519 research outputs found
Porphyrinogenic activity and ferrochelatase-inhibitory activity of sydnones in chick embryo liver cells
Abstract3-[2-(2,4,6-Trimethylphenyl)thioethyl]-4-methylsydnone was shown to be a potent porphyrinogenic agent in chick embryo liver cells. The accumulation of protoporphyrin IX was consistent with the finding that ferrochelatase activity was inhibited. 3-Benzyl-4-phenylsydnone did not inhibit ferrochelatase activity and protoporphyrin IX was found to constitute only a minor fraction of the porphyrins. These results support the idea that the porphyrinogenicity of 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone is due to its catalytic activation by cytochrome P-450 leading to heme alkylation and formation of N-vinylprotoporphyrin IX which inhibits ferrochelatase
Evaluating the effectiveness of neoadjuvant chemotherapy in reducing mastectomy for women with breast cancer
Background: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. Methods: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. Results: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. Conclusions: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment
Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States
Background Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Study Design Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Results Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69–0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74–0.83). Conclusions Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓
A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0 fb-1 of pp collisions at √s=7 TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101 TeV/c2 and MLQ(B0→e±μ∓)>126 TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
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