Identification, validation and clinical implementation of cancer biomarkers: Translational strategies of the EORTC PathoBiology Group

AbstractThe increasing demand for personalized cancer therapy requires a strong, intense, and continuous collaboration between pre-clinical and clinical investigators. As a part of the EORTC Translational Research Divison, the EORTC PathoBiology Group (EORTC PBG), focuses on discovery and validation of cancer biomarkers, providing both scientific evidence as well as quality assurance. The clinically relevant target-identification and validation studies carried out in the last decades within the EORTC PBG represent a paradigm for EORTC studies in which laboratory investigations on human biologic material are used to support the development of drugs directed to defined target molecules. The experience acquired within the EORTC PBG with respect to standardization of cancer biomarker test kits and reagents, quality assessment/assurance of cancer biomarker determinations, development of standard operating procedures for assessment of these markers as well as instruction of methodologies and teaching of ethical issues represent a valuable contribution of the EORTC PBG to the onco-translational strategies of the EORTC

Predicting band gaps of semiconductors with quantum chemistry

The following article gives a brief introduction to quantum chemistry and its application to the prediction of band gaps of inorganic and organic semiconductors. Two important quantum chemistry concepts —Density Functional Theory (DFT) and Coupled Cluster Theory (CC)— are shortly explained. These two concepts are used to calculate the optical and the transport band gap of a set of semiconductors modelled with an electrostatic embedding approach

On the Role of Hydrogen Bonding in Gas-Phase S N 2 Reactions at Silicon

The shape of the potential energy surface (PES) of gas-phase SN2reactions at silicon is determined by the type of nucleophile, the leaving group, andsubstituents which remain bonded to silicon. In this study, we present PES scans alongthe reaction coordinate of six symmetrical SN2 reactions: X−+ SiR3X→XSiR3+X−,where X = Cl or F and R = H, Me, or OMe. While thefluorine systems and theClSiH3Cl system only give single-well PESs, ClSiMe3Cl and ClSi(OMe)3Cl give triple-and double-well PESs with stable pre- and post-reaction complexes. A complementarybonding analysis (energy decomposition analysis, quantum theory of atoms in molecules, and natural bond orbitals) reveals that theleaving group (X−) is stabilized by hydrogen bonding in the XSiMe3X and XSi(OMe)3X systems. It is shown that this so farneglected stabilizing contribution, along withσ-hole bonding, is responsible for the shapes of the PESs of ClSiMe3Cl andClSi(OMe)3Cl in the gas phase

Sila-Ibuprofen

The synthesis, characterization, biological activity,and toxicology of sila-ibuprofen, a silicon derivative of the most common nonsteroidal anti-inflammatory drug, is reported. The key improvements compared with ibuprofen are a four times higher solubility in physiological media and a lower melting enthalpy,which are attributed to the carbon−silicon switch. The improved solubility is of interest for postsurgical intravenous administration.A potential for pain relief is rationalized via inhibition experiments of cyclooxygenases I and II (COX-I and COX-II) as well as via a set of newly developed methods that combine molecular dynamics,quantum chemistry, and quantum crystallography. The binding affinity of sila-ibuprofen to COX-I and COX-II is quantified in terms of London dispersion and electrostatic interactions in the active receptor site. This study not only shows the potential of sila-ibuprofen for medicinal application but also improves our understanding of the mechanism of action of the inhibition process