Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation

Perfusion and oxygenation of experimental tumours were studied during angiotensin II (AT II) administration whereby the rate of the continuous AT II infusion was chosen to increase the mean arterial blood pressure (MABP) by 50–70 mmHg. In subcutaneous DS- sarcomas the red blood cell (RBC) flux was assessed using the laser Doppler technique and the mean tumour oxygen partial pressure (p O 2) was measured polarographically using O 2-sensitive catheter and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact of AT II on tumour p O 2 was also mainly tumour volume-related. In small tumours oxygenation decreased with increasing MABP during AT II infusion, whereas in large tumours a positive relationship between blood pressure and O 2 status was found. This disparate behaviour might be the result of the co-existence of two functionally distinct populations of tumour vessels. In small tumours, perfusion decreases presumably due to vasoconstriction of pre-existing host vessels feeding the tumour. In larger malignancies, newly formed tumour vessels predominate and seem not to have this vasoresponsive capability (lack of smooth muscle cells and/or AT receptors), resulting in an improvement of perfusion which is not tumour-related per se, but is due to the increased perfusion pressure. © 2000 Cancer Research Campaig

Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia

This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O2) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO2) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO2 was significantly improved (median pO2=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion

Progress in the determination of the J/ψ−πJ/\psi-\pi cross section

Improving previous calculations, we compute the $J/\psi \pi\to {charmed mesons}$ cross section using QCD sum rules. Our sum rules for the $J/\psi \pi\to \bar{D} D^*$, $D \bar{D}^*$, ${\bar D}^* D^*$ and ${\bar D} D$ hadronic matrix elements are constructed by using vaccum-pion correlation functions, and we work up to twist-4 in the soft-pion limit. Our results suggest that, using meson exchange models is perfectly acceptable, provided that they include form factors and that they respect chiral symmetry. After doing a thermal average we get $\sim 0.3$ mb at T=150\MeV.Comment: 22 pages, RevTeX4 including 7 figures in ps file

Hard probes in heavy ion collisions at the LHC: heavy flavour physics

We present the results from the heavy quarks and quarkonia working group. This report gives benchmark heavy quark and quarkonium cross sections for $pp$ and $pA$ collisions at the LHC against which the $AA$ rates can be compared in the study of the quark-gluon plasma. We also provide an assessment of the theoretical uncertainties in these benchmarks. We then discuss some of the cold matter effects on quarkonia production, including nuclear absorption, scattering by produced hadrons, and energy loss in the medium. Hot matter effects that could reduce the observed quarkonium rates such as color screening and thermal activation are then discussed. Possible quarkonium enhancement through coalescence of uncorrelated heavy quarks and antiquarks is also described. Finally, we discuss the capabilities of the LHC detectors to measure heavy quarks and quarkonia as well as the Monte Carlo generators used in the data analysis.Comment: 126 pages Latex; 96 figures included. Subgroup report, to appear in the CERN Yellow Book of the workshop: Hard Probes in Heavy Ion Collisions at the LHC. See also http://a.home.cern.ch/f/frixione/www/hvq.html for a version with better quality for a few plot

Charmonium from Statistical Hadronization of Heavy Quarks -- a Probe for Deconfinement in the Quark-Gluon Plasma

We review the statistical hadronization picture for charmonium production in ultra-relativistic nuclear collisions. Our starting point is a brief reminder of the status of the thermal model description of hadron production at high energy. Within this framework an excellent account is achieved of all data for hadrons built of (u,d,s) valence quarks using temperature, baryo-chemical potential and volume as thermal parameters. The large charm quark mass brings in a new (non-thermal) scale which is explicitely taken into account by fixing the total number of charm quarks produced in the collision. Emphasis is placed on the description of the physical basis for the resulting statistical hadronization model. We discuss the evidence for statistical hadronization of charmonia by analysis of recent data from the SPS and RHIC accelerators. Furthermore we discuss an extension of this model towards lower beam energies and develop arguments about the prospects to observe medium modifications of open and hidden charm hadrons. With the imminent start of the LHC accelerator at CERN, exciting prospects for charmonium production studies at the very high energy frontier come into reach. We present arguments that, at such energies, charmonium production becomes a fingerprint of deconfinement: even if no charmonia survive in the quark-gluon plasma, statistical hadronization at the QCD phase boundary of the many tens of charm quarks expected in a single central Pb-Pb collision could lead to an enhanced, rather than suppressed production probability when compared to results for nucleon-nucleon reactions scaled by the number of hard collisions in the Pb-Pb system.Comment: review article, 27 pages, Landoldt review volume "Relativistic Heavy Ion Physics", Reinhard Stock, edito

Evidence for non-hadronic interactions of charm degrees of freedom in heavy-ion collisions at relativistic energies

Within the Hadron-String Dynamics (HSD) transport approach we study the suppression pattern of charmonia at RHIC with respect to centrality and rapidity employing various model concepts such as variants of the 'comover absorption' model or the 'charmonium melting' scenario. We find that especially the ratio of the forward to mid-rapidity nuclear modification factors of J/Psi (R_AA (forward) / R_AA (mid)) cannot be explained by the interactions with 'formed' comoving mesons or by the 'color screening mechanism' alone. Only when incorporating interactions of the c or c-bar quark with a pre-hadronic medium satisfactory results are obtained. A detailed comparison to the PHENIX data demonstrates that non-hadronic interactions are mandatory to describe the narrowing of the J/Psi rapidity distribution from p+p to central Au+Au collisions. The Psi' to J/Psi ratio is found to be crucial in disentangling the different charmonium absorption scenarios especially in the RHIC energy range. Furthermore, a comparison of the transport calculations to the statistical model of Gorenstein and Gazdzicki as well as the statistical hadronization model of Andronic et al. shows differences in the energy dependence as well as centrality dependence of the J/Psi to pion ratio which may be exploited experimentally to disentangle different concepts. We find additionally that the collective flow of charm in the HSD transport appears compatible with the data at SPS energies but substantially underestimates the data at top RHIC energies such that the large elliptic flow v_2 of charm seen experimentally has to be attributed to early interactions of non-hadronic degrees of freedom.Comment: 35 pages, 16 Figs, v2: additional figure and corresponding changes to the tex