585 research outputs found
Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposureâresponse analysis
Purpose: This study assessed the effect of lurbinectedin, a highly selective inhibitor of oncogenic transcription, on the change from baseline in Fridericiaâs corrected QT interval (ÂżQTcF) and electrocardiography (ECG) morphological patterns, and lurbinectedin concentrationâÂżQTcF (C-ÂżQTcF) relationship, in patients with advanced solid tumors. Methods: Patients with QTcF = 500 ms, QRS < 110 ms, PR < 200 ms, and normal cardiac conduction and function received lurbinectedin 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks. ECGs were collected in triplicate via 12-lead digital recorder in treatment cycle 1 and 2 and analyzed centrally. ECG collection time-matched blood samples were drawn to measure lurbinectedin plasma concentration. No effect on QTc interval was concluded if the upper bound (UB) of the least square (LS) mean two-sided 90% confidence intervals (CI) for ÂżQTcF at each time point was < 20 ms. C-ÂżQTcF was explored using linear mixed-effects analysis. Results: A total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ÂżQTcF was 9.6 ms, thus lower than the more conservative 10 ms threshold established at the ICH E14 guideline for QT studies in healthy volunteers. C-ÂżQTcF was better fit by an effect compartment model, and the 90% CI of predicted ÂżQTcF at Cmax was 7.81 ms, also below the 10 ms threshold of clinical concern. Conclusions: ECG parameters and C-ÂżQTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization
A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis
BACKGROUND: Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. METHODS: A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m(2 )(n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m(2 )(n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. RESULTS: No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. CONCLUSION: The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality
Histological response of peritoneal carcinomatosis after hyperthermic intraperitoneal chemoperfusion (HIPEC) in experimental investigations
BACKGROUND: In selected patients with peritoneal carcinomatosis from colorectal cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. The aim of this study was to evaluate the tumor response of peritoneal carcinomatosis in tumor-bearing rats treated with HIPEC. METHODS: CC531 colon carcinoma (2,5 Ă 10(6 )cells), implanted intraperitoneally in Wag/Rija rats, was treated by hyperthermic intraperitoneal chemotherapy. After 10 days of tumor growth the animals were randomized into five groups of six animals each: group I: control (n = 6), group II: sham operated animals (n = 6), group III: hyperthermic intraperitoneal perfusion (HIP) without cytostatic drugs, group IV: HIPEC with mitomycin C in a concentration of 15 mg/m(2 )(n = 6), group V: mitomycin C i.p. alone in a concentration of 10 mg/m(2 )(n = 6). After 10 days the extent of tumor spread and histological outcome were analysed by autopsy. RESULTS: All control animals developed extensive intraperitoneal tumor growth. Histological tumor load was significantly reduced in group III and group V and was lowest in group IV. In group II tumor load was significantly higher than in group I. Implanted metastases were significantly decreased in group IV compared with group I and group II. CONCLUSION: These findings indicate that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread
Differential branching fraction and angular analysis of the decay B0âKâ0ÎŒ+ÎŒâ
The angular distribution and differential branching fraction of the decay B 0â K â0 ÎŒ + ÎŒ â are studied using a data sample, collected by the LHCb experiment in pp collisions at sâ=7 TeV, corresponding to an integrated luminosity of 1.0 fbâ1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Measurement of the relative rate of prompt Ïc0, Ïc1 and Ïc2 production at âs=7TeV
Prompt production of charmonium Ïc0, Ïc1 and Ïc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of âs=7TeV. The Ïc mesons are identified through their decay to J/ÏÎł, with J/ÏâÎŒ+muâ using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fbâ1 collected by the LHCb detector, is used to measure the relative prompt production rate of Ïc1 and Ïc2 in the rapidity range 2.0<y<4.5 as a function of the J/Ï transverse momentum from 3 to 20 GeV/c. First evidence for Ïc0 meson production at a hadron collider is also presented
Measurements of the branching fractions of B+âppK+ decays
The branching fractions of the decay B+ â ppÌK+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component MppÌ < 2.85 GeV/c2 and the branching fractions via the resonant ccÌ states η c(1S) and Ï(2S) relative to the decay via a J/Ï intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained
Search for the decay Bs0âD*âϱ
A search for the decay Bs0âD*âϱ is presented using a data sample corresponding to an integrated luminosity of 1.0ââfb-1 of pp collisions collected by LHCb. This decay is expected to be mediated by a W-exchange diagram, with little contribution from rescattering processes, and therefore a measurement of the branching fraction will help us to understand the mechanism behind related decays such as Bs0âÏ+Ï- and Bs0âDD- . Systematic uncertainties are minimized by using B0âD*âϱ as a normalization channel. We find no evidence for a signal, and set an upper limit on the branching fraction of B(Bs0âD*âϱ)<6.1(7.8)Ă10-6 at 90% (95%) confidence level
Search for CP violation in decays
A model-independent search for direct CP violation in the Cabibbo suppressed
decay in a sample of approximately 370,000 decays is
carried out. The data were collected by the LHCb experiment in 2010 and
correspond to an integrated luminosity of 35 pb. The normalized Dalitz
plot distributions for and are compared using four different
binning schemes that are sensitive to different manifestations of CP violation.
No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
Measurements of the branching fractions of the decays B°s â Dâs K± and B°s â DÂŻsÏ+
The decay mode B°s â Dâs K± allows for one of the theoretically cleanest measurements of the CKM angle Îł through the study of time-dependent CP violation. This paper reports a measurement of its branching fraction relative to the Cabibbo-favoured mode B°s â DÂŻsÏ+ based on a data sample corresponding to 0.37 fbÂŻÂč of proton-proton collisions at âs = 7TeV collected in 2011 with the LHCb detector. In addition, the ratio of B meson production fractions fs/fd, determined from semileptonic decays, together with the known branching fraction of the control channel B°s â DÂŻsÏ+ is used to perform an absolute measurement of the branching fractions: B(B°s â DÂŻsÏ+) = (2.95 ± 0.05 ± 0.17 -0.22 +0.18) Ă 10ÂŻÂł ; B(B°s â Dâs K±) = (1.90 ± 0.12 ± 0.13 -0.14 +0.12) Ă 10ÂŻ4 ; where the first uncertainty is statistical, the second the experimental systematic uncertainty, and the third the uncertainty due to f s/f
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