As this is a single-arm study, it remains undecided whether promotion info serum Ang-2 is a specific outcome predictor for bevacizumab or chemotherapy or for the combination of both. Irrespective of its specific predictive properties, however, measurements of pre-therapeutic serum Ang-2 could be valuable. For example, CRC patients awaiting secondary resection of metastases could be stratified by serum Ang-2 levels into risk groups. Whereas patients with low serum Ang-2 are likely to benefit from neoadjuvant bevacizumab-containing treatment, patients with high serum Ang-2 could require escalation of chemotherapy or use of other biologicals such as EGFR antibodies in patients with wild type k-ras oncogene or Ang-2 inhibitors that are currently in clinical development (Hu and Cheng, 2009).

Although definitive judgement on the role of Ang-2 as a specific biomarker of outcome to bevacizumab in CRC or other cancers will require analysis of large numbers of blood samples from phase III clinical trials comparing bevacizumab-containing therapy with chemotherapy alone, the promising results of this study should encourage researchers to further investigate the predictive value of Ang-2 in cancer treatment. Acknowledgments Dr U Fiedler (Heidelberg) is acknowledged for providing the human Ang-2 expression plasmid. VG and OC were funded by the Centre of Molecular Medicine Cologne (CMMC). Part of this work was funded by Mrs R Maassen (Erkelenz), the Moritz-Stiftung the Hilde-Kopp-Stiftung (Cologne) and the Marga and Walter Boll Stiftung (Kerpen).

Footnotes Supplementary Information accompanies the paper on British Journal of Cancer website (http://www.nature.com/bjc) Supplementary Material Supplementary Figures Click here for additional data file.(1.5M, ppt) Supplementary Table 1 Click here for additional data file.(75K, doc) Supplementary Table 2 Click here for additional data file.(68K, doc) Supplementary Table 3 Click here for additional data file.(45K, doc) Supplementary Figure Legends Click here for additional data file.(32K, doc)
consumption of high-fat, high-calorie (HF) diets leads to hyperphagia and obesity together with obesity-related phenotypes such as insulin resistance. Part of the obesigenic effect of a HF diet is via induction of hyperphagia via a number of different mechanisms, including impairment of the lipid-induced activation of the vagal afferent pathway (35).

Attention has recently focused on the role of the intestinal microbiota in the regulation of adiposity and body weight. Germ-free mice ingesting a HF diet are not hyperphagic, do not gain weight or adiposity, and do not display other metabolic effects, such as insulin resistance, associated with consumption of HF diets seen in conventionally raised mice. Conventionalization of germ-free mice with microbiota from lean mice or from genetically or diet-induced Carfilzomib obese mice results in recapitulation of the original phenotype (5).