343 research outputs found
The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration
Objective The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. Methods Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase, and the p70S6 kinase were assessed. Overexpression of a protein that maintains complex-I supported mitochondrial respiration (NDI1) was used to establish the importance of this pathway for mediating the anti-proliferative effects of Canagliflozin. Results Clinically achievable concentrations of Canagliflozin, but not Dapagliflozin, inhibit cellular proliferation and clonogenic survival of prostate and lung cancer cells alone and in combination with ionizing radiation and the chemotherapy Docetaxel. Canagliflozin reduced glucose uptake, mitochondrial complex-I supported respiration, ATP, and lipogenesis while increasing the activating phosphorylation of AMPK. The overexpression of NDI1 blocked the anti-proliferative effects of Canagliflozin indicating reductions in mitochondrial respiration are critical for anti-proliferative actions. Conclusion These data indicate that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations
Particle density fluctuations
Event-by-event fluctuations in the multiplicities of charged particles and
photons at SPS energies are discussed. Fluctuations are studied by controlling
the centrality of the reaction and rapidity acceptance of the detectors.
Results are also presented on the event-by-event study of correlations between
the multiplicity of charged particles and photons to search for DCC-like
signals.Comment: Talk presented at Quark Matter 2002, Nantes, Franc
Suppression of High-p_T Neutral Pion Production in Central Pb+Pb Collisions at sqrt{s_NN} = 17.3 GeV Relative to p+C and p+Pb Collisions
Neutral pion transverse momentum spectra were measured in p+C and p+Pb
collisions at sqrt{s_NN} = 17.4 GeV at mid-rapidity 2.3 < eta_lab < 3.0 over
the range 0.7< p_T < 3.5 GeV/c. The spectra are compared to pi0 spectra
measured in Pb+Pb collisions at sqrt{s_NN} = 17.3 GeV in the same experiment.
For a wide range of Pb+Pb centralities (N_part < 300) the yield of pi0's with
p_T > 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled
with the number of nucleon-nucleon collisions (N_coll), while for central Pb+Pb
collisions with N_part > 350 the pi0 yield is suppressed.Comment: 5 pages, 4 figure
Search for DCC in 158A GeV Pb+Pb Collisions
A detailed analysis of the phase space distributions of charged particles and
photons have been carried out using two independent methods. The results
indicate the presence of nonstatistical fluctuations in localized regions of
phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199
Pion Freeze-Out Time in Pb+Pb Collisions at 158 A GeV/c Studied via pi-/pi+ and K-/K+ Ratios
The effect of the final state Coulomb interaction on particles produced in
Pb+Pb collisions at 158 A GeV/c has been investigated in the WA98 experiment
through the study of the pi-/pi+ and K-/K+ ratios measured as a function of
transverse mass. While the ratio for kaons shows no significant transverse mass
dependence, the pi-/pi+ ratio is enhanced at small transverse mass values with
an enhancement that increases with centrality. A silicon pad detector located
near the target is used to estimate the contribution of hyperon decays to the
pi-/pi+ ratio. The comparison of results with predictions of the RQMD model in
which the Coulomb interaction has been incorporated allows to place constraints
on the time of the pion freeze-out.Comment: 9 pages, 12 figure
Present Status and Future of DCC Analysis
Disoriented Chiral Condensates (DCC) have been predicted to form in high
energy heavy ion collisions where the approximate chiral symmetry of QCD has
been restored. This leads to large imbalances in the production of charged to
neutral pions. Sophisticated analysis methods are being developed to
disentangle DCC events out of the large background of events with
conventionally produced particles. We present a short review of current
analysis methods and future prospects.Comment: 12 pages, 5 figures. Invited talk presented at the 13th International
Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 97),
Tsukuba, Japan, 1-5 Dec 199
Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry
Two-particle correlations have been measured for identified negative pions
from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all
dimensions have been obtained. A multi-dimensional study of the radii as a
function of kT is presented, including a full correction for the resolution
effects of the apparatus. The cross term Rout-long of the standard fit in the
Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised
Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a
boost invariant expansion. The shapes of the correlation functions in Qinv and
Qspace have been analyzed in detail. They are not Gaussian but better
represented by exponentials. As a consequence, fitting Gaussians to these
correlation functions may produce different radii depending on the acceptance
of the experimental setup used for the measurement.Comment: 13 pages including 10 figure
Search for Disoriented Chiral Condensates in 158 AGeV Pb+Pb Collisions
The restoration of chiral symmetry and its subsequent breaking through a
phase transition has been predicted to create regions of Disoriented Chiral
Condensates (DCC). This phenomenon has been predicted to cause anomalous
fluctuations in the relative production of charged and neutral pions in
high-energy hadronic and nuclear collisions. The WA98 experiment has been used
to measure charged and photon multiplicities in the central region of 158 AGeV
Pb+Pb collisions at the CERN SPS. In a sample of 212646 events, no clear DCC
signal can be distinguished. Using a simple DCC model, we have set a 90% C.L.
upper limit on the maximum DCC production allowed by the data.Comment: 20 Pages, LaTeX, uses elsart.cls, 8 eps figures included, submitted
to Physics Letters
Proximity effect at superconducting Sn-Bi2Se3 interface
We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions
down to 250 mK and in different magnetic fields. A number of conductance
anomalies were observed below the superconducting transition temperature of Sn,
including a small gap different from that of Sn, and a zero-bias conductance
peak growing up at lower temperatures. We discussed the possible origins of the
smaller gap and the zero-bias conductance peak. These phenomena support that a
proximity-effect-induced chiral superconducting phase is formed at the
interface between the superconducting Sn and the strong spin-orbit coupling
material Bi2Se3.Comment: 7 pages, 8 figure
Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV
PHENIX has measured the centrality dependence of charged hadron p_T spectra
from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T
decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction
of the contribution from hard scattering to high p_T hadron production. For
central collisions the yield at high p_T is shown to be suppressed compared to
binary nucleon-nucleon collision scaling of p+p data. This suppression is
monotonically increasing with centrality, but most of the change occurs below
30% centrality, i.e. for collisions with less than about 140 participating
nucleons. The observed p_T and centrality dependence is consistent with the
particle production predicted by models including hard scattering and
subsequent energy loss of the scattered partons in the dense matter created in
the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to
Phys. Lett. B. Revised to address referee concerns. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are publicly available at
http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
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