Trastuzumab in Esophagogastric Cancer: HER2-Testing and Treatment Reality outside Clinical Studies in Germany

We analysed trends over time in palliative first-line chemotherapy in patients with locally advanced or metastatic esophagogastric cancer. Special focus was on frequency and quality of HER2-testing and trends in drug use in combination with trastuzumab. Earlier published data about patients treated outside clinical studies showed a relatively low rate of HER2-testing and insufficient test quality. A total of 2,808 patients retrospectively documented in Therapiemonitor® from 2006 to 2013 were analysed regarding treatment intensity and trends in used drugs. Data on HER2-testing and therapies were analysed in two cohorts documented in 2010 and 2011 (1) compared to 2012 and 2013 (2). Treatment intensity increased: 49.3% of patients received at least a triplet in 2013 compared to 10.1% in 2006. In cohort 2 HER2 expression was tested in 79.1% of the cases. Still, in 26.9% testing was not done as requested by guidelines. Good performance status, multiple metastases, age ≤ 65 years, the objective “to prevent progression,” good cognitive capabilities, estimated good compliance, and social integration positively influenced the probability of HER2-testing; comorbidities negatively affected it. Usage of the combination of fluoropyrimidines and cisplatin with trastuzumab declined from 67% in cohort 1 to 50% in cohort 2

Quantitative profiling of the membrane proteome in a halophilic archaeon

We present a large scale quantitation study of the membrane proteome from Halobacterium salinarum. To overcome problems generally encountered with membrane proteins, we established a membrane preparation protocol that allows the application of most proteomic techniques originally developed for soluble proteins. Proteins were quantified using two complementary approaches. For gel-based quantitation, DIGE labeling was combined with two-dimensional gel electrophoresis on an improved 16-benzyldimethyl-n-hexadecylammonium chloride/SDS system. MS-based quantitation was carried out by combining gel-free separation with the recently developed isotope-coded protein labeling technique. Good correlations between these two independent quantitation strategies were obtained. From computational analysis we conclude that labeling of free amino groups by isotope-coded protein labeling (Lys and free N termini) is better suited for membrane proteins than Cys-based labeling strategies but that quantitation of integral membrane proteins remains cumbersome compared with soluble proteins. Nevertheless we could quantify 155 membrane proteins; 101 of these had transmembrane domains. We compared two growth states that strongly affect the energy supply of the cells: aerobic versus anaerobic/phototrophic conditions. The photosynthetic protein bacteriorhodopsin is the most highly regulated protein. As expected, several other membrane proteins involved in aerobic or anaerobic energy metabolism were found to be regulated, but in total, however, the number of regulated proteins is rather small