492 research outputs found
Tumor slice culture system to assess drug response of primary breast cancer
Background
The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment.
Methods
We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange.
Results
We could maintain tissue cultures for at least 7 days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors.
Conclusion
This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment
Performance of BRCA1/2 mutation prediction models in male breast cancer patients
To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ("Myriad"). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources
Tumor slice culture system to assess drug response of primary breast cancer
Background: The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment. Methods: We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange. Results: We could maintain tissue cultures for at least 7days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors. Conclusion: This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment
Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV
A search for pair-production of supersymmetric particles under the assumption
that R-parity is violated via a dominant LQDbar coupling has been performed
using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV.
The observed candidate events in the data are in agreement with the Standard
Model expectation. This result is translated into lower limits on the masses of
charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for
m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81
GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the
95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure
Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits
The WWgamma triple gauge boson coupling parameters are studied using p-pbar
-> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were
collected with the DO detector from an integrated luminosity of 162 pb^{-1}
delivered by the Fermilab Tevatron Collider. The cross section times branching
fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV
and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum)
pb. The one-dimensional 95% confidence level limits on anomalous couplings are
-0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events
We present a measurement of the top quark pair ttbar production cross section
in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1}
of data collected by the DO detector at the Fermilab Tevatron Collider. We
select events with one charged lepton (electron or muon), large missing
transverse energy, and at least four jets, and extract the ttbar content of the
sample based on the kinematic characteristics of the events. For a top quark
mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1}
(syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging
We present a measurement of the top quark pair () production cross
section () in collisions at TeV
using 230 pb of data collected by the D0 experiment at the Fermilab
Tevatron Collider. We select events with one charged lepton (electron or muon),
missing transverse energy, and jets in the final state. We employ
lifetime-based b-jet identification techniques to further enhance the
purity of the selected sample. For a top quark mass of 175 GeV, we
measure pb, in
agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let
The RECAP Test Rapidly and Reliably Identifies Homologous Recombination-Deficient Ovarian Carcinomas
Recent studies have shown that the efficacy of PARP inhibitors in epithelial ovarian
carcinoma (EOC) is related to tumor-specific defects in homologous recombination (HR) and extends
beyond BRCA1/2 deficient EOC. A robust method with which to identify HR-deficient (HRD)
carcinomas is therefore of utmost clinical importance. In this study, we investigated the proficiency of
a functional HR assay based on the detection of RAD51 foci, the REcombination CAPacity (RECAP)
test, in identifying HRD tumors in a cohort of prospectively collected epithelial ovarian carcinomas
(EOCs). Of the 39 high-grade serous ovarian carcinomas (HGSOC), the RECAP test detected 26%
(10/39) to be HRD, whereas ovarian carcinomas of other histologic subtypes (n = 10) were all
HR-proficient (HRP). Of the HRD tumors that could be sequenced, 8/9 showed pathogenic BRCA1/2
variants or BRCA1 promoter hypermethylation, indicating that the RECAP test reliably identifies
HRD, including but not limited to tumors related to BRCA1/2 deficiency. Furthermore, we found a
trend towards better overall survival (OS) of HGSOC patients with RECAP-identified HRD tumors
compared to patients with HRP tumors. This study shows that the RECAP test is an attractive alternative to DNA-based HRD tests, and further development of a clinical grade RECAP test is
clearly warranted
Measurement of the ratios of the Z/G* + >= n jet production cross sections to the total inclusive Z/G* cross section in ppbar collisions at sqrt(s) = 1.96 TeV
We present a study of events with Z bosons and jets produced at the Fermilab
Tevatron Collider in ppbar collisions at a center of mass energy of 1.96 TeV.
The data sample consists of nearly 14,000 Z/G* -> e+e- candidates corresponding
to the integrated luminosity of 0.4 fb-1 collected using the D0 detector.
Ratios of the Z/G* + >= n jet cross sections to the total inclusive Z/G* cross
section have been measured for n = 1 to 4 jet events. Our measurements are
found to be in good agreement with a next-to-leading order QCD calculation and
with a tree-level QCD prediction with parton shower simulation and
hadronization.Comment: 7 pages, 2 figures, slightly modified, submitted to Phys. Lett.
Measurement of the Isolated Photon Cross Section in p-pbar Collisions at sqrt{s}=1.96 TeV
The cross section for the inclusive production of isolated photons has been
measured in p anti-p collisions at sqrt{s}=1.96 TeV with the D0 detector at the
Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV
and have pseudorapidity |eta|<0.9. The cross section is compared with the
results from two next-to-leading order perturbative QCD calculations. The
theoretical predictions agree with the measurement within uncertainties.Comment: 7 pages, 5 figures, submitted to Phys.Lett.
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