636 research outputs found
Reduced dose and intermittent treatment with lapatinib and trastuzumab for potent blockade of the HER pathway in HER2/neu-overexpressing breast tumor xenografts.
Efficacy and cost-effectiveness of an outcall program to reduce carer burden and depression among carers of cancer patients (PROTECT) : rationale and design of a randomized controlled trial
Published: 6 January 2014BACKGROUND: Carers provide extended and often unrecognized support to people with cancer. The aim of this study is to test the hypothesis that excessive carer burden is modifiable through a telephone outcall intervention that includes supportive care, information and referral to appropriate psycho-social services. Secondary aims include estimation of changes in psychological health and quality of life. The study will determine whether the intervention reduces unmet needs among patient dyads. A formal economic program will also be conducted. METHODS/DESIGN: This study is a single-blind, multi-centre, randomized controlled trial to determine the efficacy and cost-efficacy of a telephone outcall program among carers of newly diagnosed cancer patients. A total of 230 carer/patient dyads will be recruited into the study; following written consent, carers will be randomly allocated to either the outcall intervention program (n = 115) or to a minimal outcall / attention control service (n = 115). Carer assessments will occur at baseline, at one and six months post-intervention. The primary outcome is change in carer burden; the secondary outcomes are change in carer depression, quality of life, health literacy and unmet needs. The trial patients will be assessed at baseline and one month post-intervention to determine depression levels and unmet needs. The economic analysis will include perspectives of both the health care sector and broader society and comprise a cost-consequences analysis where all outcomes will be compared to costs. DISCUSSION: This study will contribute to our understanding on the potential impact of a telephone outcall program on carer burden and provide new evidence on an approach for improving the wellbeing of carers.Patricia M Livingston, Richard H Osborne, Mari Botti, Cathy Mihalopoulos, Sean McGuigan, Leila Heckel, Kate Gunn, Jacquie Chirgwin, David M Ashley and Melinda William
Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue
A new family of periplasmic-binding proteins that sense arsenic oxyanions
Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that's role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer
PURPOSE: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). METHODS:Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. RESULTS:Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by (18)FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively).CONCLUSIONS:The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active
BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer
The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case–control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% Cl 0.3–12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. © 1999 Cancer Research Campaig
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.
Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies
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