Background and purpose: Several anticancer drugs with diverse chemical structures can induce differentiation of cancer cells. This study was undertaken to explore the potential contribution of ...caspase‐3 to pharmacologically‐induced differentiation of K562 cells.
Experimental approach: We assessed differentiation by measuring the expression of glycophorin A and haemoglobin synthesis in K562 cells treated with low concentrations of doxorubicin, hydroxyurea, cytosine arabinoside, cisplatin and haemin. Caspase‐3 activation, mitochondrial membrane potential dissipation and viability were assessed by FACS. GATA‐1‐binding activity was evaluated by EMSA.
Key results: Treatment of K562 cells with low concentrations of the tested drugs activated caspase‐3 but did not trigger detectable apoptosis. Instead, elevated levels of haemoglobin‐positive and glycophorin A/caspase‐3‐double‐positive cells were observed, suggesting involvement of caspase‐3 in drug‐induced differentiation. Inhibition of caspase‐3 activity significantly reduced the ability of K562 cells to execute the differentiation programme. Mitochondrial membrane potential dissipation was observed, indicating involvement of the mitochondrial pathway. Binding activity of GATA‐1, transcription factor responsible for differentiation and cell survival, was not diminished by increased caspase‐3 activity during drug‐stimulated differentiation.
Conclusions and implications: Our results could explain how anticancer drugs, with diverse structures and modes of action, can stimulate erythroid differentiation in leukaemic cells with appropriate genetic backgrounds. Our findings imply that some similarities exist between pharmacologically‐induced differentiation of erythroleukaemic cells and normal erythropoiesis, both involving caspase‐3 activation at high levels of anti‐apoptotic protein Bcl‐XL and chaperone protein Hsp70 (heat shock protein 70). Therefore, the functions of caspase‐3, unrelated to cell death, can be extended to pharmacologically‐induced differentiation of some cancer cells.
Neuroendocrine control of metabolism Kuliczkowska-Plaksej, J.; Milewicz, A.; Jakubowska, J.
Gynecological endocrinology,
03/2012, Letnik:
28, Številka:
S1
Journal Article
Recenzirano
Metabolism is controlled through homeostatic system consisting of central centers, gut hormones, hormones from adipose tissue and the other hormonal axes. This cooperation is based on cross-talk ...between central and peripheral signals. Among them the hypothalamus plays a crucial role, with interconnected nuclei forming neuronal circuits. Other regions in the brain, such as the brain stem, the endocannabinoid system, the vagal afferents, are also involved in energy balance. The second component is peripheral source of signals − the gastrointestinal tract hormones. Additionally, adipokines from adipose tissue, thyrotropic, gonadotropic and somatotropic axes play a role in energy homeostasis. Knowledge about all components of this neuroendocrine circuit will be helpful in developing novel therapeutic approaches against the metabolic syndrome and its components.
Abstract Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisions at $$\sqrt{s_{\mathrm {NN}}}$$ s NN $$=$$ = 2.76 TeV using the ALICE detector at the ...CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range $$|\eta |<0.8$$ | η | < 0.8 and transverse momentum $$0.2< p_{\mathrm{T}} < 2.0$$ 0.2 < p T < 2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The $$\eta $$ η and $$p_{\mathrm{T}}$$ p T dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions.
Abstract We report on the inclusive $$\text {J}/\psi $$ J / ψ production cross section measured at the CERN Large Hadron Collider in proton–proton collisions at a center-of-mass energy ...$$\sqrt{s}~=~13$$ s = 13 TeV. The $$\text {J}/\psi $$ J / ψ mesons are reconstructed in the $$\text {e}^{+}\text {e}^{-}$$ e + e - decay channel and the measurements are performed at midrapidity ( $$|y|<0.9$$ | y | < 0.9 ) in the transverse-momentum interval $$0<p_{\mathrm{T}} <40$$ 0 < p T < 40 GeV/ $$c$$ c , using a minimum-bias data sample corresponding to an integrated luminosity $$L_{\text {int}} = 32.2~\text {nb}^{-1}$$ L int = 32.2 nb - 1 and an Electromagnetic Calorimeter triggered data sample with $$L_{\text {int}} = 8.3~\mathrm {pb}^{-1}$$ L int = 8.3 pb - 1 . The $$p_{\mathrm{T}}$$ p T -integrated $$\text {J}/\psi $$ J / ψ production cross section at midrapidity, computed using the minimum-bias data sample, is $$\text {d}\sigma /\text {d}y|_{y=0} = 8.97\pm 0.24~(\text {stat})\pm 0.48~(\text {syst})\pm 0.15~(\text {lumi})~\mu \text {b}$$ d σ / d y | y = 0 = 8.97 ± 0.24 ( stat ) ± 0.48 ( syst ) ± 0.15 ( lumi ) μ b . An approximate logarithmic dependence with the collision energy is suggested by these results and available world data, in agreement with model predictions. The integrated and $$p_{\mathrm{T}}$$ p T -differential measurements are compared with measurements in pp collisions at lower energies and with several recent phenomenological calculations based on the non-relativistic QCD and Color Evaporation models.
Abstract Two-particle Azimuthal correlations are measured with the ALICE apparatus in pp collisions at $$\sqrt{s} = 13$$ s = 13 TeV to explore strangeness- and multiplicity-related effects in the ...fragmentation of jets and the transition regime between bulk and hard production, probed with the condition that a strange meson ( $$\mathrm {K_S}^{0}$$ K S 0 ) or baryon ( $$\Lambda $$ Λ ) with transverse momentum $$p_{\mathrm T} >3$$ p T > 3 GeV/ $$c$$ c is produced. Azimuthal correlations between kaons or $$\Lambda $$ Λ hyperons with other hadrons are presented at midrapidity for a broad range of the trigger ( $$3< p_\mathrm {T}^\mathrm {trigg} < 20$$ 3 < p T trigg < 20 GeV/ $$c$$ c ) and associated particle $$p_{\mathrm T}$$ p T (1 GeV/ $$c$$ c $$< p_\mathrm {T}^\mathrm {assoc} < p_\mathrm {T}^\mathrm {trigg} $$ < p T assoc < p T trigg ), for minimum-bias events and as a function of the event multiplicity. The near- and away-side peak yields are compared for the case of either $$\mathrm {K_S}^{0}$$ K S 0 or $$\Lambda $$ Λ ( $${\overline{\Lambda }}$$ Λ ¯ ) being the trigger particle with that of inclusive hadrons (a sample dominated by pions). In addition, the measurements are compared with predictions from PYTHIA 8 and EPOS LHC event generators.
Coherent $$\ rm {NN}}}~=~5.02$$ s NN = 5.02 TeV ALICE Collaboration; S. Acharya; G. Aglieri Rinella ...
The European physical journal. C, Particles and fields,
08/2021, Letnik:
81, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Abstract The coherent photoproduction of $$\mathrm{J}/\psi $$ J / ψ and $${\uppsi '}$$ ψ ′ mesons was measured in ultra-peripheral Pb–Pb collisions at a center-of-mass energy $$\sqrt{s_{\mathrm ...{NN}}}~=~5.02$$ s NN = 5.02 TeV with the ALICE detector. Charmonia are detected in the central rapidity region for events where the hadronic interactions are strongly suppressed. The $$\mathrm{J}/\psi $$ J / ψ is reconstructed using the dilepton ( $$l^{+} l^{-}$$ l + l - ) and proton–antiproton decay channels, while for the $${\uppsi '}$$ ψ ′ the dilepton and the $$l^{+} l^{-} \pi ^{+} \pi ^{-}$$ l + l - π + π - decay channels are studied. The analysis is based on an event sample corresponding to an integrated luminosity of about 233 $$\mu {\mathrm{b}}^{-1}$$ μ b - 1 . The results are compared with theoretical models for coherent $$\mathrm{J}/\psi $$ J / ψ and $${\uppsi '}$$ ψ ′ photoproduction. The coherent cross section is found to be in a good agreement with models incorporating moderate nuclear gluon shadowing of about 0.64 at a Bjorken-x of around $$6\times 10^{-4}$$ 6 × 10 - 4 , such as the EPS09 parametrization, however none of the models is able to fully describe the rapidity dependence of the coherent $$\mathrm{J}/\psi $$ J / ψ cross section including ALICE measurements at forward rapidity. The ratio of $${\uppsi '}$$ ψ ′ to $$\mathrm{J}/\psi $$ J / ψ coherent photoproduction cross sections was also measured and found to be consistent with the one for photoproduction off protons.
Abstract The production of $$\phi $$ ϕ mesons has been studied in pp collisions at LHC energies with the ALICE detector via the dimuon decay channel in the rapidity region $$2.5< y < 4$$ 2.5 < y < 4 .... Measurements of the differential cross section $$\mathrm{d}^2\sigma /\mathrm{d}y \mathrm{d}p_{\mathrm {T}}$$ d 2 σ / d y d p T are presented as a function of the transverse momentum ( $$p_{\mathrm {T}}$$ p T ) at the center-of-mass energies $$\sqrt{s}=5.02$$ s = 5.02 , 8 and 13 TeV and compared with the ALICE results at midrapidity. The differential cross sections at $$\sqrt{s}=5.02$$ s = 5.02 and 13 TeV are also studied in several rapidity intervals as a function of $$p_{\mathrm {T}}$$ p T , and as a function of rapidity in three $$p_{\mathrm {T}}$$ p T intervals. A hardening of the $$p_{\mathrm {T}}$$ p T -differential cross section with the collision energy is observed, while, for a given energy, $$p_{\mathrm {T}}$$ p T spectra soften with increasing rapidity and, conversely, rapidity distributions get slightly narrower at increasing $$p_{\mathrm {T}}$$ p T . The new results, complementing the published measurements at $$\sqrt{s}=2.76$$ s = 2.76 and 7 TeV, allow one to establish the energy dependence of $$\phi $$ ϕ meson production and to compare the measured cross sections with phenomenological models. None of the considered models manages to describe the evolution of the cross section with $$p_{\mathrm {T}}$$ p T and rapidity at all the energies.
Abstract The first measurement of the production of pions, kaons, (anti-)protons and $$\phi $$ ϕ mesons at midrapidity in Xe–Xe collisions at $$\sqrt{s_{\mathrm{NN}}} = 5.44~\text {TeV}$$ s NN = 5.44 ...TeV is presented. Transverse momentum ( $$p_{\mathrm{T}}$$ p T ) spectra and $$p_{\mathrm{T}}$$ p T -integrated yields are extracted in several centrality intervals bridging from p–Pb to mid-central Pb–Pb collisions in terms of final-state multiplicity. The study of Xe–Xe and Pb–Pb collisions allows systems at similar charged-particle multiplicities but with different initial geometrical eccentricities to be investigated. A detailed comparison of the spectral shapes in the two systems reveals an opposite behaviour for radial and elliptic flow. In particular, this study shows that the radial flow does not depend on the colliding system when compared at similar charged-particle multiplicity. In terms of hadron chemistry, the previously observed smooth evolution of particle ratios with multiplicity from small to large collision systems is also found to hold in Xe–Xe. In addition, our results confirm that two remarkable features of particle production at LHC energies are also valid in the collision of medium-sized nuclei: the lower proton-to-pion ratio with respect to the thermal model expectations and the increase of the $$\phi $$ ϕ -to-pion ratio with increasing final-state multiplicity.