Cdx1 and c-Myc Foster the Initiation of Transdifferentiation of the Normal Esophageal Squamous Epithelium toward Barrett's Esophagus

Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD). Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined.To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett's esophagus, we performed a microarray analysis of normal esophageal, Barrett's esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett's esophagus.These data demonstrate the ability of Cdx1 and c-myc to initiate the earliest stages of transdifferentiation of esophageal keratinocytes toward a cell fate characteristic of Barrett's esophagus

VILIP-1 Expression In Vivo Results in Decreased Mouse Skin Keratinocyte Proliferation and Tumor Development

VILIP-1, a member of the neuronal Ca2+ sensor protein family, is able to act as a tumor suppressor in carcinoma cells by inhibiting cell proliferation and migration. In order to study the role of VILIP-1 in skin carcinogenesis we generated transgenic mice overexpressing VILIP-1 in epidermis under the control of the bovine keratin K5 promoter (K5-VILIP-1). We studied the susceptibility of FVB wild type and VILIP-1 transgenic mice to chemically mediated carcinogenesis. After 30 weeks of treatment with a two-stage carcinogenesis protocol, all animals showed numerous skin tumors. Nevertheless, K5-VILIP-1 mice showed decreased squamous cell carcinoma (SCC) multiplicity of ∼49% (p<0.02) with respect to the corresponding SCC multiplicity observed in wild type (WT) mice. In addition, the relative percentage of low-grade cutaneous SCCs grade I (defined by the differentiation pattern according to the Broders grading scale) increased approximately 50% in the K5-VILIP1 mice when compared with SCCs in WT mice. Similar tendency was observed using a complete carcinogenesis protocol for skin carcinogenesis using benzo(a)pyrene (B(a)P). Further studies of tumors and primary epidermal keratinocyte cultures showed that matrix metalloproteinase 9 (MMP-9) levels and cell proliferation decreased in K5-VILIP-1 mice when compared with their wild counterparts. In addition tissue inhibitor of metalloproteinase 1 (TIMP-1) expression was higher in K5-VILIP-1 keratinocytes. These results show that VILIP-1 overexpression decreases the susceptibility to skin carcinogenesis in experimental mouse cancer models, thus supporting its role as a tumor suppressor gene

Observation of charge-dependent azimuthal correlations and possible local strong parity violation in heavy ion collisions

Parity-odd domains, corresponding to non-trivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in non-central collisions. To study this effect, we investigate a three particle mixed harmonics azimuthal correlator which is a \P-even observable, but directly sensitive to the charge separation effect. We report measurements of this observable using the STAR detector in Au+Au and Cu+Cu collisions at $\sqrt{s_{NN}}$=200 and 62~GeV. The results are presented as a function of collision centrality, particle separation in rapidity, and particle transverse momentum. A signal consistent with several of the theoretical expectations is detected in all four data sets. We compare our results to the predictions of existing event generators, and discuss in detail possible contributions from other effects that are not related to parity violation.Comment: 17 pages, 14 figures, as accepted for publication in Physical Review C

Longitudinal Spin Transfer to Λ\Lambda and Λˉ\bar{\Lambda} Hyperons in Polarized Proton-Proton Collisions at s\sqrt{s} = 200 GeV

The longitudinal spin transfer, $D_{LL}$, from high energy polarized protons to $\Lambda$ and $\bar{\Lambda}$ hyperons has been measured for the first time in proton-proton collisions at $\sqrt{s} = 200 \mathrm{GeV}$ with the STAR detector at RHIC. The measurements cover pseudorapidity, $\eta$, in the range $|\eta| < 1.2$ and transverse momenta, $p_\mathrm{T}$, up to $4 \mathrm{GeV}/c$. The longitudinal spin transfer is found to be $D_{LL}= -0.03\pm 0.13(\mathrm{stat}) \pm 0.04(\mathrm{syst})$ for inclusive $\Lambda$ and $D_{LL} = -0.12 \pm 0.08(\mathrm{stat}) \pm 0.03(\mathrm{syst})$ for inclusive $\bar{\Lambda}$ hyperons with $= 0.5$ and $= 3.7 \mathrm{GeV}/c$. The dependence on $\eta$ and $p_\mathrm{T}$ is presented.Comment: 5 pages, 4 figure

Studies of di-jet survival and surface emission bias in Au+Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at RHIC. Pairs of back-to-back high transverse momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two- and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudo-rapidity or relative azimuthal angle from d+Au to central Au+Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.Comment: By the STAR Collaboration. 6 pages, 2 figure

Elliptic flow from two- and four-particle correlations in Au + Au collisions at sqrt{s_{NN}} = 130 GeV

Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (non-flow correlations). Using data for Au + Au collisions at sqrt{s_{NN}} = 130 GeV from the STAR TPC, it is found that four-particle correlation analyses can reliably separate flow and non-flow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of two. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.Comment: minor text change

Rapidity and centrality dependence of proton and antiproton production from 197Au + 197Au collisions at √SNN = 130 GeV

We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account

System size and energy dependence of near-side di-hadron correlations

Two-particle azimuthal ($\Delta\phi$) and pseudorapidity ($\Delta\eta$) correlations using a trigger particle with large transverse momentum ($p_T$) in $d$+Au, Cu+Cu and Au+Au collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV and 200~GeV from the STAR experiment at RHIC are presented. The \ns correlation is separated into a jet-like component, narrow in both $\Delta\phi$ and $\Delta\eta$, and the ridge, narrow in $\Delta\phi$ but broad in $\Delta\eta$. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated $p_T$. The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at $\sqrt{s_{{NN}}}$ = 200 GeV, is also found in Cu+Cu collisions and in collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV, but is found to be substantially smaller at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV than at $\sqrt{s_{{NN}}}$ = 200 GeV for the same average number of participants ($\langle N_{\mathrm{part}}\rangle$). Measurements of the ridge are compared to models.Comment: 17 pages, 14 figures, submitted to Phys. Rev.