3,985 research outputs found
Reply to Comment of Gazdzicki and Heinz on Strangeness Enhancement in and
The Comment of Gazdzicki and Heinz is flawed because their assumed baryon
stopping power in is inconsistent with data and because they ignored half
the analysis based on the VENUS model. The Comment continues the misleading
presentation of strangeness enhancement by focusing on ratios of integrated
yields. Those ratios discard essential experimental information on the rapidity
dependence of produced and obscure discrepancies between different
data sets. Our conclusion remains that the NA35 minimum bias data on
indicate an anomalous enhancement of central
rapidity strangeness in few nucleon reactions that points to non-equilibrium
dynamics as responsible for strangeness enhancement in nuclear reactions.Comment: revtex file, 6 pages, submitted to Phys. Rev.
AUM302, a novel triple kinase PIM/PI3K/ mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor
Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy
Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.
Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation
Strangeness Enhancement in p-A Collisions: Consequences for the Interpretation of Strangeness Production in A-A Collisions
Published measurements of semi-inclusive Lambda production in p-Au collisions
at the AGS are used to estimate the yields of singly strange hadrons in
nucleus-nucleus A-A collisions. Results of a described extrapolation technique
are shown and compared to measurements of K+ production in Si-Al, Si-Au, and
Au-Au collisions at the AGS and net Lambda production in Su-Su, S-Ag, Pb-Pb,
and inclusive p-A collisions at the SPS. The extrapolations can account for
more than 75% of the measured strange particle yields in all of the studied
systems except for very central Au-Au collisions at the AGS where RQMD
comparisons suggest large re-scattering contributions.Comment: 9 pages, 4 figure
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
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
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
Antideuteron and deuteron production in mid-central Pb+Pb collisions at 158 GeV
Production of deuterons and antideuterons was studied by the NA49 experiment
in the 23.5% most central Pb+Pb collisions at the top SPS energy of
=17.3 GeV. Invariant yields for and were measured
as a function of centrality in the center-of-mass rapidity range .
Results for together with previously published
measurements are discussed in the context of the coalescence model. The
coalescence parameters were deduced as a function of transverse momentum
and collision centrality.Comment: 9 figure
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
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.
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