial region for leptonic decay modes is $\sigma_{W^\pm Z \rightarrow \ell^{'} \nu \ell \ell}^{\textrm{fid.}} = 63.2 \pm 3.2$ (stat.) $\pm 2.6$ (sys.) $\pm 1.5$ (lumi.) fb. In comparison, the next-to-leading-order Standard Model prediction is $53.4^{+3.6}_{-2.8}$ fb. The extrapolation of the measurement from the fiducial to the total phase space yields $\sigma_{W^{\pm}Z}^{\textrm{tot.}} = 50.6 \pm 2.6$ (stat.) $\pm 2.0$ (sys.) $\pm 0.9$ (th.) $\pm 1.2$ (lumi.) pb, in agreement with a recent next-to-next-to-leading-order calculation of $48.2^{+1.1}_{-1.0}$ pb. The cross section as a function of jet multiplicity is also measured, together with the charge-dependent $W^+Z$ and $W^-Z$ cross sections and their ratio

Search for Higgs and ZZ Boson Decays to J/ψγJ/\psi\gamma and Υ(nS)γ\Upsilon(nS)\gamma with the ATLAS Detector

A search for the decays of the Higgs and $Z$ bosons to $J/\psi\gamma$ and $\Upsilon(nS)\gamma$ ($n=1,2,3$) is performed with $pp$ collision data samples corresponding to integrated luminosities of up to $20.3\mathrm{fb}^{-1}$ collected at $\sqrt{s}=8\mathrm{TeV}$ with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% CL upper limits are placed on the branching fractions. In the $J/\psi\gamma$ final state the limits are $1.5\times10^{-3}$ and $2.6\times10^{-6}$ for the Higgs and $Z$ bosons, respectively, while in the $\Upsilon(1S,2S,3S)\,\gamma$ final states the limits are $(1.3,1.9,1.3)\times10^{-3}$ and $(3.4,6.5,5.4)\times10^{-6}$, respectively

Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H??????? and H???ZZ*???4??? Decay Channels at s\sqrt{s}=8??????TeV with the ATLAS Detector

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3~fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb-1 of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ*→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σpp→H=33.0±5.3 (stat)±1.6 (syst)  pb. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions