833 research outputs found
Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia
Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes
Centrosome clustering and Cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors
Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001)
Know Your Current Ih: Interaction with a Shunting Current Explains the Puzzling Effects of Its Pharmacological or Pathological Modulations
The non-specific, hyperpolarization activated, Ih current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K+ current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling Ih actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on Ih channel is able to explain virtually all experimental findings on Ih up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by Ih
Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV
We present limits on anomalous WWZ and WW-gamma couplings from a search for
WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p
-> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron
Collider during the 1992-1995 run. The data sample corresponds to an integrated
luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling
parameters, the 95% CL limits on the CP-conserving couplings are
-0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a
form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also
presented.Comment: 11 pages, 2 figures, 2 table
Search For Heavy Pointlike Dirac Monopoles
We have searched for central production of a pair of photons with high
transverse energies in collisions at TeV using of data collected with the D\O detector at the Fermilab Tevatron in
1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could
rescatter pairs of nearly real photons into this final state via a box diagram.
We observe no excess of events above background, and set lower 95% C.L. limits
of on the mass of a spin 0, 1/2, or 1 Dirac
monopole.Comment: 12 pages, 4 figure
The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV
Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we
have measured the inclusive dijet mass spectrum in the central pseudorapidity
region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also
measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| <
1.0). The order alpha_s^3 QCD predictions are in good agreement with the data
and we rule out models of quark compositeness with a contact interaction scale
< 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let
Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV
A search has been carried out for events in the channel p-barp --> gamma
gamma jet jet. Such a signature can characterize the production of a
non-standard Higgs boson together with a W or Z boson. We refer to this
non-standard Higgs, having standard model couplings to vector bosons but no
coupling to fermions, as a "bosonic Higgs." With the requirement of two high
transverse energy photons and two jets, the diphoton mass (m(gamma gamma))
distribution is consistent with expected background. A 90(95)% C.L. upper limit
on the cross section as a function of mass is calculated, ranging from
0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma
gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a
bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching
ratios and corresponding new mass limit
Zgamma Production in pbarp Collisions at sqrt(s)=1.8 TeV and Limits on Anomalous ZZgamma and Zgammagamma Couplings
We present a study of Z +gamma + X production in p-bar p collisions at
sqrt{S}=1.8 TeV from 97 (87) pb^{-1} of data collected in the eegamma
(mumugamma) decay channel with the D0 detector at Fermilab. The event yield and
kinematic characteristics are consistent with the Standard Model predictions.
We obtain limits on anomalous ZZgamma and Zgammagamma couplings for form factor
scales Lambda = 500 GeV and Lambda = 750 GeV. Combining this analysis with our
previous results yields 95% CL limits |h{Z}_{30}| < 0.36, |h{Z}_{40}| < 0.05,
|h{gamma}_{30}| < 0.37, and |h{gamma}_{40}| < 0.05 for a form factor scale
Lambda=750 GeV.Comment: 17 Pages including 2 Figures. Submitted to PR
A Measurement of the W Boson Mass
We report a measurement of the W boson mass based on an integrated luminosity
of 82 pb from \ppbar collisions at TeV recorded in
1994--1995 by the \Dzero detector at the Fermilab Tevatron. We identify W
bosons by their decays to and extract the mass by fitting the transverse
mass spectrum from 28,323 W boson candidates. A sample of 3,563 dielectron
events, mostly due to Z to ee decays, constrains models of W boson production
and the detector. We measure \mw=80.44\pm0.10(stat)\pm0.07(syst)~GeV. By
combining this measurement with our result from the 1992--1993 data set, we
obtain \mw=80.43\pm0.11 GeV.Comment: 11 pages, 5 figure
Probing Hard Color-Singlet Exchange in ppbar Collisions at root-s=630 GeV and 1800 GeV
We present results on dijet production via hard color-singlet exchange in
proton-antiproton collisions at root-s = 630 GeV and 1800 GeV using the DZero
detector. The fraction of dijet events produced via color-singlet exchange is
measured as a function of jet transverse energy, separation in pseudorapidity
between the two highest transverse energy jets, and proton-antiproton
center-of-mass energy. The results are consistent with a color-singlet fraction
that increases with an increasing fraction of quark-initiated processes and
inconsistent with two-gluon models for the hard color-singlet.Comment: 16 pages, 6 figure
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