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Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.
In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.
In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).
The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).
Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.
Measurement of cold nuclear matter effects for inclusive J/ψ in p+Au collisions at √sNN = 200 GeV
(2022)
Measurement by the STAR experiment at RHIC of the cold nuclear matter (CNM) effects experienced by inclusive J/ψ at mid-rapidity in 0-100% p+Au collisions at √sNN = 200 GeV is presented. Such effects are quantified utilizing the nuclear modification factor, RpAu, obtained by taking a ratio of J/ψ yield in p+Au collisions to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The differential J/ψ yield in both p+p and p+Au collisions is measured through the dimuon decay channel, taking advantage of the trigger capability provided by the Muon Telescope Detector in the RHIC 2015 run. Consequently, the J/ψ RpAu is derived within the transverse momentum (pT) range of 0 to 10 GeV/c. A suppression of approximately 30% is observed for pT < 2 GeV/c, while J/ψ RpAu becomes compatible with unity for pT greater than 3 GeV/c, indicating the J/ψ yield is minimally affected by the CNM effects at high pT. Comparison to a similar measurement from 0-20% central Au+Au collisions reveals that the observed strong J/ψ suppression above 3 GeV/c is mostly due to the hot medium effects, providing strong evidence for the formation of the quark-gluon plasma in these collisions. Several model calculations show qualitative agreement with the measured J/ψ RpAu, while their agreement with the J/ψ yields in p+p and p+Au collisions is worse.
We report on the measurements of directed flow v1 and elliptic flow v2 for hadrons (π±, K ±, K0 S , p, φ, Λ and ) from Au+Au collisions at √sN N = 3 GeV and v2 for (π±, K ±, p and p) at 27 and 54.4 GeV with the STAR experiment. While at the two higher energy midcentral collisions the numberof-constituent-quark (NCQ) scaling holds, at 3 GeV the v2 at midrapidity is negative for all hadrons and the NCQ scaling is absent. In addition, the v1 slopes at midrapidity for almost all observed hadrons are found to be positive, implying dominant repulsive baryonic interactions. The features of negative v2 and positive v1 slope at 3 GeV can be reproduced with a baryonic mean-field in transport model calculations. These results imply that the medium in such collisions is likely characterized by baryonic interactions.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in √sNN = 3 GeV Au+Au collisions. In this paper, we report measurements of the first- and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in √sNN = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
Investigation of the linear and mode-coupled flow harmonics in Au+Au collisions at √sNN = 200 GeV
(2020)
Flow harmonics (vn) of the Fourier expansion for the azimuthal distributions of hadrons are commonly employed to quantify the azimuthal anisotropy of particle production relative to the collision symmetry planes. While lower order Fourier coefficients (v2 and v3) are more directly related to the corresponding eccentricities of the initial state, the higher-order flow harmonics (vn>3) can be induced by a modecoupled response to the lower-order anisotropies, in addition to a linear response to the same-order anisotropies. These higher-order flow harmonics and their linear and mode-coupled contributions can be used to more precisely constrain the initial conditions and the transport properties of the medium in theoretical models. The multiparticle azimuthal cumulant method is used to measure the linear and mode-coupled contributions in the higher-order anisotropic flow, the mode-coupled response coefficients, and the correlations of the event plane angles for charged particles as functions of centrality and transverse momentum in Au+Au collisions at nucleon-nucleon center-of-mass energy √sN N= 200 GeV. The results are compared to similar LHC measurements as well as to several viscous hydrodynamic calculations with varying initial conditions.
Measurement of groomed jet substructure observables in p+p collisions at √s = 200 GeV with STAR
(2020)
In this letter, measurements of the shared momentum fraction (zg) and the groomed jet radius (Rg), as defined in the SoftDrop algorithm, are reported in p+p collisions at √s = 200 GeV collected by the STAR experiment. These substructure observables are differentially measured for jets of varying resolution parameters from R = 0.2 − 0.6 in the transverse momentum range 15 < pT,jet < 60 GeV/c. These studies show that, in the pT,jet range accessible at √s = 200 GeV and with increasing jet resolution parameter and jet transverse momentum, the zg distribution asymptotically converges to the DGLAP splitting kernel for a quark radiating a gluon. The groomed jet radius measurements reflect a momentum-dependent narrowing of the jet structure for jets of a given resolution parameter, i.e., the larger the pT,jet, the narrower the first splitting. For the first time, these fully corrected measurements are compared to Monte Carlo generators with leading order QCD matrix elements and leading log in the parton shower, and to state-of-the-art theoretical calculations at next-to-leading-log accuracy. We observe that PYTHIA 6 with parameters tuned to reproduce RHIC measurements is able to quantitatively describe data, whereas PYTHIA 8 and HERWIG 7, tuned to reproduce LHC data, are unable to provide a simultaneous description of both zg and Rg, resulting in opportunities for fine parameter tuning of these models for p+p collisions at RHIC energies. We also find that the theoretical calculations without non-perturbative corrections are able to qualitatively describe the trend in data for jets of large resolution parameters at high pT,jet, but fail at small jet resolution parameters and low jet transverse momenta.
We report results on the total and elastic cross sections in proton-proton collisions at √s = 200 GeV obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section was measured in the squared four-momentum transfer range 0.045 ≤ −t ≤ 0.135 GeV2. The value of the exponential slope parameter B of the elastic differential cross section dσ/dt ∼ e−Bt in the measured −t range was found to be B = 14.32 ± 0.09(stat.)+0.13 −0.28(syst.) GeV−2. The total cross section σtot, obtained from extrapolation of the dσ/dt to the optical point at −t = 0, is σtot = 54.67 ± 0.21(stat.)+1.28 −1.38(syst.) mb. We also present the values of the elastic cross section σel = 10.85 ± 0.03(stat.)+0..49 −0.41(syst.) mb, the elastic cross section integrated within the STAR t-range σ det el = 4.05 ± 0.01(stat.)+0.18−0.17(syst.) mb, and the inelastic cross section σinel = 43.82 ± 0.21(stat.)+1.37−1.44(syst.) mb. The results are compared with the world data
We report the first multi-differential measurements of strange hadrons of K −, φ and − yields as well as the ratios of φ/K − and φ/− in Au+Au collisions at √sNN = 3 GeV with the STAR experiment fixed target configuration at RHIC. The φ mesons and − hyperons are measured through hadronic decay channels, φ → K + K − and Ξ− → Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the φ/K − and φ/− ratios while the result of canonical ensemble (CE) calculations reproduce φ/K −, with the correlation length rc ∼ 2.7 fm, and φ/−, rc ∼ 4.2 fm, for the 0-10% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3 GeV implies a rather different medium property at high baryon density.
We report a measurement of cumulants and correlation functions of event-by-event proton multiplicity distributions from fixed-target Au+Au collisions at sNN−−−√ = 3 GeV measured by the STAR experiment. Protons are identified within the rapidity (y) and transverse momentum (pT) region −0.9<y<0 and 0.4<pT<2.0 GeV/c in the center-of-mass frame. A systematic analysis of the proton cumulants and correlation functions up to sixth-order as well as the corresponding ratios as a function of the collision centrality, pT, and y are presented. The effect of pileup and initial volume fluctuations on these observables and the respective corrections are discussed in detail. The results are compared to calculations from the hadronic transport UrQMD model as well as a hydrodynamic model. In the most central 5\% collisions, the value of proton cumulant ratio C4/C2 is negative, drastically different from the values observed in Au+Au collisions at higher energies. Compared to model calculations including Lattice QCD, a hadronic transport model, and a hydrodynamic model, the strong suppression in the ratio of C4/C2 at 3 GeV Au+Au collisions indicates an energy regime dominated by hadronic interactions.
We report the first multi-differential measurements of strange hadrons of K−, ϕ and Ξ− yields as well as the ratios of ϕ/K− and ϕ/Ξ− in Au+Au collisions at sNN−−−√=3GeV with the STAR experiment fixed target configuration at RHIC. The ϕ mesons and Ξ− hyperons are measured through hadronic decay channels, ϕ→K+K− and Ξ−→Λπ−. Collision centrality and rapidity dependence of the transverse spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At the collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the ϕ/K− ratio while the result of canonical ensemble (CE) calculations reproduce well the ratios of ϕ/K−, with the correlation length rc∼2.7\,fm, and ϕ/Ξ−, rc∼4.2\,fm, for the 0-10\% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3GeV implies a rather different medium property at high baryon density.
We report the first multi-differential measurements of strange hadrons of K−, ϕ and Ξ− yields as well as the ratios of ϕ/K− and ϕ/Ξ− in Au+Au collisions at sNN−−−√=3GeV with the STAR experiment fixed target configuration at RHIC. The ϕ mesons and Ξ− hyperons are measured through hadronic decay channels, ϕ→K+K− and Ξ−→Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the ϕ/K− ratio while the result of canonical ensemble (CE) calculations reproduce well the ratios of ϕ/K−, with the correlation length rc∼2.7\,fm, and ϕ/Ξ−, rc∼4.2\,fm, for the 0-10\% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3GeV implies a rather different medium property at high baryon density.
We report the first multi-differential measurements of strange hadrons of K−, ϕ and Ξ− yields as well as the ratios of ϕ/K− and ϕ/Ξ− in Au+Au collisions at sNN−−−√=3GeV with the STAR experiment fixed target configuration at RHIC. The ϕ mesons and Ξ− hyperons are measured through hadronic decay channels, ϕ→K+K− and Ξ−→Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the ϕ/K− and ϕ/Ξ− ratios while the result of canonical ensemble (CE) calculations reproduce ϕ/K−, with the correlation length rc∼2.7\,fm, and ϕ/Ξ−, rc∼4.2\,fm, for the 0-10\% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3GeV implies a rather different medium property at high baryon density.
We report the first multi-differential measurements of strange hadrons of K−, ϕ and Ξ− yields as well as the ratios of ϕ/K− and ϕ/Ξ− in Au+Au collisions at sNN−−−√=3GeV with the STAR experiment fixed target configuration at RHIC. The ϕ mesons and Ξ− hyperons are measured through hadronic decay channels, ϕ→K+K− and Ξ−→Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the ϕ/K− and ϕ/Ξ− ratios while the result of canonical ensemble (CE) calculations reproduce ϕ/K−, with the correlation length rc∼2.7\,fm, and ϕ/Ξ−, rc∼4.2\,fm, for the 0-10\% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3GeV implies a rather different medium property at high baryon density.
The STAR Collaboration reports measurements of back-to-back azimuthal correlations of di-π0s produced at forward pseudorapidities (2.6<η<4.0) in p+p, p+Al, and p+Au collisions at a center-of-mass energy of 200 GeV. We observe a clear suppression of the correlated yields of back-to-back π0 pairs in p+Al and p+Au collisions compared to the p+p data. The observed suppression of back-to-back pairs as a function of event activity and transverse momentum suggests nonlinear gluon dynamics arising at high parton densities. The larger suppression found in p+Au relative to p+Al collisions exhibits a dependence of the saturation scale, Q2s, on the mass number, A. The suppression in high-activity p+Au collisions is consistent with theoretical predictions including gluon saturation effects.
The STAR Collaboration reports measurements of back-to-back azimuthal correlations of di-π0s produced at forward pseudorapidities (2.6<η<4.0) in p+p, p+Al, and p+Au collisions at a center-of-mass energy of 200 GeV. We observe a clear suppression of the correlated yields of back-to-back π0 pairs in p+Al and p+Au collisions compared to the p+p data. The observed suppression of back-to-back pairs as a function of transverse momentum suggests nonlinear gluon dynamics arising at high parton densities. The larger suppression found in p+Au relative to p+Al collisions exhibits a dependence of the saturation scale, Q2s, on the mass number, A. A linear scaling of the suppression with A1/3 is observed with a slope of −0.09 ± 0.01.
We report measurements of the longitudinal double-spin asymmetry, ALL, for inclusive jet and dijet production in polarized proton-proton collisions at midrapidity and center-of-mass energy s√ = 510 GeV, using the high luminosity data sample collected by the STAR experiment in 2013. These measurements complement and improve the precision of previous STAR measurements at the same center-of-mass energy that probe the polarized gluon distribution function at partonic momentum fraction 0.015 ≲x≲ 0.25. The dijet asymmetries are separated into four jet-pair topologies, which provide further constraints on the x dependence of the polarized gluon distribution function. These measurements are in agreement with previous STAR measurements and with predictions from current next-to-leading order global analyses. They provide more precise data at low dijet invariant mass that will better constraint the shape of the polarized gluon distribution function of the proton.
We report measurements of the longitudinal double-spin asymmetry, ALL, for inclusive jet and dijet production in polarized proton-proton collisions at midrapidity and center-of-mass energy s√ = 510 GeV, using the high luminosity data sample collected by the STAR experiment in 2013. These measurements complement and improve the precision of previous STAR measurements at the same center-of-mass energy that probe the polarized gluon distribution function at partonic momentum fraction 0.015 ≲x≲ 0.25. The dijet asymmetries are separated into four jet-pair topologies, which provide further constraints on the x dependence of the polarized gluon distribution function. These measurements are in agreement with previous STAR measurements and with predictions from current next-to-leading order global analyses. They provide more precise data at low dijet invariant mass that will better constraint the shape of the polarized gluon distribution function of the proton.
Measurement of cold nuclear matter effects for inclusive J/ψ in p+Au collisions at √sNN = 200 GeV
(2021)
Measurement by the STAR experiment at RHIC of the cold nuclear matter (CNM) effects experienced by inclusive J/ψ at mid-rapidity in p+Au collisions at sNN−−−√ = 200 GeV is presented. Such effects are quantified utilizing the nuclear modification factor, RpAu, obtained by taking a ratio of J/ψ yield in p+Au collisions to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The differential J/ψ yield in both p+p and p+Au collisions is measured through the dimuon decay channel, taking advantage of the trigger capability provided by the Muon Telescope Detector in the RHIC 2015 run. Consequently, the J/ψ RpAu is derived within the transverse momentum (pT) range of 0 to 10 GeV/c. A suppression of approximately 30% is observed for pT<2 GeV/c, while J/ψ RpAu becomes compatible with unity for pT greater than 3 GeV/c, indicating the J/ψ yield is minimally affected by the CNM effects at high pT. Comparison to a similar measurement from 0-20% central Au+Au collisions reveals that the observed strong J/ψ suppression above 3 Gev/c is mostly due to the hot medium effects, providing strong evidence for the formation of the quark-gluon plasma in these collisions. Several model calculations show qualitative agreement with the measured J/ψ RpAu, while their agreement with the J/ψ yield in p+p and p+Au collisions is worse.
Measurement of cold nuclear matter effects for inclusive J/ψ in p+Au collisions at √sNN = 200 GeV
(2022)
Measurement by the STAR experiment at RHIC of the cold nuclear matter (CNM) effects experienced by inclusive J/ψ at mid-rapidity in 0-100\% p+Au collisions at sNN−−−√ = 200 GeV is presented. Such effects are quantified utilizing the nuclear modification factor, RpAu, obtained by taking a ratio of J/ψ yield in p+Au collisions to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The differential J/ψ yield in both p+p and p+Au collisions is measured through the dimuon decay channel, taking advantage of the trigger capability provided by the Muon Telescope Detector in the RHIC 2015 run. Consequently, the J/ψ RpAu is derived within the transverse momentum (pT) range of 0 to 10 GeV/c. A suppression of approximately 30% is observed for pT<2 GeV/c, while J/ψ RpAu becomes compatible with unity for pT greater than 3 GeV/c, indicating the J/ψ yield is minimally affected by the CNM effects at high pT. Comparison to a similar measurement from 0-20% central Au+Au collisions reveals that the observed strong J/ψ suppression above 3 Gev/c is mostly due to the hot medium effects, providing strong evidence for the formation of the quark-gluon plasma in these collisions. Several model calculations show qualitative agreement with the measured J/ψ RpAu, while their agreement with the J/ψ yields in p+p and p+Au collisions is worse.
Azimuthal anisotropy measurement of (multi-)strange hadrons in Au+Au collisions at √sNN = 54.4 GeV
(2023)
Azimuthal anisotropy of produced particles is one of the most important observables used to access the collective properties of the expanding medium created in relativistic heavy-ion collisions. In this paper, we present second (v2) and third (v3) order azimuthal anisotropies of K0S, ϕ, Λ, Ξ and Ω at mid-rapidity (|y|<1) in Au+Au collisions at sNN−−−√ = 54.4 GeV measured by the STAR detector. The v2 and v3 are measured as a function of transverse momentum and centrality. Their energy dependence is also studied. v3 is found to be more sensitive to the change in the center-of-mass energy than v2. Scaling by constituent quark number is found to hold for v2 within 10%. This observation could be evidence for the development of partonic collectivity in 54.4 GeV Au+Au collisions. Differences in v2 and v3 between baryons and anti-baryons are presented, and ratios of v3/v3/22 are studied and motivated by hydrodynamical calculations. The ratio of v2 of ϕ mesons to that of anti-protons (v2(ϕ)/v2(p¯)) shows centrality dependence at low transverse momentum, presumably resulting from the larger effects from hadronic interactions on anti-proton v2.