85 research outputs found

    Clinical Validation of a Multiplex Kit for RAS Mutations in Colorectal Cancer: Results of the RASKET (RAS KEy Testing) Prospective, Multicenter Study

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    AbstractBackgroundRAS (KRAS and NRAS) testing is required to predict anti-epidermal growth factor receptor (EGFR) treatment efficacy in metastatic colorectal cancer (CRC). Although direct sequencing (DS) with manual microdissection (MMD) is widely used, a diagnostic kit providing rapid detections of RAS mutations would be clinically beneficial. We evaluated the MEBGENTM RASKET KIT (RASKET KIT), a multiplex assay using PCR-reverse sequence specific oligonucleotide and xMAP® technology to concurrently detect exon 2, 3, and 4 RAS mutations in a short turnaround time (4.5h/96-specimens).MethodsFormalin-fixed paraffin-embedded (FFPE) tissues were obtained from 308 consenting patients with histologically-confirmed CRC at six hospitals in Japan. For the RASKET KIT, we used only 50–100ng DNA from each FFPE specimen not processed by MMD. The primary endpoint was the concordance rate between RAS mutations identified with the RASKET KIT and two reference assays (DS with MMD and TheraScreen® K-RAS Mutation Kit). As the secondary endpoints, we evaluated the concordance rate between DS and the RASKET KIT for RAS mutations in the wild-type KRAS exon 2 population and the genotyping performance of the RASKET KIT compared with DS.FindingsAmong 307 analyzable specimens, the reference assays detected 140 (45.6%, 140/307) RAS mutations: 111 KRAS exon 2 and 29 other (minor) RAS mutations. The RASKET KIT detected 143 (46.6%, 143/307) mutations: 114 KRAS exon 2 and 29 minor RAS mutations. The between-method concordance rate was 96.7% (297/307) (95% CI: 94.1–98.4%). Minor RAS mutations were detected in 15.7% (30/191) of the wild-type KRAS exon 2 population (n=191); the concordance rate was 98.4% (188/191) (95% CI: 95.5–99.7%). The concordance rate of RAS genotyping was 100% (139/139) (95% CI: 97–100%).InterpretationThe RASKET KIT provides rapid and precise detections of RAS mutations and consequently, quicker and more effective anti-EGFR therapy for CRC (Study ID: UMIN000011784).FundingMedical & Biological Laboratories Co., Ltd. (MBL). MBL had roles in study design, data collection, data analysis, and writing of the report for the study

    Three-dimensional electronic structure in ferromagnetic Fe3Sn2\textrm{Fe}_3\textrm{Sn}_2 with breathing kagome bilayers

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    A large anomalous Hall effect (AHE) has been observed in ferromagnetic Fe3Sn2\textrm{Fe}_3\textrm{Sn}_2 with breathing kagome bilayers. To understand the underlying mechanism for this, we investigate the electronic structure of Fe3Sn2\textrm{Fe}_3\textrm{Sn}_2 by angle-resolved photoemission spectroscopy (ARPES). In particular, we use both vacuum ultraviolet light (VUV) and soft x ray (SX), which allow surface-sensitive and relatively bulk-sensitive measurements, respectively, and distinguish bulk states from surface states, which should be unlikely related to the AHE. While VUV-ARPES observes two-dimensional bands mostly due to surface states, SX-ARPES reveals three-dimensional band dispersions with a periodicity of the rhombohedral unit cell in the bulk. Our data show a good consistency with a theoretical calculation based on density functional theory, suggesting a possibility that Fe3Sn2\textrm{Fe}_3\textrm{Sn}_2 is a magnetic Weyl semimetal.Comment: 6 pages, 4 figure

    Multiple phosphorus chemical sites in heavily phosphorus-doped diamond

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    We have performed high-resolution core level photoemission spectroscopy on a heavily phosphorus (P)-doped diamond film in order to elucidate the chemical sites of doped-phosphorus atoms in diamond. P 2p core level study shows two bulk components, providing spectroscopic evidence for multiple chemical sites of doped-phosphorus atoms. This indicates that only a part of doped-phosphorus atoms contribute to the formation of carriers. From a comparison with band calculations, possible origins for the chemical sites are discussed

    Analysis on photoemission spectrum of superconducting FeSe

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    In this paper, we present the result of soft X-ray photoemission spectroscopy and its comparison with the density functional calculation. Although local density approximation seems to be a good starting point for describing the electronic structure of FeSe, the simulated spectrum poorly reproduced the structure around E(B) = 2 eV. This result suggests the necessity of theoretical treatment beyond local density approximation

    Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second-line antiangiogenic therapies : exploratory analyses of the RAISE trial and validation in an electronic medical record data set

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    In the RAISE trial, ramucirumab+leucovorin/fluorouracil/irinotecan (FOLFIRI) improved the median overall survival (mOS) of patients with previously treated metastatic colorectal cancer versus patients treated with placebo+FOLFIRI but had a higher incidence of neutropaenia, leading to more chemotherapy dose modifications and discontinuations. Thus, we conducted an exploratory post-hoc analysis of RAISE and a retrospective, observational analysis of electronic medical record (EMR) data to determine and verify the association of neutropaenia, baseline absolute neutrophil count (ANC) and survival. The RAISE analysis used the study safety population (n=1057). IMS Health Oncology Database (IMS EMR) was the source for the real-world data set (n=617). RAISE patients with treatment-emergent neutropaenia had improved mOS compared with those without (ramucirumab arm: 16.1 vs 10.7 months, HR=0.57, p<0.0001; placebo arm: 12.7 vs 10.7 months, HR=0.76, p=0.0065). RAISE patients with low ANC versus high baseline ANC also had longer mOS (ramucirumab arm: 15.2 vs 8.9 months, HR=0.49, p<0.0001; placebo arm: 13.2 vs 7.3 months, HR=0.50, p<0.0001). The results were similar for IMS EMR low versus high baseline ANC (bevacizumab+FOLFIRI patients: 14.9 vs 7.7 months, HR=0.59, p<0.0001; FOLFIRI alone: 14.6 vs 5.4 months, HR=0.37, p<0.0001). Patients in the RAISE trial with low baseline ANC were more likely to develop neutropaenia (OR: ramucirumab arm=2.62, p<0.0001; placebo arm=2.16, p=0.0003). Neutropaenia during treatment, and subsequent dose modifications or discontinuations, do not compromise treatment efficacy. Baseline ANC is a strong prognostic factor for survival and is associated with treatment-emergent neutropaenia in the analysed population. , Results
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