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  • Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer
    Publication . Herbst, A; Vdovin, N; Gacesa, S; Philipp, A; Nagel, D; Holdt, LM; Op den Winkel, M; Heinemann, V; Stieber, P; Graeven, U; Reinacher-Schick, A; Arnold, D; Ricard, I; Mansmann, U; Hegewisch-Becker, S; Kolligs, F T
    Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab.
    2017-05-01Journal article Open access Show more
  • Measurement of differential cross sections for top quark pair production using the lepton+jets final state in proton-proton collisions at 13 TeV
    Publication . CMS collaboration (2274 authors); Calpas, Betty; Nayak, Aruna; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Di Francesco, Agostino; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Hollar, Jonathan; Leonardo, Nuno; Lloret Iglesias, Lara; Rodrigues Antunes, Joao; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Vischia, Pietro; David Tinoco Mendes, Andre; Silva, Pedro; Musella, Pasquale; Pela, Joao
    Differential and double-differential cross sections for the production of top quark pairs in proton-proton collisions at 13 TeV are measured as a function of jet multiplicity and of kinematic variables of the top quarks and the top quark-antiquark system. This analysis is based on data collected by the CMS experiment at the LHC corresponding to an integrated luminosity of 2.3  fb−1. The measurements are performed in the lepton+jets decay channels with a single muon or electron in the final state. The differential cross sections are presented at particle level, within a phase space close to the experimental acceptance, and at parton level in the full phase space. The results are compared to several standard model predictions.
    2017-05-01Journal article Open access Show more