Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth

The vascular endothelial growth factor (VEGF) receptor is a major target for anti-angiogenesis-based cancer treatment. Here we report the treatment effect of ionizing radiation in combination with the novel orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 on endothelial cell proliferation in vitro and with tumour xenografts in vivo. Combined treatment of human umbilical vein endothelial cells with increasing doses of PTK787/ZK222584 and ionizing radiation abrogated VEGF-dependent proliferation in a dose-dependent way, but inhibition of endothelial cell proliferation was not due to apoptosis induction. In vivo, a combined treatment regimen of PTK787/ZK222584 (4 × 100 mg/kg) during 4 consecutive days in combination with ionizing radiation (4 × 3 Gy) exerted a substantial tumour growth delay for radiation-resistant p53-disfunctional tumour xenografts derived from SW480 colon adenocarcinoma cells while each treatment modality alone had only a minimal effect on tumour size and neovascularization. SW480 tumours from animals that received a combined treatment regimen, displayed not only an extended tumour growth delay but also a significant decrease in the number of microvessels in the tumour xenograft. These results support the model of a cooperative antitumoural effect of angiogenesis inhibitor and irradiation and show that the orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 is suitable for combination therapy with irradiation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Gauge Singlet Scalars as Cold Dark Matter

In light of recent interest in minimal extensions of the Standard Model and gauge singlet scalar cold dark matter, we provide an arXiv preprint of the paper, published as Phys.Rev. D50 (1994) 3637, which presented the first detailed analysis of gauge singlet scalar cold dark matter.Comment: 37 pages, 11 figures, LaTe

Breeding Experience and the Heritability of Female Mate Choice in Collared Flycatchers

Heritability in mate preferences is assumed by models of sexual selection, and preference evolution may contribute to adaptation to changing environments. However, mate preference is difficult to measure in natural populations as detailed data on mate availability and mate sampling are usually missing. Often the only available information is the ornamentation of the actual mate. The single long-term quantitative genetic study of a wild population found low heritability in female mate ornamentation in Swedish collared flycatchers. One potentially important cause of low heritability in mate ornamentation at the population level is reduced mate preference expression among inexperienced individuals.Applying animal model analyses to 21 years of data from a Hungarian collared flycatcher population, we found that additive genetic variance was 50 percent and significant for ornament expression in males, but less than 5 percent and non-significant for mate ornamentation treated as a female trait. Female breeding experience predicted breeding date and clutch size, but mate ornamentation and its variance components were unrelated to experience. Although we detected significant area and year effects on mate ornamentation, more than 85 percent of variance in this trait remained unexplained. Moreover, the effects of area and year on mate ornamentation were also highly positively correlated between inexperienced and experienced females, thereby acting to remove difference between the two groups.The low heritability of mate ornamentation was apparently not explained by the presence of inexperienced individuals. Our results further indicate that the expression of mate ornamentation is dominated by temporal and spatial constraints and unmeasured background factors. Future studies should reduce unexplained variance or use alternative measures of mate preference. The heritability of mate preference in the wild remains a principal but unresolved question in evolutionary ecology

Multiplicity distributions at high energies as a sum of Poissonian-like distributions

It is shown that at collider energies experimental multiplicity distributions are well parameterized by a sum of Gupta-Sarma distributions. This extends earlier description of the lower energy data by the two parameter sum of Poissonians. Implications of the proposed parametrization for LHC are discussed.Comment: 16 pages, Latex, 4 EPS figure

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

High p_T Spectra of Identified Particles Produced in Pb+Pb Collisions at 158GeV/nucleon Beam Energy

Transverse momentum spectra of pi^{+/-}, p, pbar, K^{+/-}, K^0_s and Lambda at midrapidity were measured at high p_T in Pb+Pb collisions at 158GeV/nucleon beam energy by the NA49 experiment. Particle yield ratios (p/pi, K/pi and Lambda/K^0_s) show an enhancement of the baryon/meson ratio for p_T>2GeV/c. The nuclear modification factor R_{CP} is extracted and compared to RHIC measurements and pQCD calculations.Comment: Quark Matter 2005 parallel section proceeding

Upper Limit of D0 Production in Central Pb-Pb Collisions at 158A GeV

Results are presented from a search for the decays D0 -> Kmin piplus and D0bar -> Kplus pimin in a sample of 3.8x10^6 central Pb-Pb events collected with a beam energy of 158A GeV by NA49 at the CERN SPS. No signal is observed. An upper limit on D0 production is derived and compared to predictions from several models.Comment: REVTEX 5 pages, 4 figure

NA49 results on hadron production: indications of the onset of deconfinement ?

The NA49 experiment at the CERN SPS measured the energy and system size dependence of particle production in A+A collisions. A change of the energy dependence of several hadron production properties at low SPS energies is observed which suggests a scenario requiring the onset of deconfinement.Comment: XXXV International Symposium on Multiparticle Dynamics 200

Energy dependence of particle ratio fluctuations in central Pb+Pb collisions from sNN=\sqrt{s_{_{NN}}} =~6.3 to 17.3 GeV

We present measurements of the energy dependence of event-by-event fluctuations in the K/pi and (p + \bar{p})/pi multiplicity ratios in heavy ion collisions at the CERN SPS. The particle ratio fluctuations were obtained for central Pb+Pb collisions at five collision energies, \sqrt{s_{_{NN}}}, between 6.3 and 17.3 GeV. After accounting for the effects of finite-number statistics and detector resolution, we extract the strength of non-statistical fluctuations at each energy. For the K/pi ratio, larger fluctuations than expected for independent particle production are found at all collision energies. The fluctuations in the (p + \bar{p})/pi ratio are smaller than expectations from independent particle production, indicating correlated pion and proton production from resonance decays. For both ratios, the deviation from purely statistical fluctuations shows an increase towards lower collision energies. The results are compared to transport model calculations, which fail to describe the energy dependence of the K/pi ratio fluctuations.Comment: 11 pages, 10 figures, update to published versio