Objective "A link between inflammation and cancer has been suspected over a long period of time and in recent years genetic evidence supporting such notion could be obtained. Several signaling pathways, such as NF-κB and STAT3, could be identified by our group as well as other groups to play important roles during tumor promotion and progression. Chronic inflammation leads to the formation of reactive oxygen and nitrogen species, which are known to cause DNA damage and inactivation of DNA repair mechanisms, thereby presumably inducing tumor-initiating mutations. On the other hand, oxidative stress has been documented to trigger apoptosis and cellular senescence. However, in vivo evidence demonstrating the consequences of increased oxidative stress on tumor development in a distinct genetic model is lacking. Selenoproteins of the glutathione peroxidase and thioredoxin reductase family are important anti-oxidant scavenger systems. Using cell type specific inactivation (epithelial cells an myeloid cells) of several of these family members in various well established and relevant models of inflammation-associated and sporadic colon tumorigenesis we will directly examine the role of these anti-oxidant systems. These models will allow us to genetically determine the outcome of increased lipid peroxidation and accumulation of reactive oxygen species in each cell type and to address whether cancer development is supported or inhibited under such conditions and will help to identify which phase of tumor development is affected. Furthermore, we expect to obtain results that will determine whether increased levels of ROS/RNS found during chronic inflammation are capable of initiating tumorigenesis. Our proposed experiments are supposed to provide fundamental insight into the molecular changes in the tumor microenvironment, which will ultimately help to identify novel strategies to prevent and treat colorectal cancer." Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutation Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG Address Paul ehrlich strasse 42-44 60596 Frankfurt Germany See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Robert Dornberger (Mr.) Principal investigator Florian Greten (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 038 672,25 Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG Germany EU contribution € 1 038 672,25 Address Paul ehrlich strasse 42-44 60596 Frankfurt See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Robert Dornberger (Mr.) Principal investigator Florian Greten (Prof.) Links Contact the organisation Opens in new window Website Opens in new window KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Participation ended Germany EU contribution € 461 327,78 Address Ismaninger strasse 22 81675 Muenchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Inge Linder (Ms.) Links Contact the organisation Opens in new window Website Opens in new window
