Taken together, our novel data show that inhibition http://www.selleckchem.com/products/kpt-330.html of Rho-kinase signalling ameliorates tissue damage in pancreatitis. Indeed, our findings show that Rho-kinase regulates trypsinogen activation in pancreatitis and that interference with Rho-kinase activity decreased MIP-2 formation, neutrophil activation (Mac-1 expression) and recruitment in the pancreas. Thus, our results not only elucidate important signalling mechanisms in pancreatitis but also suggest that targeting Rho-kinase activity may be a useful approach to protect against pathological tissue damage in SAP.

Acknowledgments This work was supported by grants from the Swedish Medical Research Council (2009-4872), Crafoordska stiftelsen, Einar och Inga Nilssons stiftelse, Harald och Greta Jaenssons stiftelse, Greta och Johan Kocks stiftelser, Fr?ken Agnes Nilssons stiftelse, Franke och Margareta Bergqvists stiftelse f?r fr?mjande av cancerforskning, Magnus Bergvalls stiftelse, Mossfelts stiftelse, Nanna Svartz stiftelse, Ruth och Richard Julins stiftelse, Svenska L?kares?llskapet, Allm?na sjukhusets i Malm? stiftelse f?r bek?mpande av cancer, MAS fonder, Malm? University Hospital and Lund University. D Awla and A Abdulla are supported by a fellowship from the Kurdistan regional government and the Nanakali Group. Glossary Abbreviations i.p. intraperitoneal MIP-2 macrophage inflammatory protein-2 MNL monomorphonuclear leucocytes MPO myeloperoxidase MOPS 3-(morpholino) propanesulphonic acid PBS phosphate-buffered saline PMNL polymorphonuclear leucocytes RIA radioimmunoassay SAP severe acute pancreatitis TAP trypsinogen activating peptide Conflict of interest The authors state no conflict of interest.

Supporting Information Teaching Materials; Figs 1�C7 as PowerPoint slide. Click here to view.(459K, pptx)
The overall survival (OS) time of patients with metastatic colorectal cancer (CRC) has increased owing to novel therapeutic strategies combining chemotherapy with monoclonal antibodies against vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). Whereas mutations in the k-ras oncogene predict outcome to EGFR antibody treatment in patients with metastatic CRC (Lievre et al, 2006; Karapetis et al, 2008), equivalent biomarkers for the VEGF antibody, bevacizumab, are currently lacking (Jubb et al, 2006b; Sessa et al, 2008), mainly because the specific molecular determinants of clinical response and resistance to the drug are unknown. Similarly, there are currently no established biomarkers predicting outcome to chemotherapy in CRC (De Roock et al, 2009). Originally, it Brefeldin_A was anticipated that traditional markers of tumour angiogenesis would predict outcome to bevacizumab.