Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). ...However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.
This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.
Nanocrystalline La1‐xSrxCoO3‐δ (LSC) thin films with a nominal Sr‐content of x = 0.4 were deposited on Ce0.9Gd0.1O1.95 electrolyte substrates using a low temperature sol‐gel process. The structural ...and chemical properties of the LSC thin films were studied after thermal treatment, which included a calcination step and a variable, extended annealing time at 700 °C or 800 °C. Transmission electron microscopy combined with selected‐area electron diffraction, energy‐dispersive X‐ray spectrometry, and scanning transmission electron microscopy tomography was applied for the investigation of grain size, porosity, microstructure, and analysis of the local chemical composition and element distribution on the nanoscale. The area specific resistance (ASR) values of the thin film LSC cathodes, which include the lowest ASR value reported so far (ASRchem = 0.023 Ωcm2 at 600 °C) can be interpreted on the basis of the structural and chemical characterization.
Nanocrystalline and porous La0.6Sr0.4CoO3‐δ cathodes for intermediate‐temperature solid oxide fuel cells can be fabricated by sol‐gel dip coating. The achieved microstructure is investigated by means of scanning transmission electron microscopy tomography. The high porosity (up to 45%) and resulting large surface area are key features for the outstanding electrochemical performance of the cathodes.
Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W = 1748 MeV to W = 2045 MeV). The data ...cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη′ threshold Eγ = 1447 MeV (W = 1896 MeV). The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N (1895)1/2− nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.
New data on the polarization observables T, P, and H for the reaction γp→pπ(0) are reported. The results are extracted from azimuthal asymmetries when a transversely polarized butanol target and a ...linearly polarized photon beam are used. The data were taken at the Bonn electron stretcher accelerator ELSA using the CBELSA/TAPS detector. These and earlier data are used to perform a truncated energy-independent partial wave analysis in sliced-energy bins. This energy-independent analysis is compared to the results from energy-dependent partial wave analyses.
The aim of this study was to identify K-ras mutations as marker for isolated tumor cells in liver, lymph node, and bone marrow specimens of colorectal cancer patients. To detect these, a PCR-RFLP ...assay was used with a sensitivity exceeding that of routine histopathology by at least 1 order of magnitude. In addition, the ratio of mutated versus wild-type alleles was determined by an internal standard. Of 199 patients, 74 (37.5%) were found to bear a K-ras-positive tumor. Of these, 60 (81%) were mutated in codon 12 and 14 (19%) in codon 13 (P < 0.001). In addition, 14 organs were found K-ras positive, 13 of which were from 12 patients with a K-ras-positive tumor (16%) and 1 from a patient with a K-ras-negative tumor (0.8%). Eight patients exhibited liver involvement and 6 showed lymph node involvement. Remarkably, no bone marrow specimen was found K-ras positive (P < 0.017 versus liver involvement). Sequence analysis of tumor DNA revealed that GGT (Gly) was replaced by GAT (Asp; 35%), GTT (Val; 32%), AGT (Ser; 13%), GCT (Ala; 10%), TGT (Cys; 8%), and CGT (Arg; 2%) for codon 12, and by GAC (Asp) as the only type of mutation for codon 13. In colorectal carcinomas the ratio of K-ras mutated versus wild-type alleles ranged over 4 orders of magnitude (10(0)-10(-4), median: 10(-2)) and was correlated with both, residual tumor load (R1/2; P = 0.028) and distant metastasis (M1; P = 0.057). These results show that detection of K-ras mutated alleles by PCR-RFLP in patients with colorectal carcinoma may aid in the identification of isolated tumor cells. High ratios of K-ras alleles were correlated with certain negative prognostic parameters (R,M). In accord with its function as a primary filter for colorectal carcinoma cells, the liver was more often contaminated with K-ras-positive cells than bone marrow.
The polarization observables T,E,P,H, and G in photoproduction of η mesons off protons are measured for photon energies from threshold to W=2400 MeV (T), 2280 MeV (E), 1620 MeV (P,H), or 1820 MeV ...(G), covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, JüBo, and BnGa partial-wave analyses. A refit within the BnGa approach including further data yields precise branching ratios for the Nη decay of nucleon resonances. A Nη-branching ratio of 0.33±0.04 for N(1650)1/2− is found, which reduces the large and controversially discussed Nη-branching ratio difference of the two lowest mass JP=1/2−-resonances significantly.
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This paper reports on a measurement of the double-polarization observable
G
in
π
0
photoproduction off the proton using the CBELSA/TAPS experiment at the ELSA accelerator in Bonn. The observable
G
...is determined from reactions of linearly polarized photons with longitudinally polarized protons. The polarized photons are produced by bremsstrahlung off a diamond radiator of well-defined orientation. A frozen spin butanol target provides the polarized protons. The data cover the photon energy range from 617 to 1325 MeV and a wide angular range. The experimental results for
G
are compared to predictions by the Bonn-Gatchina (BnGa), Jülich-Bonn (JüBo), MAID and SAID partial wave analyses. Implications of the new data for the pion photoproduction multipoles are discussed.
Nanocrystalline La₁₋ₓ SrₓCoO₃₋δ (LSC) thin films with a nominal Sr content x = 0.5 were deposited on 3.5 mol% yttria-stabilized zirconia (YSZ) substrates by a low-temperature sol–gel process followed ...by a rapid thermal annealing procedure at temperatures up to 900 °C. The structural and chemical stability of the as-prepared nanocrystalline LSC and demixing effects within the thin film or at the LSC/YSZ interface were studied after long-time exposure at temperatures between 700 °C and 1,000 °C. The grain size and surface topography were analyzed by scanning electron microscopy. Transmission electron microscopy combined with selected-area electron diffraction, energy-dispersive X-ray spectrometry, and electron-spectroscopic imaging was applied for the investigation of the microstructure and the analysis of the local chemical composition and element distribution on the nanoscale. Chemical potential calculations, which were performed to assess the decomposition of LSC/YSZ as a function of temperature, show good agreement with the experimental results.
Cullin (CUL)-dependent ubiquitin ligases form a class of structurally related multisubunit enzymes that control the rapid and selective degradation of important regulatory proteins involved in cell ...cycle progression and development, among others. The CUL3-BTB ligases belong to this class of enzymes and despite recent findings on their molecular composition, our knowledge on their functions and substrates remains still very limited. In contrast to budding and fission yeast, CUL3 is an essential gene in metazoans. The model plant Arabidopsis thaliana encodes two related CUL3 genes, called CUL3A and CUL3B. We recently reported that cul3a loss-of-function mutants are viable but exhibit a mild flowering and light sensitivity phenotype. We investigated the spatial and temporal expression of the two CUL3 genes in reproductive tissues and found that their expression patterns are largely overlapping suggesting possible functional redundancy. Thus, we investigated the consequences on plant development of combined Arabidopsis cul3a cul3b loss-of-function mutations. Homozygous cul3b mutant plants developed normally and were fully fertile. However, the disruption of both the CUL3A and CUL3B genes reduced gametophytic transmission and caused embryo lethality. The observed embryo abortion was found to be under maternal control. Arrest of embryogenesis occurred at multiple stages of embryo development, but predominantly at the heart stage. At the cytological level, CUL3 loss-of-function mutations affected both embryo pattern formation and endosperm development.
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