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Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.
Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors
Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab
We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using
a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with
the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass
distribution is obtained that is consistent with W decay and inconsistent with
the background prediction by 3.3 standard deviations. From this peak we measure
the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the
presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet
channel.Comment: 20 pages, 4 figures, submitted to PR
Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider
We have searched in collisions at = 1.8 TeV for events
with three charged leptons and missing transverse energy. In the Minimal
Supersymmetric Standard Model, we expect trilepton events from
chargino-neutralino (\chione \chitwo) pair production, with subsequent decay
into leptons. We observe no candidate , ,
or events in 106 pb integrated
luminosity. We present limits on the sum of the branching ratios times cross
section for the four channels: \sigma_{\chione\chitwo}\cdot
BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and
M_\chitwo > 82.2 \mgev\sp for , ~\mgev\sp and
M_\squark= M_\gluino.Comment: 9 pages and 3 figure
Search for charged Higgs decays of the top quark using hadronic tau decays
We present the result of a search for charged Higgs decays of the top quark,
produced in collisions at 1.8 TeV. When the charged
Higgs is heavy and decays to a tau lepton, which subsequently decays
hadronically, the resulting events have a unique signature: large missing
transverse energy and the low-charged-multiplicity tau. Data collected in the
period 1992-1993 at the Collider Detector at Fermilab, corresponding to
18.70.7~pb, exclude new regions of combined top quark and charged
Higgs mass, in extensions to the standard model with two Higgs doublets.Comment: uuencoded, gzipped tar file of LaTeX and 6 Postscript figures; 11 pp;
submitted to Phys. Rev.
Inclusive jet cross section in collisions at TeV
The inclusive jet differential cross section has been measured for jet
transverse energies, , from 15 to 440 GeV, in the pseudorapidity region
0.10.7. The results are based on 19.5 pb of data
collected by the CDF collaboration at the Fermilab Tevatron collider. The data
are compared with QCD predictions for various sets of parton distribution
functions. The cross section for jets with GeV is significantly
higher than current predictions based on O() perturbative QCD
calculations. Various possible explanations for the high- excess are
discussed.Comment: 8 pages with 2 eps uu-encoded figures Submitted to Physical Review
Letter
Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions
We describe a measurement of the charge asymmetry of leptons from W boson
decays in the rapidity range 0 enu, munu events from
110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The
asymmetry data constrain the ratio of d and u quark momentum distributions in
the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry
predictions that use parton distribution functions obtained from previously
published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree
with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur
Measurement of the Associated Production Cross Section in Collisions at TeV
We present the first measurement of associated direct photon + muon
production in hadronic collisions, from a sample of 1.8 TeV
collisions recorded with the Collider Detector at Fermilab. Quantum
chromodynamics (QCD) predicts that these events are primarily from the Compton
scattering process , with the final state charm quark producing
a muon. Hence this measurement is sensitive to the charm quark content of the
proton. The measured cross section of is compared to a
leading-order QCD parton shower model as well as a next-to-leading-order QCD
calculation.Comment: 12 pages, 4 figures Added more detailed description of muon
background estimat
Measurement of J/Psi and Psi(2S) Polarization in ppbar Collisions at sqrt(s) = 1.8 TeV
We have measured the polarization of J/Psi and Psi(2S) mesons produced in
p\bar{p} collisions at \sqrt{s} = 1.8 TeV, using data collected at CDF during
1992-95.
The polarization of promptly produced J/Psi [Psi(2S)] mesons is isolated from
those produced in B-hadron decay, and measured over the kinematic range 4[5.5]
< P_T < 20 GeV/c and |y| < 0.6. For P_T \gessim 12 GeV/c we do not observe
significant polarization in the prompt component.Comment: Revised version, accepted for publication in Physical Review Letter
Measurement of the Helicity of W Bosons in Top Quark Decays
We use the transverse momentum spectrum of leptons in the decay chain t-->bW
with W-->l nu to measure the helicity of the W bosons in the top quark rest
frame. Our measurement uses a ttbar sample isolated in 106 +/- 4 inverse
picobarns of data collected in ppbar collisions at sqrt(s)=1.8 TeV with the CDF
detector at the Fermilab Tevatron. Assuming a standard V--A weak decay, we find
that the fraction of W's with zero helicity in the top rest frame is F_0 = 0.91
+/- 0.37 (stat) +/- 0.13 (syst), consistent with the standard model prediction
of F_0=0.70 for a top mass of 175 GeV/c**2.Comment: Submitted to PRL. 8 pages, 2 figure
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