The majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a... Show moreThe majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a significant number of patients do not derive clinical benefit, and no predictive patient selection biomarker is currently available. Using mass spectrometry-based proteomics, we have profiled tumour resection material of 2 independent, multi-centre cohorts of in total 67 patients with NSCLC who underwent ACT. Unsupervised cluster analysis of both cohorts revealed a poor response/survival sub-cluster composed of similar to 25% of the patients, that displayed a strong epithelial-mesenchymal transition signature and stromal phenotype. Beyond this stromal sub-population, we identified and validated platinum response prediction biomarker candidates involved in pathways relevant to the mechanism of action of platinum drugs, such as DNA damage repair, as well as less anticipated processes such as those related to the regulation of actin cytoskeleton. Integration with pre-clinical proteomics data supported a role for several of these candidate proteins in platinum response prediction. Validation of one of the candidates (HMGB1) in a third independent patient cohort using immunohistochemistry highlights the potential of translating these proteomics results to clinical practice. Show less
Granda Marulanda, L.P.; Builes, S.; Koper, M.T.M.; Calle-Vallejo, F. 2019
Solvation can significantly modify the adsorption energy of species at surfaces, thereby influencing the performance of electrocatalysts and liquid‐phase catalysts. Thus, it is important to... Show moreSolvation can significantly modify the adsorption energy of species at surfaces, thereby influencing the performance of electrocatalysts and liquid‐phase catalysts. Thus, it is important to understand adsorbate solvation at the nanoscale. Here we evaluate the effect of van der Waals (vdW) interactions described by different approaches on the solvation energy of *OH adsorbed on near‐surface alloys (NSAs) of Pt. Our results show that the studied functionals can be divided into two groups, each with rather similar average *OH solvation energies: (1) PBE and PW91; and (2) vdW functionals, RPBE, PBE‐D3 and RPBE‐D3. On average, *OH solvation energies are less negative by ∼0.14 eV in group (2) compared to (1), and the values for a given alloy can be extrapolated from one functional to another within the same group. Depending on the desired level of accuracy, these concrete observations and our tabulated values can be used to rapidly incorporate solvation into models for electrocatalysis and liquid‐phase catalysis. Show less
Cao, K.; Lent, R. van; Kleyn, A.W.; Kurahashi, M.; Juurlink, L.B.F. 2019
Four-way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA-damage repair. In this study, a new mononuclear platinum(II)... Show moreFour-way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA-damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5 '-d(CGTACG)-3 ' specifically into a 4WJ-like motif. In the crystal structure of the 1-CGTACG adduct, the distorted-square-planar platinum complex binds to the core of the 4WJ-like motif through pi-pi stacking and hydrogen bonding, without forming any platinum-nitrogen coordination bonds. Our observations suggest that the specific molecular properties of the metal complex are crucially responsible for triggering the selective assembly of this peculiar DNA superstructure. Show less
