100 research outputs found
LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial
Background
Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary.
Methods
In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety.
Results
A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B.
Conclusions
AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH
Although the anti-cancer properties of 3BP have been described previously, its selectivity for cancer cells still needs to be explained. In the work reported here we characterized the kinetic parameters of radiolabelled [14C]-3BP uptake in three breast cancer cell lines that display different levels of resistance to 3BP: ZR-75-1 < MCF-7 < SK-BR-3. At pH 6.0 the affinity of cancer cells for 3BP transport, correlates with their sensitivity, a pattern that does not occur at pH 7.4. In the three cell lines, the uptake of 3BP is dependent on the proton motive force and is decreased by MCTs inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP. Here, we demonstrate that this phenotype is accompanied by an increase in affinity for 3BP uptake. Our results confirm the role of MCTs, especially MCT-1 in 3BP uptake and the importance of CD147 glycosylation in this process. We find that the affinity for 3BP transport is higher when the extracellular milieu is acid. This is a typical phenotype of tumor microenvironment and explains the lack of secondary effects of 3BP already described in in vivo studies.FEDER (Fundo Europeu deDesenvolvimento
Regional), through POFC (Programa Operacional Factores de Competitividade) –
COMPETE, and by Portuguese National Funds from FCT (Fundac¸˜ao para a Ciˆencia e
Tecnologia) in the scope of the project PEst-OE/BIA/U14050/2014. JAS [grant number
SFRH/BD/76038/2011] received a fellowship from the Portuguese government from the
FCT through FSE (Fundo Social Europeu) and POPH (Programa Operacional Potencial
Humano)
Search for R-Parity Violating Decays of Scalar Fermions at LEP
A search for pair-produced scalar fermions under the assumption that R-parity
is not conserved has been performed using data collected with the OPAL detector
at LEP. The data samples analysed correspond to an integrated luminosity of
about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An
important consequence of R-parity violation is that the lightest supersymmetric
particle is expected to be unstable. Searches of R-parity violating decays of
charged sleptons, sneutrinos and squarks have been performed under the
assumptions that the lightest supersymmetric particle decays promptly and that
only one of the R-parity violating couplings is dominant for each of the decay
modes considered. Such processes would yield final states consisting of
leptons, jets, or both with or without missing energy. No significant
single-like excess of events has been observed with respect to the Standard
Model expectations. Limits on the production cross- section of scalar fermions
in R-parity violating scenarios are obtained. Constraints on the supersymmetric
particle masses are also presented in an R-parity violating framework analogous
to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.
Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2
The hadronic structure function of the photon F_2^gamma is measured as a
function of Bjorken x and of the factorisation scale Q^2 using data taken by
the OPAL detector at LEP. Previous OPAL measurements of the x dependence of
F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of
F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted
by QCD, the data show positive scaling violations in F_2^gamma. Several
parameterisations of F_2^gamma are in agreement with the measurements whereas
the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001,
Ascona, Switzerlan
Search for the Standard Model Higgs Boson with the OPAL Detector at LEP
This paper summarises the search for the Standard Model Higgs boson in e+e-
collisions at centre-of-mass energies up to 209 GeV performed by the OPAL
Collaboration at LEP. The consistency of the data with the background
hypothesis and various Higgs boson mass hypotheses is examined. No indication
of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained
on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
Search for Higgs Bosons in e+e- Collisions at 183 GeV
The data collected by the OPAL experiment at sqrts=183 GeV were used to
search for Higgs bosons which are predicted by the Standard Model and various
extensions, such as general models with two Higgs field doublets and the
Minimal Supersymmetric Standard Model (MSSM). The data correspond to an
integrated luminosity of approximately 54pb-1. None of the searches for neutral
and charged Higgs bosons have revealed an excess of events beyond the expected
background. This negative outcome, in combination with similar results from
searches at lower energies, leads to new limits for the Higgs boson masses and
other model parameters. In particular, the 95% confidence level lower limit for
the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons
can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA >
72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and
soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for
minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM
parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European
Physical Journal
A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays
The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where
Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL
detector at LEP. Lambda_b are selected by the presence of energetic Lambda
particles in bottom events tagged by the presence of displaced secondary
vertices. A fit to the momenta of the Lambda particles separates signal from B
meson and fragmentation backgrounds. The measured product branching ratio is
f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))%
Combined with a previous OPAL measurement, one obtains
f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European
Physical Journal
Measurement of the Michel Parameters in Leptonic Tau Decays
The Michel parameters of the leptonic tau decays are measured using the OPAL
detector at LEP. The Michel parameters are extracted from the energy spectra of
the charged decay leptons and from their energy-energy correlations. A new
method involving a global likelihood fit of Monte Carlo generated events with
complete detector simulation and background treatment has been applied to the
data recorded at center-of-mass energies close to sqrt(s) = M(Z) corresponding
to an integrated luminosity of 155 pb-1 during the years 1990 to 1995. If e-mu
universality is assumed and inferring the tau polarization from neutral current
data, the measured Michel parameters are extracted. Limits on non-standard
coupling constants and on the masses of new gauge bosons are obtained. The
results are in agreement with the V-A prediction of the Standard Model.Comment: 32 pages, LaTeX, 9 eps figures included, submitted to the European
Physical Journal
An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4(+) and CD8(+) T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma—often associated with T helper 1 cells—and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon
The Woody Guthrie Centennial Bibliography
This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie
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