905 research outputs found
Staging for distant metastases in operable breast cancer: a suggested expansion of the ESMO guideline recommendation for staging imaging of node-negative, hormonal receptor-negative disease
We evaluated the impact of staging procedures to detect asymptomatic distant metastases (DM) in the management of women with operable invasive breast cancer (BC, entire cohort: n = 866). Out of 472 patients with lymph node (LN)-negative disease (pN0), DM were found in four cases (detection rate: 0.8%). All four patients presented with established risk factors: hormone receptor (HR)-negative status, HER2-positive status, n = 3; âtriple-negative' disease, n = 1. Considering the subgroup of LN-negative patients whose tumors showed the risk factor ânegative HR status' (n = 66), the detection rate of DM was 6%. The detection rates of DM in higher pN categories were as follows: pN1:1.7%; pN2:9.5%; pN3:13.5%. We generally support the international guidelines, including those published by the European Society for Medical Oncology (ESMO) which emphasize that patients with early-stage BC do not profit from radiological staging for the detection of DM and recommend refraining from this. However, we would expand these guidelines and propose that screening should be carried out in node-negative patients whose tumors show established tumor-related risk factors (e.g. HR-negative and HER2-positive status), since in this particular subcohort, the detection rate of DM is with 6% similarly high as that of patients with four to nine positive LN
Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a Fluorescence Imaging Plate Reader assay
The Orai1 Ca2+ permeable ion channel is an important component of store operated Ca2+ entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure-activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains. (C) 2016 Elsevier Ltd. All rights reserved
Production of Eta-Mesons in Collisions of Nucleons and Delta-Resonances
We calculate the cross section for the production of -mesons via
\mbox{} in a relativistic One-Boson-Exchange-Model.
Using this cross section we then determine the probability for the production
of an -meson by a -resonance moving in nuclear matter. The result
is compared to prescriptions in BUU-calculations in which \et-production
proceeds both through a direct channel and through the sequential process
.Comment: revised version: large parts have been rewritten, there are two new
figures. A discusion of effects of multi-body reactions of the intermediate
pion on our results has been adde
Non-commutative desingularization of determinantal varieties, I
We show that determinantal varieties defined by maximal minors of a generic
matrix have a non-commutative desingularization, in that we construct a maximal
Cohen-Macaulay module over such a variety whose endomorphism ring is
Cohen-Macaulay and has finite global dimension. In the case of the determinant
of a square matrix, this gives a non-commutative crepant resolution.Comment: 52 pages, 3 figures, all comments welcom
Using blood test parameters to define biological age among older adults: Association with morbidity and mortality independent of chronological age validated in two separate birth cohorts
Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer
<p>Abstract</p> <p>Background</p> <p>Fibronectin 1 (<it>FN1</it>) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of <it>FN1 </it>in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.</p> <p>Methods</p> <p>212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of <it>FN1 </it>mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ÎÎCt method for calculation of relative quantities.</p> <p>Results</p> <p>Mean tissue specific <it>FN1 </it>mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean <it>FN1 </it>expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9Ă10<sup>-5</sup>; Wilcoxon rank sum test). Patients with advanced disease had higher <it>FN1 </it>expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher <it>FN1 </it>mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).</p> <p>Conclusions</p> <p>To our knowledge, this is the first study to show that <it>FN1 </it>mRNA expression is higher in RCC compared to normal renal tissue. <it>FN1 </it>mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.</p
Strong fragmentation of low-energy electromagnetic excitation strength in Sn
Results of nuclear resonance fluorescence experiments on Sn are
reported. More than 50 transitions with MeV were
detected indicating a strong fragmentation of the electromagnetic excitation
strength. For the first time microscopic calculations making use of a complete
configuration space for low-lying states are performed in heavy odd-mass
spherical nuclei. The theoretical predictions are in good agreement with the
data. It is concluded that although the E1 transitions are the strongest ones
also M1 and E2 decays contribute substantially to the observed spectra. In
contrast to the neighboring even Sn, in Sn the
component of the two-phonon quintuplet built on top of
the 1/2 ground state is proved to be strongly fragmented.Comment: 4 pages, 3 figure
e^+e^- production from pp reactions at BEVALAC energies
We have performed a detailed study of dilepton production from pp collisions
including the subthreshold production via baryonic resonances (N(1520),
N(1700)) in addition to the conventional dilepton sources as and Dalitz decays and direct decays of vector mesons (). The role of baryonic resonances in production from
nucleon-nucleon collisions is studied in comparison to the DLS data which are
well described.Comment: 19 pages, revtex, including 7 postscript figures, to be published in
Nucl. Phys.
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