110 research outputs found
WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics
Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Î-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Î-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe
Abnormal Placental Development and Early Embryonic Lethality in EpCAM-Null Mice
BACKGROUND: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs
First observation of a doubly charged tetraquark and its neutral partner
A combined amplitude analysis is performed for the decays and , which are
related by isospin symmetry. The analysis is based on data collected by the
LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8
and 13. The full data sample corresponds to an integrated
luminosity of 9. Two new resonant states with masses of
and widths of
are observed, which decay to and
respectively. The former state indicates the first observation of
a doubly charged open-charm tetraquark state with minimal quark content
, and the latter state is a neutral tetraquark composed of
quarks. Both states are found to have spin-parity ,
and their resonant parameters are consistent with each other, which suggests
that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb
public pages
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
Angular Analysis of the B+ -> K*(+)mu(+) mu(-) Decay
We present an angular analysis of the
B
+
â
K
*
+
(
â
K
0
S
Ï
+
)
Ό
+
Ό
â
decay using
9
â
â
fb
â
1
of
p
p
collision data collected with the LHCb experiment. For the first time, the full set of
C
P
-averaged angular observables is measured in intervals of the dimuon invariant mass squared. Local deviations from standard model predictions are observed, similar to those in previous LHCb analyses of the isospin-partner
B
0
â
K
*
0
Ό
+
Ό
â
decay. The global tension is dependent on which effective couplings are considered and on the choice of theory nuisance parameters
Precise determination of the B-s(0)-B-s(-0) oscillation frequency
Mesons comprising a beauty quark and a strange quark can oscillate between
particle (B0s) and antiparticle (B0s) flavour eigenstates, with a frequency
given by the mass difference between heavy and light mass eigenstates, deltams.
Here we present ameasurement of deltams using B0s2DsPi decays produced in
proton-proton collisions collected with the LHCb detector at the Large Hadron
Collider. The oscillation frequency is found to be deltams = 17.7683 +- 0.0051
+- 0.0032 ps-1, where the first uncertainty is statistical and the second
systematic. This measurement improves upon the current deltams precision by a
factor of two. We combine this result with previous LHCb measurements to
determine deltams = 17.7656 +- 0.0057 ps-1, which is the legacy measurement of
the original LHCb detector.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2021-005.html (LHCb
public pages
Study of coherent production in lead-lead collisions at
Coherent production of mesons is studied in ultraperipheral lead-lead collisions at a nucleon-nucleon centre-of-mass energy of 5 TeV, using a data sample collected by the LHCb experiment corresponding to an integrated luminosity of about . The mesons are reconstructed in the dimuon final state and are required to have transverse momentum below 1 GeV. The cross-section within the rapidity range of is measured to be mb, where the first uncertainty is statistical, the second systematic and the third originates from the luminosity determination. The cross-section is also measured in rapidity intervals. The results are compared to predictions from phenomenological models
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