Cellular memory of hypoxia elicits neuroblastoma metastasis and enables invasion by non-aggressive neighbouring cells

Therapies targeting cancer metastasis are challenging owing to the complexity of the metastatic process and the high number of effectors involved. Although tumour hypoxia has previously been associated with increased aggressiveness as well as resistance to radio- and chemotherapy, the understanding of a direct link between the level and duration of hypoxia and the individual steps involved in metastasis is still missing. Using live imaging in a chick embryo model, we have demonstrated that the exposure of neuroblastoma cells to 1% oxygen for 3 days was capable of (1) enabling cell migration towards blood vessels, (2) slowing down their velocity within blood vessels to facilitate extravasation and (3) promoting cell proliferation in primary and secondary sites. We have shown that cells do not have to be hypoxic anymore to exhibit these acquired capabilities as a long-term memory of prior hypoxic exposure is kept. Furthermore, non-hypoxic cells can be influenced by neighbouring hypoxic preconditioned cells and be entrained in the metastatic progression. The acquired aggressive phenotype relies on hypoxia-inducible factor (HIF)-dependent transcription of a number of genes involved in metastasis and can be impaired by HIF inhibition. Altogether, our results demonstrate the need to consider both temporal and spatial tumour heterogeneity because cells can 'remember' an earlier environment and share their acquired phenotype with their close neighbours. As a consequence, it is necessary to monitor the correct hypoxic markers to be able to predict the consequences of the cells' history on their behaviour and their potential response to therapies

On the precision of chiral-dispersive calculations of ππ\pi\pi scattering

We calculate the combination $2a_0^{(0)}-5a_0^{(2)}$ (the Olsson sum rule) and the scattering lengths and effective ranges $a_1$, $a_2^{(I)}$ and $b_1$, $b_2^{(I)}$ dispersively (with the Froissart--Gribov representation) using, at low energy, the phase shifts for $\pi\pi$ scattering obtained by Colangelo, Gasser and Leutwyler (CGL) from the Roy equations and chiral perturbation theory, plus experiment and Regge behaviour at high energy, or directly, using the CGL parameters for $a$s and $b$s. We find mismatch, both among the CGL phases themselves and with the results obtained from the pion form factor. This reaches the level of several (2 to 5) standard deviations, and is essentially independent of the details of the intermediate energy region ($0.82\leq E\leq 1.42$ GeV) and, in some cases, of the high energy behaviour assumed. We discuss possible reasons for this mismatch, in particular in connection with an alternate set of phase shifts.Comment: Version to appear in Phys. Rev. D. Graphs and sum rule added. Plain TeX fil

S-wave Meson-Meson Scattering from Unitarized U(3) Chiral Lagrangians

An investigation of the s-wave channels in meson-meson scattering is performed within a U(3) chiral unitary approach. Our calculations are based on a chiral effective Lagrangian which includes the eta' as an explicit degree of freedom and incorporates important features of the underlying QCD Lagrangian such as the axial U(1) anomaly. We employ a coupled channel Bethe-Salpeter equation to generate poles from composed states of two pseudoscalar mesons. Our results are compared with experimental phase shifts up to 1.5 GeV and effects of the eta' within this scheme are discussed.Comment: 18 pages, 6 figure

Another look at ππ\pi\pi scattering in the scalar channel

We set up a general framework to describe $\pi\pi$ scattering below 1 GeV based on chiral low-energy expansion with possible spin-0 and 1 resonances. Partial wave amplitudes are obtained with the $N/D$ method, which satisfy unitarity, analyticity and approximate crossing symmetry. Comparison with the phase shift data in the J=0 channel favors a scalar resonance near the $\rho$ mass.Comment: 17 pages, 5 figures, REVTe

The Inverse Amplitude Method in ππ\pi\pi Scattering in Chiral Perturbation Theory to Two Loops

The inverse amplitude method is used to unitarize the two loop $\pi\pi$ scattering amplitudes of SU(2) Chiral Perturbation Theory in the $I=0,J=0$, $I=1,J=1$ and $I=2,J=0$ channels. An error analysis in terms of the low energy one-loop parameters $\bar l_{1,2,3,4,}$ and existing experimental data is undertaken. A comparison to standard resonance saturation values for the two loop coefficients $\bar b_{1,2,3,4,5,6}$ is also carried out. Crossing violations are quantified and the convergence of the expansion is discussed.Comment: (Latex, epsfig) 30 pages, 13 figures, 8 table

Meson-Meson Scattering in the Quark Model: Spin Dependence and Exotic Channels

We apply a quark interchange model to spin-dependent and exotic meson-meson scattering. The model includes the complete set of standard quark model forces, including OGE spin-orbit and tensor and scalar confinement spin-orbit. Scattering amplitudes derived assuming SHO and Coulomb plus linear plus hyperfine meson wavefunctions are compared. In I=2 pi pi we find approximate agreement with the S-wave phase shift from threshold to 1.5 GeV, where we predict an extremum that is supported by the data. Near threshold we find rapid energy dependence that may reconcile theoretical estimates of small scattering lengths with experimental indications of larger ones based on extrapolation of measurements at moderate kpi^2. In PsV scattering we find that the quark-quark L*S and T forces map into L*S and T meson-meson interactions, and the P-wave L*S force is large. Finally we consider scattering in J^PC-exotic channels, and note that some of the Deck effect mechanisms suggested as possible nonresonant origins of the pi_1(1400) signal are not viable in this model.Comment: 51 pages, 10 figures, uses epsf.sty epsfig.st

A global fit of ππ\pi\pi and πK\pi K elastic scattering in ChPT with dispersion relations

We apply the one-loop results of the $SU(3)_L\times SU(3)_R$ ChPT suplemented with the inverse amplitude method to fit the available experimental data on $\pi\pi$ and $\pi K$ scattering. With esentially only three parameters we describe accurately data corresponding to six different channels, namely $(I,J)=(0,0), (2,0), (1,1), (1/2,0), (3/2,0)$ and $(1/2,1)$. In addition we reproduce the first resonances of the $(1,1)$ and $(1/2,1)$ channel with the right mass corresponding to the $\rho$ and the $K^*(892)$ particles.Comment: 19 pages, 5 figures available on request, FT/UCM/10/9

Pion Mass Effects in the Large NN Limit of \chiPT

We compute the large $N$ effective action of the $O(N+1)/O(N)$ non-linear sigma model including the effect of the pion mass to order $m^2_{\pi}/f_{\pi}^2$. This action is more complex than the one corresponding to the chiral limit not only because of the pion propagators but also because chiral symmetry produce new interactions proportional to $m^2_{\pi}/f_{\pi}^2$. We renormalize the action by including the appropriate counter terms and find the renormalization group equations for the corresponding couplings. Then we estudy the unitarity propierties of the scattering amplitudes. Finally our results are applied to the particular case of the linear sigma model and also are used to fit the pion scattering phase shifts.Comment: FT/UCM/18/9

Measurement of triple gauge boson couplings from WW production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb^-1. After combining with our previous measurements at centre-of-mass energies of 161-183 GeV we obtain k_g=0.97 +0.20 -0.16, g_1^z=0.991 +0.060 -0.057 and lambda_g=-0.110 +0.058 -0.055, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their SM values. These results are consistent with the Standard Model expectations.Comment: 28 pages, 8 figures, submitted to Eur. Phys. J.

Measurement of the Hadronic Cross-Section for the Scattering of Two Virtual Photons at LEP

The interaction of virtual photons is investigated using the reaction e+e- -> e+e- hadrons based on data taken by the OPAL experiment at e+e- centre-of-mass energies sqrt(s_ee)=189-209 GeV, for W>5 GeV and at an average Q^2 of 17.9 GeV^2. The measured cross-sections are compared to predictions of the Quark Parton Model (QPM), to the Leading Order QCD Monte Carlo model PHOJET to the NLO prediction for the reaction e+e- -> e+e-qqbar, and to BFKL calculations. PHOJET, NLO e+e- -> e+e-qqbar, and QPM describe the data reasonably well, whereas the cross-section predicted by a Leading Order BFKL calculation is too large.Comment: 30 pages, 10 figures, Submitted to Eur.Phys.J.