Checkerboard local density of states in striped domains pinned by vortices

Within a Green's function formalism we calculate the electronic structure around static extended magnetic and non-magnetic perturbations in a d-wave superconductor. In partucular, we discuss recent elastic neutron scattering and scanning tunneling experiments on High-T_c cuprates exposed to an applied magnetic field. A physical picture consisting of antiferromagnetic vortex cores operating as pinning centers for surrounding stripes is qualitatively consistent with the neutron data provided the stripes have the usual antiphase modulation. The low energy electronic structure in such a region reveals a checkerboard interference pattern consistent with recent scanning tunneling experiments.Comment: 5 pages, 4 figure

Renormalized mean-field theory of the neutron scattering in cuprate superconductors

The magnetic excitation spectrum of the t-t'-J-model is studied in mean-field theory and compared to inelastic neutron-scattering (INS) experiments on YBCO and BSCCO superconductors. Within the slave-particle formulation the dynamical spin response is calculated from a renormalized Fermi liquid with an effective interaction ~J in the magnetic particle--hole channel. We obtain the so-called 41meV resonance at wave vector (pi,pi) as a collective spin-1 excitation in the d-wave superconducting state. It appears sharp (undamped), if the underlying Fermi surface is hole-like with a sufficient next-nearest-neighbor hopping t'<0. The double-layer structure of YBCO or BSCCO is not important for the resonance to form. The resonance energy \omega_{res} and spectral weight at optimal doping come out comparable to experiment. The observed qualitative behavior of \omega_{res} with hole filling is reproduced in the underdoped as well as overdoped regime. A second, much broader peak becomes visible in the magnetic excitation spectrum if the 2D wave-vector is integrated over. It is caused by excitations across the maximum gap, and in contrast to the resonance its energy is almost independent of doping. At energies above or below \omega_{res} the commensurate resonance splits into incommensurate peaks, located off (pi,pi). Below \omega_{res} the intensity pattern is of `parallel' type and the dispersion relation of incommensurate peaks has a negative curvature. This is in accordance with recent INS experiments on YBCO.Comment: 17pp including 14 figure

Prognostic value of Lynch syndrome, BRAF V600E, and RAS mutational status in dMMR/MSI-H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts.

BACKGROUND: Current knowledge on prognostic biomarkers (especially BRAF V600E /RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors. METHODS: This observational cohort study combined a population-based Dutch cohort (2014-2019) and a large French multicenter cohort (2007-2017). All mCRC patients with a histologically proven dMMR tumor were included. RESULTS: In our real-world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first-line palliative systemic chemotherapy. Mean age of first-line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAF V600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66-1.72), BRAF V600E mutational status (HR: 1.02, 95% CI: 0.67-1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64-1.59), with similar results for PFS. CONCLUSION: BRAF V600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision-making in dMMR mCRC patients and underline the complex heterogeneity of mCRC

Prognostic Significance and Gene Expression Profiles of p53 Mutations in Microsatellite-Stable Stage III Colorectal Adenocarcinomas

Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI) and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA), and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and by immunohistochemistry (IHC). Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58%) than in MSI (30%) phenotypes. Both univariate (log-rank, P = 0.025) and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25–5.08) analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets

Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients

BACKGROUND: RAS mutations have been shown to confer resistance to anti-EGFR treatment. We analyzed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. METHODS: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumors harboring RAS & BRAF WT and RAS mutations. The prognostic value of each individual mutation was also tested. RESULTS: Among the 2559 pts analyzed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2,3,4 or NRAS exon 2,3,4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS & BRAF WT tumors (HR 0.77 to 1.03, all P>0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. CONCLUSION: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favor of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting.Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23