caa a22 4500 463186893 CHVBK 20180406164856.0 cr unu---uuuuu 170326e20070801xx s 000 0 eng 10.1007/s00726-007-0515-2 doi (NATIONALLICENCE)springer-10.1007/s00726-007-0515-2 Rationale for, and design of, a clinical trial targeting polyamine metabolism for colon cancer chemoprevention [Elektronische Daten] [E. W. Gerner, F. L. Meyskens Jr, S. Goldschmid, P. Lance, D. Pelot] Summary.: Polyamine metabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers. Inhibitors of ornithine decarboxylase, such as difluoromethylornithine (DFMO), and agents that stimulate polyamine acetylation and export, such as non-steroidal anti-inflammatory drugs (NSAIDS), act at least additively to arrest growth in human cell models and suppress intestinal carcinogenesis in mice. These preclinical studies provided the rationale for colon cancer prevention trials in humans. A Phase IIb clinical study comparing the combination of DFMO and the NSAID sulindac versus placebo was conducted. Endpoints were colorectal tissue polyamine and prostaglandin E2 contents and overall toxicity to participants. Participants in the Phase IIb study served as a vanguard for a randomized, placebo-controlled prospective Phase III trial of the combination of DFMO and sulindac with the primary study endpoint the prevention of colon polyps. Seventy percent of participants will have completed the three years of treatment in December 2006. Springer-Verlag, 2007 Keywords: Colon cancer - Chemoprevention - Polyamines - Difluoromethylornithine - Nonsteroidal anti-inflammatory drugs - Clinical trials nationallicence APC : Adenomatous polyposis coli nationallicence COX1 : cyclooxygenase 1 nationallicence COX2 : cyclooxygenase 2 nationallicence DFMO : difluoromethylornithine nationallicence FAP : familial adenomatous polyposis nationallicence HNPCC : hereditary non-polyposis colon cancer nationallicence NSAIDS : non-steroidal anti-inflammatory drugs nationallicence ODC : ornithine decarboxylase nationallicence PPARγ : peroxisomal proliferator activated receptor γ nationallicence SAT : spermidine/spermine N1-acetyltransferase nationallicence SNP : single nucleotide polymorphism nationallicence Gerner E. W. Arizona Cancer Center, Department of Cell Biology and Anatomy, The University of Arizona, Tucson, AZ, USA aut Meyskens Jr F. L. Chao Family Comprehensive Cancer Center, Department of Medicine, The University of California, Irvine, CA, USA aut Goldschmid S. Arizona Cancer Center, Department of Medicine, The University of Arizona, Tucson, AZ, USA aut Lance P. Arizona Cancer Center, Department of Medicine, The University of Arizona, Tucson, AZ, USA aut Pelot D. Chao Family Comprehensive Cancer Center, Department of Medicine, The University of California, Irvine, CA, USA aut Amino Acids Springer-Verlag 33/2(2007-08-01), 189-195 0939-4451 33:2<189 2007 33 726 https://doi.org/10.1007/s00726-007-0515-2 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-007-0515-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gerner E. W. Arizona Cancer Center, Department of Cell Biology and Anatomy, The University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Meyskens Jr F. L. Chao Family Comprehensive Cancer Center, Department of Medicine, The University of California, Irvine, CA, USA aut NATIONALLICENCE 700 1- Goldschmid S. Arizona Cancer Center, Department of Medicine, The University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Lance P. Arizona Cancer Center, Department of Medicine, The University of Arizona, Tucson, AZ, USA aut NATIONALLICENCE 700 1- Pelot D. Chao Family Comprehensive Cancer Center, Department of Medicine, The University of California, Irvine, CA, USA aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 33/2(2007-08-01), 189-195 0939-4451 33:2<189 2007 33 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer