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High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions.
The inclusive J/ψ production has been studied in Pn-Pb and pp collisions at the centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, using the ALICE detector at the CERN LHC. The J/ψ meson is reconstructed, in the centre-of-mass rapidity interval 2.5<y<4 and in the transverse-momentum range pT<12 GeV/c, via its decay to a muon pair. In this Letter, we present results on the inclusive J/ψ cross section in pp collisions at s√=5.02 TeV and on the nuclear modification factor RAA. The latter is presented as a function of the centrality of the collision and, for central collisions, as a function of the transverse momentum pT of the J/ψ. The measured RAA values indicate a suppression of the J/ψ in nuclear collisions and are then compared to our previous results obtained in Pb-Pb collisions at sNN−−−√=2.76 TeV. The ratio of the RAA values at the two energies is also computed and compared to calculations of statistical and dynamical models. The numerical value of the ratio for central events (0-10\% centrality) is 1.17±0.04(stat)±0.20(syst). In central events, as a function of pT, a slight increase of RAA with collision energy is visible in the region 2<pT<6 GeV/c. Theoretical calculations provide a good description of the measurements, within uncertainties.
The inclusive J/ψ production has been studied in Pn-Pb and pp collisions at the centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, using the ALICE detector at the CERN LHC. The J/ψ meson is reconstructed, in the centre-of-mass rapidity interval 2.5<y<4 and in the transverse-momentum range pT<12 GeV/c, via its decay to a muon pair. In this Letter, we present results on the inclusive J/ψ cross section in pp collisions at s√=5.02 TeV and on the nuclear modification factor RAA. The latter is presented as a function of the centrality of the collision and, for central collisions, as a function of the transverse momentum pT of the J/ψ. The measured RAA values indicate a suppression of the J/ψ in nuclear collisions and are then compared to our previous results obtained in Pb-Pb collisions at sNN−−−√=2.76 TeV. The ratio of the RAA values at the two energies is also computed and compared to calculations of statistical and dynamical models. The numerical value of the ratio for central events (0-10\% centrality) is 1.17±0.04(stat)±0.20(syst). In central events, as a function of pT, a slight increase of RAA with collision energy is visible in the region 2<pT<6 GeV/c. Theoretical calculations provide a good description of the measurements, within uncertainties.