5,555 research outputs found
Establishment of Highly Tumorigenic Human Colorectal Cancer Cell Line (CR4) with Properties of Putative Cancer Stem Cells
BACKGROUND: Colorectal cancer (CRC) has the third highest mortality rates among the US population. According to the most recent concept of carcinogenesis, human tumors are organized hierarchically, and the top of it is occupied by malignant stem cells (cancer stem cells, CSCs, or cancer-initiating cells, CICs), which possess unlimited self-renewal and tumor-initiating capacities and high resistance to conventional therapies. To reflect the complexity and diversity of human tumors and to provide clinically and physiologically relevant cancer models, large banks of characterized patient-derived low-passage cell lines, and especially CIC-enriched cell lines, are urgently needed. PRINCIPAL FINDINGS: Here we report the establishment of a novel CIC-enriched, highly tumorigenic and clonogenic colon cancer cell line, CR4, derived from liver metastasis. This stable cell line was established by combining 3D culturing and 2D culturing in stem cell media, subcloning of cells with particular morphology, co-culture with carcinoma associated fibroblasts (CAFs) and serial transplantation to NOD/SCID mice. Using RNA-Seq complete transcriptome profiling of the tumorigenic fraction of the CR4 cells in comparison to the bulk tumor cells, we have identified about 360 differentially expressed transcripts, many of which represent stemness, pluripotency and resistance to treatment. Majority of the established CR4 cells express common markers of stemness, including CD133, CD44, CD166, EpCAM, CD24 and Lgr5. Using immunocytochemical, FACS and western blot analyses, we have shown that a significant ratio of the CR4 cells express key markers of pluripotency markers, including Sox-2, Oct3/4 and c-Myc. Constitutive overactivation of ABC transporters and NF-kB and absence of tumor suppressors p53 and p21 may partially explain exceptional drug resistance of the CR4 cells. CONCLUSIONS: The highly tumorigenic and clonogenic CIC-enriched CR4 cell line may provide an important new tool to support the discovery of novel diagnostic and/or prognostic biomarkers as well as the development of more effective therapeutic strategies
Strangeness Enhancement in and Interactions at SPS Energies
The systematics of strangeness enhancement is calculated using the HIJING and
VENUS models and compared to recent data on , and
collisions at CERN/SPS energies (). The HIJING model is used to
perform a {\em linear} extrapolation from to . VENUS is used to
estimate the effects of final state cascading and possible non-conventional
production mechanisms. This comparison shows that the large enhancement of
strangeness observed in collisions, interpreted previously as possible
evidence for quark-gluon plasma formation, has its origins in non-equilibrium
dynamics of few nucleon systems. % Strangeness enhancement %is therefore traced
back to the change in the production dynamics %from to minimum bias
and central collisions. A factor of two enhancement of at
mid-rapidity is indicated by recent data, where on the average {\em one}
projectile nucleon interacts with only {\em two} target nucleons. There appears
to be another factor of two enhancement in the light ion reaction relative
to , when on the average only two projectile nucleons interact with two
target ones.Comment: 29 pages, 8 figures in uuencoded postscript fil
Semi-Inclusive Lambda and Kshort Production in p-Au Collisions at 17.5 GeV/c
The first detailed measurements of the centrality dependence of strangeness
production in p-A collisions are presented. Lambda and Kshort dn/dy
distributions from 17.5 GeV/c p-Au collisions are shown as a function of "grey"
track multiplicity and the estimated number of collisions, nu, made by the
proton. The nu dependence of the Lambda yield deviates from a scaling of p-p
data by the number of participants, increasing faster than this scaling for
nu<=5 and saturating for larger nu. A slower growth in Kshort multiplicity with
nu is observed, consistent with a weaker nu dependence of K-Kbar production
than Y-K production.Comment: 5 pages, 3 figures, formatted with RevTex, current version has
enlarged figure catpion
Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon
The transverse momentum and rapidity distributions of net protons and
negatively charged hadrons have been measured for minimum bias proton-nucleus
and deuteron-gold interactions, as well as central oxygen-gold and
sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net
protons at midrapidity in central nucleus-nucleus collisions increases both
with target mass for sulphur projectiles and with the projectile mass for a
gold target. The shape of the rapidity distributions of net protons forward of
midrapidity for d+Au and central S+Au collisions is similar. The average
rapidity loss is larger than 2 units of rapidity for reactions with the gold
target. The transverse momentum spectra of net protons for all reactions can be
described by a thermal distribution with `temperatures' between 145 +- 11 MeV
(p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The
multiplicity of negatively charged hadrons increases with the mass of the
colliding system. The shape of the transverse momentum spectra of negatively
charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and
central nucleus-nucleus collisions. The mean transverse momentum is almost
constant in the vicinity of midrapidity and shows little variation with the
target and projectile masses. The average number of produced negatively charged
hadrons per participant baryon increases slightly from p+p, p+A to central
S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.
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
Report from NA49
The most recent data of NA49 on hadron production in nuclear collisions at
CERN SPS energies are presented. Anomalies in the energy dependence of pion and
kaon production in central Pb+Pb collisions are observed. They suggest that the
onset of deconfinement is located at about 30 AGeV. Large multiplicity and
transverse momentum fluctuations are measured for collisions of intermediate
mass systems at 158 AGeV. The need for a new experimental programme at the CERN
SPS is underlined.Comment: invited talk presented at Quark Matter 2004, 10 page
System-size dependence of strangeness production in nucleus-nucleus collisions at sqrt{s_{NN}}=17.3 GeV
Emission of pi, K, phi and Lambda was measured in near-central C+C and Si+Si
collisions at 158 AGeV beam energy. Together with earlier data for p+p, S+S and
Pb+Pb, the system-size dependence of relative strangeness production in
nucleus-nucleus collisions is obtained. Its fast rise and the saturation
observed at about 60 participating nucleons can be understood as onset of the
formation of coherent partonic subsystems of increasing size.Comment: Phys.Rev.Lett in print; version2: changes made according to the
request of the referee
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
Measurement of event-by-event transverse momentum and multiplicity fluctuations using strongly intensive measures and in nucleus-nucleus collisions at the CERN Super Proton Synchrotron
Results from the NA49 experiment at the CERN SPS are presented on
event-by-event transverse momentum and multiplicity fluctuations of charged
particles, produced at forward rapidities in central Pb+Pb interactions at beam
momenta 20, 30, 40, 80, and 158 GeV/c, as well as in systems of
different size (, C+C, Si+Si, and Pb+Pb) at 158 GeV/c. This publication
extends the previous NA49 measurements of the strongly intensive measure
by a study of the recently proposed strongly intensive measures of
fluctuations and . In the explored kinematic
region transverse momentum and multiplicity fluctuations show no significant
energy dependence in the SPS energy range. However, a remarkable system size
dependence is observed for both and , with the
largest values measured in peripheral Pb+Pb interactions. The results are
compared with NA61/SHINE measurements in collisions, as well as with
predictions of the UrQMD and EPOS models.Comment: 12 pages, 14 figures, to be submitted to PR
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